250 research outputs found
Kondo effect in side coupled double quantum-dot molecule
Electron tunneling through a double quantum dot molecule side attached to a
quantum wire, in the Kondo regime, is studied. The mean-field finite-U
slave-boson formalism is used to obtain the solution of the problem. We found
conductance cancelations when the molecular energies of the side attached
double quantum-dot cross the Fermi energy. We investigate the many body
molecular Kondo states as a function of the parameters of the system.Comment: 12 pages, 7 figures. Submitted to Solid State Com
3-Ethenyl-1-(4-methylphenylsulfonyl)-1H-indole
Two independent but very similar molecules comprise the asymmetric unit of the title compound, C17H15NO2S. The molecules have L-shapes with the dihedral angles between the fused-ring system (r.m.s. deviations = 0.036 and 0.019 Å, respectively) and the benzene ring being almost the same, i.e. 82.98 (12) and 84.46 (13)°, respectively. The terminal ethenyl group is almost coplanar with the ring to which it is connected [C—C—C—C torsion angles = −173.7 (4) and −171.7 (4)°, respectively]. Supramolecular arrays parallel to (-124) stabilized by C—H⋯O and C—H⋯π interactions feature in the crystal packing
Stroma Transcriptomic and Proteomic Profile of Prostate Cancer Metastasis Xenograft Models Reveals Prognostic Value of Stroma Signatures.
Resistance acquisition to androgen deprivation treatment and metastasis progression are a major clinical issue associated with prostate cancer (PCa). The role of stroma during disease progression is insufficiently defined. Using transcriptomic and proteomic analyses on differentially aggressive patient-derived xenografts (PDXs), we investigated whether PCa tumors predispose their microenvironment (stroma) to a metastatic gene expression pattern. RNA sequencing was performed on the PCa PDXs BM18 (castration-sensitive) and LAPC9 (castration-resistant), representing different disease stages. Using organism-specific reference databases, the human-specific transcriptome (tumor) was identified and separated from the mouse-specific transcriptome (stroma). To identify proteomic changes in the tumor (human) versus the stroma (mouse), we performed human/mouse cell separation and subjected protein lysates to quantitative Tandem Mass Tag labeling and mass spectrometry. Tenascin C (TNC) was among the most abundant stromal genes, modulated by androgen levels in vivo and highly expressed in castration-resistant LAPC9 PDX. The tissue microarray of primary PCa samples (n = 210) showed that TNC is a negative prognostic marker of the clinical progression to recurrence or metastasis. Stroma markers of osteoblastic PCa bone metastases seven-up signature were induced in the stroma by the host organism in metastatic xenografts, indicating conserved mechanisms of tumor cells to induce a stromal premetastatic signature. A 50-gene list stroma signature was identified based on androgen-dependent responses, which shows a linear association with the Gleason score, metastasis progression and progression-free survival. Our data show that metastatic PCa PDXs, which differ in androgen sensitivity, trigger differential stroma responses, which show the metastasis risk stratification and prognostic biomarker potential
[(2R,3S,6S)-3-Acetyloxy-6-(1-phenyl-1H-1,2,3-triazol-4-yl)-3,6-dihydro-2H-pyran-2-yl]methyl acetate
In the title compound, C18H19N3O5, the 3,6-dihydro-2H-pyran ring adopts a half-chair, distorted towards a half-boat, conformation with Q
T = 0.5276(14) Å. The benzene ring is twisted out of the place of the triazole ring [dihedral angle = 23.54 (8)°]. In the crystal, supramolecular layers in the ac plane are formed through C—H⋯O and C—H⋯π(triazole) interactions. These stack along the b axis being connected by C—H⋯N contacts
Detecting Mental Health Behaviours Using Mobile Interactions (DeMMI):an Exploratory Study Focusing on Binge Eating
Background: Binge eating is a subjective loss of control while eating, leading to the consumption of large amounts of food. It can cause significant emotional distress and is often accompanied by purging behaviors (eg, meal skipping, over-exercising or vomiting). Objective: The aim of this study was to explore the potential for mobile sensing to detect indicators for binge eating episodes, with a view toward informing the design of future context-aware mobile interventions. Methods: Our study was conducted in two stages. The first involved the development of the DeMMI app. As part of this, we conducted a consultation session to explore whether the types of sensor data we were proposing to capture were seen to be useful and appropriate, as well as gathering feedback on some specific app features relating to self-report. The second stage involved carrying out a 6-week period of data collection with 10 participants experiencing binge eating (logging both their mood and episodes of binge eating) and 10 control participants (logging only mood). An optional interview was conducted post-study discussing their experience with using the app, 8 participants (3 binge eating and 5 controls) consented. Results: Findings showed unique differences in the types of sensor data that were triangulated with individuals’ episodes (with nearby Bluetooth devices, screen and app usage features, mobility features, and mood scores showing relevance). Participants had a largely positive opinion about the app, its unobtrusive role, and its ease of use. Interacting with the app increased their awareness of and reflection around mood and their phone usage patterns. Moreover, they expressed no privacy concerns as the study information sheet alleviated these. Conclusions: In this study, we contribute a series of recommendations for future studies wishing to scale our approach, and for the design of bespoke mobile interventions to support this population
Using topology and neighbor information to overcome adverse vehicle density conditions
Vehicular networks supporting cooperative driving on the road have attracted much attention due to the plethora of new possibilities they offer to modern Intelligent Transportation Systems. However, research works regarding vehicular networks usually obviate assessing their proposals in scenarios including adverse vehicle densities, i.e., density values that significantly differ from the average values, despite such densities can be quite common in real urban environments (e.g. traffic jams). In this paper, we study the effect of these hostile conditions on the performance of different schemes providing warning message dissemination. The goal of these schemes is to maximize message delivery effectiveness, something difficult to achieve in adverse density scenarios. In addition, we propose the Neighbor Store and Forward (NSF) scheme, designed to be used under low density conditions, and the Nearest Junction Located (NJL) scheme, specially developed for high density conditions. Simulation results demonstrate that our proposals are able to outperform existing warning message dissemination schemes in urban environments under adverse vehicle density conditions. In particular, NSF reduces the warning notification time in low vehicle density scenarios, while increasing up to 23.3% the percentage of informed vehicles. As for high vehicle density conditions, NJL is able to inform the same percentage of vehicles than other existing approaches, while reducing the number of messages up to 46.73%This work was partially supported by the Ministerio de Ciencia e Innovacion, Spain, under Grant TIN2011-27543-C03-01, by the Fundacion Universitaria Antonio Gargallo and the Obra Social de Ibercaja, under Grant 2013/B010, as well as the Government of Aragon and the European Social Fund (T91 Research Group).Sanguesa, JA.; Fogue, M.; Garrido, P.; Martinez, FJ.; Cano Escribá, JC.; Tavares De Araujo Cesariny Calafate, CM. (2014). Using topology and neighbor information to overcome adverse vehicle density conditions. Transportation Research Part C: Emerging Technologies. 42:1-13. https://doi.org/10.1016/j.trc.2014.02.010S1134
World Psychiatric Association-Asian Journal of Psychiatry Commission on Public Mental Health.
Although there is considerable evidence showing that the prevention of mental illnesses and adverse outcomes and mental health promotion can help people lead better and more functional lives, public mental health remains overlooked in the broader contexts of psychiatry and public health. Likewise, in undergraduate and postgraduate medical curricula, prevention and mental health promotion have often been ignored. However, there has been a recent increase in interest in public mental health, including an emphasis on the prevention of psychiatric disorders and improving individual and community wellbeing to support life trajectories, from childhood through to adulthood and into older age. These lifespan approaches have significant potential to reduce the onset of mental illnesses and the related burdens for the individual and communities, as well as mitigating social, economic, and political costs. Informed by principles of social justice and respect for human rights, this may be especially important for addressing salient problems in communities with distinct vulnerabilities, where prominent disadvantages and barriers for care delivery exist. Therefore, this Commission aims to address these topics, providing a narrative overview of relevant literature and suggesting ways forward. Additionally, proposals for improving mental health and preventing mental illnesses and adverse outcomes are presented, particularly amongst at-risk populations
Clinical Role of CA125 in Worsening Heart Failure A BIOSTAT-CHF Study Subanalysis
OBJECTIVES The aim of this study was to evaluate the association between antigen carbohydrate 125 (CA125) and the risk of 1-year clinical outcomes in patients with worsening heart failure (HF).BACKGROUND CA125 is a widely available biomarker that is up-regulated in patients with acute HF and has been postulated as a useful marker of congestion and risk stratification.METHODS hi a large multicenter cohort of patients with worsening HF, either in-hospital or in the outpatient setting, the independent associations between CA125 and 1-year death and the composite of death/HF readmission (adjusted for outcome-specific prognostic risk score [BIOSTAT risk score]) were determined by using the Royston-Parmar method (N = 2356). In a sensitivity analysis, the prognostic implications of CA125 were also adjusted for a composite congestion score (CCS). Data were validated in the B1OSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure validation) cohort (N = 1,630).RESULTS Surrogates of congestion, such as N-terminal pro-B-type natriuretic peptide and CCS, emerged as independent predictors of CA125. In muttivariabte survival analyses, higher CA125 was associated with an increased risk of mortality and the composite of death/HF readmission (p <0.001 for both comparisons), even after adjustment for the CCS (p <0.010 for both comparisons). The addition of CA125 to the B1OSTAT score led to a significant risk reclassification for both outcomes (category-free net reclassification improvement 0.137 [p <0.001] and 0.104 [p 0.003] respectively). AR outcomes were confirmed in an independent validation cohort.CONCLUSIONS In patients with worsening HF, higher levels of CA125 were positively associated with parameters of congestion. Furthermore, CA125 remained independently associated with a higher risk of clinical outcomes, even beyond a predefined risk model and clinical surrogates of congestion. (C) 2020 by the American College of Cardiology Foundation.</p
The PCSK9-LDL Receptor Axis and Outcomes in Heart Failure:BIOSTAT-CHF Subanalysis
Background:
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression.
Objectives:
The aim of this study was to determine whether the PCSK9-LDLR axis could predict risk in patients with heart failure (HF).
Methods:
The BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) is a multicenter, multinational, prospective, observational study that included patients with worsening HF signs and/or symptoms. The primary endpoints were all-cause mortality and the composite of mortality or unscheduled hospitalizations for HF. We implemented Cox proportional hazard regression to determine the simultaneously adjusted effect of PCSK9 and LDLR on both outcomes when added to the previously validated BIOSTAT-CHF risk scores.
Results:
This study included 2,174 patients (mean age: 68 ± 12 years; 53.2% had a history of ischemic heart disease). Median (interquartile range) PCSK9 and LDLR levels were 1.81 U/ml (1.45 to 2.18) and 2.98 U/ml (2.45 to 3.53), respectively. During follow-up, 569 deaths (26.2%) and 896 (41.2%) composite endpoints were ascertained. A multivariable analysis, which included BIOSTAT-CHF risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.49; p = 0.020) and the composite endpoint (HR: 1.21; 95% CI: 1.05 to 1.40; p = 0.010). A similar analysis for LDLR revealed a negative association with mortality (HR: 0.86; 95% CI: 0.76 to 0.98; p = 0.025) and the composite endpoint (HR: 0.92; 95% CI: 0.83 to 1.01; p = 0.087). Including PCSK9 and LDLR improved risk score performance.
Conclusions:
The PCSK9-LDLR axis was associated with outcomes in patients with HF. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF
Analysis of human mini-exome sequencing data from Genetic Analysis Workshop 17 using a Bayesian hierarchical mixture model
Next-generation sequencing technologies are rapidly changing the field of genetic epidemiology and enabling exploration of the full allele frequency spectrum underlying complex diseases. Although sequencing technologies have shifted our focus toward rare genetic variants, statistical methods traditionally used in genetic association studies are inadequate for estimating effects of low minor allele frequency variants. Four our study we use the Genetic Analysis Workshop 17 data from 697 unrelated individuals (genotypes for 24,487 autosomal variants from 3,205 genes). We apply a Bayesian hierarchical mixture model to identify genes associated with a simulated binary phenotype using a transformed genotype design matrix weighted by allele frequencies. A Metropolis Hasting algorithm is used to jointly sample each indicator variable and additive genetic effect pair from its conditional posterior distribution, and remaining parameters are sampled by Gibbs sampling. This method identified 58 genes with a posterior probability greater than 0.8 for being associated with the phenotype. One of these 58 genes, PIK3C2B was correctly identified as being associated with affected status based on the simulation process. This project demonstrates the utility of Bayesian hierarchical mixture models using a transformed genotype matrix to detect genes containing rare and common variants associated with a binary phenotype
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