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Reflections on learning how to play a violin left-handed: Motor Learning aspects Background Playing the violin is a highly-skilled activity, requiring a high level of motor control, combined with other cognitive skills that include... more
Reflections on learning how to play a violin left-handed: Motor Learning aspects Background Playing the violin is a highly-skilled activity, requiring a high level of motor control, combined with other cognitive skills that include processing rhythm and intonation, and reading musical notation, with the goal of emotional expression. But adult expert violinists remember very little about the process of first learning how to play. Purpose This qualitative study aimed to describe what an expert violinist/ violin teacher would reveal about the learning challenges encountered in relearning her skill ‘left-handed’ and the learning strategies adopted to overcome them. Normally a violinist uses the left hand to stop the strings, while the right hand is responsible for drawing the bow across the strings to make the sound; in this experiment the violin and bow were held in the opposite hands. Methods A qualitative approach was undertaken, in which the expert player (VM) recorded her responses...
Most men, regardless of the breadth of differences in life experience, recognise that fathering today is different to how they were fathered. While society has changed, few men discuss these changes with other men or have the opportunity... more
Most men, regardless of the breadth of differences in life experience, recognise that fathering today is different to how they were fathered. While society has changed, few men discuss these changes with other men or have the opportunity to talk about them with health professionals. This guide is primarily focused on engaging fathers in community services, health contexts and programs who otherwise are often less involved for a wide variety of reasons. It has been written to support health professionals to engage with the fathers in the families that they work with, encourage them to discuss the significance of the role they play and the impact that this has on other family members. The term ‘father’ in this guide reflects the different ideas, responsibilities, duties, and activities that men play today in family life. In contemporary society, a father can be both biological and social and described as the significant male role model in a child’s life. Men who are the significant ro...
Phytoplankton require carbon dioxide (CO2) as the primary substrate for carbon fixation and therefore growth. The response of phytoplankton to variability in partial pressure of CO2 (pCO2) depends upon inorganic carbon acquisition and the... more
Phytoplankton require carbon dioxide (CO2) as the primary substrate for carbon fixation and therefore growth. The response of phytoplankton to variability in partial pressure of CO2 (pCO2) depends upon inorganic carbon acquisition and the efficiency of these process. Shifts in phytoplankton community structure are expected, but it is unclear whether these shifts will favor more- or less-nutritious phytoplankton to support fisheries and aquaculture production of human food. To anticipate how both natural and anthropogenic changes in ocean pCO2 (a predicted doubling in atmospheric pCO2 over the next century) will affect the base of the marine food web, we have begun efforts to determine competitive interactions between phytoplankton species under experimentally-simulated ocean-acidification conditions. We will characterize physiological (i.e., lipid and fatty acid composition) and growth responses to different pCO2/pH conditions of species representing main phytoplankton functional gr...
DNA methylation is one of a number of modes of epigenetic gene regulation. Here, we profile the DNA methylome, transcriptome, and global occupancy of histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac) in a series of mouse... more
DNA methylation is one of a number of modes of epigenetic gene regulation. Here, we profile the DNA methylome, transcriptome, and global occupancy of histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac) in a series of mouse embryonic stem cells (mESCs) with varying DNA methylation levels to study the effects of DNA methylation on deposition of histone modifications. We find that genome-wide DNA demethylation alters occupancy of histone modifications at both promoters and enhancers. This is reversed upon remethylation by Dnmt expression. DNA methylation promotes H3K27me3 deposition at bivalent promoters, while opposing H3K27me3 at silent promoters. DNA methylation also reversibly regulates H3K27ac and H3K27me3 at previously identified tissue-specific enhancers. These effects require DNMT catalytic activity. Collectively, our data show that DNA methylation is essential and instructive for deposition of specific histone modifications across regulatory regions, which together...
Knowledge of length-weight relationships for commercially exploited fish is an important tool for assessing and managing of fish stocks. However, analyses of length-weight relationship fisheries data typically do not consider the inherent... more
Knowledge of length-weight relationships for commercially exploited fish is an important tool for assessing and managing of fish stocks. However, analyses of length-weight relationship fisheries data typically do not consider the inherent differences in length-weight relationships for fish caught from different habitats, seasons, or years, and this can affect the utility of these data for developing condition indices or calculating fisheries biomass. Here, we investigated length-weight relationships for ribbonfish Trichiurus lepturus in the waters of the Arabian Sea off Oman collected during three periods (2001-02, 2007-08, and 2014-15) and showed that a multivariate modelling approach that considers the areas and seasons in which ribbonfish were caught improved estimation of length-weight relationships. We used the outputs of these models to explore spatio-temporal variations in condition indices and relative weights among ribbonfish, revealing fish of 85-125 cm were in the best ov...
Electronic medical records (EMRs) are capturing increasing amounts of data per patient. For clinicians to efficiently and accurately understand a patient's clinical state, better ways are needed to determine when and how to display... more
Electronic medical records (EMRs) are capturing increasing amounts of data per patient. For clinicians to efficiently and accurately understand a patient's clinical state, better ways are needed to determine when and how to display EMR data. We built a prototype system that records how physicians view EMR data, which we used to train models that predict which EMR data will be relevant in a given patient. We call this approach a Learning EMR (LEMR). A physician used the prototype to review 59 intensive care unit (ICU) patient cases. We used the data-access patterns from these cases to train logistic regression models that, when evaluated, had AUROC values as high as 0.92 and that averaged 0.73, supporting that the approach is promising. A preliminary usability study identified advantages of the system and a few concerns about implementation. Overall, 3 of 4 ICU physicians were enthusiastic about features of the prototype.
Schott had delivered blanks for large lenses and prisms since many decades. Glass and glass ceramics objects with dimensions above 300 mm diameter or edge lengths will remain challenges for a glass manufacturer. This holds especially when... more
Schott had delivered blanks for large lenses and prisms since many decades. Glass and glass ceramics objects with dimensions above 300 mm diameter or edge lengths will remain challenges for a glass manufacturer. This holds especially when the quality specifications exceed the ...
ABSTRACT A positive safety culture among construction firms is known to be an invaluable means by which accident prevention and employee safety on sites can be improved. Workers of small construction firms strive to create and maintain... more
ABSTRACT A positive safety culture among construction firms is known to be an invaluable means by which accident prevention and employee safety on sites can be improved. Workers of small construction firms strive to create and maintain safe working environments for each other and for the safety of stakeholders. Based on the organisational and safety cultures developed within small construction firms, the workers have been known to incorporate informal and situational practices in order to improve site and project safety. This paper investigates the safety cultures found in small construction firms including workers' informal practices in relation to hazard identification and accident prevention. The paper is based on a research project that has an overall aim of investigating 'good' safety practices of workers of small construction firms in the East Midlands region of the United Kingdom. In this qualitative research, rich data was acquired through semi-structured interviews and non-participant observations from five construction sites. Findings from the empirical work suggest that owners and experienced workers of small construction firms significantly shape the outcome of the firms' safety cultures. For example, when they show initiative for producing safe working environments, other workers are compelled to follow suit and vice-versa. Furthermore, workers of small construction firms undertake 'informal' practices that help improve safety on site including informal risk assessment and subsequent management of hazardous events. In addition, new and less experienced worker receive effective guidance and vital on-the-job training in a way that is not documented. Unlike much research in the field, this project seeks to identify and encourage activities and approaches that help workers of small construction firms create working attitudes and environments.
Mobilized peripheral blood hematopoietic stem cells (PBSCs) demonstrate accelerated engraftment compared with bone marrow; however, mechanisms responsible for enhanced engraftment remain unknown. PBSCs mobilized by GRObeta... more
Mobilized peripheral blood hematopoietic stem cells (PBSCs) demonstrate accelerated engraftment compared with bone marrow; however, mechanisms responsible for enhanced engraftment remain unknown. PBSCs mobilized by GRObeta (GRObeta(Delta4)/CXCL2(Delta4)) or the combination of GRObeta(Delta4) plus granulocyte colony-stimulating factor (G-CSF) restore neutrophil and platelet recovery faster than G-CSF-mobilized PBSCs. To determine mechanisms responsible for faster hematopoietic recovery, we characterized immunophenotype and function of the GRObeta-mobilized grafts. PBSCs mobilized by GRObeta(Delta4) alone or with G-CSF contained significantly more Sca-1(+)-c-kit(+)-lineage(-) (SKL) cells and more primitive CD34(-)-SKL cells compared with cells mobilized by G-CSF and demonstrated superior competitive long-term repopulation activity, which continued to increase in secondary and tertiary recipients. GRObeta(Delta4)-mobilized SKL cells adhered better to VCAM-1(+) endothelial cells compared with G-CSF-mobilized cells. GRObeta(Delta4)-mobilized PBSCs did not migrate well to the chemokine stromal derived factor (SDF)-1alpha in vitro that was associated with higher CD26 expression. However, GRObeta(Delta4)-mobilized SKL and c-Kit(+) lineage(-) (KL) cells homed more efficiently to marrow in vivo, which was not affected by selective CXCR4 and CD26 antagonists. These data suggest that GRObeta(Delta4)-mobilized PBSCs are superior in reconstituting long-term hematopoiesis, which results from differential mobilization of early stem cells with enhanced homing and long-term repopulating capacity. In addition, homing and engraftment of GRObeta(Delta4)-mobilized cells is less dependent on the SDF-1alpha/CXCR4 axis.
We have identified a novel regulatory erythroid kinase (REDK) that is homologous to a family of dual-specificity kinases. The yeast homolog of REDK negatively regulates cell division, suggesting a similar function for REDK, which is... more
We have identified a novel regulatory erythroid kinase (REDK) that is homologous to a family of dual-specificity kinases. The yeast homolog of REDK negatively regulates cell division, suggesting a similar function for REDK, which is primarily localized in the nucleus. REDK is present in hematopoietic tissues, such as bone marrow and fetal liver, but the RNA is expressed at significant levels only in erythroid or erythropoietin (EPO)-responsive cells. Two novel forms of cDNA (long and short) for REDK have been isolated that appear to be alternative splice products and imply the presence of polypeptides with differing amino termini. The ratio of short-to-long forms of REDK increases dramatically in CD34(+) cells cultured with EPO, suggesting differing regulation and function for each form. REDK is predominantly found in nuclear, rather than cytoplasmic, protein extracts, and immunoprecipitated REDK is active in phosphorylating histones H2b, H3, myelin basic protein, and other coimmuno...
A nonpeptidyl small molecule SB 247464, capable of activating granulocyte-colony-stimulating factor (G-CSF) signal transduction pathways, was identified in a high-throughput assay in cultured cells. Like G-CSF, SB 247464 induced tyrosine... more
A nonpeptidyl small molecule SB 247464, capable of activating granulocyte-colony-stimulating factor (G-CSF) signal transduction pathways, was identified in a high-throughput assay in cultured cells. Like G-CSF, SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated primary murine bone marrow cells to form granulocytic colonies in vitro. It also elevated peripheral blood neutrophil counts in mice. The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464, suggesting that the compound acts by oligomerizing receptor chains. The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand.
Myelosuppression has been observed with several multikinase angiogenesis inhibitors in clinical studies, although the frequency and severity varies among the different agents. Inhibitors targeting vascular endothelial growth factor... more
Myelosuppression has been observed with several multikinase angiogenesis inhibitors in clinical studies, although the frequency and severity varies among the different agents. Inhibitors targeting vascular endothelial growth factor receptor (VEGFR) often inhibit other kinases, which may contribute to their adverse-event profiles. Kinase selectivity of pazopanib, sorafenib, and sunitinib was evaluated in a panel of 242 kinases. Cellular potency was measured using autophosphorylation assays. Effect on human bone marrow progenitor growth in the presence of multiple growth factors was evaluated and correlated with the kinase selectivity. Sunitinib inhibited more kinases than pazopanib and sorafenib, at potencies within 10-fold of VEGFR-2. All three compounds potently inhibited VEGFR-2, platelet-derived growth factor receptor-beta and c-Kit, However, pazopanib was less active against Flt-3 in both kinase and cellular assays. The inhibitory properties of pazopanib, sorafenib, and sunitini...
Natural host defenses against pathogens require efficient production of mature effector cells. Impairment of this function results in invasive infections in cancer patients or in other patients with suppressed immune systems such as burn... more
Natural host defenses against pathogens require efficient production of mature effector cells. Impairment of this function results in invasive infections in cancer patients or in other patients with suppressed immune systems such as burn or surgical patients. The hematopoietic factors, chemokines, and interleukins, which stimulate host defense mechanisms, offer new therapeutic venues. Since the late 1980s, clinical trials of CSFs
Pyrimidineacetic acids and (pyrimidinyloxy)acetic acids were synthesized by alkylation, with methyl bromoacetate or tert-butyl bromoacetate as alkylating agents. Alkylation reaction at the nitrogen or oxygen atom for different substrates... more
Pyrimidineacetic acids and (pyrimidinyloxy)acetic acids were synthesized by alkylation, with methyl bromoacetate or tert-butyl bromoacetate as alkylating agents. Alkylation reaction at the nitrogen or oxygen atom for different substrates was found to be solvent dependent. N-Alkylation was favored in ethereal solvent, e.g., tetrahydrofuran and dimethoxyethane, whereas O-alkylation was predominant in dimethylformamide. These compounds were tested in vitro to determine their ability to inhibit bovine lens aldose reductase. Selected compounds were assayed in vivo, in a 4-day galactose-fed rat model. The decrease in galactitol from the control was determined in lens, nerve, and diaphragm. Several of the 6-oxopyrimidine-1-acetic acids and (pyrimidinyl-4-oxy)acetic acids were found to be potent inhibitors of bovine lens aldose reductase. A study was also undertaken to determine in vitro the transport behavior of selected compounds in the isolated rat sciatic nerve. A discussion of the structure-activity relationship of this class of compounds with reference to their intrinsic biochemical activity is reported. It is concluded, in general, that ability of a compound to penetrate the tissue membrane plays an important role in the genesis of in vivo lens aldose reductase (LAR) inhibitory activity.
Using computed tomography of lumbar spine pedicles, pedicle morphology was documented in 30 patients with adolescent idiopathic scoliosis. Lumbar pedicles are relatively symmetrical in patients with adolescent idiopathic scoliosis;... more
Using computed tomography of lumbar spine pedicles, pedicle morphology was documented in 30 patients with adolescent idiopathic scoliosis. Lumbar pedicles are relatively symmetrical in patients with adolescent idiopathic scoliosis; however, a statistically significant difference was found between males and females at L2-L4. A trend for increased transverse pedicle width was observed on the concavity versus the convexity. At levels L3-L5, 90% of the pedicles were >5.5 mm but pedicles Li and 12 were smaller, only >5.5 mm in 34% and 42%, respectively. Safe insertion of 5.5-mm screws is possible at 13-15, but more cephalic pedicles necessitate caution.
A lemma of Fouquet implies that a claw-free graph contains an induced $C_5$, contains no odd hole, or is quasi-line. In this paper we use this result to give an improved shortest-odd-hole algorithm for claw-free graphs by exploiting the... more
A lemma of Fouquet implies that a claw-free graph contains an induced $C_5$, contains no odd hole, or is quasi-line. In this paper we use this result to give an improved shortest-odd-hole algorithm for claw-free graphs by exploiting the structural relationship between line graphs and quasi-line graphs suggested by Chudnovsky and Seymour's structure theorem for quasi-line graphs. Our approach involves
Five years ago, it was first demonstrated that there are considerable, stable individual differences in performance impairment due to sleep deprivation. The discovery of this new phenotype, which has been labeled... more
Five years ago, it was first demonstrated that there are considerable, stable individual differences in performance impairment due to sleep deprivation. The discovery of this new phenotype, which has been labeled 'trototype', led to a surge of research activity aiming to identify predictors. Genes involved in the adenosinergic and circadian regulation of sleep have been identified as candidate predictors of individuals' resistance or susceptibility to performance impairment resulting from sleep deprivation. Furthermore, brain regions potentially involved in the expression of individual differences in vulnerability to sleep loss have been found. This research has provided new insights into the mechanisms underlying sleep/wake regulation and responses to loss of sleep. To date, however, it remains unknown how much of the phenotypic variability is explained by any of the putative predictors of trototype. The existence of substantial, phenotypic individual differences in performance impairment consequent to sleep loss has important implications for fatigue risk management in operational settings and for the symptomology and treatment of sleep disorders, putting a premium on the discovery of reliable predictors.
Graph theory analysis of biological networks, such as protein-protein interactions (PPIs), gene regulatory, metabolic, etc., has identified a strong relationship between topology of these networks and the underlying cellular function and... more
Graph theory analysis of biological networks, such as protein-protein interactions (PPIs), gene regulatory, metabolic, etc., has identified a strong relationship between topology of these networks and the underlying cellular function and biological processes (Sharan et al. Mol Syst Biol 3:88, 2007). We focus on PPI networks, in which nodes correspond to proteins and edges represent interactions among the proteins. The size of these networks is ever growing, and thus efficient identification of various network motifs and dense sub-networks has become necessary. Predicting highly connected sub-graphs in a PPI network is important to biologists as it may help to identify biologically meaningful protein complexes, and with further integrative analysis may lead to identifying dynamic assembly of individual subunits in these complexes. In this chapter, we describe one method for predicting protein complexes in two steps. The first step is to partition the nodes of a PPI network (i.e. prot...
SB-251353 is an N-terminal truncated form of the human CXC chemokine GROb. Recombinant SB-251353 was profiled in murine and rhesus monkey peripheral blood stem cell mobilization and trans- plantation models. SB-251353 rapidly and... more
SB-251353 is an N-terminal truncated form of the human CXC chemokine GROb. Recombinant SB-251353 was profiled in murine and rhesus monkey peripheral blood stem cell mobilization and trans- plantation models. SB-251353 rapidly and transiently mobilized hematopoietic stem cells and neutrophils into the peripheral blood after a single subcutaneous injec- tion. Transplantation of equivalent num- bers of hematopoietic stem cells mobi-
Time series monitoring changes in titanium and stainless steel rod curvature kept at a constant temperature of 37 C as a function of time. To assess the possibility of loss of curvature in titanium rods after scoliosis surgery. Titanium... more
Time series monitoring changes in titanium and stainless steel rod curvature kept at a constant temperature of 37 C as a function of time. To assess the possibility of loss of curvature in titanium rods after scoliosis surgery. Titanium rods have gained use in scoliosis surgery due to their excellent biocompatibility, while allowing medical personnel to obtain undistorted magnetic resonance imaging scans following surgery. However, the impression of several clinicians has been that when screw pullout and/or loss of sagittal balance occurs, it may be due to the rods losing some of their curvature. Five 6-mm rods of differing compositions and lengths (titanium 300 and 100 mm, stainless steel 300 and 100 mm, prebent titanium 85 mm) were bent at room temperature with a 3-point rod bender, then placed in an incubator at 37 C. Digital photographs were taken every 2 weeks and analyzed to extract the radius of curvature of each rod. The Ti rods had a significantly decreasing curvature with time. The prebent Ti and stainless steel rods did not exhibit significant change in curvature. Titanium rods bent at room temperature and then exposed to body temperature over time tend to exhibit "metal memory"; they gradually revert to their original shape. This may result in loss of sagittal balance and/or proximal screw pullout.
Two cases of cervical spondylolysis are presented. Both cases were discovered during radiographic examination after incidental trauma. The first patient experienced transient quadriplegia that spontaneously resolved and the other... more
Two cases of cervical spondylolysis are presented. Both cases were discovered during radiographic examination after incidental trauma. The first patient experienced transient quadriplegia that spontaneously resolved and the other experienced only neck pain. Further radiographic evaluation of the first patient revealed significant spinal cord compromise, ultimately requiring decompression and fusion. The second patient's cervical spine proved stable to dynamic studies and was without cord compromise.
Measurements have been made to determine the solubility of ethane, C2H6, in aqueous solutions of four different surfactants of the linear alkanesulfonate class at 25 degrees C. The surfactants, sodium 1-pentanesulfonate, sodium... more
Measurements have been made to determine the solubility of ethane, C2H6, in aqueous solutions of four different surfactants of the linear alkanesulfonate class at 25 degrees C. The surfactants, sodium 1-pentanesulfonate, sodium 1-hexanesulfonate, sodium 1-heptanesulfonate, and sodium 1-octanesulfonate, all share a common head group (-SO-3) and counter ion (Na+), and differ only in the length of the alkyl chain attached to the head group. The solubility of ethane has been determined as a function of surfactant concentration for each surfactant. At surfactant concentrations below the critical micelle concentration (CMC), the solubility of ethane is quite low and differs only slightly from the solubility of ethane in pure water. At concentrations greater than the CMC, the solubility of ethane exhibits a gradual increase with surfactant concentration. At high surfactant concentrations, well in excess of the CMC, the solubility of ethane is found to increase as a linear function of surfactant concentration. From this data it becomes possible to determine the fractional population of the surfactant in the free and micellized states. The solubility data measured for ethane is interpreted in terms of the mass-action model for micelle formation.
Nine children with progressive congenital scoliosis underwent bilateral posterior spinal fusion supplemented with transpedicular convex anterior hemiepiphysiodesis. The average preoperative curve was 52 degrees. The average age at surgery... more
Nine children with progressive congenital scoliosis underwent bilateral posterior spinal fusion supplemented with transpedicular convex anterior hemiepiphysiodesis. The average preoperative curve was 52 degrees. The average age at surgery was 9 years and 1 month and the average follow-up period was 3 years and 6 months. Curve progression was arrested in all cases, and curve correction greater than 10 degrees was achieved in four patients.
Review of 27 consecutive patients who underwent video-assisted thoracoscopic surgery (VATS) in the prone position for anterior release and discectomy. To convey the benefits and safety of this new technique for treating spinal deformities... more
Review of 27 consecutive patients who underwent video-assisted thoracoscopic surgery (VATS) in the prone position for anterior release and discectomy. To convey the benefits and safety of this new technique for treating spinal deformities through VATS. All reports using VATS for spinal deformities describe the patient in the lateral position. This is the first study to demonstrate the benefits and safety of the prone position. The patient is positioned prone, prepared, and draped allowing room for lateral portals on the convexity of the curve. Traditionally, a double-lumen endotracheal tube is used to deflate the ipsilateral lung. Prone positioning eliminates this need, because gravity aids in retraction of the lung. All procedures were successfully performed using the VATS technique with the patient prone. After the anterior release and discectomy, posterior instrumentation (n = 27), costoplasty (n = 16), and fusion (n = 27) were performed. The time (n = 20) and blood loss (n = 16) for the anterior approach averaged 129 +/- 35 minutes and 221 +/- 231 mL, respectively. The mean number of disks resected was 3.3 +/- 0.7 (range, 2-5). The prone position is both safe and effective for VATS when treating spinal deformity. The current results confirm that there is no need to insert a double-lumen tube, there is gravity-assisted correction of kyphosis when the patient is prone, and significant operative time is saved with the elimination of repositioning and redraping before the posterior procedure. Surgical times and blood loss compare very favorably with those reported for VATS in the lateral position.
The solubility of naphthalene in compressed ethane and nitrous oxide has been measured over pressure ranges of 1–60 atm at temperatures ranging from 20°–68°C. Second cross virial coefficients representing naphthalene–gas pair interactions... more
The solubility of naphthalene in compressed ethane and nitrous oxide has been measured over pressure ranges of 1–60 atm at temperatures ranging from 20°–68°C. Second cross virial coefficients representing naphthalene–gas pair interactions are evaluated from the data. It is shown that when allowance is made for the effect of quadrupole moment on the critical temperatures of quadrupolar gases, ordinary combining
The solubility of anthracene in compressed methane, ethylene, ethane, and carbon dioxide has been measured over pressure ranges of 1–100 atm and temperature ranges of 63–185°C. Second cross virial coefficients representing anthracene–gas... more
The solubility of anthracene in compressed methane, ethylene, ethane, and carbon dioxide has been measured over pressure ranges of 1–100 atm and temperature ranges of 63–185°C. Second cross virial coefficients representing anthracene–gas pair interactions have been evaluated from this data. It is shown that when allowance is made for the effect of the molecular quadrupole moment on the critical constants
There have been several recent claims of black hole binaries in globular clusters. I show that these candidate systems could instead be ultracompact X-ray binaries (UCXBs) in which a neutron star accretes from a white dwarf. They would... more
There have been several recent claims of black hole binaries in globular clusters. I show that these candidate systems could instead be ultracompact X-ray binaries (UCXBs) in which a neutron star accretes from a white dwarf. They would represent a slightly earlier evolutionary stage of known globular cluster UCXBs such as 4U 1820-30, with white dwarf masses ~0.2 M sun and orbital periods below 5 minutes. Accretion is slightly super-Eddington and makes these systems ultraluminous sources with rather mild beaming factors b ~ 0.3. Their theoretical luminosity function flattens slightly just above L Edd and then steepens at ~3L Edd. It predicts of order two detections in elliptical galaxies such as NGC 4472, as observed. The very bright X-ray source HLX-1 lies off the plane of its host S0a galaxy. If this is an indication of globular cluster membership, it could conceivably be a more extreme example of a UCXB with white dwarf mass M 2 ~= 0.34 M sun. The beaming here is tighter (b ~ (2.5-9) × 10-3), but the system's distance of 95 Mpc easily eliminates any need to invoke improbable alignment of the beam for detection. If its position instead indicates membership of a satellite dwarf galaxy, HLX-1 could have a much higher accretor mass ~1000 M sun
Hearing aids use amplitude compression to compensate for the effects of loudness recruitment. The compression speed that gives the best speech intelligibility varies among individuals. Moore [(2008). Trends Amplif. 12, 300-315] suggested... more
Hearing aids use amplitude compression to compensate for the effects of loudness recruitment. The compression speed that gives the best speech intelligibility varies among individuals. Moore [(2008). Trends Amplif. 12, 300-315] suggested that an individual's sensitivity to temporal fine structure (TFS) information may affect which compression speed gives most benefit. This hypothesis was tested using normal-hearing listeners with a simulated hearing loss. Sentences in a competing talker background were processed using multi-channel fast or slow compression followed by a simulation of threshold elevation and loudness recruitment. Signals were either tone vocoded with 1-ERB(N)-wide channels (where ERB(N) is the bandwidth of normal auditory filters) to remove the original TFS information, or not processed further. In a second experiment, signals were vocoded with either 1 - or 2-ERB(N)-wide channels, to test whether the available spectral detail affects the optimal compression speed. Intelligibility was significantly better for fast than slow compression regardless of vocoder channel bandwidth. The results suggest that the availability of original TFS or detailed spectral information does not affect the optimal compression speed. This conclusion is tentative, since while the vocoder processing removed the original TFS information, listeners may have used the altered TFS in the vocoded signals.
ABSTRACT We show that the firefighter problem is NP-complete for cubic graphs. We also show that given a rooted tree of maximum degree three in which every leaf is the same distance from the root, it is NP- complete to decide whether or... more
ABSTRACT We show that the firefighter problem is NP-complete for cubic graphs. We also show that given a rooted tree of maximum degree three in which every leaf is the same distance from the root, it is NP- complete to decide whether or not there is a strategy that protects every leaf from the fire, which starts at the root. By contrast, we describe a polynomial time algorithm to decide if it is possible to save a given subset of the vertices of a graph with maximum degree three, provided the fire breaks out at a vertex of degree at most two.
The STIF (spinopelvic transiliac fixation) technique for lumbosacral fusion was developed by the authors as an alternative to the Luque-Galveston technique. The results observed in this initial series of 27 neuromuscular scoliosis... more
The STIF (spinopelvic transiliac fixation) technique for lumbosacral fusion was developed by the authors as an alternative to the Luque-Galveston technique. The results observed in this initial series of 27 neuromuscular scoliosis patients treated with the STIF technique are reported. With a minimum of 24 months of radiographic follow-up in 19 patients, the percentage of correction of scoliosis curvature and pelvic obliquity was superior to that reported in the literature. The rates of complications and pseudarthrosis in this series are typical for this patient population. The STIF technique facilitates compression across the sacroiliac joints, which promotes sacroiliac joint fusion and can provide a stable base for curvature correction and lumbosacral fusion. Despite the severe coronal and sagittal plane curves in this group of patients, total operative time also compares favorably to that reported in the literature. The STIF technique requires a well-developed posterior iliac apophysis, which may not be present in younger pediatric patients.
Steady state accretion discs larger than ~ 0.01-0.1 pc are known to be gravitationally unstable for the accretion rates needed to explain super-massive black hole (SMBH) activity. We propose that SMBH are fed by a succession of mass... more
Steady state accretion discs larger than ~ 0.01-0.1 pc are known to be gravitationally unstable for the accretion rates needed to explain super-massive black hole (SMBH) activity. We propose that SMBH are fed by a succession of mass deposition events with randomly directed angular momenta. Because of incomplete angular momentum cancellation a warped accretion disc forms in the inner few parsec. The orientation of the disc performs a random walk. Deposition of new material promotes SMBH accretion at rates much faster than viscous. Observational implications of this picture include: (i) lighter accretion discs that can fuel AGN and quasars and yet avoid star formation at R >> 0.1 pc; (ii) star formation inside the disc is not a function of mass accretion rate only. It can take place at high or low accretion rates, e.g., when too few clouds arrive in the inner region. An example of this might be the central parsec of our Galaxy. (iii) The discs can form Compton-thick obscuring st...
Visceral function is essential for survival. Discreet regions of the human brain controlling visceral function have been postulated from animal studies (Cechetto and Saper [1987] J. Comp. Neurol. 262:27-45) and suspected from lethal... more
Visceral function is essential for survival. Discreet regions of the human brain controlling visceral function have been postulated from animal studies (Cechetto and Saper [1987] J. Comp. Neurol. 262:27-45) and suspected from lethal cardiac arrythmias (Cechetto [1994] Integr. Physiol. Behv. Sci. 29:362-373). However, these visceral sites remain uncharted in the normal human brain. We used 4-Tesla functional magnetic resonance imaging (fMRI) to identify changes in activity in discrete regions of the human brain previously identified in animal studies to be involved in visceral control. Five male subjects underwent heart rate (HR) and/or blood pressure (BP) altering tests: maximal inspiration (MX), Valsalva's maneuver (VM), and isometric handgrip (HG). Increased neuronal activity was observed during MX, VM, and HG, localized in the insular cortex, in the posterior regions of the thalamus, and in the medial prefrontal cortex. To differentiate special visceral (taste) regions from general visceral (HR, BP) regions in these areas, response to gustatory stimulation was also examined; subjects were administered saline (SAL) and sucrose (SUC) solutions as gustatory stimuli. Gustatory stimulation increased activity in the ventral insular cortex at a more inferior level than the cardiopulmonary stimuli. The observed neural activation is the first demonstration of human brain activity in response to visceral stimulation as measured by fMRI.
A quasi-line graph is a graph in which the neighbourhood of any vertex can be covered by two cliques; every line graph is a quasi-line graph. Reed conjectured that for any graph G, (G) d 1 2(( G) + 1 + !(G))e (13). We prove that the... more
A quasi-line graph is a graph in which the neighbourhood of any vertex can be covered by two cliques; every line graph is a quasi-line graph. Reed conjectured that for any graph G, (G) d 1 2(( G) + 1 + !(G))e (13). We prove that the conjecture holds if G is a quasi-line graph, extending a result of King,
ABSTRACT Benzene is widely used by chemical industries and exposure to benzene has been shown experimentally to be immunotoxic in adult animals. This study addressed whether exposure of fetuses in utero to benzene compromises the... more
ABSTRACT Benzene is widely used by chemical industries and exposure to benzene has been shown experimentally to be immunotoxic in adult animals. This study addressed whether exposure of fetuses in utero to benzene compromises the development of fetal B lymphopoiesis and whether B-lymphocyte development recovers postnatally. Pregnant BALB/C dams were given intraperitoneal injections of benzene (100 mg/kg, twice daily) from day 12.5 of gestation through day 19.5 of gestation. Phenotypic analysis revealed that fetal liver cell suspensions from embryos exposed in utero contained fewer pre-B cells and B cells than corresponding controls. Fetal liver cell cultures established from these embryos also produced fewer B cells. In contrast, levels of pre-B cells were elevated in the livers of 8-day-old neonates that had been exposed to benzene in utero. Moreover, responsiveness to the B-cell mitogen, LPS, was significantly decreased in spleen cell cultures derived from these neonates. These results indicate that in utero exposure to high concentrations of benzene alters fetal B lymphopoiesis and may compromise immune responsiveness postnatally.
Is Accountability a standard that transcends time and culture? Does it retain any meaning for an electronically mediated society? Older norms of fairness, reciprocity and of individual responsibility appeared to be inadequate ethical... more
Is Accountability a standard that transcends time and culture? Does it retain any meaning for an electronically mediated society? Older norms of fairness, reciprocity and of individual responsibility appeared to be inadequate ethical guides during the Iran/Contra Hearings. ...
Mobilized peripheral blood hematopoietic stem cells (PBSCs) demonstrate accelerated engraftment compared with bone marrow; however, mechanisms responsible for enhanced engraftment remain unknown. PBSCs mobilized by GRObeta... more
Mobilized peripheral blood hematopoietic stem cells (PBSCs) demonstrate accelerated engraftment compared with bone marrow; however, mechanisms responsible for enhanced engraftment remain unknown. PBSCs mobilized by GRObeta (GRObeta(Delta4)/CXCL2(Delta4)) or the combination of GRObeta(Delta4) plus granulocyte colony-stimulating factor (G-CSF) restore neutrophil and platelet recovery faster than G-CSF-mobilized PBSCs. To determine mechanisms responsible for faster hematopoietic recovery, we characterized immunophenotype and function of the GRObeta-mobilized grafts. PBSCs mobilized by GRObeta(Delta4) alone or with G-CSF contained significantly more Sca-1(+)-c-kit(+)-lineage(-) (SKL) cells and more primitive CD34(-)-SKL cells compared with cells mobilized by G-CSF and demonstrated superior competitive long-term repopulation activity, which continued to increase in secondary and tertiary recipients. GRObeta(Delta4)-mobilized SKL cells adhered better to VCAM-1(+) endothelial cells compared with G-CSF-mobilized cells. GRObeta(Delta4)-mobilized PBSCs did not migrate well to the chemokine stromal derived factor (SDF)-1alpha in vitro that was associated with higher CD26 expression. However, GRObeta(Delta4)-mobilized SKL and c-Kit(+) lineage(-) (KL) cells homed more efficiently to marrow in vivo, which was not affected by selective CXCR4 and CD26 antagonists. These data suggest that GRObeta(Delta4)-mobilized PBSCs are superior in reconstituting long-term hematopoiesis, which results from differential mobilization of early stem cells with enhanced homing and long-term repopulating capacity. In addition, homing and engraftment of GRObeta(Delta4)-mobilized cells is less dependent on the SDF-1alpha/CXCR4 axis.
The cystine moiety of the novel hematoregulatory peptide HP-5b has been substituted with an achiral N,N′-bis(carboxymethyl)-1,4-diaminobutane unit. The resulting compound was also a potent hematoregulatory agent, suggesting that... more
The cystine moiety of the novel hematoregulatory peptide HP-5b has been substituted with an achiral N,N′-bis(carboxymethyl)-1,4-diaminobutane unit. The resulting compound was also a potent hematoregulatory agent, suggesting that N,N′-bis(carboxymethyl)-1,4-diaminobutane can function as an effective achiral cystine replacement in this molecular series.
Diagnosis and management of myeloma in the very elderly patient is challenging. Treatment options have vastly improved for elderly myeloma patients but still require the clinician to personalize therapy. In this paper, we offer... more
Diagnosis and management of myeloma in the very elderly patient is challenging. Treatment options have vastly improved for elderly myeloma patients but still require the clinician to personalize therapy. In this paper, we offer evidence-based, pragmatic advice on how to overcome six of the main challenges likely to arise: 1) diagnosis of myeloma in this age group, 2) assessment of the need for treatment, and the fitness for combination chemotherapy, 3) provision of the best quality of supportive care, 4) choice of combination chemotherapy in those fit enough for it, 5) treatment of relapsed myeloma, and 6) provision of end of life care. With an increased burden of comorbidities and a reduced resilience to treatment and its associated toxicities, the management of myeloma in this age group requires a different approach to that in younger patients to maximize both quality and length of life.
Ambulatory care sensitive (ACS) conditions are health problems that could be prevented or ameliorated with adequate access to primary care services. To determine the extent to which ACS conditions account for care received by children in... more
Ambulatory care sensitive (ACS) conditions are health problems that could be prevented or ameliorated with adequate access to primary care services. To determine the extent to which ACS conditions account for care received by children in U.S. emergency departments (EDs) and the patient charges for this care. A retrospective, cross-sectional analysis of the 2010 Nationwide Emergency Department Sample was performed. Patients 0-19 years of age were included and visits for ACS conditions were identified. Main outcome measures were the percentage of visits for ACS conditions, regression models predicting presentation for ACS conditions based on patient demographic characteristics, and ED charges for ACS ED visits. Of almost 30 million pediatric ED visits in the United States in 2010, 13.2% were for exclusively ACS conditions. Patients with public or no insurance were 1.2 times more likely than privately insured patients to present for an ACS condition. Lower household income (adjusted odds ratio [aOR] 1.49; 95% confidence interval [CI] 1.33-1.66) and younger patient age (aOR = 2.55; 95% CI 2.41-2.69) were also predictive of an ACS ED visit. The total of charges for ACS visits was almost $3 billion, of which publicly insured patients accounted for $1.5 billion. Almost one in seven U.S. pediatric ED visits may be preventable by quality primary care. Patients with public insurance and lower income are more likely than other groups to present with ACS conditions. Better access to and use of primary care services could reduce health care costs and relieve ED overcrowding.
ABSTRACT Background & aims Type 2 intestinal failure (IF) is a specific disease entity, the management of which requires multidisciplinary clinical expertise combined with appropriate infrastructure. Accurate UK costs for... more
ABSTRACT Background & aims Type 2 intestinal failure (IF) is a specific disease entity, the management of which requires multidisciplinary clinical expertise combined with appropriate infrastructure. Accurate UK costs for providing such services are unavailable. We made an assessment of these costs at our hospital, categorising patients according to whether it was an index admission (IA), readmission (RA) or admission for definitive surgery (SA). Methods A structured search was undertaken to record all activity captured electronically for 25 patients with type 2 IF. These data were combined with clinical information to generate a cost model. Results Lengths of stay were median 94 days, range (8–297) IA; 7, (1–75) RA and 28, (7–135) SA (p < 0.001). Total minimum admission costs were median £47,865, range (6341–119,542) IA; £3838, (717–32,472) for RA and 21,974, (6532–69,602) for SA (p < 0.001). This equated to minimum costs per patient day of £442 IA, £468 RA, and £726 SA. Overall, there was an income shortfall of 55.3% per patient. Conclusions Better costing mechanisms are needed in relation to IF patients to allow for heterogeneity, resource utilisation and varied length of stay, these should be on a cost per patient day basis depending on admission type.
... Integrated real-time roof monitoring. Auteur(s) / Author(s). Shen Bao-tang (1) ; Guo Hua (1) ; King Andrew (1) ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s). (1) CSIRO Exploration and Mining, QLD4069, Kenmore,... more
... Integrated real-time roof monitoring. Auteur(s) / Author(s). Shen Bao-tang (1) ; Guo Hua (1) ; King Andrew (1) ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s). (1) CSIRO Exploration and Mining, QLD4069, Kenmore, Australia Résumé / Abstract. ...
Chronic angiotensin II (Ang II) infusion, in rats fed high salt, engages the sympathetic nervous system to increase venomotor tone. The splanchnic sympathetic nervous system is the most important regulator of venous tone, indicating that... more
Chronic angiotensin II (Ang II) infusion, in rats fed high salt, engages the sympathetic nervous system to increase venomotor tone. The splanchnic sympathetic nervous system is the most important regulator of venous tone, indicating that splanchnic sympathetic nervous system activity may be increased in Ang II salt hypertension. We hypothesized that celiac ganglionectomy (CGx), to selectively disrupt sympathetic innervation to the splanchnic circulation, would attenuate arterial pressure (AP), and venous tone increases in Ang II salt hypertension. Rats fed 2% or 0.4% NaCl were instrumented to allow AP measurement by radiotelemetry at the same time as surgical CGx or sham operation. Ang II was delivered by minipump (150 ng/kg per minute) for 14 days. CGx reduced AP independent of salt diet during control. CGx markedly attenuated Ang II hypertension in rats on 2% NaCl but had little effect in rats fed 0.4% NaCl. To test the possibility that CGx exerted its effects via renal denervation, rats were subjected to the same protocol but received selective bilateral renal denervation. Renal denervation decreased AP during control but had no protective effect on Ang II hypertension and actually tended to exacerbate the pressor response. Finally, separate groups of rats underwent CGx or sham operation and were instrumented to allow repeated measures of mean circulatory filling pressure, an index of venous tone. In addition to attenuating Ang II salt hypertension, CGx completely prevented Ang II salt-induced increases in mean circulatory filling pressure and substantially attenuated depressor responses to acute ganglion blockade. We conclude that, in the presence of high salt, Ang II activates the splanchnic sympathetic nervous system to increase venomotor tone and AP.
... Andrew H. Buchanan Department of Civil Engineering, University of Canterbury, Christchurch, New Zealand and Andrew B. King Building Research Association of ... Unprotected light timber framing loses strength rapidly in a fire but can... more
... Andrew H. Buchanan Department of Civil Engineering, University of Canterbury, Christchurch, New Zealand and Andrew B. King Building Research Association of ... Unprotected light timber framing loses strength rapidly in a fire but can be protected with gypsum plaster or similar ...
Postprandial hypertriglyceridemia has been identified as a major independent risk factor for future cardiovascular events. Therefore, inhibition of triglyceride synthesis has enormous therapeutic potential in the treatment of metabolic... more
Postprandial hypertriglyceridemia has been identified as a major independent risk factor for future cardiovascular events. Therefore, inhibition of triglyceride synthesis has enormous therapeutic potential in the treatment of metabolic disorders. Diacylglycerol acyltransferase (DGAT) enzymes catalyze the final and only committed step in triglyceride biosynthesis and have thus been identified as potential therapeutic targets to combat human cardio-metabolic diseases. Significant interest in DGAT-1 inhibitors has emerged in the last several years. To provide a perspective on the exciting features of this enzyme for targeting metabolic diseases, a summary of the biology and pharmacology surrounding the DGAT enzymes is presented. Following this is a discussion of the various chemotypes that have been disclosed within relevant patent applications published in 2008. Specifically, the similarities and differences of the chemical structures and the biological data that are provided to support the corresponding claims are presented. Small molecule and biologic-based DGAT inhibitors have been successfully used for the preclinical validation of DGAT enzymes as targets for the treatment of metabolic diseases. Given the advanced stage in which some of the chemical matter resides, it is expected that DGAT inhibitors will enter the clinic in the coming years.
... Ulrich J. Griesser* ‡ , Ram KR Jetti ‡ , Mairi F. Haddow ‡ , Thomas Brehmer § , David C. Apperley , Andrew King and Robin K. Harris. Institute of Pharmacy, University of Innsbruck, Innrain 52, 6020 Innsbruck, Austria, Institute ...
Ьг вижг й и в анз з згб вги и гв в дж а б в жн Ќв и гвз ж ж ей ж К Ь ж ж з ззйб иг б а ж л и и зи в ж гвЙ зижй из йз в аг джг ж бб в НН зй з йв к жз г аа к ж а з Дй к ОЕ Эк ж и з и г и жбз Ди ОЕ Ь жб гжб жгб и з и г йв игжз Д ОЕ йв Дг и... more
Ьг вижг й и в анз з згб вги и гв в дж а б в жн Ќв и гвз ж ж ей ж К Ь ж ж з ззйб иг б а ж л и и зи в ж гвЙ зижй из йз в аг джг ж бб в НН зй з йв к жз г аа к ж а з Дй к ОЕ Эк ж и з и г и жбз Ди ОЕ Ь жб гжб жгб и з и г йв игжз Д ОЕ йв Дг и ЌжзиЙгж ж а в й йв жан в и джг ж бЕ в и з и ...
The purpose of this study was to investigate total body norepinephrine (NE) kinetics as an index of global sympathetic nervous system (SNS) outflow in a rat model of chronic ANG II-salt hypertension. Male Sprague-Dawley rats fed a 0.4%... more
The purpose of this study was to investigate total body norepinephrine (NE) kinetics as an index of global sympathetic nervous system (SNS) outflow in a rat model of chronic ANG II-salt hypertension. Male Sprague-Dawley rats fed a 0.4% (normal salt, NS) or 2% (HS) NaCl diet were instrumented with arterial and venous catheters. After 5 days of recovery and a 3-day control period, ANG II (150 ng.kg(-1).min(-1)) was given subcutaneously by minipump for 14 days. Plasma NE levels and total body NE spillover and clearance were determined on control day 3 and ANG II infusion days 7 and 14 using radioisotope dilution principles. To perform this analysis, 3H-NE and NE were measured in arterial plasma after a 90-min infusion of tracer amounts of 3H-NE. Mean arterial pressure (MAP) was similar during the control period in NS and HS rats; however, MAP increased to a higher level in HS rats. During the control period, plasma NE tended to be lower in rats on HS, whereas NE clearance tended to be higher in HS rats. As a result NE spillover was similar in NS and HS rats during the control period. In NS rats, plasma NE, NE spillover, and NE clearance were unchanged by ANG II. In contrast, in rats on the HS diet, plasma NE and NE spillover increased during ANG II infusion, whereas NE clearance was unchanged. In conclusion, a HS diet alone or ANG II infusion in animals fed NS do not affect global sympathetic outflow. However, the additional hypertensive response to ANG II in animals fed HS is accompanied by SNS activation.
The New Zealand Society for Earthquake Engineering has organised field reconnaissance missions following virtually all of the major international earthquakes over the past two decades. A range of lessons has been identified, predominantly... more
The New Zealand Society for Earthquake Engineering has organised field reconnaissance missions following virtually all of the major international earthquakes over the past two decades. A range of lessons has been identified, predominantly in relation to the physical and built environments. As technical understanding of the issues in these areas has matured, awareness of the need for greater emphasis to
RiskScape New Zealand is a national multi-hazard impact model that presents relative risks and community exposure to a range of natural hazards. The prototype currently under development will consider the impact of five of the most... more
RiskScape New Zealand is a national multi-hazard impact model that presents relative risks and community exposure to a range of natural hazards. The prototype currently under development will consider the impact of five of the most commonly encountered natural hazard (including earthquakes and tsunami) on three representative New Zealand communities. The model evolution recognizes the conflict between the GIS presentational
Comprehensive cardiovascular assessment in conscious rodents by utilizing telemetry has been limited by the restriction of current devices to one pressure channel. The purpose of this study was to test and validate a dual pressure... more
Comprehensive cardiovascular assessment in conscious rodents by utilizing telemetry has been limited by the restriction of current devices to one pressure channel. The purpose of this study was to test and validate a dual pressure transmitter that allows the simultaneous measurement of arterial pressure (AP) and left ventricular pressure (LVP) in conscious freely moving rats. Six rats were surgically implanted with dual pressure transmitters. Baseline hemodynamics and circadian rhythm were observed to return within 7days. AP, heart rate (HR), LVP and indices of left ventricular contractility were stable and demonstrated a prominent circadian rhythm over a two-week period of uninterrupted recordings. Administration of the vasodilator nifedipine produced the anticipated dose-dependent decrease in AP which was accompanied by a baroreflex mediated increase in HR and cardiac contractility. The negative inotrope verapamil produced the expected dose-dependent decreases in AP and cardiac co...
Repetitive brief episodes of soft-tissue collapse within the upper airway during sleep characterize obstructive sleep apnea (OSA), an extremely common and disabling disorder. Failure to maintain the patency of the upper airway is caused... more
Repetitive brief episodes of soft-tissue collapse within the upper airway during sleep characterize obstructive sleep apnea (OSA), an extremely common and disabling disorder. Failure to maintain the patency of the upper airway is caused by the combination of sleep-related loss of compensatory dilator muscle activity and aerodynamic forces promoting closure. The prediction of soft-tissue movement in patient-specific airway 3D mechanical models is emerging as a useful contribution to clinical understanding and decision making. Such modeling requires reliable estimations of the pharyngeal wall pressure forces. While nasal obstruction has been recognized as a risk factor for OSA, the need to include the nasal cavity in upper-airway models for OSA studies requires consideration, as it is most often omitted because of its complex shape. A quantitative analysis of the flow conditions generated by the nasal cavity and the sinuses during inspiration upstream of the pharynx is presented. Resu...
Environmental issues, while of growing interest, have been outside the main focus of business scholarship. This position on the periphery may have been a good thing. It allowed scholars of business and the environment to consider unusual... more
Environmental issues, while of growing interest, have been outside the main focus of business scholarship. This position on the periphery may have been a good thing. It allowed scholars of business and the environment to consider unusual theories and evaluate overlooked phenomenon. In doing so, they created a body of research that provides new insights on two topics of mainstream
Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder [Nature 310:683... more
Regional glucose metabolic rates were measured in patients with panic disorder during the performance of auditory discrimination. Those regions examined by Reiman and colleagues in their blood flow study of panic disorder [Nature 310:683 (1984)] were examined with a higher resolution positron emission tomography (PET) scanner and with the tracer [F-18]-2-fluoro-2-deoxyglucose (FDG). In contrast to the blood flow findings of Reiman et al., we did not find global gray metabolic differences between patients with panic disorder and normal controls. Consistent with the findings of Reiman et al. [Nature; Am J Psychiatry 143:469 (1986)], we found hippocampal region asymmetry. We also found metabolic decreases in the left inferior parietal lobule and in the anterior cingulate (trend), as well as an increase in the metabolic rate of the medial orbital frontal cortex (trend) of panic disorder patients. It is unclear whether the continuous performance task (CPT) enhanced or diminished findings...
In theory, cerebral biopsies could provide the diagnosis in a significant proportion of patients with neurodegenerative diseases, however, there are considerable ethical barriers. Previous series of cerebral biopsies have shown variable... more
In theory, cerebral biopsies could provide the diagnosis in a significant proportion of patients with neurodegenerative diseases, however, there are considerable ethical barriers. Previous series of cerebral biopsies have shown variable diagnostic accuracy but have understandably suffered because of lack of post-mortem tissue with which to compare the diagnosis. To determine the accuracy of such biopsies in neurodegenerative disease we took small biopsy-sized samples of predominantly fresh post-mortem brain tissue from frontal and temporal lobes in 62 cases. These were processed as for a biopsy and stained for H&E, p62, tau, Aβ, α-synuclein, and TDP-43. The sections were assessed blind by 3 neuropathologists and the results compared with the final post-mortem diagnosis. The agreement and sensitivity in most cases was good especially: controls; Alzheimer's disease (AD); multiple system atrophy (MSA); frontotemporal lobar degeneration with TDP-43 positive inclusions and/or motor n...
Voluntary industry management standards are emerging as an important new form of industrial coordination. They now regulate management practices in industries as diverse as electronics and entertainment. One goal of these standards is the... more
Voluntary industry management standards are emerging as an important new form of industrial coordination. They now regulate management practices in industries as diverse as electronics and entertainment. One goal of these standards is the differentiation of well- management firms. Unfortunately, theories of diffusion suggest that such differentiation may be short lived. Adoption of a management standard by high quality firms
This paper introduces a generic framework for multi-risk modelling developed in the project `Regional RiskScape' at the Research Organization GNS Science and the National Institute of Water and Atmospheric Research Ltd. (NIWA) in New... more
This paper introduces a generic framework for multi-risk modelling developed in the project `Regional RiskScape' at the Research Organization GNS Science and the National Institute of Water and Atmospheric Research Ltd. (NIWA) in New Zealand. Our goal was to develop a generic technology for modelling risks from multiple natural hazards and for multiple risk elements. The framework is independent on
We present a technique for automatic intensity-based image-to-physical registration of a 3-D segmentation for image-guided interventions. The registration aligns the segmentation with tracked and calibrated 3-D ultrasound (US) images of... more
We present a technique for automatic intensity-based image-to-physical registration of a 3-D segmentation for image-guided interventions. The registration aligns the segmentation with tracked and calibrated 3-D ultrasound (US) images of the target region. The technique uses a probabilistic framework and explicitly incorporates a model of the US image acquisition process. The rigid body registration parameters are varied to maximise the likelihood that the real US image(s) were formed using the US imaging model from the probe transducer position. The proposed technique is validated on images segmented from cardiac magnetic resonance imaging (MRI) data and 3-D US images acquired from 3 volunteers and 1 patient. We show that the accuracy of the algorithm is 2.6-4.2mm and the capture range is 9-18mm. The proposed technique has the potential to provide accurate image-to-physical registrations for a range of image guidance applications.
Previous studies suggest that spin-offs will locate in close proximity to the firm from which they spawned. As a result of this process, clusters of entrepreneurial activity tend to develop around a few strong parent firms. But do all... more
Previous studies suggest that spin-offs will locate in close proximity to the firm from which they spawned. As a result of this process, clusters of entrepreneurial activity tend to develop around a few strong parent firms. But do all spin-offs really stay close to home? In this article, we investigate which firms choose to stay nearby and which tend to leave. We test the predictive power of existing theories of location choice, and we develop a new theory particular to spin-off firms. We demonstrate that spin-off firms choose heterogeneous technological and market strategies, and we hypothesize that firms with more aggressive strategies have a greater need to maintain relationships that allow access to knowledge and facilitate coordination with complementors. We find supporting evidence of our arguments by analyzing the location and strategy decisions of intra- industry spin-offs in the disk drive industry.
Research Interests:
This paper presents the evaluation of the use of multimodality skin markers for the registration of cardiac magnetic resonance (MR) image data to x-ray fluoroscopy data for the guidance of cardiac electrophysiology procedures. The... more
This paper presents the evaluation of the use of multimodality skin markers for the registration of cardiac magnetic resonance (MR) image data to x-ray fluoroscopy data for the guidance of cardiac electrophysiology procedures. The approach was validated using a phantom study and 3 patients undergoing pulmonary vein (PV) isolation for the treatment of paroxysmal atrial fibrillation. In the patient study, skin markers were affixed to the patients' chest and used to register pre-procedure cardiac MR image data to intra-procedure ...
BackgroundAmyotrophic lateral sclerosis (ALS) is a primary progressive neurodegenerative disease characterised by neuronal loss of lower motor neurons (in the spinal cord and brainstem) and/or upper motor neurons (in the motor cortex) and... more
BackgroundAmyotrophic lateral sclerosis (ALS) is a primary progressive neurodegenerative disease characterised by neuronal loss of lower motor neurons (in the spinal cord and brainstem) and/or upper motor neurons (in the motor cortex) and subsequent denervation atrophy of skeletal muscle.AimA comprehensive examination of muscle pathology from a cohort of clinically confirmed ALS patients, including an investigation of inflammation, complement activation, and deposition of abnormal proteins in order to compare them with findings from an age-matched, control group.Material and methods31 muscle biopsies from clinically confirmed ALS patients and 20 normal controls underwent a comprehensive protocol of histochemical and immunohistochemical stains, including HLA-ABC, C5b-9, p62, and TDP-43.ResultsNeurogenic changes were confirmed in 30/31 ALS cases. In one case, no neurogenic changes could be detected. Muscle fibre necrosis was seen in 5/31 cases and chronic mononuclear inflammatory cell infiltration in 5/31 (2 of them overlapped with those showing muscle necrosis). In four biopsies there was an increase in the proportion of cytochrome oxidase (COX) negative fibres (2-3%). p62 faintly stained cytoplasmic bodies in eight cases and none were immunoreactive to TDP-43.ConclusionThis large series of muscle biopsies from patients with ALS demonstrates neurogenic atrophy is a nearly uniform finding and that mild mitochondrial abnormalities and low-grade inflammation can be seen and do not rule out the diagnosis of ALS. These findings could lend support to the notion that ALS is a complex and heterogeneous disorder.
This paper provides an update of progress that has taken place over the last 18 months in the development of the new Earthquake Loadings Standard. In that time this standard has become dis-jointed, in that is it is no longer a joint... more
This paper provides an update of progress that has taken place over the last 18 months in the development of the new Earthquake Loadings Standard. In that time this standard has become dis-jointed, in that is it is no longer a joint Australia/New Zealand Standard. The separation has permitted a New Zealand focus to be reintroduced. This focus has permitted several changes such as the performance objectives being clarified and linked more directly with expectations from the material standards. In addition, the seismicity maps have been slightly modified to account for new science, variable Sp provisions have been introduced, a minimum base shear has been reintroduced, permissible interstorey drift limits have been revised, detailing is more closely linked to material strains (section curvature) and the integrated time-history analysis procedures re- assessed, particularly when near-fault effects are present.
Research Interests:
Page 1. LEAN AND GREEN? AN EMPIRICAL EXAMINATION OF THE RELATIONSHIP BETWEEN LEAN PRODUCTION AND ENVIRONMENTAL PERFORMANCE* ANDREW A. KING AND MICHAEL J. LENOX Stern School ...
The transactive response (TAR) DNA binding protein 43 (TDP-43) has been recently implicated as a major component of ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS, motor neuron disease: MND) and ALS-related disorders. In... more
The transactive response (TAR) DNA binding protein 43 (TDP-43) has been recently implicated as a major component of ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS, motor neuron disease: MND) and ALS-related disorders. In this study, we examined abnormal TDP-43 pathology in 13 sporadic ALS (SALS), six familial ALS (FALS) with and without Cu/Zn superoxide dismutase (SOD1) mutations (SOD1-FALS and non-SOD1-FALS), Guam ALS, two frontotemporal lobar degeneration with MND/ALS (FTLD-MND/ALS), one FTLD with ubiquitin-only-immunoreactive inclusions (FTLD-U) and two progressive supranuclear palsy (PSP). Sections from the spinal cord were processed for immunohistochemistry using antibodies against TDP-43, ubiquitin, p62, cystatin C, phosphorylated tau protein (P-tau; AT8), alpha-synuclein and phosphorylated neurofilament protein (P-NF). In 12 out of 13 SALS and both Guam ALS cases ubiquitin and p62-immunoreactive (IR) neuronal inclusions co-localized with TDP-43. In three out of four SOD1-FALS and one of two non-SOD1-FALS cases, TDP-43-IR inclusions were absent despite the presence of p62 and/or ubiquitin-IR inclusions. However, a single TDP-43-IR neuronal inclusion co-localized with p62 and ubiquitin in one SOD1-FALS (His48Gln) case. Except for one neuron in a Guam case, all TDP-43-IR neuronal inclusions were negative for P-tau (AT8). TDP-43-IR glial inclusions and neurites were also demonstrated. The TDP-43 is a consistent component of the ubiquitinated inclusions in SALS and Guam ALS, but TDP-43-IR inclusions are absent or scarce in SOD1-FALS.
Thiocoraline is a thiodepsipeptide antitumor agent that belongs to the family of bisintercalator natural products that bind duplex DNA through their two planar intercalating moieties. In thiocoraline, the 3-hydroxyquinaldic acid (3HQA)... more
Thiocoraline is a thiodepsipeptide antitumor agent that belongs to the family of bisintercalator natural products that bind duplex DNA through their two planar intercalating moieties. In thiocoraline, the 3-hydroxyquinaldic acid (3HQA) chromophores required for intercalation are derived from L-Trp. We have expressed the Micromonospora sp. ML1 tryptophan 2,3-dioxygenase(TDO) TioF, purified it from E. coli, and confirmed its role in the irreversible oxidation of L-Trp to N-formylkynurenine, the proposed first step during 3HQA biosynthesis. We have established that TioF is a catalyst with broader specificity than other TDOs, but that is less promiscuous than indoleamine 2,3-dioxygenases. TioF was found to display activity with various L-Trp analogs (serotonin, D-Trp, and indole). The TioF reaction products generated during this study will be used as substrates for subsequent analysis of the other enzymes involved in 3HQA biosynthesis.
In comparison with other large cardiovascular trials, we note that the ACTIVE investigators are assiduous in excluding patients with documented peptic ulcer disease. They have shown a significant reduction in minor bleeding in those... more
In comparison with other large cardiovascular trials, we note that the ACTIVE investigators are assiduous in excluding patients with documented peptic ulcer disease. They have shown a significant reduction in minor bleeding in those receiving oral anticoagulants (568 vs 481, ...
AAPS 25th Anniversary. Developing Science. Impacting health. American Association of Pharmaceutical Scientists. About AAPS: Contact Us; Directions; Careers at AAPS; Policies & Governance; Awards, Fellows, and Travelships; Affiliate... more
AAPS 25th Anniversary. Developing Science. Impacting health. American Association of Pharmaceutical Scientists. About AAPS: Contact Us; Directions; Careers at AAPS; Policies & Governance; Awards, Fellows, and Travelships; Affiliate & links. Membership & Volunteers: ...
Abstract—This paper discusses the design and testing of an air-craft electric fuel pump drive. The drive is a modular, four-phase, fault-tolerant system which is designed to meet the specification with a fault in any one of the phases.... more
Abstract—This paper discusses the design and testing of an air-craft electric fuel pump drive. The drive is a modular, four-phase, fault-tolerant system which is designed to meet the specification with a fault in any one of the phases. The motor employed has a permanent-...
New Zealand has experienced community damage from every conceivable natural hazard. Events such as earthquake (both shaking and fault rupture), volcanic activity (both near-field effects and distil ash deposition), tsunami, flooding,... more
New Zealand has experienced community damage from every conceivable natural hazard. Events such as earthquake (both shaking and fault rupture), volcanic activity (both near-field effects and distil ash deposition), tsunami, flooding, storm (wind, snow/ice and ...
Research Interests:
Energy efficiency differs by building use and type as well as prevailing climatic conditions. This paper introduces a framework for assessing particular building design configurations against relevant performance criteria which can permit... more
Energy efficiency differs by building use and type as well as prevailing climatic conditions. This paper introduces a framework for assessing particular building design configurations against relevant performance criteria which can permit design improvement through the use of multi-objective optimisation. The resulting generalised model has the potential to give new insight to the engineering challenges facing the design of carbon-neutral
Since the industrial revolution, most people have assumed that en-vironmental change happens slowly and predictably and can be reversed at will (Timmerman, 1986). Theoretical and empirical discoveries have demonstrated that humankind can... more
Since the industrial revolution, most people have assumed that en-vironmental change happens slowly and predictably and can be reversed at will (Timmerman, 1986). Theoretical and empirical discoveries have demonstrated that humankind can cause unexpected, precipitous, and ...
Optineurin (OPTN) is a multifunctional protein involved in vesicular trafficking, signal transduction and gene expression. OPTN mutations were described in eight Japanese patients with familial and sporadic amyotrophic lateral sclerosis... more
Optineurin (OPTN) is a multifunctional protein involved in vesicular trafficking, signal transduction and gene expression. OPTN mutations were described in eight Japanese patients with familial and sporadic amyotrophic lateral sclerosis (FALS, SALS). OPTN-positive inclusions co-localising with TDP-43 were described in SALS and in FALS with SOD-1 mutations, potentially linking two pathologically distinct pathways of motor neuron degeneration. We have explored the abundance of OPTN inclusions using a range of antibodies in postmortem tissues from 138 cases and controls including sporadic and familial ALS, frontotemporal lobar degeneration (FTLD) and a wide range of neurodegenerative proteinopathies. OPTN-positive inclusions were uncommon and detected in only 11/32 (34%) of TDP-43-positive SALS spinal cord and 5/15 (33%) of FTLD-TDP. Western blot of lysates from FTLD-TDP frontal cortex and TDP-43-positive SALS spinal cord revealed decreased levels of OPTN protein compared to controls (p < 0.05), however, this correlated with decreased neuronal numbers in the brain. Large OPTN inclusions were not detected in FALS with SOD-1 and FUS mutation, respectively, or in FTLD-FUS cases. OPTN-positive inclusions were identified in a few Alzheimer's disease (AD) cases but did not co-localise with tau and TDP-43. Occasional striatal neurons contained granular cytoplasmic OPTN immunopositivity in Huntington's disease (HD) but were absent in spinocerebellar ataxia type 3. No OPTN inclusions were detected in FTLD-tau and α-synucleinopathy. We conclude that OPTN inclusions are relatively rare and largely restricted to a minority of TDP-43 positive ALS and FTLD-TDP cases. Our results do not support the proposition that OPTN inclusions play a central role in the pathogenesis of ALS, FTLD or any other neurodegenerative disorder.
AbstracL The objective of control generation in logic programming is to auto-matically derive a computation rule for a program that is efficient and yet does not compromise program correctness. Progress in solving this important problem... more
AbstracL The objective of control generation in logic programming is to auto-matically derive a computation rule for a program that is efficient and yet does not compromise program correctness. Progress in solving this important problem has been slow and, to date, only ...
Reasoning about termination is a key issue in logic program development. One classic technique for proving termination is to construct a well-founded order on goals that decreases between successive goals in a derivation. In practise,... more
Reasoning about termination is a key issue in logic program development. One classic technique for proving termination is to construct a well-founded order on goals that decreases between successive goals in a derivation. In practise, this is achieved with the ...
Ordering optimisations are optimisations that can be applied to a concurrent logic program when the atoms of a clause are known to be ordered. In this paper ordering optimisations are reviewed, reformulated and refined. The paper explains... more
Ordering optimisations are optimisations that can be applied to a concurrent logic program when the atoms of a clause are known to be ordered. In this paper ordering optimisations are reviewed, reformulated and refined. The paper explains how ordering optimisations can be realised in terms of abstract interpretation and shows that by, building on schedule analysis, simple, efficient and accurate
Serialisation analysis reduces the time a concurrent logic program spends communicating and scheduling. It fits granularity analysis and schedule analysis into a single unified framework for partitioning a program into grains for parallel... more
Serialisation analysis reduces the time a concurrent logic program spends communicating and scheduling. It fits granularity analysis and schedule analysis into a single unified framework for partitioning a program into grains for parallel evaluation and ordering grains for sequential evaluation. Serialisation analysis is simple, avoids the complexity of thresholding, and unlike previous proposals for controlling granularity, is based on threads.
Strictness analysis is crucial for the efficient implementation of the lazy functional languages. A related technique for the concurrent logic languages (CLLs) called schedule analysis is presented which divides at compile-time a CLL... more
Strictness analysis is crucial for the efficient implementation of the lazy functional languages. A related technique for the concurrent logic languages (CLLs) called schedule analysis is presented which divides at compile-time a CLL program into threads of totally ordered ...
Sharing information is useful in specialising, optimising and parallelising logic programs and thus sharing analysis is an important topic of both abstract interpretation and logic programming. Sharing analyses infer which pairs of... more
Sharing information is useful in specialising, optimising and parallelising logic programs and thus sharing analysis is an important topic of both abstract interpretation and logic programming. Sharing analyses infer which pairs of program variables can never be ...
Abstract. The intrinsic cost of polyhedra has lead to research on more tractable sub-classes of linear inequalities. Rather than committing to the precision of such a sub-class, this paper presents a projection algorithm that works... more
Abstract. The intrinsic cost of polyhedra has lead to research on more tractable sub-classes of linear inequalities. Rather than committing to the precision of such a sub-class, this paper presents a projection algorithm that works directly on any sparse system of inequalities and which ...
... Florence Benoy and Andy King Computing Laboratory, University of Kent at Canterbury, CT2 7NF, UK. {pm benoy, am king} @ukc. ac. uk ... 3 Preliminaries 3.1 Concrete Semantics To express the widening and explain the implementation it is... more
... Florence Benoy and Andy King Computing Laboratory, University of Kent at Canterbury, CT2 7NF, UK. {pm benoy, am king} @ukc. ac. uk ... 3 Preliminaries 3.1 Concrete Semantics To express the widening and explain the implementation it is helpful to clarify the semantics. ...
Temporal variability complicates testing the influences of environmental variability on microbial community structure and thus function. An in-field bioreactor system was developed to assess oxic versus anoxic manipulations on in-situ... more
Temporal variability complicates testing the influences of environmental variability on microbial community structure and thus function. An in-field bioreactor system was developed to assess oxic versus anoxic manipulations on in-situ groundwater communities. Each sample was sequenced (16S SSU rRNA genes, average 10,000 reads) and biogeochemical parameters monitored by quantifying 53 metals, 12 organic acids, 14 anions and 3 sugars. Changes in dissolved oxygen (DO), pH, and other variables were similar across bioreactors. Sequencing revealed a complex community that fluctuated in-step with the groundwater community, and responded to DO. This also directly influenced the pH and so the biotic impacts of DO and pH shifts are correlated. A null model demonstrated that bioreactor communities were driven in part by experimental conditions but also by stochastic variability and did not accurately capture alterations in diversity during perturbations. We identified two groups of abundant OT...
The regulation of toxic chemicals in Canada has undergone many twists and turns in the last 40 years. This paper describes the emergence of a new alliance, one which brought together people from a broad range of backgrounds to formulate... more
The regulation of toxic chemicals in Canada has undergone many twists and turns in the last 40 years. This paper describes the emergence of a new alliance, one which brought together people from a broad range of backgrounds to formulate common strategy to address the continuing use and dissemination of toxic chemicals, especially carcinogens. In just over a decade, Canada's largest municipality, Toronto, adopted a bylaw which introduced a comprehensive scheme for community right-to-know about toxic chemicals being used, released, and disposed-the first in the country. The bylaw represents the success of a network that integrated experience and expertise from community activism, environment, labour, public health, politics and cancer prevention.
Two genes, hgcA and hgcB, are essential for microbial mercury (Hg)-methylation. Detection and estimation of their abundance, in conjunction with Hg concentration, bioavailability and biogeochemistry is critical in determining potential... more
Two genes, hgcA and hgcB, are essential for microbial mercury (Hg)-methylation. Detection and estimation of their abundance, in conjunction with Hg concentration, bioavailability and biogeochemistry is critical in determining potential hot spots of methylmercury (MeHg) generation in at-risk environments. We developed broad-range degenerate PCR primers spanning known hgcAB genes to determine the presence of both genes in diverse environments. These primers were tested against an extensive set of pure cultures with published genomes, including 13 Deltaproteobacteria, nine Firmicutes, and nine methanogenic Archaea A distinct PCR product at the expected size was confirmed for all hgcAB(+) strains tested via Sanger sequencing. Additionally, we developed clade-specific degenerate quantitative primers (qPCR) that targeted hgcA for each of the three dominant Hg-methylating clades. The clade-specific qPCR primers amplified hgcA from 64%, 88% and 86% of tested pure cultures of Deltaproteobact...
Abstract. Accurate variable sharing information is crucial both in the automatic parallelisation and in the optimisation of sequential logic pro-grams. Analysis for possible variable sharing is thus an important topic in logic programming... more
Abstract. Accurate variable sharing information is crucial both in the automatic parallelisation and in the optimisation of sequential logic pro-grams. Analysis for possible variable sharing is thus an important topic in logic programming and many analyses have been proposed ...
ABSTRACT Laura, Gary, Bridget, Chris and Theresa have been referred to social services. Laura is an 83 year old White British lesbian. Her civil partner died last year and she now lives alone in their large multi-storey house in a rural... more
ABSTRACT Laura, Gary, Bridget, Chris and Theresa have been referred to social services. Laura is an 83 year old White British lesbian. Her civil partner died last year and she now lives alone in their large multi-storey house in a rural area. She has several private pensions. Her eyesight is deteriorating and she can no longer drive. She is lonely and depressed. Gary is a single 70 year old gay man of African Caribbean decent, living in an inner city local authority flat, and reliant upon state pensions and other forms of welfare support. He is showing signs of memory loss and confusion. Bridget is a 65 year old bi-identifying woman of White Irish Catholic origins. She lives in the suburbs with her partner, Chris, 69, a White British bisexual man who has Multiple Sclerosis, needing increasing care and support. Their daughter is supportive, but lives a long distance away. Theresa, 61, is a heterosexual trans woman with an Asian/White British heritage, who transitioned three years ago. She has a son, but they are estranged. She lives in a sheltered housing scheme for people with mental health issues. Theresa has complained that staff are discriminating against her. What would good practice look like for each of these people?
The HEMS Beamline at the German high-brilliance synchrotron radiation storage ring PETRA III is fully tunable between 30 and 250 keV and optimized for sub-micrometer focusing. Approximately 70 % of the beamtime will be dedicated to... more
The HEMS Beamline at the German high-brilliance synchrotron radiation storage ring PETRA III is fully tunable between 30 and 250 keV and optimized for sub-micrometer focusing. Approximately 70 % of the beamtime will be dedicated to Materials Research. Fundamental research will encompass metallurgy, physics and chemistry with first experiments planned for the investigation of the relationship between macroscopic and micro-structural
With the increasing miniaturization of Micro-Electro-Mechanical Systems (MEMS) heat dissipation is rapidly becoming a problem to further development in micro-electronics industries. Jet impingement cooling has often been identified as a... more
With the increasing miniaturization of Micro-Electro-Mechanical Systems (MEMS) heat dissipation is rapidly becoming a problem to further development in micro-electronics industries. Jet impingement cooling has often been identified as a method with the potential to pro- vide the high rates of heat transfer needed for rapid heat removal. To this end an in-depth numerical study of jet impingement will be
Monoterpenoids are important flavour compounds produced by many plant species, including grapes (Vitis vinifera) and hops (Humulus lupulus). Biotransformation reactions involving monoterpenoids have been characterized in filamentous... more
Monoterpenoids are important flavour compounds produced by many plant species, including grapes (Vitis vinifera) and hops (Humulus lupulus). Biotransformation reactions involving monoterpenoids have been characterized in filamentous fungi, but few examples have been observed in yeasts. As monoterpenoids are in contact with yeasts during beer and wine production, biotransformation reactions may occur during the fermentation of these beverages. This paper describes the biotransformation of monoterpene alcohols, of significance in the alcoholic beverage industries, by three yeast species. All three species analysed had the ability to convert monoterpenoids. Saccharomyces cerevisiae and Kluyveromyces lactis reduced geraniol into citronellol, whilst all three yeasts produced linalool from both geraniol and nerol. Monocyclic alpha-terpineol was formed from both linalool and nerol, by all three yeasts. alpha-Terpineol was then converted into the diol cis-terpin hydrate. K. lactis and Torulaspora delbrueckii also had the ability to form geraniol from nerol. Finally, the stereospecificity of terpenoid formation was analysed. Both (+) and (-) enantiomers of linalool and alpha-terpineol were formed in roughly equal quantities, from either geraniol or nerol.
The article is a case study centring on the mass-market fiction weekly the Family Herald and its Supplements. It argues that affect and its possibilities for political and economic critique are often ignored as... more
The article is a case study centring on the mass-market fiction weekly the Family Herald and its Supplements. It argues that affect and its possibilities for political and economic critique are often ignored as "supplements" in the study of periodicals. After a methodological introduction, the piece suggests that the Family Herald Supplement may have resulted from the intervention of an
This paper presents four new feature extraction operators (based on gradient filters), which can be used to extract various edge and corner properties of images. Each of these operators consists of a bilinear combination of 1st and 2nd... more
This paper presents four new feature extraction operators (based on gradient filters), which can be used to extract various edge and corner properties of images. Each of these operators consists of a bilinear combination of 1st and 2nd order derivatives of the luminance image, and is either invariant or equivariant to rotations of the image. A brief outline of these invariance and equivariance properties is given. The computational requirements of calculating the operators are stated, and some results of their application on clean and noisy images are presented. In these results, an image pyramid is used to show how a multiresolution approach can give robust estimates in the presence of noise
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ABSTRACT The free surface and flow field structure generated by the uniform acceleration of a rigid plate, inclined at an angle α∈(0,π) to the exterior horizontal, as it advances into an initially stationary and horizontal strip of... more
ABSTRACT The free surface and flow field structure generated by the uniform acceleration of a rigid plate, inclined at an angle α∈(0,π) to the exterior horizontal, as it advances into an initially stationary and horizontal strip of inviscid incompressible fluid, is studied in the large-time limit via the method of matched asymptotic expansions. The small-time limit of the solution to this problem was studied in detail in [the author, P. G. Chamberlain and J. Billingham, Q. J. Mech. Appl. Math. 61, No. 4, 581–614 (2008; Zbl 1153.76019)]. We assume that after an initial constant acceleration, the velocity of the plate reaches a terminal value in finite time and remains at that velocity thereafter. The structure of the large-time solution includes a steady bore propagating away from the plate with constant speed, together with an algebraically decaying wave field behind the bore, up to the plate, which demonstrates that there are no localized trapped waves excited near to the plate, with all energy radiating away from the plate as t→∞.
How an animal moves through its environment directly impacts its survival, reproduction, and thus biological fitness. A basic measure describing how an individual (or group) travels through its environment is Day Path Length (DPL), i.e.,... more
How an animal moves through its environment directly impacts its survival, reproduction, and thus biological fitness. A basic measure describing how an individual (or group) travels through its environment is Day Path Length (DPL), i.e., the distance travelled in a 24-hour period. Here, we investigate the ecological determinants of baboon (Papio spp.) troop DPL and movements at local and continental scales. At the continental scale we explore the ecological determinants of annual mean DPL for 47 baboon troops across 23 different populations, updating a classic study by Dunbar (Behav Ecol Sociobiol 31: 35-49, 1992). We find that variation in baboon DPLs is predicted by ecological dissimilarity across the genus range. Troops that experience higher average monthly rainfall and anthropogenic influences have significantly shorter DPL, whilst troops that live in areas with higher average annual temperatures have significantly longer DPL. We then explore DPLs and movement characteristics (the speed and distribution of turning angles) for yellow baboons (Papio cynocephalus) at a local scale, in the Issa Valley of western Tanzania. We show that our continental-scale model is a good predictor of DPL in Issa baboons, and that troops move significantly slower, and over shorter distances, on warmer days. We do not find any effect of season or the abundance of fruit resources on the movement characteristics or DPL of Issa baboons, but find that baboons moved less during periods of high fruit availability. Overall, this study emphasises the ability of baboons to adapt their ranging behaviour to a range of ecological conditions and highlights how investigations of movement patterns at different spatial scales can provide a more thorough understanding of the ecological determinants of movement.
The majority of prolactinomas respond to dopamine agonist therapy, but a proportion are resistant, requiring other treatments including surgery and/or radiotherapy. Temozolomide is an oral chemotherapy agent, which has been used as a... more
The majority of prolactinomas respond to dopamine agonist therapy, but a proportion are resistant, requiring other treatments including surgery and/or radiotherapy. Temozolomide is an oral chemotherapy agent, which has been used as a salvage therapy to treat aggressive pituitary adenomas and carcinomas, including prolactinomas, unresponsive to all conventional treatment. We report three patients where temozolomide was used in the treatment of refractory prolactinomas. Case 1 describes a patient with a highly invasive prolactinoma, resistant to all conventional therapy, which responded dramatically to temozolomide used as a salvage treatment. In case 2, temozolomide was used after incomplete surgical resection to relieve chiasmal compression and avoid chiasm exposure to radiotherapy. In case 3, temozolomide enabled radiotherapy to be deferred in a 16-year old with a resistant prolactinoma. In all three cases, the tumours were negative by immunostaining for methylguanine methyltransferase (MGMT). A review of the published literature reveals 51 reported cases of temozolomide treatment for pituitary tumours, including 20 prolactinomas. Fifteen of the 20 prolactinomas showed a good response to temozolomide. Our analysis demonstrates a strong association between MGMT-negative staining and a good response to temozolomide (OR 9.35, P = 0.0030). Current clinical practice is to use temozolomide as a salvage therapy after all conventional modalities of treatment have failed. We suggest that, in selected cases, consideration should be given to using temozolomide earlier in the treatment algorithm.
Bitter acids (α and β types) account for more than 30% of the fresh weight of hop (Humulus lupulus) glandular trichomes and are well known for their contribution to the bitter taste of beer. These multiprenylated chemicals also show... more
Bitter acids (α and β types) account for more than 30% of the fresh weight of hop (Humulus lupulus) glandular trichomes and are well known for their contribution to the bitter taste of beer. These multiprenylated chemicals also show diverse biological activities, some of which have potential benefits to human health. The bitter acid biosynthetic pathway has been investigated extensively, and the genes for the early steps of bitter acid synthesis have been cloned and functionally characterized. However, little is known about the enzyme(s) that catalyze three sequential prenylation steps in the β-bitter acid pathway. Here, we employed a yeast (Saccharomyces cerevisiae) system for the functional identification of aromatic prenyltransferase (PT) genes. Two PT genes (HlPT1L and HlPT2) obtained from a hop trichome-specific complementary DNA library were functionally characterized using this yeast system. Coexpression of codon-optimized PT1L and PT2 in yeast, together with upstream genes, ...
263 safety has been formally proved through abstract interpretation. In more pragmatic terms it means that the thresholding conditions inferred by the analysis guarantee that fine-grained processes are never spawned. Note, however, that... more
263 safety has been formally proved through abstract interpretation. In more pragmatic terms it means that the thresholding conditions inferred by the analysis guarantee that fine-grained processes are never spawned. Note, however, that not spawning fine-grained processes ...
Schedule Analysis of Concurrent Logic Programs [Andy King and Paul Soper Pepartment of Electronics and Computer Science, university of Southampton, Southampton, S09 5NH, UK| ^mk@ecs.soton.ac.uk, pjs@ecs.soton.ac.uk LA.bstract A... more
Schedule Analysis of Concurrent Logic Programs [Andy King and Paul Soper Pepartment of Electronics and Computer Science, university of Southampton, Southampton, S09 5NH, UK| ^mk@ecs.soton.ac.uk, pjs@ecs.soton.ac.uk LA.bstract A compilation technique is proposed ...
This article examines the representation of indigenous sexuality on Australian television drama since the 1970s, suggesting the political importance of such representations. In 1976 Justine Saunders became the first regular indigenous... more
This article examines the representation of indigenous sexuality on Australian television drama since the 1970s, suggesting the political importance of such representations. In 1976 Justine Saunders became the first regular indigenous character on an Australian television drama series, as the hairdresser Rhonda Jackson in Number 96. She was presented as sexually attractive, but this was expressed through a rape scene
The ‘black is beautiful’ movement began in the United States in the early 1960s, and changed mainstream attitudes towards the body, fashion and personal aesthetics, gaining African-American people a new sense of pride in being – and being... more
The ‘black is beautiful’ movement began in the United States in the early 1960s, and changed mainstream attitudes towards the body, fashion and personal aesthetics, gaining African-American people a new sense of pride in being – and being called – ‘black’. In Australia the movement also had implications for changing the political meanings of ‘black’ in white society. However, it
... criticism. The work of such feminist scholars as Karlyn Kohrs Campbell and CherylGlenn has shown that female practices of expression operate from rhetor-ical systems previously unaccounted for in classical rhetorical theory. ...
Page 1. The Changing Culture of Rhetorical Studies (Editor's Note: We introduce this symposium by reprinting Horner's luncheon address at the 1996 meeting of the Rhetoric Society of Amer-ica and later published in Making... more
Page 1. The Changing Culture of Rhetorical Studies (Editor's Note: We introduce this symposium by reprinting Horner's luncheon address at the 1996 meeting of the Rhetoric Society of Amer-ica and later published in Making ...
This article presents some of the findings from a mixed-methods case study that investigated collaborative learning for pairs of higher education students working in a music studio on a drum kit recording. A stratified purposive sampling... more
This article presents some of the findings from a mixed-methods case study that investigated collaborative learning for pairs of higher education students working in a music studio on a drum kit recording. A stratified purposive sampling technique was used and students were ...
1Dept of Chemical Engineering, University of Sydney, NSW, 2006, Australia 2Dept of Chemical Engineering, University of Queensland, Qld, 4072, Australia 3Institut Universitaire Professionnalisé de Chimie Appliquée, Université... more
1Dept of Chemical Engineering, University of Sydney, NSW, 2006, Australia 2Dept of Chemical Engineering, University of Queensland, Qld, 4072, Australia 3Institut Universitaire Professionnalisé de Chimie Appliquée, Université d'Orléans, UFR Sciences, BP 6759, 45067, Orléans, ...
This article advocates incorporating biographical narratives into social work practice involving older lesbian, gay and bisexual service users. Offering a critique of ‘sexuality-blind’ conditions in current policy and practice, the... more
This article advocates incorporating biographical narratives into social work practice involving older lesbian, gay and bisexual service users. Offering a critique of ‘sexuality-blind’ conditions in current policy and practice, the discussion draws on qualitative data to illustrate the potential benefits of narrative approaches for both practitioners and service users.
ABSTRACT 1.Predation plays a fundamental role in evolutionary processes, driving changes in prey morphology, physiology, and behaviour. With organisms being increasingly exposed to rapid environmental changes, there is growing interest in... more
ABSTRACT 1.Predation plays a fundamental role in evolutionary processes, driving changes in prey morphology, physiology, and behaviour. With organisms being increasingly exposed to rapid environmental changes, there is growing interest in understanding individual phenotypic plasticity in responses to changes in predation pressure.2.Behavioural and physiological responses to predator exposure are of particular interest as differences in predation pressure are often reflected in correlated suites of behavioural and hormonal profiles across populations. Within populations, the association between endocrine profiles and behaviour is less understood, and often lacking.3.Adopting a reaction norm approach and a repeated measures design, we assessed within-population effects of changes in perceived predation risk on endocrinology and behaviour in three-spined sticklebacks (Gasterosteus aculeatus). We repeatedly exposed subjects to a robotic model predator, and assessed their behavioural response. The fish showed consistent behavioural profiles and were less active and shyer when predation risk was higher.4.Using non-invasive waterborne hormone analysis, we assessed basal cortisol as well as the cortisol response to changes in predation risk. Individuals showed significantly higher cortisol levels following exposure to the model predator. Individual post- predator exposure cortisol was repeatable but unrelated to behavioural responses. Accounting for between versus within subject effects, we found that basal cortisol and shyness were positively related within individuals, i.e. individuals overall were shyer on days they had higher cortisol levels. We also tested if basal testosterone predicted risky behaviour and found no evidence for this hypothesis.5.No individual differences in hormonal or behavioural responses to changes in predation risk were found, suggesting that individuals are not constrained by their personalities in their ability to cope with a potentially harmful threat.6.Overall, we show that individuals of different personalities are equally “flexible” in their response to changes in predation pressure. Our study offers novel insight into consistent individual differences and plasticity in hormones and behaviour as well as their interplay within populations. Future studies should assess the applicability of these findings to other changes in the environment, as well as the effects of social context on endocrine and behavioural reaction norms.This article is protected by copyright. All rights reserved.
Empty capsids of foot-and-mouth disease virus (FMDV) type A22 Iraq 24/64, whose structure has been solved by X-ray crystallography, are unusual for picornaviruses since they contain VP2 and VP4, the cleavage products of the protein... more
Empty capsids of foot-and-mouth disease virus (FMDV) type A22 Iraq 24/64, whose structure has been solved by X-ray crystallography, are unusual for picornaviruses since they contain VP2 and VP4, the cleavage products of the protein precursor VP0. Both the N terminus of VP1 and the C terminus of VP4, which pack together close to the icosahedral threefold symmetry axis where three pentamers associate, are more disordered in the empty capsid than they are in the RNA-containing virus. The ordering of these termini in the presence of RNA strengthens interactions within a single protomer and between protomers belonging to different pentamers. The disorder in the FMDV empty capsid forms a subset of that seen in the poliovirus empty capsid, which has VP0 intact. Thus, VP0 cleavage confers stability on the picornavirus capsid over and above that attributable to RNA encapsidation. In both FMDV and poliovirus empty capsids, the internal disordering uncovers a conserved histidine which has been...
The domain of positive Boolean functions, Pos, is by now well established for the analysis of the variable dependencies that arise within logic programs. Analyses based on Pos that use binary decision diagrams (BDDs) have been shown to be... more
The domain of positive Boolean functions, Pos, is by now well established for the analysis of the variable dependencies that arise within logic programs. Analyses based on Pos that use binary decision diagrams (BDDs) have been shown to be efficient for a wide range of ...
1 GKSS Research Centre, D-21502 Geesthacht, Germany 2 Joint Research Centre, 1755 LE Petten, The Netherlands 3 School of Materials, University of Manchester, M13 9PL, UK 4 ESRF, Grenoble, France and MATEIS, INSA de Lyon, Villeurbanne,... more
1 GKSS Research Centre, D-21502 Geesthacht, Germany 2 Joint Research Centre, 1755 LE Petten, The Netherlands 3 School of Materials, University of Manchester, M13 9PL, UK 4 ESRF, Grenoble, France and MATEIS, INSA de Lyon, Villeurbanne, France ...
Although many studies have examined the precedence effect (PE), few have tested whether it shows a buildup and breakdown in nonhuman animals comparable to that seen in humans. These processes are thought to reflect the ability of the... more
Although many studies have examined the precedence effect (PE), few have tested whether it shows a buildup and breakdown in nonhuman animals comparable to that seen in humans. These processes are thought to reflect the ability of the auditory system to adjust to a listener's acoustic environment, and their mechanisms are still poorly understood. In this study, ferrets were trained on a two-alternative forced-choice task to discriminate the azimuthal direction of brief sounds. In one experiment, pairs of noise bursts were presented from two loudspeakers at different interstimulus delays (ISDs). Results showed that localization performance changed as a function of ISD in a manner consistent with the PE being operative. A second experiment investigated buildup and breakdown of the PE by measuring the ability of ferrets to discriminate the direction of a click pair following presentation of a conditioning train. Human listeners were also tested using this paradigm. In both species, performance was better when the test clicks and conditioning train had the same ISD but deteriorated following a switch in the direction of the leading and lagging sounds between the conditioning train and test clicks. These results suggest that ferrets, like humans, experience a buildup and breakdown of the PE.
For our programming convenience we have implemented an extensible robotic control framework in the Java program- ming language. This framework manages some of the tedious details in robotics programming (sensor - behavior integra- tion... more
For our programming convenience we have implemented an extensible robotic control framework in the Java program- ming language. This framework manages some of the tedious details in robotics programming (sensor - behavior integra- tion and concurrency issues) as well as enforces a modular programming style that works well when a team is involved with robot software development. Wediscuss how thisframe- work allows for modular software development. As an exam- ple we show how a laser range data based object detection algorithm can be implemented as a framework sensor mod- ule and how information provided by that new module can be utilization by the planning and mobility modules.
The KSU Willie entry in the Semantic Vision Challenge will use a variety of classifiers, some standard classifiers and some newly developed classifiers, to learn the classi-fication of images downloaded from the web. KSU Willie will use... more
The KSU Willie entry in the Semantic Vision Challenge will use a variety of classifiers, some standard classifiers and some newly developed classifiers, to learn the classi-fication of images downloaded from the web. KSU Willie will use those classifiers ...
Cortical sensory neurons are commonly characterized using the receptive field, the linear dependence of their response on the stimulus. In primary auditory cortex neurons can be characterized by their spectrotemporal receptive fields, the... more
Cortical sensory neurons are commonly characterized using the receptive field, the linear dependence of their response on the stimulus. In primary auditory cortex neurons can be characterized by their spectrotemporal receptive fields, the spectral and temporal features of a sound that linearly drive a neuron. However, receptive fields do not capture the fact that the response of a cortical neuron results from the complex nonlinear network in which it is embedded. By fitting a nonlinear feedforward network model (a network receptive field) to cortical responses to natural sounds, we reveal that primary auditory cortical neurons are sensitive over a substantially larger spectrotemporal domain than is seen in their standard spectrotemporal receptive fields. Furthermore, the network receptive field, a parsimonious network consisting of 1-7 sub-receptive fields that interact nonlinearly, consistently better predicts neural responses to auditory stimuli than the standard receptive fields....
The harmonic structure of sounds is an important grouping cue in auditory scene analysis. The ability of ferrets to detect mistuned harmonics was measured using a go/no-go task paradigm. Psychometric functions plotting sensitivity as a... more
The harmonic structure of sounds is an important grouping cue in auditory scene analysis. The ability of ferrets to detect mistuned harmonics was measured using a go/no-go task paradigm. Psychometric functions plotting sensitivity as a function of degree of mistuning were used to evaluate behavioral performance using signal detection theory. The mean (± standard error of the mean) threshold for mistuning detection was 0.8 ± 0.1 Hz, with sensitivity indices and reaction times depending on the degree of mistuning. These data provide a basis for investigation of the neural basis for the perception of complex sounds in ferrets, an increasingly used animal model in auditory research.
We present verication,methods,for logic programs,with delay declarations. The veried,prop- erties are termination and freedom from errors related to built-ins. Concerning termination, we present two,approaches. The,rst approach,tries to... more
We present verication,methods,for logic programs,with delay declarations. The veried,prop- erties are termination and freedom from errors related to built-ins. Concerning termination, we present two,approaches. The,rst approach,tries to eliminate the well-known,problem of speculative output,bindings. The second,approach,is based,on identifying the predicates for which,the textual position of an atom,using this predicate is irrelevant with respect to termination. Three features are distinctive of
There are many applications where precise mode analysis is required. However, within the framework of abstract interpretation, the precision of an analyser depends, in part, on the expressiveness of the abstract domain and its associated... more
There are many applications where precise mode analysis is required. However, within the framework of abstract interpretation, the precision of an analyser depends, in part, on the expressiveness of the abstract domain and its associated abstraction function. This paper considers abstract domains for polymorphically typed logic programs where each nonvariable symbol is explicitly typed. We show how to construct precise
Good metrics of the performance of a statistical or computational model are essential for model comparison and selection. Here, we address the design of performance metrics for models that aim to predict neural responses to sensory... more
Good metrics of the performance of a statistical or computational model are essential for model comparison and selection. Here, we address the design of performance metrics for models that aim to predict neural responses to sensory inputs. This is particularly difficult because the responses of sensory neurons are inherently variable, even in response to repeated presentations of identical stimuli. In this situation, standard metrics (such as the correlation coefficient) fail because they do not distinguish between explainable variance (the part of the neural response that is systematically dependent on the stimulus) and response variability (the part of the neural response that is not systematically dependent on the stimulus, and cannot be explained by modeling the stimulus-response relationship). As a result, models which perfectly describe the systematic stimulus-response relationship may appear to perform poorly. Two metrics have previously been proposed which account for this i...
Social density processes impact the activity and order of collective behaviours in a variety of biological systems. Much effort has been devoted to understanding how density of people affects collective human motion in the context of... more
Social density processes impact the activity and order of collective behaviours in a variety of biological systems. Much effort has been devoted to understanding how density of people affects collective human motion in the context of pedestrian flows. However, there is a distinct lack of empirical data investigating the effects of social density on human behaviour in cooperative contexts. Here, we examine the functioning and performance of human teams in a central-place foraging arena using high-resolution GPS data. We show that team functioning (level of coordination) is greatest at intermediate social densities, but contrary to our expectations, increased coordination at intermediate densities did not translate into improved collective foraging performance, and foraging accuracy was equivalent across our density treatments. We suggest that this is likely a consequence of foragers relying upon visual channels (local information) to achieve coordination but relying upon auditory channels (global information) to maximise foraging returns. These findings provide new insights for the development of more sophisticated models of human collective behaviour that consider different networks for communication (e.g. visual and vocal) that have the potential to operate simultaneously in cooperative contexts.
Economical cultivation of the oilseed crop Jatropha curcas is currently hampered in part due to the non-availability of purpose-bred cultivars. Although genetic maps and genome sequence data exist for this crop, marker-assisted breeding... more
Economical cultivation of the oilseed crop Jatropha curcas is currently hampered in part due to the non-availability of purpose-bred cultivars. Although genetic maps and genome sequence data exist for this crop, marker-assisted breeding has not yet been implemented due to a lack of available marker-trait association studies. To identify the location of beneficial alleles for use in plant breeding, we performed quantitative trait loci (QTL) analysis for a number of agronomic traits in two biparental mapping populations. The mapping populations segregated for a range of traits contributing to oil yield, including plant height, stem diameter, number of branches, total seeds per plant, 100-seed weight, seed oil content and fatty acid composition. QTL were detected for each of these traits and often over multiple years, with some variation in the phenotypic variance explained between different years. In one of the mapping populations where we recorded vegetative traits, we also observed ...
Developmental adjustments in the balance of excitation and inhibition are thought to constrain the plasticity of sensory areas of the cortex. It is unknown however, how changes in excitatory or inhibitory neurochemical expression... more
Developmental adjustments in the balance of excitation and inhibition are thought to constrain the plasticity of sensory areas of the cortex. It is unknown however, how changes in excitatory or inhibitory neurochemical expression (glutamate, γ-aminobutyric acid (GABA)) contribute to skill acquisition during development. Here we used single-voxel proton magnetic resonance spectroscopy ((1) H-MRS) to reveal how differences in cortical glutamate vs. GABA ratios relate to face proficiency and working memory abilities in children and adults. We show that higher glutamate levels in the inferior frontal gyrus correlated positively with face processing proficiency in the children, but not the adults, an effect which was independent of age-dependent differences in underlying cortical gray matter. Moreover, we found that glutamate/GABA levels and gray matter volume are dissociated at the different maturational stages. These findings suggest that increased excitation during development is link...
Morphinan alkaloids from opium poppy are used for pain relief. Direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high reticuline poppy mutants revealed a genetic... more
Morphinan alkaloids from opium poppy are used for pain relief. Direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)- reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline while the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.
The precise encoding of temporal features of auditory stimuli by the mammalian auditory system is critical to the perception of biologically important sounds, including vocalizations, speech, and music. In this study, auditory... more
The precise encoding of temporal features of auditory stimuli by the mammalian auditory system is critical to the perception of biologically important sounds, including vocalizations, speech, and music. In this study, auditory gap-detection behavior was evaluated in adult pigmented ferrets (Mustelid putorius furo) using bandpassed stimuli designed to widely sample the ferret's behavioral and physiological audiogram. Animals were tested under positive operant conditioning, with psychometric functions constructed in response to gap-in-noise lengths ranging from 3 to 270 ms. Using a modified version of this gap-detection task, with the same stimulus frequency parameters, we also tested a cohort of normal-hearing human subjects. Gap-detection thresholds were computed from psychometric curves transformed according to signal detection theory, revealing that for both ferrets and humans, detection sensitivity was worse for silent gaps embedded within low-frequency noise compared with hi...
Despite numerous studies of auditory cortical processing in the ferret (Mustela putorious), very little is known about the connections between the different regions of the auditory cortex that have been characterised cytoarchitectonically... more
Despite numerous studies of auditory cortical processing in the ferret (Mustela putorious), very little is known about the connections between the different regions of the auditory cortex that have been characterised cytoarchitectonically and physiologically. We examined the distribution of retrograde and anterograde labelling after injecting tracers into one or more regions of ferret auditory cortex. Injections of different tracers at frequency-matched locations in the core areas, the primary auditory cortex (A1) and anterior auditory field (AAF), of the same animal revealed the presence of reciprocal connections with overlapping projections to and from discrete regions within the posterior pseudosylvian and suprasylvian fields (PPF and PSF), suggesting that these connections are frequency specific. In contrast, projections from the primary areas to the anterior dorsal field (ADF) on the anterior ectosylvian gyrus were scattered and non-overlapping, consistent with the non-tonotopi...
The localization of sounds in space is based on spatial cues that arise from the acoustical properties of the head and external ears. Individual differences in localization cue values result from variability in the shape and dimensions of... more
The localization of sounds in space is based on spatial cues that arise from the acoustical properties of the head and external ears. Individual differences in localization cue values result from variability in the shape and dimensions of these structures. We have mapped spatial response fields of high-frequency neurons in ferret primary auditory cortex using virtual sound sources based either on the animal's own ears or on the ears of other subjects. For 73% of units, the response fields measured using the animals' own ears differed significantly in shape and/or position from those obtained using spatial cues from another ferret. The observed changes correlated with individual differences in the acoustics. These data are consistent with previous reports showing that humans localize less accurately when listening to virtual sounds from other individuals. Together these findings support the notion that neural mechanisms underlying auditory space perception are calibrated by e...
ABSTRACT The role of the superior colliculus in attending and orienting to sensory stimuli is facilitated by the presence within this midbrain nucleus of superimposed maps of different sensory modalities. We have studied the steps... more
ABSTRACT The role of the superior colliculus in attending and orienting to sensory stimuli is facilitated by the presence within this midbrain nucleus of superimposed maps of different sensory modalities. We have studied the steps involved in the development of topographically-aligned maps of visual and auditory space in the ferret superior colliculus. Injections of fluorescent beads into the superficial layers showed that the projection from the contralateral retina displays topographic order on the day of birth (PO). Recordings made from these layers at the time of eye opening, approximately 1 month later, revealed the presence of an adult-like map of visual space. In contrast, the auditory space map in the deeper layers emerged gradually over a much longer period of postnatal life. In adult ferrets in which one eye had been deviated laterally just before eye opening, the auditory spatial tuning of single units recorded in the contralateral superior colliculus was shifted by a corresponding amount, so that the registration of the visual and auditory maps was maintained. Chronic application of the NMDA-receptor antagonist MK801 disrupted the normal development of the auditory space map, but had no effect on the visual map in either juvenile or adult animals, or on the auditory map once it had matured. These findings indicate that visual cues may play an instructive role, possibly via a Hebbian mechanism of synaptic plasticity, in the development of appropriately tuned auditory responses, thereby ensuring that the neural representations of both modalities share the same coordinates. Changes observed in the auditory representation following partial lesions of the superficial layers at PO suggest that these layers may provide the source of the visual signals responsible for experience-induced plasticity in auditory spatial tuning.
The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic... more
The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic keratosis), and phorbol derivatives such as resiniferatoxin and prostratin, which are undergoing investigation for the treatment of severe pain and HIV, respectively. Despite the interest in these diterpenoids, their biosynthesis is poorly understood at present, with the only characterized step being the conversion of geranylgeranyl pyrophosphate into casbene. Here, we report a physical cluster of diterpenoid biosynthetic genes from castor (Ricinus communis), including casbene synthases and cytochrome P450s from the CYP726A subfamily. CYP726A14, CYP726A17, and CYP726A18 were able to catalyze 5-oxidation of casbene, a conserved oxidation step in the biosynthesis of this family of medicinally important diterpenoids. CYP726A16 catalyzed 7,8-epoxidation of 5-ket...
Herding of sheep by dogs is a powerful example of one individual causing many unwilling individuals to move in the same direction. Similar phenomena are central to crowd control, cleaning the environment and other engineering problems.... more
Herding of sheep by dogs is a powerful example of one individual causing many unwilling individuals to move in the same direction. Similar phenomena are central to crowd control, cleaning the environment and other engineering problems. Despite single dogs solving this 'shepherding problem' every day, it remains unknown which algorithm they employ or whether a general algorithm exists for shepherding. Here, we demonstrate such an algorithm, based on adaptive switching between collecting the agents when they are too dispersed and driving them once they are aggregated. Our algorithm reproduces key features of empirical data collected from sheep-dog interactions and suggests new ways in which robots can be designed to influence movements of living and artificial agents.
According to ANSI, pitch is defined as that attribute according to which sounds can be ordered on a scale from low to high. However, most studies of pitch so far asked merely whether a subject can detect a pitch change, not whether he can... more
According to ANSI, pitch is defined as that attribute according to which sounds can be ordered on a scale from low to high. However, most studies of pitch so far asked merely whether a subject can detect a pitch change, not whether he can also determine the direction of the pitch change. Using behavioural testing after operand conditioning we have
Using theories on group identity and voluntary risk taking, data gathered through seven focus groups involving 43 fraternity members were analyzed to understand the ways in which the members construct the problems of and solutions to... more
Using theories on group identity and voluntary risk taking, data gathered through seven focus groups involving 43 fraternity members were analyzed to understand the ways in which the members construct the problems of and solutions to excessive drinking. Control emerged as a metaconcept that is both an undercurrent and interconnection to the expressed opinions. The possession and practice of control discriminated three levels of in-group versus out-group membership. Perspectives on solutions were predicated upon the perceived risk of lack of control and intergroup dynamics. Implications on intervention and policy efforts are discussed.
The domain of positive Boolean functions, Pos, is by now well established for the analysis of the variable dependencies that arise within logic programs. Analyses based on Pos that use binary decision diagrams have been shown to be... more
The domain of positive Boolean functions, Pos, is by now well established for the analysis of the variable dependencies that arise within logic programs. Analyses based on Pos that use binary decision diagrams have been shown to be efficient for a wide range of practical programs. However, independent of the representation, assuming that P != NP , an (unwidened) Pos
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