590 research outputs found
Regions-based two dimensional continua: The Euclidean case
We extend the work presented in [7, 8] to a regions-based, two-dimensional, Euclidean theory. The goal is to recover the classical continuum on a point-free basis. We first derive the Archimedean property for a class of readily postulated orientations of certain special regions, âgeneralized quadrilateralsâ (intended as parallelograms), by which we cover the entire space. Then we generalize this to arbitrary orientations, and then establishing an isomorphism between the space and the usual point-based R Ă R. As in the one-dimensional case, this is done on the basis of axioms which contain no explicit âextremal clauseâ (to the effect that âthese are the only ways of generating regionsâ), and we have no axiom of induction other than ordinary numerical (mathematical) induction. Finally, having explicitly defined âpointâ and âlineâ, we will derive the characteristic Parallelâs Postulate (Playfair axiom) from regions-based axioms, and point the way toward deriving key Euclidean metrical properties
No evidence for a common self-bias across cognitive domains
It is generally acknowledged that humans have an egocentric bias; processing self-related stimuli in a specialised, preferential manner. The self-bias has been studied within cognitive domains such as memory, attention and perception; but never across cognitive domains in order to assess whether self-biases are a product of a common bias, or independent. This has relevance for conditions such as Autism Spectrum Disorder: certain self-biases are reduced in those with autism, but the pattern of results is not consistent across different cognitive domains. Self-bias was measured across the attentional and perceptual domains on two well-established tasks: the attentional blink (attention) and shape-label matching (perception) tasks. Processing of each participant's own name was compared to processing of the name of another individual very familiar to the participant (to control for familiarity), and the name of an unfamiliar other. In the attentional domain, the attentional blink for the participant's own name was reduced compared to that for the name of a familiar or unfamiliar other. In the perceptual domain, participants showed stronger associations between their own name and a geometric shape than between the other classes of names and associated shapes. Thus, strong evidence of a self-bias, independent of familiarity, was found on both tasks. However, across two experiments, the magnitude of the self-bias on the attentional blink and shape-label matching tasks was not correlated, supporting the idea that self-biases across cognitive domains are distinct. Furthermore, in contrast with extant models, neither type of self-bias was predicted by autistic traits
Kidney after nonrenal transplantation-the impact of alemtuzumab induction
BACKGROUND.: Calcineurin inhibitor nephrotoxicity in nonrenal allograft recipients can lead to end-stage renal disease and the need for kidney transplantation. We sought to evaluate the role of alemtuzumab induction in this population. PATIENTS AND METHODS.: We evaluated 144 patients undergoing kidney transplantation after nonrenal transplantation between May 18, 1998, and October 8, 2007. Seventy-two patients transplanted between January 15, 2003, and October 8, 2007, received alemtuzumab induction and continued their pretransplant immunosuppression. Seventy-two patients transplanted between May 18, 1998, and July 21, 2007, did not receive alemtuzumab induction, but received additional steroids and maintenance immunosuppression. Donor and recipient demographics were comparable. RESULTS.: Overall, 1-and 3-year patient survival and renal function were comparable between the two groups. One-and 3-year graft survival was 93.0% and 75.3% in the alemtuzumab group and 83.3% and 68.7% in the no alemtuzumab group, respectively (P=0.051). The incidence of acute rejection was lower in the alemtuzumab group, 15.3%, than in the no alemtuzumab group, 41.7% (P=0.0001). The incidence of delayed graft function was lower in the alemtuzumab group, 9.7%, than in the no alemtuzumab group, 25.0% (P=0.003). The incidence of viral complications was comparable. CONCLUSION.: Alemtuzumab induction with simple resumption of baseline immunosuppression in patients undergoing kidney transplantation after nonrenal transplantation represents a reasonable immunosuppressive strategy. Copyright © 2009 by Lippincott Williams & Wilkins
Knowledge transfer within strategic partnerships: the case of HRM in the Brazilian motor industry supply chain
This paper investigates knowledge transfer (KT) of human resource management (HRM) across strategic partnerships in the Brazilian automotive industry, and the contextual factors impacting on KT within the supply chain. Case-study research in automotive companies and suppliers in Brazil is used to illustrate how in automotive industries, relationships with suppliers have traditionally been viewed as close, strategic partnerships, but over time, there has been a move towards more attenuated, supply chains, involving a shift towards more remote suppliers for basic components, and arms length relationships with them. In turn, this has impacted on how knowledge on HR has been transferred from manufacturers to suppliers. Both strategic partnerships and KT have been affected by internal drives towards cost cutting and talent retention, and external factors such as global competition through cheap imports, legislation, taxes, and unions. Evidence on the sometimes contradictory attitudes towards KT contributes towards the broader literatures on international HRM and KT in emerging economies, while the gradual unwinding of relationships has implications for policy and practice
The use of displacement damage dose to correlate degradation in solar cells exposed to different radiations
It has been found useful in the past to use the concept of 'equivalent fluence' to compare the radiation response of different solar cell technologies. Results are usually given in terms of an equivalent 1 MeV electron or an equivalent 10 MeV proton fluence. To specify cell response in a complex space-radiation environment in terms of an equivalent fluence, it is necessary to measure damage coefficients for a number of representative electron and proton energies. However, at the last Photovoltaic Specialist Conference we showed that nonionizing energy loss (NIEL) could be used to correlate damage coefficients for protons, using measurements for GaAs as an example. This correlation means that damage coefficients for all proton energies except near threshold can be predicted from a measurement made at one particular energy. NIEL is the exact equivalent for displacement damage of linear energy transfer (LET) for ionization energy loss. The use of NIEL in this way leads naturally to the concept of 10 MeV equivalent proton fluence. The situation for electron damage is more complex, however. It is shown that the concept of 'displacement damage dose' gives a more general way of unifying damage coefficients. It follows that 1 MeV electron equivalent fluence is a special case of a more general quantity for unifying electron damage coefficients which we call the 'effective 1 MeV electron equivalent dose'
"Women's rights, the European Court and Supranational Constitutionalism"
This analysis examines supranational constitutionalism in the European Union. In particular, the study focuses on the role of the European Court of Justice in the creation of womenâs rights. I examine the interaction between the Court and member state governments in legal integration, and also the integral role that womenâs advocates â both individual activists and groups â have played in the development of EU social provisions. The findings suggest that this litigation dynamic can have the effect of fueling the integration process by creating new rights that may empower social actors and EU organizations, with the ultimate effect of diminishing member state government control over the scope and direction of EU law. This study focuses specifically on gender equality law, yet provides a general framework for examining the case law in subsequent legal domains, with the purpose of providing a more nuanced understanding of supranational governance and constitutionalism
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A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170).
UNLABELLED: We sought to evaluate the efficacy of WEE1 inhibitor adavosertib in patients with solid tumor malignancies (cohort A) and clear cell renal cell carcinoma (ccRCC; cohort B). NCT03284385 was a parallel cohort, Simon two-stage, phase II study of adavosertib (300 mg QDAY by mouth on days 1-5 and 8-12 of each 21-day cycle) in patients with solid tumor malignancies harboring a pathogenic SETD2 mutation. The primary endpoint was the objective response rate. Correlative assays evaluated the loss of H3K36me3 by IHC, a downstream consequence of SETD2 loss, in archival tumor tissue. Eighteen patients were enrolled (9/cohort). The median age was 60 years (range 45-74). The median duration of treatment was 1.28 months (range 0-24+). No objective responses were observed in either cohort; accrual was halted following stage 1. Minor tumor regressions were observed in 4/18 (22%) evaluable patients. Stable disease (SD) was the best overall response in 10/18 (56%) patients, including three patients with SD > 4 months. One patient with ccRCC remains on treatment for >24 months. The most common adverse events of any grade were nausea (59%), anemia (41%), diarrhea (41%), and neutropenia (41%). Nine patients (50%) experienced a Grade â„3 adverse event. Of eight evaluable archival tissue samples, six (75%) had a loss of H3K36me3 by IHC. Adavosertib failed to exhibit objective responses in SETD2-altered ccRCC and other solid tumor malignancies although prolonged SD was observed in a subset of patients. Combination approaches may yield greater depth of tumor response. SIGNIFICANCE: WEE1 inhibition with adavosertib monotherapy demonstrated limited clinical activity in patients with SETD2-altered solid tumors despite compelling preclinical data indicating a synthetic lethal effect, which did not translate into robust tumor regression. Loss of the H3K36me3 trimethylation mark caused by SETD2-deficiency was confirmed in the majority of evaluable tumors. A subset of patients derived clinical benefit as manifested by minor tumor regressions and prolonged SD
Error-analysis and comparison to analytical models of numerical waveforms produced by the NRAR Collaboration
The Numerical-Relativity-Analytical-Relativity (NRAR) collaboration is a
joint effort between members of the numerical relativity, analytical relativity
and gravitational-wave data analysis communities. The goal of the NRAR
collaboration is to produce numerical-relativity simulations of compact
binaries and use them to develop accurate analytical templates for the
LIGO/Virgo Collaboration to use in detecting gravitational-wave signals and
extracting astrophysical information from them. We describe the results of the
first stage of the NRAR project, which focused on producing an initial set of
numerical waveforms from binary black holes with moderate mass ratios and
spins, as well as one non-spinning binary configuration which has a mass ratio
of 10. All of the numerical waveforms are analysed in a uniform and consistent
manner, with numerical errors evaluated using an analysis code created by
members of the NRAR collaboration. We compare previously-calibrated,
non-precessing analytical waveforms, notably the effective-one-body (EOB) and
phenomenological template families, to the newly-produced numerical waveforms.
We find that when the binary's total mass is ~100-200 solar masses, current EOB
and phenomenological models of spinning, non-precessing binary waveforms have
overlaps above 99% (for advanced LIGO) with all of the non-precessing-binary
numerical waveforms with mass ratios <= 4, when maximizing over binary
parameters. This implies that the loss of event rate due to modelling error is
below 3%. Moreover, the non-spinning EOB waveforms previously calibrated to
five non-spinning waveforms with mass ratio smaller than 6 have overlaps above
99.7% with the numerical waveform with a mass ratio of 10, without even
maximizing on the binary parameters.Comment: 51 pages, 10 figures; published versio
PARP inhibitor efficacy depends on CD8+ T cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer.
Combinatorial clinical trials of PARP inhibitors with immunotherapies are ongoing, yet the immunomodulatory effects of PARP inhibition have been incompletely studied. Here, we sought to dissect the mechanisms underlying PARP inhibitor-induced changes in the tumor microenvironment of BRCA1-deficient triple-negative breast cancer (TNBC). We demonstrate that the PARP inhibitor olaparib induces CD8+ T cell infiltration and activation in vivo, and that CD8+ T cell depletion severely compromises anti-tumor efficacy. Olaparib-induced T cell recruitment is mediated through activation of the cGAS/STING pathway in tumor cells with paracrine activation of dendritic cells and is more pronounced in HR-deficient compared to HR-proficient TNBC cells and in vivo models. CRISPR-knockout of STING in cancer cells prevents proinflammatory signaling and is sufficient to abolish olaparib-induced T cell infiltration in vivo. These findings elucidate an additional mechanism of action of PARP inhibitors and provide rationale for combining PARP inhibition with immunotherapies for the treatment of TNBC
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