Axially symmetric and latitudinally propagating nonlinear patterns in rotating spherical convection

We report a nonlinear phenomenon discovered in the classical problem of thermal convection in rapidly rotating, self-gravitating, internally heated Boussinesq fluid spheres. When linear convective instability (the most unstable mode of convection) is in the form of an axially symmetric, equatorially antisymmetric torsional oscillation, its equatorial symmetry must be broken by nonlinear effects and, consequently, the key properties of the primary solution bifurcating from the instability cannot be predicted on the basis of linear solutions at the onset of convection. We reveal that, when the supercritical Rayleigh number is in the vicinity of its critical value, the primary nonlinear solution is in the form of an axially symmetric, equatorially nonsymmetric, latitudinally propagating spatiotemporal pattern whose amplitude varies periodically, representing an unusual nonlinear phenomenon of thermal convection in rotating fluid spheres

Annotation of Allosteric Compounds to Enhance Bioactivity Modeling for Class A GPCRs

Proteins often have both orthosteric and allosteric binding sites. Endogenous ligands, such as hormones and neurotransmitters, bind to the orthosteric site, while synthetic ligands may bind to orthosteric or allosteric sites, which has become a focal point in drug discovery. Usually, such allosteric modulators bind to a protein noncompetitively with its endogenous ligand or substrate. The growing interest in allosteric modulators has resulted in a substantial increase of these entities and their features such as binding data in chemical libraries and databases. Although this data surge fuels research focused on allosteric modulators, binding data is unfortunately not always clearly indicated as being allosteric or orthosteric. Therefore, allosteric binding data is difficult to retrieve from databases that contain a mixture of allosteric and orthosteric compounds. This decreases model performance when statistical methods, such as machine learning models, are applied. In previous work we generated an allosteric data subset of ChEMBL release 14. In the current study an improved text mining approach is used to retrieve the allosteric and orthosteric binding types from the literature in ChEMBL release 22. Moreover, convolutional deep neural networks were constructed to predict the binding types of compounds for class A G protein-coupled receptors (GPCRs). Temporal split validation showed the model predictiveness with Matthews correlation coefficient (MCC) = 0.54, sensitivity allosteric = 0.54, and sensitivity orthosteric = 0.94. Finally, this study shows that the inclusion of accurate binding types increases binding predictions by including them as descriptor (MCC = 0.27 improved to MCC = 0.34; validated for class A GPCRs, trained on all GPCRs). Although the focus of this study is mainly on class A GPCRs, binding types for all protein classes in ChEMBL were obtained and explored. The data set is included as a supplement to this study, allowing the reader to select the compounds and binding types of interest.Medicinal Chemistr

Photon-Phonon-assisted tunneling through a single-molecular quantum dot

Based on exactly mapping of a many-body electron-phonon interaction problem onto a one-body problem, we apply the well-established nonequilibrium Green function technique to solve the time-dependent phonon-assisted tunneling at low temperature through a single-molecular quantum dot connected to two leads, which is subject to a microwave irradiation field. It is found that in the presence of the electron-phonon interaction and the microwave irradiation field, the time-average transmission and the nonlinear differential conductance display additional peaks due to pure photon absorption or emission processes and photon-absorption-assisted phonon emission processes. The variation of the time-average current with frequency of the microwave irradiation field is also studied.Comment: 9 pages, 6 figures, submitted to Phys. Rev. B. accepted by Phys. Rev.

A multi-center diabetes eye screening study in community settings: Study design and methodology

Purpose: Diabetes is the leading cause of new cases of blindness among adults aged 20-74 years within the United States. The Innovative Network for Sight Research group (INSIGHT) designed the Diabetic Eye Screening Study (DESS) to examine the feasibility and short-term effectiveness of non-mydriatic diabetic retinopathy (DR) screening for adults with diabetes in community-based settings.Methods: Study enrollment began in December 2011 at four sites: an internal medicine clinic at a county hospital in Birmingham, Alabama; a Federally-qualified community healthcare center in Miami-Dade County, Florida; a university-affiliated outpatient pharmacy in Philadelphia, Pennsylvania; and a medical home in Winston-Salem, North Carolina. People 18 years or older with previously diagnosed diabetes were offered free DR screening using non-mydriatic retinal photography that was preceded by a brief questionnaire addressing demographic information and previous eye care use. Visual acuity was also measured for each eye. Images were evaluated at a telemedicine reading center by trained evaluators using the National Health System DR grading classification. Participants and their physicians were sent screening report results and telephoned for a follow-up survey 3 months post-screening to determine whether participants had sought follow-up comprehensive eye care and their experiences with the screening process.Results: Target enrollment at each site was a minimum of 500 persons. Three of the four sites met this enrollment goal.Conclusion: The INSIGHT/DESS is intended to establish the feasibility and short-term effectiveness of DR screening using non-mydriatic retinal photography in persons with diabetes who seek services in community-based clinic and pharmacy settings

Collecting the data but missing the point: Validity of hand hygiene audit data

Background: Monitoring of hand hygiene compliance (HHC) by observation has been used in healthcare for more than a decade to provide assurance of infection control practice. The validity of this information is rarely tested. Aim: To examine the process and validity of collecting and reporting HHC data based on direct observation of compliance. Methods: Five years of HHC data routinely collected in one large National Health Service hospital trust were examined. The data collection process was reviewed by survey and interview of the auditors. HHC data collected for other research purposes undertaken during this period were compared with the organizational data set. Findings: After an initial increase, the reported HHC remained unchanged close to its intended target throughout this period. Examination of the data collection process revealed changes, including local interpretations of the data collection system, which invalidated the results. A minority of auditors had received formal training in observation and feedback of results. Conclusion: Whereas observation of HHC is the current gold standard, unless data collection definitions and methods are unambiguous, published, carefully supervised, and regularly monitored, variations may occur which affect the validity of the data. If the purpose of HHC monitoring is to improve practice and minimize transmission of infection, then a focus on progressively improving performance rather than on achieving a target may offer greater opportunities to achieve this

Evaluation of a Web-Based Training in Smoking Cessation Counseling Targeting U.S. Eye-Care Professionals

Background. Smoking causes blindness-related diseases. Eye-care providers are uniquely positioned to help their patients quit smoking. Aims. Using a pre-/postevaluation design, this study evaluated a web-based training in smoking cessation counseling targeting eye-care providers. Method. The training was developed based on the 3A1R protocol: “Ask about smoking, Advise to quit, Assess willingness to quit, and Refer to tobacco quitlines,” and made available in the form of a web-based video presentation. Providers (n = 654) at four academic centers were invited to participate. Participants completed pretraining, posttraining, and 3-month follow-up surveys. Main outcomes were self-reported improvement in their motivation, confidence, and counseling practices at 3-month follow-up. Generalized linear mixed models for two time-points (pretraining and 3-month) were conducted for these outcomes. Results. A total of 113 providers (54.0% males) participated in the study (17.7% response rate). At the 3-month evaluation, 9.8% of participants reported improvement in their motivation. With respect to the 3A1R, 8% reported improvement in their confidence for Ask, 15.5% for Advise, 28.6% for Assess, and 37.8% for Refer. Similarly, 25.5% reported improvement in their practices for Ask, 25.5% for Advise, 37.2% for Assess, and 39.4% for Refer to tobacco quitlines (p <.001 for all except for Refer confidence p =.05). Discussion. Although participation rate was low, the program effectively improved providers’ smoking cessation counseling practices. Conclusions. Including training in smoking cessation counseling in ophthalmology curriculums, and integrating the 3A1R protocol into the electronic medical records systems in eye-care settings, might promote smoking cessation practices in these settings

SyNDI : Synchronous network data integration framework

Background: Systems biology takes a holistic approach by handling biomolecules and their interactions as big systems. Network based approach has emerged as a natural way to model these systems with the idea of representing biomolecules as nodes and their interactions as edges. Very often the input data come from various sorts of omics analyses. Those resulting networks sometimes describe a wide range of aspects, for example different experiment conditions, species, tissue types, stimulating factors, mutants, or simply distinct interaction features of the same network produced by different algorithms. For these scenarios, synchronous visualization of more than one distinct network is an excellent mean to explore all the relevant networks efficiently. In addition, complementary analysis methods are needed and they should work in a workflow manner in order to gain maximal biological insights. Results: In order to address the aforementioned needs, we have developed a Synchronous Network Data Integration (SyNDI) framework. This framework contains SyncVis, a Cytoscape application for user-friendly synchronous and simultaneous visualization of multiple biological networks, and it is seamlessly integrated with other bioinformatics tools via the Galaxy platform. We demonstrated the functionality and usability of the framework with three biological examples - we analyzed the distinct connectivity of plasma metabolites in networks associated with high or low latent cardiovascular disease risk; deeper insights were obtained from a few similar inflammatory response pathways in Staphylococcus aureus infection common to human and mouse; and regulatory motifs which have not been reported associated with transcriptional adaptations of Mycobacterium tuberculosis were identified. Conclusions: Our SyNDI framework couples synchronous network visualization seamlessly with additional bioinformatics tools. The user can easily tailor the framework for his/her needs by adding new tools and datasets to the Galaxy platform.</p

Stokes-operator-squeezed continuous-variable polarization states

We investigate nonclassical Stokes-operator variances in continuous-wave polarization-squeezed laser light generated from one and two optical parametric amplifiers. A general expression of how Stokes-operator variances decompose into two-mode quadrature operator variances is given. Stokes parameter variance spectra for four different polarization-squeezed states have been measured and compared with a coherent state. Our measurement results are visualized by three-dimensional Stokes-operator noise volumes mapped on the quantum Poincare sphere. We quantitatively compare the channel capacity of the different continuous-variable polarization states for communication protocols. It is shown that squeezed polarization states provide 33% higher channel capacities than the optimum coherent beam protocol

Circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients

The anti-estrogen tamoxifen is characterized by a large variability in response, partly due to pharmacokinetic differences. We examined circadian variation in tamoxifen pharmacokinetics in mice and breast cancer patients. Pharmacokinetic analysis was performed in mice, dosed at six different times (24-h period). Tissue samples were used for mRNA expression analysis of drug-metabolizing enzymes. In patients, a cross-over study was performed. During three 24-h periods, after tamoxifen dosing at 8 a.m., 1 p.m., and 8 p.m., for at least 4 weeks, blood samples were collected for pharmacokinetic measurements. Differences in tamoxifen pharmacokinetics between administration times were assessed. The mRNA expression of drug-metabolizing enzymes showed circadian variation in mouse tissues. Tamoxifen exposure seemed to be highest after administration at midnight. In humans, marginal differences were observed in pharmacokinetic parameters between morning and evening administration. Tamoxifen Cmax and area under the curve (AUC)0–8 h were 20 % higher (P max was shorter (2.1 vs. 8.1 h; P = 0.001), indicating variation in absorption. Systemic exposure (AUC0–24 h) to endoxifen was 15 % higher (P < 0.001) following morning administration. The results suggest that dosing time is of marginal influence on tamoxifen pharmacokinetics. Our study was not designed to detect potential changes in clinical outcome or toxicity, based on a difference in the time of administration. Circadian rhythm may be one of the many determinants of the interpatient and intrapatient pharmacokinetic variability of tamoxifen

Search for single top quarks in the tau+jets channel using 4.8 fb−1^{-1} of ppˉp\bar{p} collision data

We present the first direct search for single top quark production using tau leptons. The search is based on 4.8 fb$^{-1}$ of integrated luminosity collected in $p\bar{p}$ collisions at $\sqrt{s}$=1.96 TeV with the D0 detector at the Fermilab Tevatron Collider. We select events with a final state including an isolated tau lepton, missing transverse energy, two or three jets, one or two of them $b$ tagged. We use a multivariate technique to discriminate signal from background. The number of events observed in data in this final state is consistent with the signal plus background expectation. We set in the tau+jets channel an upper limit on the single top quark cross section of \TauLimObs pb at the 95% C.L. This measurement allows a gain of 4% in expected sensitivity for the observation of single top production when combining it with electron+jets and muon+jets channels already published by the D0 collaboration with 2.3 fb$^{-1}$ of data. We measure a combined cross section of \SuperCombineXSall pb, which is the most precise measurement to date.Comment: 12 pages, 5 figure