Isospin Multiplet Structure in Ultra--Heavy Fermion Bound States

The coupled Bethe--Salpeter bound state equations for a $Q\bar Q$ system, where $Q=(U,D)$ is a degenerate, fourth generation, super--heavy quark doublet, are solved in several ladder approximation models. The exchanges of gluon, Higgs and Goldstone modes in the standard model are calculated in the ultra--heavy quark limit where weak $\gamma, W^\pm$ and $Z^0$ contributions are negligible. A natural $I=0$ and $I=1$ multiplet pattern is found, with large splittings occuring between the different weak iso--spin states when $M_Q$, the quark masses, are larger than values in the range $0.4 TeV<M_Q<0.8 TeV$, depending on which model is used. Consideration of ultra--heavy quark lifetime constraints and $U-D$ mass splitting constraints are reviewed to establish the plausibility of lifetime and mass degeneracy requirements assumed for this paper.Comment: 20 pages, 7 figures (hard copy available upon request), report# KU-HEP-93-2

Prompt muon contribution to the flux underwater

We present high energy spectra and zenith-angle distributions of the atmospheric muons computed for the depths of the locations of the underwater neutrino telescopes. We compare the calculations with the data obtained in the Baikal and the AMANDA muon experiments. The prompt muon contribution to the muon flux underwater due to recent perturbative QCD-based models of the charm production is expected to be observable at depths of the large underwater neutrino telescopes. This appears to be probable even at rather shallow depths (1-2 km), provided that the energy threshold for muon detection is raised above $\sim 100$ TeV.Comment: 7 pages, RevTeX, 7 eps figures, final version to be published in Phys.Rev.D; a few changes made in the text and the figures, an approximation formula for muon spectra at the sea level, the muon zenith-angle distribution table data and references adde

Atmospheric Muon Flux at Sea Level, Underground, and Underwater

The vertical sea-level muon spectrum at energies above 1 GeV and the underground/underwater muon intensities at depths up to 18 km w.e. are calculated. The results are particularly collated with a great body of the ground-level, underground, and underwater muon data. In the hadron-cascade calculations, the growth with energy of inelastic cross sections and pion, kaon, and nucleon generation in pion-nucleus collisions are taken into account. For evaluating the prompt muon contribution to the muon flux, we apply two phenomenological approaches to the charm production problem: the recombination quark-parton model and the quark-gluon string model. To solve the muon transport equation at large depths of homogeneous medium, a semi-analytical method is used. The simple fitting formulas describing our numerical results are given. Our analysis shows that, at depths up to 6-7 km w. e., essentially all underground data on the muon intensity correlate with each other and with predicted depth-intensity relation for conventional muons to within 10%. However, the high-energy sea-level data as well as the data at large depths are contradictory and cannot be quantitatively decribed by a single nuclear-cascade model.Comment: 47 pages, REVTeX, 15 EPS figures included; recent experimental data and references added, typos correcte

Lepton Fluxes from Atmospheric Charm

We reexamine the charm contribution to atmospheric lepton fluxes in the context of perturbative QCD. We include next-to-leading order corrections and discuss theoretical uncertainties due to the extrapolations of the gluon distributions at small-x. We show that the charm contribution to the atmospheric muon flux becomes dominant over the conventional contribution from pion and kaon decays at energies of about 10^5 GeV. We compare our fluxes with previous calculations.Comment: 19 pages, latex, revtex, psfi

Upper Limit on the Prompt Muon Flux Derived from the LVD Underground Experiment

We present the analysis of the muon events with all muon multiplicities collected during 21804 hours of operation of the first LVD tower. The measured depth-angular distribution of muon intensities has been used to obtain the normalization factor, A, the power index, gamma, of the primary all-nucleon spectrum and the ratio, R_c, of prompt muon flux to that of pi-mesons - the main parameters which determine the spectrum of cosmic ray muons at the sea level. The value of gamma = 2.77 +/- 0.05 (68% C.L.) and R_c < 2.0 x 10^-3 (95% C.L.) have been obtained. The upper limit to the prompt muon flux favours the models of charm production based on QGSM and the dual parton model.Comment: 10 pages, 4 figures, RevTex. To appear in Phys. Rev.

Production and Decay of Scalar Stoponium Bound States

In this paper we discuss possible signatures for the production of scalar \stst\ (stoponium) bound states \sigst\ at hadron colliders, where \st\ is the lighter scalar top eigenstate. We first study the decay of \sigst; explicit expressions are given for all potentially important decay modes. If \st\ has unsuppressed two--body decays, they will always overwhelm the annihilation decays of \sigst. Among the latter, we find that usually either the $gg$ or $hh$ final state dominates, depending on the size of the off--diagonal entry of the stop mass matrix; $h$ is the lighter neutral scalar Higgs boson of the minimal supersymmetric model. If \msig\ happens to be close to the mass of one of the neutral scalar Higgs bosons, $Q \bar{Q}$ final states dominate ($Q=b$ or $t$). \ww\ and $ZZ$ final states are subdominant. We argue that \sigst \rightarrow \gamgam decays offer the best signal for stoponium production at hadron colliders. The tevatron should be able to close the light stop window left open by LEP searches, but its mass reach is limited to \msig \leq 90 GeV. In contrast, at the LHC one should ultimately be able to probe the region \msig \leq 700 GeV, if the $hh$ partial width is not too large. We also comment on the feasibility of searching for \sigst\ production at hadron colliders in the $ZZ, \ Z \gamma$ and \fourtau\ final states, and briefly mention \sigst\ production at \gamgam\ colliders.Comment: 31 pages plus 10 figures (available from DREES@WISCPHEN); LaTeX with equation.sty; MAD/PH/808, KEK-TH-37

Genetic analysis of multifocal superficial urothelial cancers by array-based comparative genomic hybridisation

The purpose of this study was to investigate the accumulation of genetic alterations during metachronous and/or synchronous development of multifocal low-grade superficial urothelial tumours in the same patient, by using array-based comparative genomic hybridisation (array-CGH) and FGFR mutation analysis. We analysed 24 tumours (pTa-1 G1-2) from five patients. We had previously identified a clonal relationship among the tumours of each patient by microsatellite analysis. This time, unsupervised hierarchical cluster analysis revealed that the tumours from each patient were clustered together independently of the tumours from the other patients. All of the tumours from a single patient showed a set of 2–7 identical regional or whole-arm chromosomal changes. In addition, several individual alterations were also found. Cladistic diagrams revealed that the accumulation of genetic alterations could not be explained by a linear model, and the existence of a hypothetical precursor cell was assumed in four patients. In some cases, FGFR mutation seemed to occur later during multifocal tumour development. Taken together, these findings suggest that low-grade superficial urothelial tumours accumulate minor genetic alterations during multifocal development, although these tumours are genetically stable

Oxford Screening CSF and Respiratory samples ('OSCAR'):results of a pilot study to screen clinical samples from a diagnostic microbiology laboratory for viruses using Illumina next generation sequencing

ObjectivesThere is increasing interest in the use of metagenomic (next generation sequencing, NGS) approaches for diagnosis of infection. We undertook a pilot study to screen samples submitted to a diagnostic microbiology laboratory in a UK teaching hospital using Illumina HiSeq. In the short-term, this small dataset provides insights into the virome of human respiratory and cerebrospinal fluid (CSF) samples. In the longer term, assimilating metagenomic data sets of this nature can inform optimization of laboratory and bioinformatic methods, and develop foundations for the interpretation of results in a clinical context. The project underpins a larger ongoing effort to develop NGS pipelines for diagnostic use. Data descriptionOur data comprise a complete metagenomic dataset from 20 independent samples (10 CSF and 10 respiratory) submitted to the clinical microbiology laboratory for a large UK teaching hospital (Oxford University Hospitals NHS Foundation Trust). Sequences have been uploaded to the European Nucleotide Archive and are also presented as Krona plots through which the data can be interactively visualized. In the longer term, further optimization is required to better define sensitivity and specificity of this approach to clinical samples.</p

Elevated calpain activity in acute myelogenous leukemia correlates with decreased calpastatin expression

Calpains are intracellular cysteine proteases that have crucial roles in many physiological and pathological processes. Elevated calpain activity has been associated with many pathological states. Calpain inhibition can be protective or lethal depending on the context. Previous work has shown that c-myc transformation regulates calpain activity by suppressing calpastatin, the endogenous negative regulator of calpain. Here, we have investigated calpain activity in primary acute myelogenous leukemia (AML) blast cells. Calpain activity was heterogeneous and greatly elevated over a wide range in AML blast cells, with no correlation to FAB classification. Activity was particularly elevated in the CD34+CD38− enriched fraction compared with the CD34+CD38+ fraction. Treatment of the cells with the specific calpain inhibitor, PD150606, induced significant apoptosis in AML blast cells but not in normal equivalent cells. Sensitivity to calpain inhibition correlated with calpain activity and preferentially targeted CD34+CD38− cells. There was no correlation between calpain activity and p-ERK levels, suggesting the ras pathway may not be a major contributor to calpain activity in AML. A significant negative correlation existed between calpain activity and calpastatin, suggesting calpastatin is the major regulator of activity in these cells. Analysis of previously published microarray data from a variety of AML patients demonstrated a significant negative correlation between calpastatin and c-myc expression. Patients who achieved a complete remission had significantly lower calpain activity than those who had no response to treatment. Taken together, these results demonstrate elevated calpain activity in AML, anti-leukemic activity of calpain inhibition and prognostic potential of calpain activity measurement

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council