336 research outputs found
Situationally edited empathy: an effect of socio-economic structure on individual choice
Criminological theory still operates with deficient models of the offender as agent, and of social influences on the agentâs decision-making process. This paper takes one âemotionâ, empathy, which is theoretically of considerable importance in influencing the choices made by agents; particularly those involving criminal or otherwise harmful action. Using a framework not of rational action, but of ârationalised actionâ, the paper considers some of the effects on individual psychology of social, economic, political and cultural structure. It is suggested that the climate-setting effects of these structures promote normative definitions of social situations which allow unempathic, harmful action to be rationalised through the situational editing of empathy. The âcrime is normalâ argument can therefore be extended to include the recognition that the uncompassionate state of mind of the criminal actor is a reflection of the self-interested values which govern non-criminal action in wider society
Atenolol versus losartan in children and young adults with Marfan's syndrome
BACKGROUND : Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers.
METHODS : We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events.
RESULTS : From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [+/- SD] age, 11.5 +/- 6.5 years in the atenolol group and 11.0 +/- 6.2 years in the losartan group), who had an aorticroot z score greater than 3.0. The baseline-adjusted rate of change (+/- SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139 +/- 0.013 and -0.107 +/- 0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups.
CONCLUSIONS : Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aorticroot dilatation between the two treatment groups over a 3-year period
Does entropic force always imply the Newtonian force law?
We study the entropic force by introducing a bound between
entropy and area which was derived by imposing the non-gravitational collapse
condition. In this case, applying a modified entropic force to this system does
not lead to the Newtonian force law.Comment: 11 pages, version to appear in EPJ
Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a)
The B apolipoproteins, apo-B48 and apo-B100, are key structural proteins in those classes of lipoproteins considered to be atherogenic [e.g., chylomicron remnants, \u3b2-VLDL, LDL, oxidized LDL, and Lp(a)]. Here we describe the development of transgenic mice expressing high levels of human apo-B48 and apo-B100. A 79.5-kb human genomic DNA fragment containing the entire human apo-B gene was isolated from a P1 bacteriophage library and microinjected into fertilized mouse eggs. 16 transgenic founders expressing human apo-B were generated, and the animals with the highest expression had plasma apo-B100 levels nearly as high as those of normolipidemic humans ( 3c50 mg/dl). The human apo-B100 in transgenic mouse plasma was present largely in lipoproteins of the LDL class as shown by agarose gel electrophoresis, chromatography on a Superose 6 column, and density gradient ultracentrifugation. When the human apo-B transgenic founders were crossed with transgenic mice expressing human apo(a), the offspring that expressed both transgenes had high plasma levels of human Lp(a). Both the human apo-B and Lp(a) transgenic mice will be valuable resources for studying apo-B metabolism and the role of apo-B and Lp(a) in atherosclerosis
On the origin of plankton patchiness
Plankton is the productive base of aquatic ecosystems and plays a major role
in the global control of atmospheric carbon dioxide. Nevertheless, after
intensive study, the factors that drive its spatial distribution are still far
from being clear. The models proposed so far show very limited agreement with
actual data as many of their results are not consistent with field
observations. Here we show that fluctuations and turbulent diffusion in
standard prey-predator models are able to accurately and consistently explain
plankton field observations at mesoscales (1-100 km). This includes not only
the spatial pattern but also its temporal evolution. We explicitly elucidate
the interplay between physical and biological factors, suggesting that the form
in which small scale biotic fluctuations are transferred to larger scales may
constitute one of the key elements in determining the spatial distribution of
plankton in the sea.Comment: 16 pages, 3 figure
Superconductors with Magnetic Impurities: Instantons and Sub-gap States
When subject to a weak magnetic impurity potential, the order parameter and
quasi-particle energy gap of a bulk singlet superconductor are suppressed.
According to the conventional mean-field theory of Abrikosov and Gor'kov, the
integrity of the energy gap is maintained up to a critical concentration of
magnetic impurities. In this paper, a field theoretic approach is developed to
critically analyze the validity of the mean field theory. Using the
supersymmetry technique we find a spatially homogeneous saddle-point that
reproduces the Abrikosov-Gor'kov theory, and identify instanton contributions
to the density of states that render the quasi-particle energy gap soft at any
non-zero magnetic impurity concentration. The sub-gap states are associated
with supersymmetry broken field configurations of the action. An analysis of
fluctuations around these configurations shows how the underlying supersymmetry
of the action is restored by zero modes. An estimate of the density of states
is given for all dimensionalities. To illustrate the universality of the
present scheme we apply the same method to study `gap fluctuations' in a normal
quantum dot coupled to a superconducting terminal. Using the same instanton
approach, we recover the universal result recently proposed by Vavilov et al.
Finally, we emphasize the universality of the present scheme for the
description of gap fluctuations in d-dimensional superconducting/normal
structures.Comment: 18 pages, 9 eps figure
Klein tunneling in graphene: optics with massless electrons
This article provides a pedagogical review on Klein tunneling in graphene,
i.e. the peculiar tunneling properties of two-dimensional massless Dirac
electrons. We consider two simple situations in detail: a massless Dirac
electron incident either on a potential step or on a potential barrier and use
elementary quantum wave mechanics to obtain the transmission probability. We
emphasize the connection to related phenomena in optics, such as the
Snell-Descartes law of refraction, total internal reflection, Fabry-P\'erot
resonances, negative refraction index materials (the so called meta-materials),
etc. We also stress that Klein tunneling is not a genuine quantum tunneling
effect as it does not necessarily involve passing through a classically
forbidden region via evanescent waves. A crucial role in Klein tunneling is
played by the conservation of (sublattice) pseudo-spin, which is discussed in
detail. A major consequence is the absence of backscattering at normal
incidence, of which we give a new shorten proof. The current experimental
status is also thoroughly reviewed. The appendix contains the discussion of a
one-dimensional toy model that clearly illustrates the difference in Klein
tunneling between mono- and bi-layer graphene.Comment: short review article, 18 pages, 14 figures; v3: references added,
several figures slightly modifie
Review article: the future of microbiome-based therapeutics
Published online 24 May 2022Background: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic.Aim: This review summarises the current developments in microbiome- based medicines and provides insight into the next steps required for therapeutic development.Methods: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical inter-ventions. Key literature was identified through Pubmed searches with the following key words, âmicrobiomeâ, âmicrobiome biomarkersâ, âprobioticsâ, âprebioticsâ, âsynbioticsâ, âfaecal microbiota transplantâ, âlive biotherapeuticsâ, âmicrobiome mimeticsâ and âpostbioticsâ.Results: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, ra-tionally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics.Conclusions: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.Emily L. Gulliver, Remy B. Young, Michelle Chonwerawong, Gemma L. D'Adamo, Tamblyn Thomason, James T. Widdop, Emily L. Rutten, Vanessa Rossetto Marcelino, Robert V. Bryant, Samuel P. Costello, Claire L. O'Brien, Georgina L. Hold, Edward M. Giles, Samuel C. Forste
GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation.
Strategies aimed at mimicking or enhancing the action of the incretin hormone glucagon-like peptide 1 (GLP-1) therapeutically improve glucose-stimulated insulin secretion (GSIS); however, it is not clear whether GLP-1 directly drives insulin secretion in pancreatic islets. Here, we examined the mechanisms by which GLP-1 stimulates insulin secretion in mouse and human islets. We found that GLP-1 enhances GSIS at a half-maximal effective concentration of 0.4 pM. Moreover, we determined that GLP-1 activates PLC, which increases submembrane diacylglycerol and thereby activates PKC, resulting in membrane depolarization and increased action potential firing and subsequent stimulation of insulin secretion. The depolarizing effect of GLP-1 on electrical activity was mimicked by the PKC activator PMA, occurred without activation of PKA, and persisted in the presence of PKA inhibitors, the KATP channel blocker tolbutamide, and the L-type Ca(2+) channel blocker isradipine; however, depolarization was abolished by lowering extracellular Na(+). The PKC-dependent effect of GLP-1 on membrane potential and electrical activity was mediated by activation of Na(+)-permeable TRPM4 and TRPM5 channels by mobilization of intracellular Ca(2+) from thapsigargin-sensitive Ca(2+) stores. Concordantly, GLP-1 effects were negligible in Trpm4 or Trpm5 KO islets. These data provide important insight into the therapeutic action of GLP-1 and suggest that circulating levels of this hormone directly stimulate insulin secretion by ÎČ cells.We thank David Wiggins for excellent technical assistance. This work was supported by the Medical Research Council, Diabetes UK (to R. Ramracheya ), Oxford Biomedical Research Centre (to A. Tarasov), the Wellcome Trust (Senior Investigator Awards to A. Galione and P. Rorsman), the Warwick Impact Fund (to C. Weston and G. Ladds), the Biotechnology and Biological Sciences Research Council (to G. Ladds), the Knut and Alice Wallenberg Foundation (to P. Rorsman), and the Swedish Research Council (to P. Rorsman). The initial stages of M. Shigetoâs stay in Oxford were supported by a fellowship from Kawasaki Medical School.This is the final version of the article. It was first available from the American Society for Clinical Investigation via http://dx.doi.org/10.1172/JCI8197
Characterization and Calibration of the CheMin Mineralogical Instrument on Mars Science Laboratory
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