Huntington's disease is a fatal, neurodegenerative movement disorder characterized by preferentia... more Huntington's disease is a fatal, neurodegenerative movement disorder characterized by preferential and extensive striatal degeneration. Here, we used fast-scan cyclic voltammetry to study the mobilization and efflux of reserve pool dopamine in striatal brain slices from Huntington's disease model R6/2 mice. When applying stimulus trains of 120 pulses, evoked dopamine release in wild-type slices was greater than that in R6/2 slices at the higher frequencies (50 and 60 Hz). To quantify cytosolic and reserve pool dopamine levels, amphetamine-induced dopamine efflux was measured after pre-treatment with either tetrabenazine or alpha-methyl-ptyrosine. Slices from 12-week old R6/2 mice released less dopamine than slices from wild-type mice, while no difference was noted in slices from 6-week old mice. The vesicular release of reserve pool dopamine, mobilized by treatment with cocaine, was shorter lived in R6/2 slices compared to wild-type slices even though peak dopamine release was the same. Moreover, the number of dopamine reserve pool vesicles in R6/2 mice was less than half of that in wild-type. Therefore, our data suggest that the same number of dopamine molecules are present in each reserve pool vesicle in WT and R6/2 mice and that these vesicles are readily mobilized in both genotypes; however, R6/2 mice have fewer dopamine reserve pool vesicles available for mobilization.
Presently, most CubeSat components and buses are generally not appropriate for missions where sig... more Presently, most CubeSat components and buses are generally not appropriate for missions where significant or indeterminate risk of failure is unacceptable. This has precluded their use in many cases where their attributes could otherwise enable or enhance mission objectives. However, in the future, CubeSats and SmallSats, which deviate from CubeSat form factors but often incorporate CubeSat components and subsystems, will address challenges that many presently consider to be beyond the platform’s capabilities. This growing potential utility, combined with the limited volume of successful CubeSat flight heritage, is driving an interagency effort to improve small satellite mission confidence. The Small Satellite Reliability Initiative (SSRI)—an activity with broad participation from civil, DoD, and commercial space systems providers and stakeholders—has been targeting this challenge. This paper will update the community on how the public-private collaboration is being executed. It wil...
Let (X, B, µ) be a probability space and let T 1 ,. .. , T l be l commuting invertible measure pr... more Let (X, B, µ) be a probability space and let T 1 ,. .. , T l be l commuting invertible measure preserving transformations of X. We show that if the group of transformations generated by T 1 ,. .. , T l is totally ergodic, then the averages
Targeting autophagy in cancer cells and in the tumor microenvironment are current goals of cancer... more Targeting autophagy in cancer cells and in the tumor microenvironment are current goals of cancer therapy. However, components of canonical autophagy play roles in other biological processes, adding complexity to this goal. One such alternative function of autophagy proteins is LC3-associated phagocytosis (LAP), which functions in phagosome maturation and subsequent signaling events. Here, we show that impairment of LAP in the myeloid compartment, rather than canonical autophagy, induces control of tumor growth by tumor-associated macrophages (TAM) upon phagocytosis of dying tumor cells. Single-cell RNA sequencing (RNA-seq) analysis revealed that defects in LAP induce pro-inflammatory gene expression and trigger STING-mediated type I interferon responses in TAM. We found that the anti-tumor effects of LAP impairment require tumor-infiltrating T cells, dependent upon STING and the type I interferon response. Therefore, autophagy proteins in the myeloid cells of the tumor microenviron...
Huntington's disease (HD) is a fatal neurodegenerative disorder that is characterized by dege... more Huntington's disease (HD) is a fatal neurodegenerative disorder that is characterized by degeneration of the striatum. Here, fast-scan cyclic voltammetry at carbon-fiber microelectrodes was used to uncover regional differences in dopamine (DA) release in the caudate putamen of R6/2 and wild-type control mice. We found a decreasing ventral-to-dorsal gradient in DA release, evoked by a single electrical stimulus pulse, in aged R6/2 mice. Moreover, under more intense stimulation conditions (120 pulses), DA release was significantly attenuated in the dorsal, but not in the ventral caudate. Autoradiography measurements using [H]WIN 35,428 revealed that the overall density of DA transporter (DAT) protein molecules was significantly less in R6/2 mice compared to WT control mice; however, quadrants of the caudate putamen were not differentially altered in the R6/2 mice. These data collectively suggest that DA release in the dorsal caudate region is more vulnerable with age progression c...
The American journal of emergency medicine, Jan 29, 2017
Myocardial infarction and stroke are two of the leading causes of death in the U.S. Both diseases... more Myocardial infarction and stroke are two of the leading causes of death in the U.S. Both diseases have clinical practice guidelines (CPGs) specific to the emergency department (ED) that improve patient outcomes. Our primary objectives were to estimate differences in ED adherence across CPGs for these diseases and identify patient, provider, and environmental factors associated with adherence. Design: Retrospective study at 3 hospitals in Colorado using standard medical record review. Consecutive adults (≥18) hospitalized for acute coronary syndrome (ACS), ST-elevation myocardial infarction (STEMI), or acute ischemic stroke (AIS), who were admitted to the hospital from the ED and for whom the ED diagnosed or initiated treatment. ED adherence to the CPG (primary); in-hospital mortality and length-of-stay (secondary). Multivariable logistic regression using generalized estimating equations was used. Among 1053 patients, ED care was adherent in 84% with significant differences in adhere...
Emergency medicine Australasia : EMA, Jan 28, 2016
Evidence-based decision-making tools are widely used to guide cervical spine assessment in adult ... more Evidence-based decision-making tools are widely used to guide cervical spine assessment in adult trauma patients. Similar tools validated for use in injured children are lacking. A paediatric-specific approach is appropriate given important differences in cervical spine anatomy, mechanism of spinal injury and concerns over ionising radiation in children. The present study aims to survey physicians' knowledge and application of cervical spine assessment in injured children. A cross-sectional survey of physicians actively engaged in trauma care within a paediatric trauma centre was undertaken. Participation was voluntary and responses de-idenitified. The survey comprised 20 questions regarding initial assessment, imaging, immobilisation and perioperative management. Physicians' responses were compared with available current evidence. Sixty-seven physicians (28% registrars, 17% fellows and 55.2% consultants) participated. Physicians rated altered mental state, intoxication and ...
Entity-Relationship models are a common tool for specification and design of information systems.... more Entity-Relationship models are a common tool for specification and design of information systems.They use a graphical technique for displaying the objects of the system and relatioshipsamong them. The design process can be enhanced by specifying constraints of the system and thenatural environment for these is the categorical notion of sketch. Here we argue that the finite-limit,finite-coproduct sketches with a terminal
The Sketch Data Model (SkDM) is a new semantic modelling paradigm based on category theory (speci... more The Sketch Data Model (SkDM) is a new semantic modelling paradigm based on category theory (specifically on categorical universal algebra), which has been used successfully in several consultancies with major Australian companies. This paper describes the sketch data model and investigates the view update problem (VUP) in the sketch data model paradigm. It proposes an approach to the VUP in the SkDM, and presents a range of examples to illustrate the scope of the proposed technique. In common with previously proposed approaches, we define under what circumstances a view update can be propagated to the underlying database. Unlike many previously proposed approaches the definition is succinct and consistent, with no ad hoc exceptions, and the propagatable updates form a broad class. We argue that we avoid ad hoc exceptions by basing the definition of propagatable on the state of the underlying database. The examples demonstrate that under a range of circumstances a view schema can be shown to have propagatable views in all states, and thus state-independence can frequently be recovered.
During the past two decades, most countries in Sub-Saharan Africa undertook extensive economic re... more During the past two decades, most countries in Sub-Saharan Africa undertook extensive economic reforms to reduce the role of the government and increase the role of the market in their economies. Because of the importance of the agricultural sector in the region, agricultural market reforms occupied a central place in these liberalization efforts. Agricultural reforms included the removal of price controls, deregulation of agricultural marketing, closure of state-owned enterprises that monopolized agricultural trade, and changes in the foreign exchange market to provide greater incentives for exports. The expectation was that improving price incentives for farmers and reducing government intervention in the agricultural sector would be enough to generate a supply response and allow well-functioning markets to emerge quickly. Almost two decades later, the general consensus is that the reform programs in Sub-Saharan Africa have not met expectations. At the beginning of the 21st centur...
and-conditions-of-access.pdf This article may be used for research, teaching and private study pu... more and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.
Huntington's disease is a fatal, neurodegenerative movement disorder characterized by preferentia... more Huntington's disease is a fatal, neurodegenerative movement disorder characterized by preferential and extensive striatal degeneration. Here, we used fast-scan cyclic voltammetry to study the mobilization and efflux of reserve pool dopamine in striatal brain slices from Huntington's disease model R6/2 mice. When applying stimulus trains of 120 pulses, evoked dopamine release in wild-type slices was greater than that in R6/2 slices at the higher frequencies (50 and 60 Hz). To quantify cytosolic and reserve pool dopamine levels, amphetamine-induced dopamine efflux was measured after pre-treatment with either tetrabenazine or alpha-methyl-ptyrosine. Slices from 12-week old R6/2 mice released less dopamine than slices from wild-type mice, while no difference was noted in slices from 6-week old mice. The vesicular release of reserve pool dopamine, mobilized by treatment with cocaine, was shorter lived in R6/2 slices compared to wild-type slices even though peak dopamine release was the same. Moreover, the number of dopamine reserve pool vesicles in R6/2 mice was less than half of that in wild-type. Therefore, our data suggest that the same number of dopamine molecules are present in each reserve pool vesicle in WT and R6/2 mice and that these vesicles are readily mobilized in both genotypes; however, R6/2 mice have fewer dopamine reserve pool vesicles available for mobilization.
Presently, most CubeSat components and buses are generally not appropriate for missions where sig... more Presently, most CubeSat components and buses are generally not appropriate for missions where significant or indeterminate risk of failure is unacceptable. This has precluded their use in many cases where their attributes could otherwise enable or enhance mission objectives. However, in the future, CubeSats and SmallSats, which deviate from CubeSat form factors but often incorporate CubeSat components and subsystems, will address challenges that many presently consider to be beyond the platform’s capabilities. This growing potential utility, combined with the limited volume of successful CubeSat flight heritage, is driving an interagency effort to improve small satellite mission confidence. The Small Satellite Reliability Initiative (SSRI)—an activity with broad participation from civil, DoD, and commercial space systems providers and stakeholders—has been targeting this challenge. This paper will update the community on how the public-private collaboration is being executed. It wil...
Let (X, B, µ) be a probability space and let T 1 ,. .. , T l be l commuting invertible measure pr... more Let (X, B, µ) be a probability space and let T 1 ,. .. , T l be l commuting invertible measure preserving transformations of X. We show that if the group of transformations generated by T 1 ,. .. , T l is totally ergodic, then the averages
Targeting autophagy in cancer cells and in the tumor microenvironment are current goals of cancer... more Targeting autophagy in cancer cells and in the tumor microenvironment are current goals of cancer therapy. However, components of canonical autophagy play roles in other biological processes, adding complexity to this goal. One such alternative function of autophagy proteins is LC3-associated phagocytosis (LAP), which functions in phagosome maturation and subsequent signaling events. Here, we show that impairment of LAP in the myeloid compartment, rather than canonical autophagy, induces control of tumor growth by tumor-associated macrophages (TAM) upon phagocytosis of dying tumor cells. Single-cell RNA sequencing (RNA-seq) analysis revealed that defects in LAP induce pro-inflammatory gene expression and trigger STING-mediated type I interferon responses in TAM. We found that the anti-tumor effects of LAP impairment require tumor-infiltrating T cells, dependent upon STING and the type I interferon response. Therefore, autophagy proteins in the myeloid cells of the tumor microenviron...
Huntington's disease (HD) is a fatal neurodegenerative disorder that is characterized by dege... more Huntington's disease (HD) is a fatal neurodegenerative disorder that is characterized by degeneration of the striatum. Here, fast-scan cyclic voltammetry at carbon-fiber microelectrodes was used to uncover regional differences in dopamine (DA) release in the caudate putamen of R6/2 and wild-type control mice. We found a decreasing ventral-to-dorsal gradient in DA release, evoked by a single electrical stimulus pulse, in aged R6/2 mice. Moreover, under more intense stimulation conditions (120 pulses), DA release was significantly attenuated in the dorsal, but not in the ventral caudate. Autoradiography measurements using [H]WIN 35,428 revealed that the overall density of DA transporter (DAT) protein molecules was significantly less in R6/2 mice compared to WT control mice; however, quadrants of the caudate putamen were not differentially altered in the R6/2 mice. These data collectively suggest that DA release in the dorsal caudate region is more vulnerable with age progression c...
The American journal of emergency medicine, Jan 29, 2017
Myocardial infarction and stroke are two of the leading causes of death in the U.S. Both diseases... more Myocardial infarction and stroke are two of the leading causes of death in the U.S. Both diseases have clinical practice guidelines (CPGs) specific to the emergency department (ED) that improve patient outcomes. Our primary objectives were to estimate differences in ED adherence across CPGs for these diseases and identify patient, provider, and environmental factors associated with adherence. Design: Retrospective study at 3 hospitals in Colorado using standard medical record review. Consecutive adults (≥18) hospitalized for acute coronary syndrome (ACS), ST-elevation myocardial infarction (STEMI), or acute ischemic stroke (AIS), who were admitted to the hospital from the ED and for whom the ED diagnosed or initiated treatment. ED adherence to the CPG (primary); in-hospital mortality and length-of-stay (secondary). Multivariable logistic regression using generalized estimating equations was used. Among 1053 patients, ED care was adherent in 84% with significant differences in adhere...
Emergency medicine Australasia : EMA, Jan 28, 2016
Evidence-based decision-making tools are widely used to guide cervical spine assessment in adult ... more Evidence-based decision-making tools are widely used to guide cervical spine assessment in adult trauma patients. Similar tools validated for use in injured children are lacking. A paediatric-specific approach is appropriate given important differences in cervical spine anatomy, mechanism of spinal injury and concerns over ionising radiation in children. The present study aims to survey physicians' knowledge and application of cervical spine assessment in injured children. A cross-sectional survey of physicians actively engaged in trauma care within a paediatric trauma centre was undertaken. Participation was voluntary and responses de-idenitified. The survey comprised 20 questions regarding initial assessment, imaging, immobilisation and perioperative management. Physicians' responses were compared with available current evidence. Sixty-seven physicians (28% registrars, 17% fellows and 55.2% consultants) participated. Physicians rated altered mental state, intoxication and ...
Entity-Relationship models are a common tool for specification and design of information systems.... more Entity-Relationship models are a common tool for specification and design of information systems.They use a graphical technique for displaying the objects of the system and relatioshipsamong them. The design process can be enhanced by specifying constraints of the system and thenatural environment for these is the categorical notion of sketch. Here we argue that the finite-limit,finite-coproduct sketches with a terminal
The Sketch Data Model (SkDM) is a new semantic modelling paradigm based on category theory (speci... more The Sketch Data Model (SkDM) is a new semantic modelling paradigm based on category theory (specifically on categorical universal algebra), which has been used successfully in several consultancies with major Australian companies. This paper describes the sketch data model and investigates the view update problem (VUP) in the sketch data model paradigm. It proposes an approach to the VUP in the SkDM, and presents a range of examples to illustrate the scope of the proposed technique. In common with previously proposed approaches, we define under what circumstances a view update can be propagated to the underlying database. Unlike many previously proposed approaches the definition is succinct and consistent, with no ad hoc exceptions, and the propagatable updates form a broad class. We argue that we avoid ad hoc exceptions by basing the definition of propagatable on the state of the underlying database. The examples demonstrate that under a range of circumstances a view schema can be shown to have propagatable views in all states, and thus state-independence can frequently be recovered.
During the past two decades, most countries in Sub-Saharan Africa undertook extensive economic re... more During the past two decades, most countries in Sub-Saharan Africa undertook extensive economic reforms to reduce the role of the government and increase the role of the market in their economies. Because of the importance of the agricultural sector in the region, agricultural market reforms occupied a central place in these liberalization efforts. Agricultural reforms included the removal of price controls, deregulation of agricultural marketing, closure of state-owned enterprises that monopolized agricultural trade, and changes in the foreign exchange market to provide greater incentives for exports. The expectation was that improving price incentives for farmers and reducing government intervention in the agricultural sector would be enough to generate a supply response and allow well-functioning markets to emerge quickly. Almost two decades later, the general consensus is that the reform programs in Sub-Saharan Africa have not met expectations. At the beginning of the 21st centur...
and-conditions-of-access.pdf This article may be used for research, teaching and private study pu... more and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.
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