Nussbaum’s version of the capability approach is not only a helpful approach to development probl... more Nussbaum’s version of the capability approach is not only a helpful approach to development problems but can also be employed as a general ethical-anthropological framework in ‘advanced’ societies. This paper explores its normative force for evaluating information technologies, with a particular focus on the issue of human enhancement. It suggests that the capability approach can be a useful way of to specify a workable and adequate level of analysis in human enhancement discussions, but argues that any interpretation of what these capabilities mean is itself dependent on (interpretations of) the techno-human practices under discussion. This challenges the capability approach’s means-end dualism concerning the relation between on the one hand technology and on the other hand humans and capabilities. It is argued that instead of facing a choice between development and enhancement, we better reflect on how we want to shape human-technological practices, for instance by using the language of capabilities. For this purpose, we have to engage in a cumbersome hermeneutics that interprets dynamic relations between unstable capabilities, technologies, practices, and values. This requires us to modify the capability approach by highlighting and interpreting its interpretative dimension.
We report a pilot investigation into the utility of screening tools in Mild Cognitive Impairment ... more We report a pilot investigation into the utility of screening tools in Mild Cognitive Impairment (MCI). The Addenbrooke's Cognitive Examination-Revised (ACE-R), Montreal Cognitive Assessment (MoCA) and the novel Computer-Administered Neuropsychological Screen for Mild Cognitive Impairment (CANS-MCI) were administered to 20 elderly controls and 15 MCI cases. Non-parametric Mann–Whitney U-tests showed significant differences between groups (p < .0001) on the CANS-MCI and MoCA. The ACE-R and MoCA total scores showed high sensitivity (90%) to MCI. Area under the curve was consistently significant in discriminating controls and MCI for memory scores across all screening instruments. A useful profile of quantitative and qualitative information pertaining to cognitive functioning in MCI can be obtained with the MoCA, ACE-R, and CANS-MCI.
Lava drainback has been observed during many eruptions at Kilauea Volcano: magma erupts, degasse... more Lava drainback has been observed during many eruptions at Kilauea Volcano: magma erupts, degasses in lava fountains, collects in surface ponds, and then drains back beneath the surface. Time series data for melt inclusions from the 1959 Kilauea Iki picrite provide important evidence concerning the effects of drainback on the H2O contents of basaltic magmas at Kilauea. Melt inclusions in olivine from the first eruptive episode, before any drainback occurred, have an average H2O content of 0.7±0.2 wt.%. In contrast, many inclusions from the later episodes, erupted after substantial amounts of surface degassed lava had drained back down the vent, have H2O contents that are much lower (≥0.24 wt.% H2O). Water contents in melt inclusions from magmas erupted at Pu'u 'O'o on the east rift zone vary from 0.39–0.51 wt.% H2O in tephra from high fountains to 0.10–0.28 wt.% H2O in spatter from low fountains. The low H2O contents of many melt inclusions from Pu'u 'O'o and post-drainback episodes of Kilauea Iki reveal that prior to crystallization of the enclosing olivine host, the melts must have exsolved H2O at pressures substantially less than those in Kilauea's summit magma reservoir. Such low-pressure H2O exsolution probably occurred as surface degassed magma was recycled by drainback and mixing with less degassed magma at depth. Recognition of the effects of low-pressure degassing and drainback leads to an estimate of 0.7 wt.% H2O for differentiated tholeiitic magma in Kilauea's summit magma storage reservoir. Data for MgO-rich submarine glasses (Clague et al. 1995) and melt inclusions from Kilauea Iki demonstrate that primary Kilauean tholeiitic magma has an H2O/K2O mass ratio of ∼1.3. At transition zone and upper mantle depths in the Hawaiian plume source, H2O probably resides partly in a small amount of hydrous silicate melt.
Naunyn-schmiedebergs Archives of Pharmacology, 1992
The action of the cervane alkaloid, imperialine, has been assessed at M1, M2 and M3 receptors in ... more The action of the cervane alkaloid, imperialine, has been assessed at M1, M2 and M3 receptors in functional assays and at M1, M2, M3 and putative M4 sites in binding studies. In functional studies, imperialine acted as a selective surmountable antagonist at M2 receptors in guinea-pig isolated atria and uterus (−log KB = 7.7 and 7.4, respectively), in comparison to M1, receptors in canine isolated saphenous vein (−log KB = 6.9) or M3 receptors in a range of guinea-pig isolated smooth muscles including ileum, trachea, fundus, seminal vesicle or oesophagus (−log KB = 6.6–6.8). In rat aorta, the −log KB value at the M3 receptor (5.9) was slightly, but significantly, lower. In competition radioligand binding studies, imperialine was also selective toward to M2 sites in rat myocardium (−log Ki = 7.2) with respect to M1 and M3 sites (rat cerebral cortex, rat submaxillary gland; −log Ki = 6.1 and 5.7, respectively). However, it did not significantly discriminate between rat cardiac M2 sites and putative M4 sites in rabbit lung (−log Ki = 6.9). Imperialine resembles the alkaloid himbacine in terms of its pharmacological profile at muscarinic receptor subtypes in that it acts as an M2 selective antagonist with respect to M1 or M3 sites. It may also provide a second, commercially available, antagonist with which to discriminate between M1 and M4 receptors.
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Trace-element and preliminary Sr- and O-isotopic data are reported for a transitional alkaline-su... more Trace-element and preliminary Sr- and O-isotopic data are reported for a transitional alkaline-sub-alkaline lava series (MVS) from Patmos, Greece. The lava types belonging to this series are ne-trachybasalt, hy-trachybasalt, hy-trachyandesite and Q-trachyte. Rb, Sr and Ba contents, as well as K/Rb ratios, of the ne-trachybasalts differ from those of alkali basalts of oceanic islands and those of K-rich alkaline lavas of continental regions and are consistent with the occurrence of these volcanics in a destructive plate margin environment. Qualitatively, the variations shown by many trace elements throughout the MVS are explicable in terms of magma evolution via fractional crystallization involving removal of the observed phenocryst phases. Cross-cutting REE patterns can be explained by removal of small amounts of apatite. However, certain features of the data cannot be reconciled with the operation of fractional crystallization alone. These are: a) the compatible behavior of Ba throughout the MVS; b) the moderately (as opposed to highly) incompatible behavior of Zr, Rb and Nb relative to Th; and c) the significant decrease of K/Th, Rb/Th, Zr/Th, Zr/Nb, Nb/Th, Yb/Th, Ta/Th, U/Th and Zr/Ta ratios especially (but not exclusively) in the mafic part of the series. Quantitative modeling indicates that the hy-trachybasalts are anomalously enriched in both highly incompatible and highly compatible elements and these lavas are shown to be hybrids formed by mixing of ne-trachybasalt and hy-trachyandesite. Mixing proportions of the end members calculated from incompatible element abundances (∼19% ne-trachybasalt) differ from those calculated from compatible element abundances (∼62% ne-trachybasalt) and are inconsistent with proportions calculated from published mineral chemical data. In addition, mixing cannot account for the observed variations in incompatible element ratios and this is taken as evidence for the simultaneous operation of assimilation. Isotopic variations (87Sr/ 86Sr from 0.7049 to 0.7076 and 18O/16O from 4.7 to 8.6‰) and the positive correlation of isotope ratios with SiO2 and Th contents provide conclusive proof that assimilation occurred. Calculations show that the isotopic characteristics and the concentrations of many trace elements in the Q-trachytes can be explained by fractional crystallization of ne-trachybasalt combined with assimilation of average continental crust (87Sr/86Sr-0.710), and that large amounts of assimilation are not necessary (Ma/Mc=0.55). REE data are not well explained by this model and suggest a crustal end-member enriched in LREE relative to the average crust. Zr and Hf data are also not well explained and indicate that the assimilant was depleted in HFSE relative to average crust or that HFSE are held back in relatively insoluble phases such as zircon in the restite during assimilation. Nevertheless, the results of the modeling demonstrate that Ba concentrations may decrease during AFC processes and that high Sr contents (∼1500 ppm in the MVS ne-trachybasalts) do not render mafic, parental magmas immune to the effects of assimilation in terms of their 87Sr/86Sr ratios. The results of this study confirm conclusions based upon major-oxide and mineral chemical data for the MVS lavas but, more importantly, show that careful analysis of trace element data allows the various processes involved in magma evolution to be identified and quantified, even in the absence of major oxide and isotopic data. Finally, it is reiterated that magma mixing and assimilation may be coupled processes in the magma chambers beneath many volcanic centers, and recognition of this fact has profound implications for studies of magmas erupted at continental margins and through continental crust.
In the quest for deciphering the neural code, theoretical advances were made which allow for the ... more In the quest for deciphering the neural code, theoretical advances were made which allow for the determination of the information rate inherent in the spike trains of nerve cells. However, up to now, the dependence of the information rate on stimulus parameters has not been studied in any neuron in a systematic way. Here, I investigate the information carried by the spike trains of H1, a motion-sensitive visual interneuron of the blowfly (Calliphora vicina) using a moving grating as a stimulus. Stimulus parameters fall in two classes: those that have only a minor effect on the information rate like increasing the frequency bandwidth or the maximum amplitude of the stimulus velocity, and those which dramatically affect the neural information rate, like varying the spatial size or the contrast of the visual pattern being moved. It appears that, for a broad range of complex stimuli, the neuron covers the stimulus with its whole response repertoire regardless of the stimulus entropy, with the information rate being limited by the noise of the stimulus and the neural hardware.
Nussbaum’s version of the capability approach is not only a helpful approach to development probl... more Nussbaum’s version of the capability approach is not only a helpful approach to development problems but can also be employed as a general ethical-anthropological framework in ‘advanced’ societies. This paper explores its normative force for evaluating information technologies, with a particular focus on the issue of human enhancement. It suggests that the capability approach can be a useful way of to specify a workable and adequate level of analysis in human enhancement discussions, but argues that any interpretation of what these capabilities mean is itself dependent on (interpretations of) the techno-human practices under discussion. This challenges the capability approach’s means-end dualism concerning the relation between on the one hand technology and on the other hand humans and capabilities. It is argued that instead of facing a choice between development and enhancement, we better reflect on how we want to shape human-technological practices, for instance by using the language of capabilities. For this purpose, we have to engage in a cumbersome hermeneutics that interprets dynamic relations between unstable capabilities, technologies, practices, and values. This requires us to modify the capability approach by highlighting and interpreting its interpretative dimension.
We report a pilot investigation into the utility of screening tools in Mild Cognitive Impairment ... more We report a pilot investigation into the utility of screening tools in Mild Cognitive Impairment (MCI). The Addenbrooke's Cognitive Examination-Revised (ACE-R), Montreal Cognitive Assessment (MoCA) and the novel Computer-Administered Neuropsychological Screen for Mild Cognitive Impairment (CANS-MCI) were administered to 20 elderly controls and 15 MCI cases. Non-parametric Mann–Whitney U-tests showed significant differences between groups (p < .0001) on the CANS-MCI and MoCA. The ACE-R and MoCA total scores showed high sensitivity (90%) to MCI. Area under the curve was consistently significant in discriminating controls and MCI for memory scores across all screening instruments. A useful profile of quantitative and qualitative information pertaining to cognitive functioning in MCI can be obtained with the MoCA, ACE-R, and CANS-MCI.
Lava drainback has been observed during many eruptions at Kilauea Volcano: magma erupts, degasse... more Lava drainback has been observed during many eruptions at Kilauea Volcano: magma erupts, degasses in lava fountains, collects in surface ponds, and then drains back beneath the surface. Time series data for melt inclusions from the 1959 Kilauea Iki picrite provide important evidence concerning the effects of drainback on the H2O contents of basaltic magmas at Kilauea. Melt inclusions in olivine from the first eruptive episode, before any drainback occurred, have an average H2O content of 0.7±0.2 wt.%. In contrast, many inclusions from the later episodes, erupted after substantial amounts of surface degassed lava had drained back down the vent, have H2O contents that are much lower (≥0.24 wt.% H2O). Water contents in melt inclusions from magmas erupted at Pu'u 'O'o on the east rift zone vary from 0.39–0.51 wt.% H2O in tephra from high fountains to 0.10–0.28 wt.% H2O in spatter from low fountains. The low H2O contents of many melt inclusions from Pu'u 'O'o and post-drainback episodes of Kilauea Iki reveal that prior to crystallization of the enclosing olivine host, the melts must have exsolved H2O at pressures substantially less than those in Kilauea's summit magma reservoir. Such low-pressure H2O exsolution probably occurred as surface degassed magma was recycled by drainback and mixing with less degassed magma at depth. Recognition of the effects of low-pressure degassing and drainback leads to an estimate of 0.7 wt.% H2O for differentiated tholeiitic magma in Kilauea's summit magma storage reservoir. Data for MgO-rich submarine glasses (Clague et al. 1995) and melt inclusions from Kilauea Iki demonstrate that primary Kilauean tholeiitic magma has an H2O/K2O mass ratio of ∼1.3. At transition zone and upper mantle depths in the Hawaiian plume source, H2O probably resides partly in a small amount of hydrous silicate melt.
Naunyn-schmiedebergs Archives of Pharmacology, 1992
The action of the cervane alkaloid, imperialine, has been assessed at M1, M2 and M3 receptors in ... more The action of the cervane alkaloid, imperialine, has been assessed at M1, M2 and M3 receptors in functional assays and at M1, M2, M3 and putative M4 sites in binding studies. In functional studies, imperialine acted as a selective surmountable antagonist at M2 receptors in guinea-pig isolated atria and uterus (−log KB = 7.7 and 7.4, respectively), in comparison to M1, receptors in canine isolated saphenous vein (−log KB = 6.9) or M3 receptors in a range of guinea-pig isolated smooth muscles including ileum, trachea, fundus, seminal vesicle or oesophagus (−log KB = 6.6–6.8). In rat aorta, the −log KB value at the M3 receptor (5.9) was slightly, but significantly, lower. In competition radioligand binding studies, imperialine was also selective toward to M2 sites in rat myocardium (−log Ki = 7.2) with respect to M1 and M3 sites (rat cerebral cortex, rat submaxillary gland; −log Ki = 6.1 and 5.7, respectively). However, it did not significantly discriminate between rat cardiac M2 sites and putative M4 sites in rabbit lung (−log Ki = 6.9). Imperialine resembles the alkaloid himbacine in terms of its pharmacological profile at muscarinic receptor subtypes in that it acts as an M2 selective antagonist with respect to M1 or M3 sites. It may also provide a second, commercially available, antagonist with which to discriminate between M1 and M4 receptors.
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Trace-element and preliminary Sr- and O-isotopic data are reported for a transitional alkaline-su... more Trace-element and preliminary Sr- and O-isotopic data are reported for a transitional alkaline-sub-alkaline lava series (MVS) from Patmos, Greece. The lava types belonging to this series are ne-trachybasalt, hy-trachybasalt, hy-trachyandesite and Q-trachyte. Rb, Sr and Ba contents, as well as K/Rb ratios, of the ne-trachybasalts differ from those of alkali basalts of oceanic islands and those of K-rich alkaline lavas of continental regions and are consistent with the occurrence of these volcanics in a destructive plate margin environment. Qualitatively, the variations shown by many trace elements throughout the MVS are explicable in terms of magma evolution via fractional crystallization involving removal of the observed phenocryst phases. Cross-cutting REE patterns can be explained by removal of small amounts of apatite. However, certain features of the data cannot be reconciled with the operation of fractional crystallization alone. These are: a) the compatible behavior of Ba throughout the MVS; b) the moderately (as opposed to highly) incompatible behavior of Zr, Rb and Nb relative to Th; and c) the significant decrease of K/Th, Rb/Th, Zr/Th, Zr/Nb, Nb/Th, Yb/Th, Ta/Th, U/Th and Zr/Ta ratios especially (but not exclusively) in the mafic part of the series. Quantitative modeling indicates that the hy-trachybasalts are anomalously enriched in both highly incompatible and highly compatible elements and these lavas are shown to be hybrids formed by mixing of ne-trachybasalt and hy-trachyandesite. Mixing proportions of the end members calculated from incompatible element abundances (∼19% ne-trachybasalt) differ from those calculated from compatible element abundances (∼62% ne-trachybasalt) and are inconsistent with proportions calculated from published mineral chemical data. In addition, mixing cannot account for the observed variations in incompatible element ratios and this is taken as evidence for the simultaneous operation of assimilation. Isotopic variations (87Sr/ 86Sr from 0.7049 to 0.7076 and 18O/16O from 4.7 to 8.6‰) and the positive correlation of isotope ratios with SiO2 and Th contents provide conclusive proof that assimilation occurred. Calculations show that the isotopic characteristics and the concentrations of many trace elements in the Q-trachytes can be explained by fractional crystallization of ne-trachybasalt combined with assimilation of average continental crust (87Sr/86Sr-0.710), and that large amounts of assimilation are not necessary (Ma/Mc=0.55). REE data are not well explained by this model and suggest a crustal end-member enriched in LREE relative to the average crust. Zr and Hf data are also not well explained and indicate that the assimilant was depleted in HFSE relative to average crust or that HFSE are held back in relatively insoluble phases such as zircon in the restite during assimilation. Nevertheless, the results of the modeling demonstrate that Ba concentrations may decrease during AFC processes and that high Sr contents (∼1500 ppm in the MVS ne-trachybasalts) do not render mafic, parental magmas immune to the effects of assimilation in terms of their 87Sr/86Sr ratios. The results of this study confirm conclusions based upon major-oxide and mineral chemical data for the MVS lavas but, more importantly, show that careful analysis of trace element data allows the various processes involved in magma evolution to be identified and quantified, even in the absence of major oxide and isotopic data. Finally, it is reiterated that magma mixing and assimilation may be coupled processes in the magma chambers beneath many volcanic centers, and recognition of this fact has profound implications for studies of magmas erupted at continental margins and through continental crust.
In the quest for deciphering the neural code, theoretical advances were made which allow for the ... more In the quest for deciphering the neural code, theoretical advances were made which allow for the determination of the information rate inherent in the spike trains of nerve cells. However, up to now, the dependence of the information rate on stimulus parameters has not been studied in any neuron in a systematic way. Here, I investigate the information carried by the spike trains of H1, a motion-sensitive visual interneuron of the blowfly (Calliphora vicina) using a moving grating as a stimulus. Stimulus parameters fall in two classes: those that have only a minor effect on the information rate like increasing the frequency bandwidth or the maximum amplitude of the stimulus velocity, and those which dramatically affect the neural information rate, like varying the spatial size or the contrast of the visual pattern being moved. It appears that, for a broad range of complex stimuli, the neuron covers the stimulus with its whole response repertoire regardless of the stimulus entropy, with the information rate being limited by the noise of the stimulus and the neural hardware.
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Papers by Harry Clague