1,507 research outputs found
The ÎŽâopioid receptor positive allosteric modulator BMS 986187 is a Gâproteinâbiased allosteric agonist
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149355/1/bph14602.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149355/2/bph14602_am.pd
Exact ground states for the four-electron problem in a Hubbard ladder
The exact ground state of four electrons in an arbitrary large two leg
Hubbard ladder is deduced from nine analytic and explicit linear equations. The
used procedure is described, and the properties of the ground state are
analyzed. The method is based on the construction in r-space of the different
type of orthogonal basis wave vectors which span the subspace of the Hilbert
space containing the ground state. In order to do this, we start from the
possible microconfigurations of the four particles within the system. These
microconfigurations are then rotated, translated and spin-reversed in order to
build up the basis vectors of the problem. A closed system of nine analytic
linear equations is obtained whose secular equation, by its minimum energy
solution, provides the ground state energy and the ground state wave function
of the model.Comment: 10 pages, 7 figure
Resonant Raman scattering off neutral quantum dots
Resonant inelastic (Raman) light scattering off neutral GaAs quantum dots
which contain a mean number, N=42, of electron-hole pairs is computed. We find
Raman amplitudes corresponding to strongly collective final states
(charge-density excitations) of similar magnitude as the amplitudes related to
weakly collective or single-particle excitations. As a function of the incident
laser frequency or the magnetic field, they are rapidly varying amplitudes. It
is argued that strong Raman peaks should come out in the spin-density channels,
not related to valence-band mixing effects in the intermediate states.Comment: Accepted in Physical Review
Roles of residues 3 and 4 in cyclic tetrapeptide ligand recognition by the Î -opioid receptor
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75723/1/j.1399-3011.2005.00220.x.pd
Differential roles of CCL2 and CCR2 in host defense to coronavirus infection.
The CC chemokine ligand 2 (CCL2, monocyte chemoattractant protein-1) is important in coordinating the immune response following microbial infection by regulating T cell polarization as well as leukocyte migration and accumulation within infected tissues. The present study examines the consequences of mouse hepatitis virus (MHV) infection in mice lacking CCL2 (CCL2(-/-)) in order to determine if signaling by this chemokine is relevant in host defense. Intracerebral infection of CCL2(-/-) mice with MHV did not result in increased morbidity or mortality as compared to either wild type or CCR2(-/-) mice and CCL2(-/-) mice cleared replicating virus from the brain. In contrast, CCR2(-/-) mice displayed an impaired ability to clear virus from the brain that was accompanied by a reduction in the numbers of antigen-specific T cells as compared to both CCL2(-/-) and wild-type mice. The paucity in T cell accumulation within the central nervous system (CNS) of MHV-infected CCR2(-/-) mice was not the result of either a deficiency in antigen-presenting cell (APC) accumulation within draining cervical lymph nodes (CLN) or the generation of virus-specific T cells within this compartment. A similar reduction in macrophage infiltration into the CNS was observed in both CCL2(-/-) and CCR2(-/-) mice when compared to wild-type mice, indicating that both CCL2 and CC chemokine receptor 2 (CCR2) contribute to macrophage migration and accumulation within the CNS following MHV infection. Together, these data demonstrate that CCR2, but not CCL2, is important in host defense following viral infection of the CNS, and CCR2 ligand(s), other than CCL2, participates in generating a protective response
Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.
BackgroundAdjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.MethodsWe did an open-label, randomised, phase 3 trial of adult patients (aged â„18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (â„4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805.FindingsBetween June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment.InterpretationAddition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC.FundingNational Cancer Institute of the National Institutes of Health
Correlated sampling in quantum Monte Carlo: a route to forces
In order to find the equilibrium geometries of molecules and solids and to
perform ab initio molecular dynamics, it is necessary to calculate the forces
on the nuclei. We present a correlated sampling method to efficiently calculate
numerical forces and potential energy surfaces in diffusion Monte Carlo. It
employs a novel coordinate transformation, earlier used in variational Monte
Carlo, to greatly reduce the statistical error. Results are presented for
first-row diatomic molecules.Comment: 5 pages, 2 postscript figure
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âDead people donât claimâ: A psychopolitical autopsy of UK austerity suicides
One of the symptoms of post financial crisis austerity in the UK has been an increase in the numbers of suicides, especially by people who have experienced welfare reform. This article develops and utilises an analytic framework of psychopolitical autopsy to explore media coverage of âausterity suicideâ and to take seriously the psychic life of austerity (internalisation, shame, anxiety), embedding it in a context of social dis-ease.
Drawing on three distinct yet interrelated areas of literature (the politics of affect and psychosocial dynamics of welfare, post and anti-colonial psychopolitics, and critical suicidology), the article aims to better understand how austerity âkillsâ. Key findings include understanding austerity suicides as embedded within an affective economy of the anxiety caused by punitive welfare retrenchment, the stigmatisation of being a recipient of benefits, and the internalisation of market logic that assigns value through âproductivityâ and conceptualises welfare entitlement as economic âburdenâ. The significance of this approach lies in its ability to widen analytic framing of suicide from an individual and psychocentric focus, to illuminate culpability of government reforms while still retaining the complexity of suicide, and thus to provide relevant policy insights about welfare reform
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