1,251 research outputs found
Scoring Aave Accounts for Creditworthiness
Scoring the creditworthiness of accounts that interact with decentralized
financial (DeFi) protocols remains an important yet unsolved problem. In this
paper, we propose a credit scoring system for those accounts that have
interacted with the Aave v2 liquidity protocol. The key component of this
system is a tree-based binary classifier that predicts "position delinquency."
To the community, we provide our method, results, and the (abridged) dataset on
which this system is built
Spatial variation in the fine-structure constant -- new results from VLT/UVES
(abridged) We present a new analysis of a large sample of quasar
absorption-line spectra obtained using UVES (the Ultraviolet and Visual Echelle
Spectrograph) on the VLT (Very Large Telescope) in Chile. In the VLT sample
(154 absorbers), we find evidence that alpha increases with increasing
cosmological distance from Earth. However, as previously shown, the Keck sample
(141 absorbers) provided evidence for a smaller alpha in the distant absorption
clouds. Upon combining the samples an apparent variation of alpha across the
sky emerges which is well represented by an angular dipole model pointing in
the direction RA=(17.3 +/- 1.0) hr, dec. = (-61 +/- 10) deg, with amplitude
(0.97 +0.22/-0.20) x 10^(-5). The dipole model is required at the 4.1 sigma
statistical significance level over a simple monopole model where alpha is the
same across the sky (but possibly different to the current laboratory value).
The data sets reveal a number of remarkable consistencies: various data cuts
are consistent and there is consistency in the overlap region of the Keck and
VLT samples. Assuming a dipole-only (i.e. no-monopole) model whose amplitude
grows proportionally with `lookback-time distance' (r=ct, where t is the
lookback time), the amplitude is (1.1 +/- 0.2) x 10^(-6) GLyr^(-1) and the
model is significant at the 4.2 sigma confidence level over the null model
[Delta alpha]/alpha = 0). We apply robustness checks and demonstrate that the
dipole effect does not originate from a small subset of the absorbers or
spectra. We present an analysis of systematic effects, and are unable to
identify any single systematic effect which can emulate the observed variation
in alpha.Comment: 47 pages, 35 figures. Accepted for publication by Monthly Notices of
the Royal Astronomical Society. Please see
http://astronomy.swin.edu.au/~mmurphy/pub.html for an ASCII version of table
A1 and the full set of Voigt profile fits for appendix
PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
Kaposi’s sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.Fil: Naipauer, Julian. Miami University; Estados Unidos. Consejo Nacional de Investigaciones CientÃficas y Técnicas; Argentina. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Rosario, Santas. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Gupta, Sachin. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Premer, Courtney. Miami University; Estados UnidosFil: Méndez SolÃs, Omayra. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Schlesinger, Mariana. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Consejo Nacional de Investigaciones CientÃficas y Técnicas; ArgentinaFil: Ponzinibbio, Maria Virginia. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Consejo Nacional de Investigaciones CientÃficas y Técnicas; ArgentinaFil: Jain, Vaibhav. University of Florida; Estados UnidosFil: Gay, Lauren. University of Florida; Estados UnidosFil: Renne, Rolf. University of Florida; Estados UnidosFil: Chan, Ho Lam. Miami University; Estados UnidosFil: Morey, Lluis. Miami University; Estados UnidosFil: Salyakina, Daria. Miami University; Estados Unidos. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados UnidosFil: Abba, MartÃn Carlos. Miami University; Estados Unidos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones CientÃficas y Técnicas; ArgentinaFil: Williams, Sion. Miami University; Estados UnidosFil: Hare, Joshua M.. Miami University; Estados UnidosFil: Goldschmidt Clermont, Pascal. Miami University; Estados UnidosFil: Mesri, Enrique Alfredo. Sylvester Comprehensive Cancer Center and Miami Center for AIDS Research; Estados Unidos. Miami University; Estados Unido
Personalised Clinical Decision Support For Diabetes Management Using Real-time Data
PEPPER (Patient Empowerment through Predictive PERsonalised decision support) is an EU-funded research project to develop a personalised clinical decision support system for Type 1 diabetes self-management. The tool provides insulin bolus dose advice and carbohydrate recommendations, tailored to the needs of individuals. The former is determined by Case-Based Reasoning (CBR), an artificial intelligence technique that adapts to new situations according to past experience. The latter uses a predictive computer model that also promotes safety by providing glucose alarms, low-glucose insulin suspension and fault detection
Preconditioning indefinite systems in interior point methods for large scale linear optimisation
A Dimer of the Toll-Like Receptor 4 Cytoplasmic Domain Provides a Specific Scaffold for the Recruitment of Signalling Adaptor Proteins
The Toll-like receptor 4 (TLR4) is a class I transmembrane receptor expressed on the surface of immune system cells. TLR4 is activated by exposure to lipopolysaccharides derived from the outer membrane of Gram negative bacteria and forms part of the innate immune response in mammals. Like other class 1 receptors, TLR4 is activated by ligand induced dimerization, and recent studies suggest that this causes concerted conformational changes in the receptor leading to self association of the cytoplasmic Toll/Interleukin 1 receptor (TIR) signalling domain. This homodimerization event is proposed to provide a new scaffold that is able to bind downstream signalling adaptor proteins. TLR4 uses two different sets of adaptors; TRAM and TRIF, and Mal and MyD88. These adaptor pairs couple two distinct signalling pathways leading to the activation of interferon response factor 3 (IRF-3) and nuclear factor κB (NFκB) respectively. In this paper we have generated a structural model of the TLR4 TIR dimer and used molecular docking to probe for potential sites of interaction between the receptor homodimer and the adaptor molecules. Remarkably, both the Mal and TRAM adaptors are strongly predicted to bind at two symmetry-related sites at the homodimer interface. This model of TLR4 activation is supported by extensive functional studies involving site directed mutagenesis, inhibition by cell permeable peptides and stable protein phosphorylation of receptor and adaptor TIR domains. Our results also suggest a molecular mechanism for two recent findings, the caspase 1 dependence of Mal signalling and the protective effects conferred by the Mal polymorphism Ser180Leu
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment
Kaposi’s sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.Centro de Investigaciones Inmunológicas Básicas y Aplicada
Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer
Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.
OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening
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