Bradykinin Type 2 Receptor BE1 Genotype Influences Bradykinin-dependent Vasodilation During Angiotensin-converting Enzyme Inhibition

To test the hypothesis that the bradykinin receptor 2 (BDKRB2) BE1+9/-9 polymorphism affects vascular responses to bradykinin, we measured the effect of intra-arterial bradykinin on forearm blood flow and tissue-type plasminogen activator (t-PA) release in 89 normotensive, nonsmoking, white American subjects in whom degradation of bradykinin was blocked by enalaprilat. BE1 genotype frequencies were +9/+9:+9/-9:-9/-9=19:42:28. BE1 genotype was associated with systolic blood pressure (121.4+/-2.8, 113.8+/-1.8, and 110.6+/-1.8 mm Hg in +9/+9, +9/-9, and -9/-9 groups, respectively; P=0.007). In the absence of enalaprilat, bradykinin-stimulated forearm blood flow, forearm vascular resistance, and net t-PA release were similar among genotype groups. Enalaprilat increased basal forearm blood flow (P=0.002) and decreased basal forearm vascular resistance (P=0.01) without affecting blood pressure. Enalaprilat enhanced the effect of bradykinin on forearm blood flow, forearm vascular resistance, and t-PA release (all P\u3c0.001). During enalaprilat, forearm blood flow was significantly lower and forearm vascular resistance was higher in response to bradykinin in the +9/+9 compared with +9/-9 and -9/-9 genotype groups (P=0.04 for both). t-PA release tended to be decreased in response to bradykinin in the +9/+9 group (P=0.08). When analyzed separately by gender, BE1 genotype was associated with bradykinin-stimulated t-PA release in angiotensin-converting enzyme inhibitor-treated men but not women (P=0.02 and P=0.77, respectively), after controlling for body mass index. There was no effect of BE1 genotype on responses to the bradykinin type 2 receptor-independent vasodilator methacholine during enalaprilat. In conclusion, the BDKRB2 BE1 polymorphism influences bradykinin type 2 receptor-mediated vasodilation during angiotensin-converting enzyme inhibition

Improving the sensitivity of Higgs boson searches in the golden channel

Leptonic decays of the Higgs boson in the ZZ* channel yield what is known as the golden channel due to its clean signature and good total invariant mass resolution. In addition, the full kinematic distribution of the decay products can be reconstructed, which, nonetheless, is not taken into account in traditional search strategy relying only on measurements of the total invariant mass. In this work we implement a type of multivariate analysis known as the matrix element method, which exploits differences in the full production and decay matrix elements between the Higgs boson and the dominant irreducible background from q bar{q} -> ZZ*. Analytic expressions of the differential distributions for both the signal and the background are also presented. We perform a study for the Large Hadron Collider at sqrt{s}=7 TeV for Higgs masses between 175 and 350 GeV. We find that, with an integrated luminosity of 2.5 fb^-1 or higher, improvements in the order of 10 - 20 % could be obtained for both discovery significance and exclusion limits in the high mass region, where the differences in the angular correlations between signal and background are most pronounced.Comment: 31 pages, 8 figures. v2: Minus signs in definitions of angles corrected. Typos fixed. Reference added. Cosmetic changes to Figure 4. Additional sentence added for clarificatio

Supersymmetry Without Prejudice at the LHC

The discovery and exploration of Supersymmetry in a model-independent fashion will be a daunting task due to the large number of soft-breaking parameters in the MSSM. In this paper, we explore the capability of the ATLAS detector at the LHC ($\sqrt s=14$ TeV, 1 fb$^{-1}$) to find SUSY within the 19-dimensional pMSSM subspace of the MSSM using their standard transverse missing energy and long-lived particle searches that were essentially designed for mSUGRA. To this end, we employ a set of $\sim 71$k previously generated model points in the 19-dimensional parameter space that satisfy all of the existing experimental and theoretical constraints. Employing ATLAS-generated SM backgrounds and following their approach in each of 11 missing energy analyses as closely as possible, we explore all of these $71$k model points for a possible SUSY signal. To test our analysis procedure, we first verify that we faithfully reproduce the published ATLAS results for the signal distributions for their benchmark mSUGRA model points. We then show that, requiring all sparticle masses to lie below 1(3) TeV, almost all(two-thirds) of the pMSSM model points are discovered with a significance $S>5$ in at least one of these 11 analyses assuming a 50\% systematic error on the SM background. If this systematic error can be reduced to only 20\% then this parameter space coverage is increased. These results are indicative that the ATLAS SUSY search strategy is robust under a broad class of Supersymmetric models. We then explore in detail the properties of the kinematically accessible model points which remain unobservable by these search analyses in order to ascertain problematic cases which may arise in general SUSY searches.Comment: 69 pages, 40 figures, Discussion adde

An Alternative Yukawa Unified SUSY Scenario

Supersymmetric SO(10) Grand Unified Theories with Yukawa unification represent an appealing possibility for physics beyond the Standard Model. However Yukawa unification is made difficult by large threshold corrections to the bottom mass. Generally one is led to consider models where the sfermion masses are large in order to suppress these corrections. Here we present another possibility, in which the top and bottom GUT scale Yukawa couplings are equal to a component of the charged lepton Yukawa matrix at the GUT scale in a basis where this matrix is not diagonal. Physically, this weak eigenstate Yukawa unification scenario corresponds to the case where the charged leptons that are in the 16 of SO(10) containing the top and bottom quarks mix with their counterparts in another SO(10) multiplet. Diagonalizing the resulting Yukawa matrix introduces mixings in the neutrino sector. Specifically we find that for a large region of parameter space with relatively light sparticles, and which has not been ruled out by current LHC or other data, the mixing induced in the neutrino sector is such that $sin^2 2\Theta_{23} \approx 1$, in agreement with data. The phenomenological implications are analyzed in some detail.Comment: 32 pages, 22 Figure

Simplified Models for LHC New Physics Searches

This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection

IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: PASC and 44 participant-reported symptoms (with severity thresholds). RESULTS: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. CONCLUSIONS AND RELEVANCE: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain