Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

DNA methylation changes associated with risk factors in tumors of the upper aerodigestive tract

Cancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are also important risk factors. While somatically acquired DNA methylation changes have been associated with UADT cancers, what triggers these events and precise epigenetic targets are poorly understood. In this study, we applied quantitative profiling of DNA methylation states in a panel of cancer-associated genes to a case-control study of UADT cancers. Our analyses revealed a high frequency of aberrant hypermethylation of several genes, including MYOD1, CHRNA3 and MTHFR in UADT tumors, whereas CDKN2A was moderately hypermethylated. Among differentially methylated genes, we identified a new gene (the nicotinic acetycholine receptor gene) as target of aberrant hypermethylation in UADT cancers, suggesting that epigenetic deregulation of nicotinic acetycholine receptors in non-neuronal tissues may promote the development of UADT cancers. Importantly, we found that sex and age is strongly associated with the methylation states, whereas tobacco smoking and alcohol intake may also influence the methylation levels in specific genes. This study identifies aberrant DNA methylation patterns in UADT cancers and suggests a potential mechanism by which environmental factors may deregulate key cellular genes involved in tumor suppression and contribute to UADT cancers.IARCIARCla Ligue National (Francaise) Contre le Cancerla Ligue National (Francaise) Contre le CancerNational Institutes of Health/National Cancer Institute (NIH/NCI), United StatesNational Institutes of Health/National Cancer Institute (NIH/NCI), United StatesAssociation pour la Recherche sur le Cancer (ARC, France)l'Association pour la Recherche sur le Cancer (ARC), Francela Ligue Nationale (Francaise) Contre le Cancer (Comite SaoneetLoire), Francela Ligue Nationale (Francaise) Contre le Cancer (Comite Saone-et-Loire), FranceSwiss Bridge AwardSwiss Bridge Awar

Divergent Genomic and Epigenomic Landscapes of Lung Cancer Subtypes Underscore the Selection of Different Oncogenic Pathways during Tumor Development

For therapeutic purposes, non-small cell lung cancer (NSCLC) has traditionally been regarded as a single disease. However, recent evidence suggest that the two major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SqCC) respond differently to both molecular targeted and new generation chemotherapies. Therefore, identifying the molecular differences between these tumor types may impact novel treatment strategy. We performed the first large-scale analysis of 261 primary NSCLC tumors (169 AC and 92 SqCC), integrating genome-wide DNA copy number, methylation and gene expression profiles to identify subtype-specific molecular alterations relevant to new agent design and choice of therapy. Comparison of AC and SqCC genomic and epigenomic landscapes revealed 778 altered genes with corresponding expression changes that are selected during tumor development in a subtype-specific manner. Analysis of >200 additional NSCLCs confirmed that these genes are responsible for driving the differential development and resulting phenotypes of AC and SqCC. Importantly, we identified key oncogenic pathways disrupted in each subtype that likely serve as the basis for their differential tumor biology and clinical outcomes. Downregulation of HNF4α target genes was the most common pathway specific to AC, while SqCC demonstrated disruption of numerous histone modifying enzymes as well as the transcription factor E2F1. In silico screening of candidate therapeutic compounds using subtype-specific pathway components identified HDAC and PI3K inhibitors as potential treatments tailored to lung SqCC. Together, our findings suggest that AC and SqCC develop through distinct pathogenetic pathways that have significant implication in our approach to the clinical management of NSCLC

Measurement of Trilinear Gauge Couplings in e+e−e^+ e^- Collisions at 161 GeV and 172 GeV

Trilinear gauge boson couplings are measured using data taken by DELPHI at 161~GeV and 172~GeV. Values for $WWV$ couplings ($V=Z, \gamma$) are determined from a study of the reactions \eeWW\ and \eeWev, using differential distributions from the $WW$ final state in which one $W$ decays hadronically and the other leptonically, and total cross-section data from other channels. Limits are also derived on neutral $ZV\gamma$ couplings from an analysis of the reaction \eegi

Search for neutral heavy leptons produced in ZZ decays

Weak isosinglet Neutral Heavy Leptons (νm) have been searched for using data collected by the DELPHI detector corresponding to 3.3 × 106 hadronic Z0 decays at LEP1. Four separate searches have been performed, for short-lived νm production giving monojet or acollinear jet topologies, and for long-lived νm giving detectable secondary vertices or calorimeter clusters. No indication of the existence of these particles has been found, leading to an upper limit for the branching ratio BR(Z0 → νmν̄) of about 1.3 × 10-6 at 95% confidence level for νm masses between 3.5 and 50 GeV/c2. Outside this range the limit weakens rapidly with the νm mass. The results are also interpreted in terms of limits for the single production of excited neutrinos. © Springer-Verlag 1997

Measurement of the B0^0 and B+^+ meson lifetimes with fully reconstructed hadronic final states

The B0 and B+ meson lifetimes have been measured in e+e- annihilation data collected in 1999 and 2000 with the BABAR detector at center-of-mass energies near the Upsilon(4S) resonance. Events are selected in which one B meson is fully reconstructed in a hadronic final state while the second B meson is reconstructed inclusively. A combined fit to the B0 and the B+ decay time difference distributions yields tau_{B0} = 1.546 +/- 0.032 (stat) +/- 0.022(syst) ps, tau_{B+} = 1.673 +/- 0.032 (stat) +/- 0.023 (syst) ps and tau_{B+} / tau_{B0} = 1.082 +/- 0.026 (stat) +/- 0.012 (syst

Insect pollinators: linking research and policy. Workshop report.

EXECUTIVE SUMMARY Pollinators interact with plants to underpin wider biodiversity, ecosystem function, ecosystem services to agricultural crops and ultimately human nutrition. The conservation of pollinators is thus an important goal. Pollinators and pollination represent a tractable example of how biodiversity can be linked to an ecosystem service. This represents a case study for exploring the impacts of various policy instruments aiming to halt/reverse the loss of ecosystem services. There is a need to understand how multiple pressures (e.g. habitat loss, fragmentation and degradation, climate change, pests and diseases, invasive species and environmental chemicals) can combine or interact to affect diversity, abundance and health of different pollinator groups. Decision makers need to balance consideration of the effects of single pressures on pollinators against the suite of other pressures on pollinators. For instance, the threat from pesticide use (with its high public and media profile) also needs to be considered in the context of the other threats facing pollinators and balanced against the need for food security. An independent review of the balance of risks across pollinator groups from pesticide use would help synthesise current knowledge into an accessible form for decision makers. To manage or lessen these threats to pollinators (wild and managed) and pollination requires improved knowledge about their basic ecology. We still need to know where and in what numbers different pollinator species occur, how they use different environments, how they interact with each other through shared plants and diseases and how wild pollinator abundance is changing. Decision makers need clear factual evidence for i) the relative contribution of different managed and wild pollinator groups to wildflower and crop pollination and ii) how this varies across different land-uses, ecosystems and regions. Addressing these basic and applied questions will improve our ability to forecast impacts on pollination service delivery to agricultural crops arising from current and future environmental changes, pesticide use and emerging diseases. The development of a long-term, multi-scale monitoring scheme to monitor trends in pollinator (wild and managed) population size and delivery of pollination services (ideally tied to data collection on land-use, pesticide applications and disease incidence at relevant spatial scales) would provide the evidence base for developing the effectiveness of policy and management interventions over time. Such a monitoring scheme would benefit from including research council organisations (e.g. CEH), governmental departments (e.g. Fera), universities, museums and NGOs (e.g. BBKA,SBA, Bumblebee Conservation Trust etc) Insect Pollinators: linking research and policy Workshop Report | 5 In the context of agricultural intensification and conservation we need to establish what type, quality and quantity of interventions (e.g. agri-environment schemes, protected areas) are needed, where to place them and how they can sustain different pollinator populations and effective pollination services. Current monitoring of the risks from diseases and pesticides requires broadening to consider other insects aside from honey bees, unless we can demonstrate that honey bees are good surrogates for all other pollinators. There is a need to increase confidence in regulatory risk assessments pertaining to pathogens and pesticides by incorporating other pollinator species, investigating chronic exposure to multiple chemicals and using field relevant dosages (specific to regions, not using other data sources as surrogates). At present the effects of spatial, social and temporal scales on the benefits stakeholders receive from pollination services are only beginning to be understood. Economic valuation of pollination services can help optimise the cost-effectiveness of service management measures and offer new opportunities to incentivise action or raise awareness among stakeholders. Novel tools and instruments (e.g. education and training) are needed to translate broad international (e.g. CBD, EU Biodiversity Strategy) and national (e.g. England‟s Biodiversity Strategy) policies into local actor (e.g. beekeeper, farmer, citizen scientist) contributions to meet biodiversity commitments Refocusing some public funding to link basic science to development of practical solutions (e.g. better crop protection products, improved disease resistance or treatment) could help science deliver better-targeted evidence for pollinator protection. Scientists need to make more use of opportunities (e.g. POSTnotes1; practitioner guides) to transfer knowledge to a broad audience in order to better influence decision maker and practitioner behaviours. Improved knowledge exchange between scientists and decision makers is important to combating threats to pollination. Central to this is improved understanding of the respective positions of policy makers and scientists. For instance, policy-makers usually need to be presented with a range of options to balance against other areas of policy. Science does not always arrive at a consensus due to uncertainties in data or models. Policy-makers need to understand that scientists are communicating the “best available knowledge at present” and that consequently it is not always possible to give a definitive answer

A simple and robust cell-based assay for the discovery of novel cytokinesis inhibitors

Cytokinesis is the last step of mitotic cell division that separates the cytoplasm of dividing cells. Small molecule inhibitors targeting either the elements of the regulatory pathways controlling cytokinesis, or the terminal effectors have been of interest as potential drug candidates for the treatment of various diseases. Here we present a detailed protocol for a cell-based cytokinesis assay that can be used for the discovery of novel cytokinesis inhibitors. The assay is performed in a 96-well plate format in 48 h. Living cells, nuclei and nuclei of dead cells are identified by a single staining step using three fluorescent dyes, followed by rapid live cell imaging. The primary signal is the nuclei-to-cell ratio (NCR). In the presence of cytokinesis inhibitors, this ratio increases over time, as the ratio of multinucleated cells increases in the population. The ratio of dead nuclei to total nuclei provides a simultaneous measure of cytotoxicity. A screening window coefficient (Z`) of 0.65 indicates that the assay is suitable for screening purposes, as the positive and negative controls are well-separated. EC50 values can be reliably determined in a single 96-well plate by using only six different compound concentrations, enabling the testing of 4 compounds per plate. An excellent test-retest reliability (R2 = 0.998) was found for EC50 values covering a ~1500-fold range of potencies. Established small molecule inhibitors of cytokinesis operating via direct action on actin dynamics or nonmuscle myosin II are used to demonstrate the robustness, simplicity and flexibility of the assay

Vagal sensory neurons mediate the Bezold–Jarisch reflex and induce syncope

Abstract: Visceral sensory pathways mediate homeostatic reflexes, the dysfunction of which leads to many neurological disorders1. The Bezold–Jarisch reflex (BJR), first described2,3 in 1867, is a cardioinhibitory reflex that is speculated to be mediated by vagal sensory neurons (VSNs) that also triggers syncope. However, the molecular identity, anatomical organization, physiological characteristics and behavioural influence of cardiac VSNs remain mostly unknown. Here we leveraged single-cell RNA-sequencing data and HYBRiD tissue clearing4 to show that VSNs that express neuropeptide Y receptor Y2 (NPY2R) predominately connect the heart ventricular wall to the area postrema. Optogenetic activation of NPY2R VSNs elicits the classic triad of BJR responses—hypotension, bradycardia and suppressed respiration—and causes an animal to faint. Photostimulation during high-resolution echocardiography and laser Doppler flowmetry with behavioural observation revealed a range of phenotypes reflected in clinical syncope, including reduced cardiac output, cerebral hypoperfusion, pupil dilation and eye-roll. Large-scale Neuropixels brain recordings and machine-learning-based modelling showed that this manipulation causes the suppression of activity across a large distributed neuronal population that is not explained by changes in spontaneous behavioural movements. Additionally, bidirectional manipulation of the periventricular zone had a push–pull effect, with inhibition leading to longer syncope periods and activation inducing arousal. Finally, ablating NPY2R VSNs specifically abolished the BJR. Combined, these results demonstrate a genetically defined cardiac reflex that recapitulates characteristics of human syncope at physiological, behavioural and neural network levels