The relevance and impact of MICA allele mismatching and MICA antibodies on renal transplantation outcome

Even when kidney allografts are well matched for HLA antigens and anti-HLA antibodies are undetected, graft rejection still occurs. There is evidence of hyperacute rejection in the absence of HLA antibodies, implicating other alloantigens. Studies have shown that some patients with graft rejection or loss have antibodies specific for the highly polymorphic MHC class I-related chain A (MICA) antigens. This thesis investigated whether mismatching MICA alleles associates with MICA antibody production and graft rejection, survival or dysfunction. Using commercial assays, MICA and HLA antibody screening of 442 recipients was performed and specificities were confirmed in a sub-group of 227 recipients using single antigen (SAg) multiplex technology. MICA antibody specificity was assigned using three independent SAg assays. In addition, MICA alleles of 227 recipients and donors were determined by development and application of DNA sequence based typing. Acute rejection (AR) was assessed by renal pathologists and classified as acute cellular rejection (ACR) or acute antibody-mediated rejection (aAMR). Graft function was assessed by estimated glomerular filtration rate (eGFR) and serum creatinine measurements. Among the cohort of 442 recipients, 33 (7.5%) produced MICA antibodies, which correlated with ACR (P=0.03). Analysis of the MICA typed cohort revealed 17 patients (7.5%) had MICA antibodies and 13 (6%) developed MICA donor-specific antibodies (DSA). Multivariate analysis revealed MICA mismatching as a significant factor associated with the presence of MICA antibodies (P=0.009) and 14 mismatched MICA residues significantly correlated with MICA antibody production. MICA and HLA antibodies significantly associated with AR and MICA-DSA and HLA-DSA correlated with decreased graft function by univariate and multivariate analysis. To conclude, mismatching of specific MICA epitopes in renal transplantation is a mechanism leading to production of MICA antibodies and MICA-DSA that associate with AR and graft dysfunction

P-Wave Charmonium Production in B-Meson Decays

We calculate the decay rates of $B$ mesons into P-wave charmonium states using new factorization formulas that are valid to leading order in the relative velocity of the charmed quark and antiquark and to all orders in the running coupling constant of QCD. We express the production rates for all four P states in terms of two nonperturbative parameters, the derivative of the wavefunction at the origin and another parameter related to the probability for a charmed-quark-antiquark pair in a color-octet S-wave state to radiate a soft gluon and form a P-wave bound state. Using existing data on $B$ meson decays into $\chi_{c1}$ to estimate the color-octet parameter, we find that the color-octet mechanism may account for a significant fraction of the $\chi_{c1}$ production rate and that $B$ mesons should decay into $\chi_{c2}$ at a similar rate.Comment: 14 page

Bidirectional Relationships between Alcohol-Specific Parental Socialization Behaviors and Adolescent Alcohol Misuse

Background: Although numerous studies have examined parental influence on adolescent alcohol misuse, few have examined how adolescents impact parental behavior or the reciprocal nature of parent-adolescent behavior relative to alcohol misuse. Objectives: This study assessed bidirectional relationships between adolescent alcohol misuse and three alcohol-specific parenting behaviors (substance-specific monitoring, permissive communication messages about alcohol, and cautionary communication messages about alcohol). Methods: Data were from 1,645 parent-adolescent dyads drawn from a longitudinal study spanning grades 6–10. A multivariate latent curve model with structured residuals was used to test study hypotheses. Results: One marginally significant result emerged (increased alcohol misuse leads to greater substance-specific monitoring) after accounting for underlying developmental processes. Conclusions: Though practical implications are limited based on the results of the study, further directions for research regarding study design and measurement are provided to more fully examine dynamic processes between parents and adolescents relative to alcohol use

Parametric Polyhedra with at least kk Lattice Points: Their Semigroup Structure and the k-Frobenius Problem

Given an integral $d \times n$ matrix $A$, the well-studied affine semigroup \mbox{ Sg} (A)=\{ b : Ax=b, \ x \in {\mathbb Z}^n, x \geq 0\} can be stratified by the number of lattice points inside the parametric polyhedra $P_A(b)=\{x: Ax=b, x\geq0\}$. Such families of parametric polyhedra appear in many areas of combinatorics, convex geometry, algebra and number theory. The key themes of this paper are: (1) A structure theory that characterizes precisely the subset \mbox{ Sg}_{\geq k}(A) of all vectors b \in \mbox{ Sg}(A) such that $P_A(b) \cap {\mathbb Z}^n$ has at least $k$ solutions. We demonstrate that this set is finitely generated, it is a union of translated copies of a semigroup which can be computed explicitly via Hilbert bases computations. Related results can be derived for those right-hand-side vectors $b$ for which $P_A(b) \cap {\mathbb Z}^n$ has exactly $k$ solutions or fewer than $k$ solutions. (2) A computational complexity theory. We show that, when $n$, $k$ are fixed natural numbers, one can compute in polynomial time an encoding of \mbox{ Sg}_{\geq k}(A) as a multivariate generating function, using a short sum of rational functions. As a consequence, one can identify all right-hand-side vectors of bounded norm that have at least $k$ solutions. (3) Applications and computation for the $k$-Frobenius numbers. Using Generating functions we prove that for fixed $n,k$ the $k$-Frobenius number can be computed in polynomial time. This generalizes a well-known result for $k=1$ by R. Kannan. Using some adaptation of dynamic programming we show some practical computations of $k$-Frobenius numbers and their relatives

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

A New Solution to the Relative Orientation Problem using only 3 Points and the Vertical Direction

This paper presents a new method to recover the relative pose between two images, using three points and the vertical direction information. The vertical direction can be determined in two ways: 1- using direct physical measurement like IMU (inertial measurement unit), 2- using vertical vanishing point. This knowledge of the vertical direction solves 2 unknowns among the 3 parameters of the relative rotation, so that only 3 homologous points are requested to position a couple of images. Rewriting the coplanarity equations leads to a simpler solution. The remaining unknowns resolution is performed by an algebraic method using Grobner bases. The elements necessary to build a specific algebraic solver are given in this paper, allowing for a real-time implementation. The results on real and synthetic data show the efficiency of this method

Reflections on IDEAL: What we have learnt from a unique calf cohort study

The year 2020 marks a decade since the final visit was made in the ‘Infectious Diseases of East African Livestock’ (IDEAL) project. However, data generation from samples obtained during this ambitious longitudinal study still continues. As the project launches its extensive open-access database and biobank to the scientific community, we reflect on the challenges overcome, the knowledge gained, and the advantages of such a project. We discuss the legacy of the IDEAL project and how it continues to generate evidence since being adopted by the Centre for Tropical Livestock Genetics and Health (CTLGH). We also examine the impact of the IDEAL project, from the authors perspective, for each of the stakeholders (the animal, the farmer, the consumer, the policy maker, the funding body, and the researcher and their institution) involved in the project and provide recommendations for future researchers who are interested in running longitudinal field studies.The Bill & Melinda Gates Foundation, the UK Government’s Department for International Development and the International Livestock Research Institute.http://www.elsevier.com/locate/prevetmedam2021Veterinary Tropical Disease

Bayesian mortality forecasting with overdispersion

The ability to produce accurate mortality forecasts, accompanied by a set of representative uncertainty bands, is crucial in the planning of public retirement funds and various life-related businesses. In this paper, we focus on one of the drawbacks of the Poisson Lee–Carter model (Brouhns et al., 2002) that imposes mean–variance equality, restricting mortality variations across individuals. Specifically, we present two models to potentially account for overdispersion. We propose to fit these models within the Bayesian framework for various advantages, but primarily for coherency. Markov Chain Monte Carlo (MCMC) methods are implemented to carry out parameter estimation. Several comparisons are made with the Bayesian Poisson Lee–Carter model (Czado et al., 2005) to highlight the importance of accounting for overdispersion. We demonstrate that the methodology we developed prevents over-fitting and yields better calibrated prediction intervals for the purpose of mortality projections. Bridge sampling is used to approximate the marginal likelihood of each candidate model to compare the models quantitatively

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02