Creep stability of the proposed AIDA mission target 65803 Didymos: I. Discrete cohesionless granular physics model

As the target of the proposed Asteroid Impact & Deflection Assessment (AIDA) mission, the near-Earth binary asteroid 65803 Didymos represents a special class of binary asteroids, those whose primaries are at risk of rotational disruption. To gain a better understanding of these binary systems and to support the AIDA mission, this paper investigates the creep stability of the Didymos primary by representing it as a cohesionless self-gravitating granular aggregate subject to rotational acceleration. To achieve this goal, a soft-sphere discrete element model (SSDEM) capable of simulating granular systems in quasi-static states is implemented and a quasi-static spin-up procedure is carried out. We devise three critical spin limits for the simulated aggregates to indicate their critical states triggered by reshaping and surface shedding, internal structural deformation, and shear failure, respectively. The failure condition and mode, and shear strength of an aggregate can all be inferred from the three critical spin limits. The effects of arrangement and size distribution of constituent particles, bulk density, spin-up path, and interparticle friction are numerically explored. The results show that the shear strength of a spinning self-gravitating aggregate depends strongly on both its internal configuration and material parameters, while its failure mode and mechanism are mainly affected by its internal configuration. Additionally, this study provides some constraints on the possible physical properties of the Didymos primary based on observational data and proposes a plausible formation mechanism for this binary system. With a bulk density consistent with observational uncertainty and close to the maximum density allowed for the asteroid, the Didymos primary in certain configurations can remain geo-statically stable without including cohesion.Comment: 66 pages, 24 figures, submitted to Icarus on 25/Aug/201

Sex Differences in Depression and Sleep Disturbance as Inter-Related Risk Factors of Diabetes

ObjectivesPrevious studies identified depression and sleep disturbance as risk factors for diabetes. Sleep disturbance and depression are known to be inter-related. Further, women relative to men are more prone to depression. Here, we investigated how depression and sleep disturbance may jointly influence the risk of diabetes and the effects of sex on these influences.MethodsUsing the data of 21,229 participants from the 2018 National Health Interview Survey, we performed multivariate logistic regression with diabetes diagnosis as the dependent variable, sex, self-reported frequency of weekly depression and nightly sleep duration, and their interactions with sex as independent variables, and age, race, income, body mass index and physical activity as covariates. We employed Bayesian and Akaike Information criteria to identify the best model, evaluated the accuracy of the model in predicting diabetes using receiver operating characteristic analysis, and computed the odds ratios of these risk factors.ResultsIn the two best models, depression frequency and sleep hours interact with sex in determining the diagnosis of diabetes, with higher depression frequency and nightly duration of sleep longer or shorter than 7 to 8 hours associated with higher likelihood of diabetes. The two models both predicted diabetes at an accuracy (area under the receiver operating characteristic curve) of 0.86. Further, these effects were stronger in men than in women at each depression and sleep level.ConclusionsDepression and sleep inter-relatedly rather than independently contributes to diabetes. Depression and sleep hours associate with diabetes more significantly in men than in women. The current findings indicate a sex-dependent relationship between depression, sleep disturbance and diabetes risk and add to a growing body of evidence linking mental and physical health

5G 3GPP-like Channel Models for Outdoor Urban Microcellular and Macrocellular Environments

For the development of new 5G systems to operate in bands up to 100 GHz, there is a need for accurate radio propagation models at these bands that currently are not addressed by existing channel models developed for bands below 6 GHz. This document presents a preliminary overview of 5G channel models for bands up to 100 GHz. These have been derived based on extensive measurement and ray tracing results across a multitude of frequencies from 6 GHz to 100 GHz, and this document describes an initial 3D channel model which includes: 1) typical deployment scenarios for urban microcells (UMi) and urban macrocells (UMa), and 2) a baseline model for incorporating path loss, shadow fading, line of sight probability, penetration and blockage models for the typical scenarios. Various processing methodologies such as clustering and antenna decoupling algorithms are also presented.Comment: To be published in 2016 IEEE 83rd Vehicular Technology Conference Spring (VTC 2016-Spring), Nanjing, China, May 201

the relationship between alcohol consumption and vascular complications and mortality in individuals with type 2 diabetes

OBJECTIVE Moderate alcohol consumption has been associated with a reduced risk of mortality and coronary artery disease. The relationship between cardiovascular health and alcohol use in type 2 diabetes is less clear. The current study assesses the effects of alcohol use among participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial. RESEARCH DESIGN AND METHODS The effects of alcohol use were explored using Cox regression models, adjusted for potential confounders. The study end points were cardiovascular events (cardiovascular death, myocardial infarction, and stroke), microvascular complications (new or worsening nephropathy or retinopathy), and all-cause mortality. RESULTS During a median of 5 years of follow-up, 1,031 (9%) patients died, 1,147 (10%) experienced a cardiovascular event, and 1,136 (10%) experienced a microvascular complication. Compared with patients who reported no alcohol consumption, those who reported moderate consumption had fewer cardiovascular events (adjusted hazard ratio [aHR] 0.83; 95% CI 0.72–0.95; P = 0.008), less microvascular complications (aHR 0.85; 95% CI 0.73–0.99; P = 0.03), and lower all-cause mortality (aHR 0.87; 96% CI 0.75–1.00; P = 0.05). The benefits were particularly evident in participants who drank predominantly wine (cardiovascular events aHR 0.78, 95% CI 0.63–0.95, P = 0.01; all-cause mortality aHR 0.77, 95% CI 0.62–0.95, P = 0.02). Compared with patients who reported no alcohol consumption, those who reported heavy consumption had dose-dependent higher risks of cardiovascular events and all-cause mortality. CONCLUSION In patients with type 2 diabetes, moderate alcohol use, particularly wine consumption, is associated with reduced risks of cardiovascular events and all-cause mortality

Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB), the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP) and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17): Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.http://deepblue.lib.umich.edu/bitstream/2027.42/78314/1/1750-1326-5-45.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/2/1750-1326-5-45.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78314/3/1750-1326-5-45-S1.PDFPeer Reviewe

Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease

Background Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes. Methods We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants. Results Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects. Conclusions Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application

Environmental Profile of a Community's Health (EPOCH): An Instrument to Measure Environmental Determinants of Cardiovascular Health in Five Countries

BACKGROUND: The environment in which people live is known to be important in influencing diet, physical activity, smoking, psychosocial and other risk factors for cardiovascular (CV) disease. However no instrument exists that evaluates communities for these multiple environmental factors and is suitable for use across different communities, regions and countries. This report describes the design and reliability of an instrument to measure environmental determinants of CV risk factors. METHOD/PRINCIPAL FINDINGS: THE ENVIRONMENTAL PROFILE OF COMMUNITY HEALTH (EPOCH) INSTRUMENT COMPRISES TWO PARTS: (I) an assessment of the physical environment, and (II) an interviewer-administered questionnaire to collect residents' perceptions of their community. We examined the inter-rater reliability amongst 3 observers from each region of the direct observation component of the instrument (EPOCH I) in 93 rural and urban communities in 5 countries (Canada, Colombia, Brazil, China and India). Data collection using the EPOCH instrument was feasible in all communities. Reliability of the instrument was excellent (Intraclass Correlation Coefficient--ICC>0.75) for 24 of 38 items and fair to good (ICC 0.4-0.75) for 14 of 38 items. CONCLUSION: This report shows data collection with the EPOCH instrument is feasible and direct observation of community measures reliable. The EPOCH instrument will enable further research on environmental determinants of health for population studies from a broad range of settings

The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

Implications For The Origin Of GRB 051103 From LIGO Observations

We present the results of a LIGO search for gravitational waves (GWs) associated with GRB 051103, a short-duration hard-spectrum gamma-ray burst (GRB) whose electromagnetically determined sky position is coincident with the spiral galaxy M81, which is 3.6 Mpc from Earth. Possible progenitors for short-hard GRBs include compact object mergers and soft gamma repeater (SGR) giant flares. A merger progenitor would produce a characteristic GW signal that should be detectable at the distance of M81, while GW emission from an SGR is not expected to be detectable at that distance. We found no evidence of a GW signal associated with GRB 051103. Assuming weakly beamed gamma-ray emission with a jet semi-angle of 30 deg we exclude a binary neutron star merger in M81 as the progenitor with a confidence of 98%. Neutron star-black hole mergers are excluded with > 99% confidence. If the event occurred in M81 our findings support the the hypothesis that GRB 051103 was due to an SGR giant flare, making it the most distant extragalactic magnetar observed to date.Comment: 8 pages, 3 figures. For a repository of data used in the publication, go to: https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=15166 . Also see the announcement for this paper on ligo.org at: http://www.ligo.org/science/Publication-GRB051103/index.ph

Search for Gravitational Wave Bursts from Six Magnetars

Soft gamma repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are thought to be magnetars: neutron stars powered by extreme magnetic fields. These rare objects are characterized by repeated and sometimes spectacular gamma-ray bursts. The burst mechanism might involve crustal fractures and excitation of non-radial modes which would emit gravitational waves (GWs). We present the results of a search for GW bursts from six galactic magnetars that is sensitive to neutron star f-modes, thought to be the most efficient GW emitting oscillatory modes in compact stars. One of them, SGR 0501+4516, is likely similar to 1 kpc from Earth, an order of magnitude closer than magnetars targeted in previous GW searches. A second, AXP 1E 1547.0-5408, gave a burst with an estimated isotropic energy >10(44) erg which is comparable to the giant flares. We find no evidence of GWs associated with a sample of 1279 electromagnetic triggers from six magnetars occurring between 2006 November and 2009 June, in GW data from the LIGO, Virgo, and GEO600 detectors. Our lowest model-dependent GW emission energy upper limits for band-and time-limited white noise bursts in the detector sensitive band, and for f-mode ringdowns (at 1090 Hz), are 3.0 x 10(44)d(1)(2) erg and 1.4 x 10(47)d(1)(2) erg, respectively, where d(1) = d(0501)/1 kpc and d(0501) is the distance to SGR 0501+4516. These limits on GW emission from f-modes are an order of magnitude lower than any previous, and approach the range of electromagnetic energies seen in SGR giant flares for the first time.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyItalian Istituto Nazionale di Fisica NucleareFrench Centre National de la Recherche ScientifiqueAustralian Research CouncilCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Educacion y CienciaConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsFoundation for Fundamental Research on Matter supported by the Netherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFoundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space Administration NNH07ZDA001-GLASTCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationRussian Space AgencyRFBR 09-02-00166aIPN JPL Y503559 (Odyssey), NASA NNG06GH00G, NASA NNX07AM42G, NASA NNX08AC89G (INTEGRAL), NASA NNG06GI896, NASA NNX07AJ65G, NASA NNX08AN23G (Swift), NASA NNX07AR71G (MESSENGER), NASA NNX06AI36G, NASA NNX08AB84G, NASA NNX08AZ85G (Suzaku), NASA NNX09AU03G (Fermi)Astronom