2,266 research outputs found
The New Germany and the New Europe. Edited by Paul B. Stares
The Brookings Institution\u27s new book, The New Germany and the New Europe, is an attempt along these lines. Actually a collection of twelve scholarly papers, it is an in-depth examination of the roiled political and economic currents that washed away the Berlin Wall and the rest of the Iron Curtain and continue to affect the flow of so much of current events. There are two more substantive shortcomings that pervade the book. The first of these; to be fair, the book shares with many of the policy debates that presently occur on the planet: a persistent failure to consider the limits on the willingness of the populations of the NATO countries to bear the costs of what is recommended, or already underway, and the consequences of reaching those limits. The second major flaw in the book is related to the first. Little consideration is given to events at the level at which most people function, namely, the household, the workplace, and the local community. Keeping these deficiencies in mind, the book does contain a great deal of information and a number of valuable insights
Section 1782 Of Title 28 (U.S. Code): Is There A Discoverability Requirement?
There is an excellent, thorough, and relatively recent discussion of the issue in a student note by Peter Metis.\u27 These remarks supplement and update that discussion
Interactions between Social/ behavioral factors and ADRB2 genotypes may be associated with health at advanced ages in China
10.1186/1471-2318-13-91BMC Geriatrics131
Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis
Smooth muscle cell (SMC) proliferation is a hallmark of vascular injury and disease. Global hypomethylation occurs during SMC proliferation in culture and in vivo during neointimal formation. Regardless of the programmed or stochastic nature of hypomethylation, identifying these changes is important in understanding vascular disease, as maintenance of a cells' epigenetic profile is essential for maintaining cellular phenotype. Global hypomethylation of proliferating aortic SMCs and concomitant decrease of DNMT1 expression were identified in culture during passage. An epigenome screen identified regions of the genome that were hypomethylated during proliferation and a region containing Collagen, type XV, alpha 1 (COL15A1) was selected by ‘genomic convergence' for characterization. COL15A1 transcript and protein levels increased with passage-dependent decreases in DNA methylation and the transcript was sensitive to treatment with 5-Aza-2′-deoxycytidine, suggesting DNA methylation-mediated gene expression. Phenotypically, knockdown of COL15A1 increased SMC migration and decreased proliferation and Col15a1 expression was induced in an atherosclerotic lesion and localized to the atherosclerotic cap. A sequence variant in COL15A1 that is significantly associated with atherosclerosis (rs4142986, P = 0.017, OR = 1.434) was methylated and methylation of the risk allele correlated with decreased gene expression and increased atherosclerosis in human aorta. In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at the intersection of genetic and epigenetic predisposition in the etiology of complex diseas
Estimating the redshift of PKS 0447-439 through its GeV-TeV emission
Context. Blazars are radio-loud active galactic nuclei (AGN) with a jet
pointing at small angles towards the observer. The overall emitted spectrum is
typically non-thermal, and in some cases the emission and/or absorption lines
are so faint as to prevent the determination of the redshift based on optical
spectroscopy methods. PKS 0447-439 is a bright blazar recently detected at very
high energy. The redshift of the source is still disputed: a recent spectral
analysis reports only a lower limit of z > 1.246, which contradicts the
previous measure of z = 0.205 reported in the literature. Aims. We aim to give
a redshift estimate of the blazar PKS 0447-439 based on combined GeV
(Fermi/LAT) and TeV (H.E.S.S.) observations. Methods. Taking into account the
absorption of TeV photons by the interaction with the extragalactic background
light (EBL), we applied the method we developed in a previous work to derive
the redshift of PKS 0447-439. Moreover, we compiled the overall spectral energy
distribution (SED) using optical-UV, soft X-ray, and -ray data, nearly
simultaneous to the H.E.S.S. observations at TeV energies. Finally we modelled
the spectral energy distribution (SED) within the framework of a homogeneous,
leptonic synchrotron self-Compton (SSC) model. Results. Using the recent TeV
spectrum measured by H.E.S.S. we obtain for PKS 0447-439 a redshift of zrec =
0.20 \pm 0.05, which is our estimate on the source distance. This value agrees
very well with the value reported in the literature and confirms that our
method can be successfully used to constrain blazars distances. Assuming this
distance, the SED can be well fitted with the above mentioned model. The
physical parameters that we find suggest a strongly matter-dominated jet.
Conclusions. Our analysis confirms that the redshift of PKS 0447-439 is likely
0.2, and supports the result present in the literature.Comment: 5 pages, 3 figures. A&A in pres
Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses
The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined
The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions
Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella
Ethical and Scientific Considerations Regarding Animal Testing and Research
In 1959, William Russell and Rex Burch published the seminal book, The Principles of Humane Experimental Technique, which emphasized reduction, refinement, and replacement of animal use, principles which have since been referred to as the ‘‘3 Rs’’. These principles encouraged researchers to work to reduce the number of animals used in experiments to the minimum considered necessary, refine or limit the pain and distress to which animals are exposed, and replace the use of animals with non-animal alternatives when possible. Despite the attention brought to this issue by Russell and Burch and since, the number of animals used in research and testing has continued to increase, raising serious ethical and scientific issues. Further, while the ‘‘3 Rs’’ capture crucially important concepts, they do not adequately reflect the substantial developments in our new knowledge about the cognitive and emotional capabilities of animals, the individual interests of animals, or an updated understanding of potential harms associated with animal research. This Overview provides a brief summary of the ethical and scientific considerations regarding the use of animals in research and testing, and accompanies a Collection entitled Animals, Research, and Alternatives: Measuring Progress 50 Years Later, which aims to spur ethical and scientific advancement
Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5
Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas)
TNFR1 inhibition with a nanobody protects against EAE development in mice
TNF has as detrimental role in multiple sclerosis (MS), however, anti-TNF medication is not working. Selective TNF/TNFR1 inhibition whilst sparing TNFR2 signaling reduces the pro-inflammatory effects of TNF but preserves the important neuroprotective signals via TNFR2. We previously reported the generation of a Nanobody-based selective inhibitor of human TNFR1, TROS that will be tested in experimental autoimmune encephalomyelitis (EAE). We specifically antagonized TNF/TNFR1 signaling using TROS in a murine model of MS, namely MOG(35-55)-induced EAE. Because TROS does not cross-react with mouse TNFR1, we generated mice expressing human TNFR1 in a mouse TNFR1-knockout background (hTNFR1 Tg), and we determined biodistribution of Tc-99m-TROS and effectiveness of TROS in EAE in those mice. Biodistribution analysis demonstrated that intraperitoneally injected TROS is retained more in organs of hTNFR1 Tg mice compared to wild type mice. TROS was also detected in the cerebrospinal fluid (CSF) of hTNFR1 Tg mice. Prophylactic TROS administration significantly delayed disease onset and ameliorated its symptoms. Moreover, treatment initiated early after disease onset prevented further disease development. TROS reduced spinal cord inflammation and neuroinflammation, and preserved myelin and neurons. Collectively, our data illustrate that TNFR1 is a promising therapeutic target in MS
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