1,074 research outputs found
Restoring Liberalism to Transnational Corporate Accountability: From Universal Jurisdiction\u27s Ashes to an Afterlife of Multilateral Avenues
Per the U.S. Supreme Court, foreign tortfeasors, including corporate human rights violators, may no longer be sued in U.S. courts by their foreign victims via the Alien Tort Statute (ATS) without a sufficient nexus to U.S. territory. This Article contends that pursuing transnational corporate accountability unilaterally through the U.S. judiciary is inconsistent with a core tenet of liberalism itself\u27a state and its constituents should not be subject to the external authority of other states. This Article engages in the recurrent debate over effective transnational corporate accountability, offering the first liberalist defense of universal jurisdiction\u27s marginalization in U.S. courts. This Article recommends further development of two alternative avenues that encourage multilateral cooperation on transnational corporate accountability: 1) inclusive public-private diplomacy convening all stakeholders, including non-state actors and 2) the widely welcomed U.N. Guiding Principles on Business and Human Rights and their use by corporate accountability NGOs, governments, and business enterprises
Our Country, Right or Wrong: The FTC Actâs Influence on National Silos in Antitrust Enforcement
Single photon source characterization with a superconducting single photon detector
Superconducting single photon detectors (SSPD) based on nanopatterned niobium
nitride wires offer single photon counting at fast rates, low jitter, and low
dark counts, from visible wavelengths well into the infrared. We demonstrate
the first use of an SSPD, packaged in a commercial cryocooler, for single
photon source characterization. The source is an optically pumped,
microcavity-coupled InGaAs quantum dot, emitting single photons on demand at
902 nm. The SSPD replaces the second silicon Avalanche Photodiode (APD) in a
Hanbury-Brown Twiss interferometer measurement of the source second-order
correlation function, g (2) (tau). The detection efficiency of the
superconducting detector system is >2 % (coupling losses included). The SSPD
system electronics jitter is 170 ps, versus 550 ps for the APD unit, allowing
the source spontaneous emission lifetime to be measured with improved
resolution.Comment: 8 page
Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma
The anti-malarial drug artesunate possesses anti-inflammatory and anti-oxidative actions in experimental asthma, comparable to corticosteroid. We hypothesized that artesunate may modulate disease-relevant metabolic alterations in allergic asthma. To explore metabolic profile changes induced by artesunate in allergic airway inflammation, we analysed bronchoalveolar lavage fluid (BALF) and serum from naĂŻve and ovalbumin-induced asthma mice treated with artesunate, using both gas and liquid chromatography-mass spectrometry metabolomics. Pharmacokinetics analyses of serum and lung tissues revealed that artesunate is rapidly converted into the active metabolite dihydroartemisinin. Artesunate effectively suppressed BALF total and differential counts, and repressed BALF Th2 cytokines, IL-17, IL-12(p40), MCP-1 and G-CSF levels. Artesunate had no effects on both BALF and serum metabolome in naĂŻve mice. Artesunate promoted restoration of BALF sterols (cholesterol, cholic acid and cortol), phosphatidylcholines and carbohydrates (arabinose, mannose and galactose) and of serum 18-oxocortisol, galactose, glucose and glucouronic acid in asthma. Artesunate prevented OVA-induced increases in pro-inflammatory metabolites from arginineâproline metabolic pathway, particularly BALF levels of urea and alanine and serum levels of urea, proline, valine and homoserine. Multiple statistical correlation analyses revealed association between altered BALF and serum metabolites and inflammatory cytokines. Dexamethasone failed to reduce urea level and caused widespread changes in metabolites irrelevant to asthma development. Here we report the first metabolome profile of artesunate treatment in experimental asthma. Artesunate restored specific metabolic perturbations in airway inflammation, which correlated well with its anti-inflammatory actions. Our metabolomics findings further strengthen the therapeutic value of using artesunate to treat allergic asthma
CMB-S4 Science Book, First Edition
This book lays out the scientific goals to be addressed by the
next-generation ground-based cosmic microwave background experiment, CMB-S4,
envisioned to consist of dedicated telescopes at the South Pole, the high
Chilean Atacama plateau and possibly a northern hemisphere site, all equipped
with new superconducting cameras. CMB-S4 will dramatically advance cosmological
studies by crossing critical thresholds in the search for the B-mode
polarization signature of primordial gravitational waves, in the determination
of the number and masses of the neutrinos, in the search for evidence of new
light relics, in constraining the nature of dark energy, and in testing general
relativity on large scales
Development of a standardized histopathology scoring system using machine learning algorithms for intervertebral disc degeneration in the mouse modelâAn ORS spine section initiative
Mice have been increasingly used as preclinical model to elucidate mechanisms and test therapeutics for treating intervertebral disc degeneration (IDD). Several intervertebral disc (IVD) histological scoring systems have been proposed, but none exists that reliably quantitate mouse disc pathologies. Here, we report a new robust quantitative mouse IVD histopathological scoring system developed by building consensus from the spine community analyses of previous scoring systems and features noted on different mouse models of IDD. The new scoring system analyzes 14 key histopathological features from nucleus pulposus (NP), annulus fibrosus (AF), endplate (EP), and AF/NP/EP interface regions. Each feature is categorized and scored; hence, the weight for quantifying the disc histopathology is equally distributed and not driven by only a few features. We tested the new histopathological scoring criteria using images of lumbar and coccygeal discs from different IDD models of both sexes, including genetic, needle-punctured, static compressive models, and natural aging mice spanning neonatal to old age stages. Moreover, disc sections from common histological preparation techniques and stains including H&E, SafraninO/Fast green, and FAST were analyzed to enable better cross-study comparisons. Fleiss\u27s multi-rater agreement test shows significant agreement by both experienced and novice multiple raters for all 14 features on several mouse models and sections prepared using various histological techniques. The sensitivity and specificity of the new scoring system was validated using artificial intelligence and supervised and unsupervised machine learning algorithms, including artificial neural networks, k-means clustering, and principal component analysis. Finally, we applied the new scoring system on established disc degeneration models and demonstrated high sensitivity and specificity of histopathological scoring changes. Overall, the new histopathological scoring system offers the ability to quantify histological changes in mouse models of disc degeneration and regeneration with high sensitivity and specificity
Neither Replication nor Simulation Supports a Role for the Axon Guidance Pathway in the Genetics of Parkinson's Disease
Susceptibility to sporadic Parkinson's disease (PD) is thought to be influenced by both genetic and environmental factors and their interaction with each other. Statistical models including multiple variants in axon guidance pathway genes have recently been purported to be capable of predicting PD risk, survival free of the disease and age at disease onset; however the specific models have not undergone independent validation. Here we tested the best proposed risk panel of 23 single nucleotide polymorphisms (SNPs) in two PD sample sets, with a total of 525 cases and 518 controls. By single marker analysis, only one marker was significantly associated with PD risk in one of our sample sets (rs6692804: Pâ=â0.03). Multi-marker analysis using the reported model found a mild association in one sample set (two sided Pâ=â0.049, odds ratio for each score changeâ=â1.07) but no significance in the other (two sided Pâ=â0.98, odds ratioâ=â1), a stark contrast to the reported strong association with PD risk (Pâ=â4.64Ă10â38, odds ratio as high as 90.8). Following a procedure similar to that used to build the reported model, simulated multi-marker models containing SNPs from randomly chosen genes in a genome wide PD dataset produced P-values that were highly significant and indistinguishable from similar models where disease status was permuted (3.13Ă10â23 to 4.90Ă10â64), demonstrating the potential for overfitting in the model building process. Together, these results challenge the robustness of the reported panel of genetic markers to predict PD risk in particular and a role of the axon guidance pathway in PD genetics in general
Recommended from our members
Model International Mobility Convention
While people are as mobile as they ever were in our globalized world, the movement of people across borders lacks global regulation. This leaves many refugees in protracted displacement and many migrants unprotected in irregular and dire situations. Meanwhile, some states have become concerned that their borders have become irrelevant. International mobilityâthe movement of individuals across borders for any length of time as visitors, students, tourists, labor migrants, entrepreneurs, long-term residents, asylum seekers, or refugeesâhas no common definition or legal framework. To address this key gap in international law, and the growing gaps in protection and responsibility that are leaving people vulnerable, the "Model International Mobility Convention" proposes a framework for mobility with the goals of reaffirming the existing rights afforded to mobile people (and the corresponding rights and responsibilities of states) as well as expanding those basic rights where warranted. In 213 articles divided over eight chapters, the Convention establishes both the minimum rights afforded to all people who cross state borders as visitors, and the special rights afforded to tourists, students, migrant workers, investors and residents, forced migrants, refugees, migrant victims of trafficking and migrants caught in countries in crisis. Some of these categories are covered by existing international legal regimes. However, in this Convention these groups are for the first time brought together under a single framework. An essential feature of the Convention is that it is cumulative. This means, for the most part, that the chapters build on and add rights to the set of rights afforded to categories of migrants covered by earlier chapters. The Convention contains not only provisions that afford rights to migrants and, to a lesser extent, States (such as the right to decide who can enter and remain in their territory). It also articulates the responsibilities of migrants vis-Ă -vis States and the rights and responsibilities of different institutions that do not directly respond to a right held by migrants
Recommended from our members
Prion-like domain mutations in hnRNPs cause multisystem proteinopathy and ALS
Summary Algorithms designed to identify canonical yeast prions predict that ~250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbor a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here, we define pathogenic mutations in PrLDs of hnRNPA2/B1 and hnRNPA1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and a case of familial ALS. Wild-type hnRNPA2 and hnRNPA1 display an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a âsteric zipperâ motif in the PrLD, which accelerates formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Importantly, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant âsteric zipperâ motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs must be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone
- âŠ