244 research outputs found
Community Structure in the United States House of Representatives
We investigate the networks of committee and subcommittee assignments in the
United States House of Representatives from the 101st--108th Congresses, with
the committees connected by ``interlocks'' or common membership. We examine the
community structure in these networks using several methods, revealing strong
links between certain committees as well as an intrinsic hierarchical structure
in the House as a whole. We identify structural changes, including additional
hierarchical levels and higher modularity, resulting from the 1994 election, in
which the Republican party earned majority status in the House for the first
time in more than forty years. We also combine our network approach with
analysis of roll call votes using singular value decomposition to uncover
correlations between the political and organizational structure of House
committees.Comment: 44 pages, 13 figures (some with multiple parts and most in color), 9
tables, to appear in Physica A; new figures and revised discussion (including
extra introductory material) for this versio
Community Structure in Congressional Cosponsorship Networks
We study the United States Congress by constructing networks between Members
of Congress based on the legislation that they cosponsor. Using the concept of
modularity, we identify the community structure of Congressmen, as connected
via sponsorship/cosponsorship of the same legislation, to investigate the
collaborative communities of legislators in both chambers of Congress. This
analysis yields an explicit and conceptually clear measure of political
polarization, demonstrating a sharp increase in partisan polarization which
preceded and then culminated in the 104th Congress (1995-1996), when
Republicans took control of both chambers. Although polarization has since
waned in the U.S. Senate, it remains at historically high levels in the House
of Representatives.Comment: 8 pages, 4 figures (some with multiple parts), to appear in Physica
A; additional background info and explanations added from last versio
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Autoreactivity and Exceptional CDR Plasticity (but Not Unusual Polyspecificity) Hinder Elicitation of the Anti-HIV Antibody 4E10
The broadly-neutralizing anti-HIV antibody 4E10 recognizes an epitope in the membrane-proximal external region of the HIV envelope protein gp41. Previous attempts to elicit 4E10 by vaccination with envelope-derived or reverse-engineered immunogens have failed. It was presumed that the ontogeny of 4E10-equivalent responses was blocked by inherent autoreactivity and exceptional polyreactivity. We generated 4E10 heavy-chain knock-in mice, which displayed significant B cell dysregulation, consistent with recognition of autoantigen/s by 4E10 and the presumption that tolerance mechanisms may hinder the elicitation of 4E10 or 4E10-equivalent responses. Previously proposed candidate 4E10 autoantigens include the mitochondrial lipid cardiolipin and a nuclear splicing factor, 3B3. However, using carefully-controlled assays, 4E10 bound only weakly to cardiolipin-containing liposomes, but also bound negatively-charged, non-cardiolipin-containing liposomes comparably poorly. 4E10/liposome binding was predominantly mediated by electrostatic interactions rather than presumed hydrophobic interactions. The crystal structure of 4E10 free of bound ligands showed a dramatic restructuring of the combining site, occluding the HIV epitope binding site and revealing profound flexibility, but creating an electropositive pocket consistent with non-specific binding of phospholipid headgroups. These results strongly suggested that antigens other than cardiolipin mediate 4E10 autoreactivity. Using a synthetic peptide library spanning the human proteome, we determined that 4E10 displays limited and focused, but unexceptional, polyspecificity. We also identified a novel autoepitope shared by three ER-resident inositol trisphosphate receptors, validated through binding studies and immunohistochemistry. Tissue staining with 4E10 demonstrated reactivity consistent with the type 1 inositol trisphosphate receptor as the most likely candidate autoantigen, but is inconsistent with splicing factor 3B3. These results demonstrate that 4E10 recognition of liposomes competes with MPER recognition and that HIV antigen and autoepitope recognition may be distinct enough to permit eliciting 4E10-like antibodies, evading autoimmunity through directed engineering. However, 4E10 combining site flexibility, exceptional for a highly-matured antibody, may preclude eliciting 4E10 by conventional immunization strategies
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Assessing metabolism and function of normothermically perfused ex vivo livers by multinuclear MR imaging and spectroscopy
Synopsis
Liver transplantation is the only cure for end-stage liver disease. Unfortunately, 20% of patients die waiting for a donor. New techniques for
preserving transplant livers, such as normothermic machine perfusion (NMP), provide an opportunity to utilise âmarginalâ (currently discarded)
donated livers if their viability can be assessed accurately. We present initial results from a CE-marked NMP system that we adapted for use in
an MRI scanner. We demonstrate the power of NMP-MRI to assess structure and metabolism in a freshly donated pig liver, dynamically over a
10-hour period. Our protocol includes H imaging, P spectroscopy, and hyperpolarised C spectroscopy.This work was funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (Grant No. 098436/Z/12/Z) and by the National
Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)
The results of a management redesign: A case study of a private child welfare agency
This paper reports on the restructuring of a large, private nonprofit, child welfare agency, and includes a description of the change objectives, the process of planning and implementing the changes, and the impact of the changes. The findings discussed here focus on changes in staff turnover and performance as well as staff perceptions of the continuation or reduction of identified organizational problems. The overall goal of the management redesign was to devolve decision-making closer to the point of service delivery. A survey with a response rate of 60.3% was the main source of information for the study. Almost 90% of the respondents reported that the redesign generated benefits, and approximately 74% identified negative consequences. The redesign was perceived by staff to reduce organizational problems related to communication, decision-making, leadership, and agency mission. Staff turnover increased during the redesign, but staff performance remained at a relatively high level
A first-principles study of the vibrational properties of crystalline tetracene under pressure
Aza-Cibalackrot: Turning on Singlet Fission Through Crystal Engineering
Singlet fission is a photophysical process that provides a pathway for more efficient harvesting of solar energy in photovoltaic devices. The design of singlet fission candidates is non-trivial and requires careful optimization of two key criteria: (1) correct energetic alignment and (2) appropriate intermolecular coupling. Meanwhile, this optimization must not come at the cost of molecular stability or feasibility for device applications. Cibalackrot is a historic and stable organic dye which, although it has been suggested to have ideal energetics, does not undergo singlet fission due to large interchromophore distances, as suggested by single crystal analysis. Thus, while the energetic alignment is satisfactory, the molecule does not have the desired intermolecular coupling. Herein, we improve this characteristic through molecular engineering with the first synthesis of an aza-cibalackrot and show, using ultrafast transient spectroscopy, that singlet fission is successfully "turned on.
Abdominal Wall Transplantation: Indications and Outcomes
Abstract Purpose of Review This article aims to review published outcomes associated with full-thickness vascularized abdominal wall transplantation, with particular emphasis on advances in the field in the last 3 years. Recent Findings Forty-six full-thickness vascularized abdominal wall transplants have been performed in 44 patients worldwide. Approximately 35% of abdominal wall transplant recipients will experience at least one episode of acute rejection in the first year after transplant, compared with rejection rates of 87.8% and 72.7% for hand and face transplant respectively. Recent evidence suggests that combining a skin containing abdominal wall transplant with an intestinal transplant does not appear to increase sensitization or de novo donor-specific antibody formation. Summary Published data suggests that abdominal wall transplantation is an effective safe solution to achieve primary closure of the abdomen after intestinal or multivisceral transplant. However, better data is needed to confirm observations made and to determine long-term outcomes, requiring standardized data collection and reporting and collaboration between the small number of active transplant centres around the worl
Discarded livers tested by normothermic machine perfusion in the VITTAL trial:Secondary end points and 5-year outcomes
Normothermic machine perfusion (NMP) enables pretransplant assessment of high-risk donor livers. The VITTAL trial demonstrated that 71% of the currently discarded organs could be transplanted with 100% 90-day patient and graft survivals. Here, we report secondary end points and 5-year outcomes of this prospective, open-label, phase 2 adaptive single-arm study. The patient and graft survivals at 60 months were 82% and 72%, respectively. Four patients lost their graft due to nonanastomotic biliary strictures, one caused by hepatic artery thrombosis in a liver donated following brain death, and 3 in elderly livers donated after circulatory death (DCD), which all clinically manifested within 6 months after transplantation. There were no late graft losses for other reasons. All the 4 patients who died during the study follow-up had functioning grafts. Nonanastomotic biliary strictures developed in donated after circulatory death livers that failed to produce bile with pH >7.65 and bicarbonate levels >25 mmol/L. Histological assessment in these livers revealed high bile duct injury scores characterized by arterial medial necrosis. The quality of life at 6 months significantly improved in all but 4 patients suffering from nonanastomotic biliary strictures. This first report of long-term outcomes of high-risk livers assessed by normothermic machine perfusion demonstrated excellent 5-year survival without adverse effects in all organs functioning beyond 1 year (ClinicalTrials.gov number NCT02740608).</p
Site-selective measurement of coupled spin pairs in an organic semiconductor
From organic electronics to biological systems, understanding the role of
intermolecular interactions between spin pairs is a key challenge. Here we show
how such pairs can be selectively addressed with combined spin and optical
sensitivity. We demonstrate this for bound pairs of spin-triplet excitations
formed by singlet fission, with direct applicability across a wide range of
synthetic and biological systems. We show that the site-sensitivity of exchange
coupling allows distinct triplet pairs to be resonantly addressed at different
magnetic fields, tuning them between optically bright singlet (S=0) and dark
triplet, quintet (S=1,2) configurations: this induces narrow holes in a broad
optical emission spectrum, uncovering exchange-specific luminescence. Using
fields up to 60 T, we identify three distinct triplet-pair sites, with exchange
couplings varying over an order of magnitude (0.3-5 meV), each with its own
luminescence spectrum, coexisting in a single material. Our results reveal how
site-selectivity can be achieved for organic spin pairs in a broad range of
systems.Comment: 8 pages, article, 7 pages, supporting informatio
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