Restoring the Balance: The Second Amendment Revisited

In this article, the Second Amendment is analyzed through a discussion of the history of the right to private arms under English common law, the Second Amendment\u27s legislative history and context, and the United States Supreme Court\u27s decision in United States v. Miller. The articles argues that the private right of keeping arms plays a fundamental role in the constitutional system of checks and balances and that the Second Amendment supports the twin goals of individual and collective defense against violence and aggression. The article concludes that efforts to limit firearms possession to the organized militia undermines these twin goals and that the theories behind such efforts do not withstand constitutional history

Self-interest And Public Interest: The Motivations Of Political Actors

Self-Interest and Public Interest in Western Politics showed that the public, politicians, and bureaucrats are often public spirited. But this does not invalidate public-choice theory. Public-choice theory is an ideal type, not a claim that self-interest explains all political behavior. Instead, public-choice theory is useful in creating rules and institutions that guard against the worst case, which would be universal self-interestedness in politics. In contrast, the public-interest hypothesis is neither a comprehensive explanation of political behavior nor a sound basis for institutional design

Age-related differences in human skin proteoglycans

Previous work has shown that versican, decorin and a catabolic fragment of decorin, termed decorunt, are the most abundant proteoglycans in human skin. Further analysis of versican indicates that four major core protein species are present in human skin at all ages examined from fetal to adult. Two of these are identified as the V0 and V1 isoforms, with the latter predominating. The other two species are catabolic fragments of V0 and V1, which have the amino acid sequence DPEAAE as their carboxyl terminus. Although the core proteins of human skin versican show no major age-related differences, the glycosaminoglycans (GAGs) of adult skin versican are smaller in size and show differences in their sulfation pattern relative to those in fetal skin versican. In contrast to human skin versican, human skin decorin shows minimal age-related differences in its sulfation pattern, although, like versican, the GAGs of adult skin decorin are smaller than those of fetal skin decorin. Analysis of the catabolic fragments of decorin from adult skin reveals the presence of other fragments in addition to decorunt, although the core proteins of these additional decorin catabolic fragments have not been identified. Thus, versican and decorin of human skin show age-related differences, versican primarily in the size and the sulfation pattern of its GAGs and decorin in the size of its GAGs. The catabolic fragments of versican are detected at all ages examined, but appear to be in lower abundance in adult skin compared with fetal skin. In contrast, the catabolic fragments of decorin are present in adult skin, but are virtually absent from fetal skin. Taken together, these data suggest that there are age-related differences in the catabolism of proteoglycans in human skin. These age-related differences in proteoglycan patterns and catabolism may play a role in the age-related changes in the physical properties and injury response of human ski

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke

BACKGROUND Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD2 score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan–Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan–Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD2 score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD2 score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.)Supported by an unrestricted grant from Sanofi and Bristol-Myers Squibb

The Incidence of Highly-Obscured Star-Forming Regions in SINGS Galaxies

Using the new capabilities of the Spitzer Space Telescope and extensive multiwavelength data from the Spitzer Infrared Nearby Galaxies Survey (SINGS), it is now possible to study the infrared properties of star formation in nearby galaxies down to scales equivalent to large HII regions. We are therefore able to determine what fraction of large, infrared-selected star-forming regions in normal galaxies are highly obscured and address how much of the star formation we miss by relying solely on the optical portion of the spectrum. Employing a new empirical method for deriving attenuations of infrared-selected star-forming regions we investigate the statistics of obscured star formation on 500pc scales in a sample of 38 nearby galaxies. We find that the median attenuation is 1.4 magnitudes in H-alpha and that there is no evidence for a substantial sub-population of uniformly highly-obscured star-forming regions. The regions in the highly-obscured tail of the attenuation distribution (A_H-alpha > 3) make up only ~4% of the sample of nearly 1800 regions, though very embedded infrared sources on the much smaller scales and lower luminosities of compact and ultracompact HII regions are almost certainly present in greater numbers. The highly-obscured cases in our sample are generally the bright, central regions of galaxies with high overall attenuation but are not otherwise remarkable. We also find that a majority of the galaxies show decreasing radial trends in H-alpha attenuation. The small fraction of highly-obscured regions seen in this sample of normal, star-forming galaxies suggests that on 500pc scales the timescale for significant dispersal or break up of nearby, optically-thick dust clouds is short relative to the lifetime of a typical star-forming region.Comment: Accepted for publication in ApJ; emulateapj style, 30 pages, 18 figures (compressed versions), 3 table

A model of membrane contraction predicting initiation and completion of bacterial cell division

Bacterial cell division involves a complex and dynamic sequence of events whereby polymers of the protein FtsZ assemble at the division plane and rearrange to achieve the goal of contracting the cell membrane at the site of cell division, thus dividing the parent cell into two daughter cells. We present a mathematical model (which we refer to as CAM-FF: Critical Accumulation of Membrane-bound FtsZ Fibres) of the assembly of the contractile ring in terms of the accumulation of short linear polymers of FtsZ that associate and dissociate from the cell membrane. In prokaryotes, the biochemical function of FtsZ is thought to underpin the assembly and at least the initial kinetic force of ring contraction. Our model extends earlier work of Surovtsev et al. [PLoS Comput. Biol., 2008, 4, e1000102] by adding (i) the kinetics of FtsZ accumulation on cell membrane anchor proteins and (ii) the physical forces required to deform the cell against its surface tension. Moreover, we provide a more rigorous treatment of intracellular diffusion and we revise some of the model parameter values in light of the experimental evidence now available. We derive a critical contraction parameter which links the chemical population dynamics of membrane-bound FtsZ molecules to the force of contraction. Using this parameter as a tool to predict the ability of the cell to initiate division, we are able to predict the division outcome in cells depleted of key FtsZ-binding proteins

Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

Non-pharmacological interventions for post-stroke emotionalism (PSE) within inpatient stroke settings: a theory of planned behavior survey

Background: Post-stroke emotionalism (PSE) is common. Trials of antidepressants for PSE suggest only modest clinical benefit and risk of side effects. There have been no trials of non-pharmacological treatments for PSE; in fact, little is known about the non-pharmacological treatments actually provided to PSE sufferers in clinical practice. Objectives: To determine the non-pharmacological interventions provided by stroke professionals, their perceived effectiveness, and the factors associated with the intention to provide them. Methods: Focus groups and published sources of information were used to construct a comprehensive list of non-pharmacological approaches for PSE. This was followed by a national (online) survey of 220 UK stroke clinicians from nursing, medicine, and the allied health professions to investigate the approaches used in clinical practice, using Theory of Planned Behavior components to determine the factors associated with intention to provide them. Results: Most respondents reported high intention to provide non-pharmacological interventions from the list that was constructed. Offering reassurance and talking to patients about goals were the commonest interventions, and distraction and tensing facial muscles least common. Respondents who perceived others to hold them professionally responsible for carrying out non-pharmacological approaches were more likely to use them, as were respondents who held more positive attitudes. Conclusions: Our survey data reveal that stroke clinicians report regular use of non-pharmacological interventions for PSE. There is a pressing need for well-conducted clinical trials to evaluate the effectiveness of these approaches

Hypoxia Inhibits Osteogenesis in Human Mesenchymal Stem Cells through Direct Regulation of RUNX2 by TWIST

Bone loss induced by hypoxia is associated with various pathophysiological conditions, however, little is known about the effects of hypoxia and related signaling pathways on osteoblast differentiation and bone formation. Because bone marrow-derived mesenchymal stem cells (MSCs) survive under hypoxic conditions and readily differentiate into osteoblasts by standard induction protocols, they are a good in vitro model to study the effects of hypoxia on osteoblast differentiation.Using human MSCs, we discovered TWIST, a downstream target of HIF-1α, was induced under hypoxia and acted as a transcription repressor of RUNX2 through binding to the E-box located on the promoter of type 1 RUNX2. Suppression of type 1 RUNX2 by TWIST under hypoxia further inhibited the expression of BMP2, type 2 RUNX2 and downstream targets of RUNX2 in MSCs.Our findings point to the important role of hypoxia-mediated signalling in osteogenic differentiation in MSCs through direct regulation of RUNX2 by TWIST, and provide a method for modifying MSC osteogenesis upon application of these cells in fracture healing and bone reconstruction

The Caravan Rolls On

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68409/2/10.1177_107554707900100103.pd