Brain region-specific expression of genes mapped within quantitative trait loci for behavioral responsiveness to acute stress in Fisher 344 and Wistar Kyoto male rats

Acute stress responsiveness is a quantitative trait that varies in severity from one individual to another; however, the genetic component underlying the individual variation is largely unknown. Fischer 344 (F344) and Wistar Kyoto (WKY) rat strains show large differences in behavioral responsiveness to acute stress, such as freezing behavior in response to footshock during the conditioning phase of contextual fear conditioning (CFC). Quantitative trait loci (QTL) have been identified for behavioral responsiveness to acute stress in the defensive burying (DB) and open field test (OFT) from a reciprocal F2 cross of F344 and WKY rat strains. These included a significant QTL on chromosome 6 (Stresp10). Here, we hypothesized that the Stresp10 region harbors genes with sequence variation(s) that contribute to differences in multiple behavioral response phenotypes between the F344 and WKY rat strains. To test this hypothesis, first we identified differentially expressed genes within the Stresp10 QTL in the hippocampus, amygdala, and frontal cortex of F344 and WKY male rats using genome-wide microarray analyses. Genes with both expression differences and non-synonymous sequence variations in their coding regions were considered candidate quantitative trait genes (QTGs). As a proof-of-concept, the F344.WKY-Stresp10 congenic strain was generated with the Stresp10 WKY donor region into the F344 recipient strain. This congenic strain showed behavioral phenotypes similar to those of WKYs. Expression patterns of Gpatch11 (G-patch domain containing 11), Cdkl4 (Cyclin dependent kinase like 4), and Drc1 (Dynein regulatory complex subunit 1) paralleled that of WKY in the F344.WKY-Stresp10 strain matching the behavioral profiles of WKY as opposed to F344 parental strains. We propose that these genes are candidate QTGs for behavioral responsiveness to acute stress

Escape from washing out of baryon number in a two-zero-texture general Zee model compatible with the large mixing angle MSW solution

We propose a two-zero-texture general Zee model, compatible with the large mixing angle Mikheyev-Smirnov-Wolfenstein solution. The washing out of the baryon number does not occur in this model for an adequate parameter range. We check the consistency of a model with the constraints coming from flavor changing neutral current processes, the recent cosmic microwave background observation, and the Z-burst scenario.Comment: 22 pages, 2 eps figures, Type set revtex

Transform-domain analysis of packet delay in network nodes with QoS-aware scheduling

In order to differentiate the perceived QoS between traffic classes in heterogeneous packet networks, equipment discriminates incoming packets based on their class, particularly in the way queued packets are scheduled for further transmission. We review a common stochastic modelling framework in which scheduling mechanisms can be evaluated, especially with regard to the resulting per-class delay distribution. For this, a discrete-time single-server queue is considered with two classes of packet arrivals, either delay-sensitive (1) or delay-tolerant (2). The steady-state analysis relies on the use of well-chosen supplementary variables and is mainly done in the transform domain. Secondly, we propose and analyse a new type of scheduling mechanism that allows precise control over the amount of delay differentiation between the classes. The idea is to introduce N reserved places in the queue, intended for future arrivals of class 1

A burst with double radio spectrum observed up to 212 GHz

We study a solar flare that occurred on September 10, 2002, in active region NOAA 10105 starting around 14:52 UT and lasting approximately 5 minutes in the radio range. The event was classified as M2.9 in X-rays and 1N in H\alpha. Solar Submillimeter Telescope observations, in addition to microwave data give us a good spectral coverage between 1.415 and 212 GHz. We combine these data with ultraviolet images, hard and soft X-rays observations and full-disk magnetograms. Images obtained from Ramaty High Energy Solar Spectroscopic Imaging data are used to identify the locations of X-ray sources at different energies and to determine the X-ray spectrum, while ultra violet images allow us to characterize the coronal flaring region. The magnetic field evolution of the active region is analyzed using Michelson Doppler Imager magnetograms. The burst is detected at all available radio-frequencies. X-ray images (between 12 keV and 300 keV) reveal two compact sources and 212 GHz data, used to estimate the radio source position, show a single compact source displaced by 25" from one of the hard X-ray footpoints. We model the radio spectra using two homogeneous sources, and combine this analysis with that of hard X-rays to understand the dynamics of the particles. Relativistic particles, observed at radio wavelengths above 50 GHz, have an electron index evolving with the typical soft-hard-soft behaviour.Comment: Submitted to Solar Physics, 20 pages, 8 fugure

Is the wear coefficient dependent upon slip amplitude in fretting?: Vingsbo and Söderberg revisited

More than 25 years ago, Vingsbo and Söderberg published a seminal paper regarding the mapping of behaviour in fretting contacts (O. Vingsbo, S. Söderberg, On fretting maps, Wear, 126 (1988) 131–147). In this paper, it was proposed that in the gross-slip fretting regime, the wear coefficient increased by between one and two orders of magnitude as the fretting displacement amplitude increased from around 20 µm to 300 µm (defined as the limits of the gross-slip regime). Since the publication of this paper, there have been many papers published in the literature regarding fretting in the gross-sliding regime where such a strong dependence of wear coefficient upon fretting displacement has not been observed, with instead, the wear coefficient being shown to be almost independent of fretting amplitude. Indeed, many researchers have demonstrated that there is a good correlation between wear volume and frictional energy dissipated in the contact for many material combinations, with the additional insight that a threshold in energy dissipated in the contact exists, below which no wear is observed (experimental data relating to fretting of a high strength steel is presented in the current paper which supports this concept). It is argued that in deriving a wear coefficient in fretting, there are two key considerations which have not always been addressed: (i) the far-field displacement amplitude is not an adequate substitute for the slip amplitude (the former is the sum of the latter together with any elastic deformation in the system between the contact and the point at which the displacement is measured); and (ii) there is a threshold in the fretting duration, below which no wear occurs and above which the rate of increase in wear volume with increasing duration is constant (this constant may be termed the wear coefficient, ktrue). Not addressing these two issues results in the derivation of a nominal wear coefficient (knominal) which is always less than ktrue. A simple analysis is presented which indicates that knominal / ktrue = 1 - A - B where A is associated with erroneously utilising the far field displacement amplitude in place of the contact slip amplitude in the calculation of the wear coefficient and B is associated with the failure to recognise that there is a threshold in fretting duration below which no wear occurs. A and B are shown to depend upon the tractional force required to initiate sliding (itself dependent upon the applied load and coefficient of friction), the system stiffness, the applied displacement amplitude, the threshold fretting duration below which no wear occurs and the number of fretting cycles in the test. Using typical values of these parameters, the ratio of knominal to ktrue has been shown to be strongly dependent upon the applied displacement amplitude over the range addressed by Vingsbo and Söderberg (with the ratio rapidly decreasing by an order of magnitude over this range). As such, it is argued that ktrue shows no strong dependence on slip amplitude in fretting, and that the strong dependence of knominal upon displacement amplitude presented by Vingsbo and Söderberg does not imply a change in ktrue as is often inferred. The routine recording of force–displacement loops in fretting is a major experimental advancement which has taken place since the publication of the paper by Vingsbo and Söderberg. It is argued that this technique must be routinely used to allow the correct interpretation of wear data in terms of the actual slip amplitude (or energy dissipated); moreover, a range of conditions should be experimentally examined to allow the threshold fretting duration below which no wear has occurred to be evaluated and its significance assessed

Trust Building in Electronic Markets: Relative Importance and Interaction Effects of Trust Building Mechanisms

We examine the relative and complementary effectiveness of trust-building strategies in online environments. While prior research has examined various antecedents to trust, we investigated two trust-building mechanisms more in depth: Web site trust and vendor reputation. We tried to understand the relative effectiveness of these two important mechanisms to provide online businesses with a clear recommendation of how to establish trust in an effective and efficient manner. Drawing from the literature on trust, we proposed vendor reputation to be more effective than Web site trust. Moreover, we examined a potential complementary effect of these mechanisms so as to provide online businesses with a deeper understanding of how to derive superior trust. We hypothesize a small such effect. The study proposes a laboratory experiment to test the model

B_s --> mu+ mu- decay in the R-parity violating minimal supergravity

We study B_s --> mu+ mu- in the context of the R-parity violating minimal supergravity in the high tan beta regime. We find that the lowest value of the branching ratio can go well below the present LHCb sensitivity and hence B_s --> mu+ mu- can even be invisible to the LHC. We also find that the present upper bound on Br(B_s --> mu+ mu-) puts strong constraint on the minimal supergravity parameter space. The constraints become more severe if the upper bound is close to its standard model prediction.Comment: 18 pages, 10 figures; version to be published in European Physical Journal

Performance of the First ANTARES Detector Line

In this paper we report on the data recorded with the first Antares detector line. The line was deployed on the 14th of February 2006 and was connected to the readout two weeks later. Environmental data for one and a half years of running are shown. Measurements of atmospheric muons from data taken from selected runs during the first six months of operation are presented. Performance figures in terms of time residuals and angular resolution are given. Finally the angular distribution of atmospheric muons is presented and from this the depth profile of the muon intensity is derived.Comment: 14 pages, 9 figure

Global assessment of dengue Virus-Specific CD4+ T cell responses in Dengue-Endemic areas

Background: Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4+ T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. Methods: HLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a “megapool” (MP) consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by intracellular cytokine staining assays. Results: We detected responses directed against a total of 431 epitopes, representing all 4 DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka, and U.S. domestic flavivirus-naïve subjects immunized with Tetravalent Dengue Live-Attenuated Vaccine (TV005). This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency ≥5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles). Conclusion: The DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location

Effectiveness of integrating a pragmatic pathway for prescribing liraglutide 3.0mg in weight management services (STRIVE study): a multicentre, open-label, parallel-group, randomized controlled trial

Summary. Background: An effective prescribing pathway for liraglutide 3 mg, an approved obesity pharmacotherapy, may improve treatment access. This trial compared a targeted prescribing pathway for liraglutide 3 mg with multiple stopping rules in specialist weight management services (SWMS) to standard SWMS care. Methods: This phase four, two-year, multicentre, open-label, parallel-group, real-world randomized clinical trial (ClinicalTrials.gov: NCT03036800) enrolled adults with BMI ≥35 kg/m2 plus prediabetes, type 2 diabetes, hypertension or sleep apnoea from five SWMS in Ireland and UK. Participants were randomly allocated (2:1, stratified by centre and BMI) to SWMS care plus a targeted prescribing pathway for once daily subcutaneous liraglutide 3 mg (intervention) with stopping rules at 16 (≥5% weight loss, WL), 32 (≥10% WL) and 52 weeks (≥15% WL) or to SWMS care alone (control) through an online randomization service. The primary outcome was WL ≥15% at 52 weeks, assessed by complete cases analysis. All randomized participants were included in safety analysis. Findings From November 28, 2017 to February 28, 2020, 434 participants were screened, and 392 randomized (260 intervention; 132 control), while 294 (201 intervention; 93 control) included in the 52 weeks complete case analysis. More intervention than control participants achieved WL ≥15% at 52 weeks [51/201 (25.4%) vs 6/93 (6.5%); odds ratio 5.18; 95% CI 2.09, 12.88; p < 0.0001]. More adverse events occurred in the intervention (238/260, 91.5%; two deaths) than control (89/132, 67.4%; no deaths) group. Interpretation: A targeted prescribing pathway for liraglutide 3 mg helps more people achieve ≥15% WL at 52 weeks than standard care alone