The running coupling of 8 flavors and 3 colors

We compute the renormalized running coupling of SU(3) gauge theory coupled to N_f = 8 flavors of massless fundamental Dirac fermions. The recently proposed finite volume gradient flow scheme is used. The calculations are performed at several lattice spacings allowing for a controlled continuum extrapolation. The results for the discrete beta-function show that it is monotonic without any sign of a fixed point in the range of couplings we cover. As a cross check the continuum results are compared with the well-known perturbative continuum beta-function for small values of the renormalized coupling and perfect agreement is found.Comment: 15 pages, 17 figures, published versio

p27 Deficiency Cooperates with Bcl-2 but Not Bax to Promote T-Cell Lymphoma

The effect of Bcl-2 on oncogenesis is complex and expression may either delay or accelerate oncogenesis. The pro-oncogenic activity is attributed to its well characterized anti-apoptotic function while the anti-oncogenic function has been attributed to its inhibition of cellular proliferation. Recent studies demonstrate that p27 may mediate the effects of Bcl-2 on cellular proliferation. We hypothesized that p27 may suppress tumor formation by Bcl-2 family members. To test this hypothesis, cell cycle inhibition and lymphoma development were examined in Lck-Bcl-2 and Lck-Bax38/1 transgenic mice deficient in p27. Strikingly, p27 deficiency synergistically cooperates with Bcl-2 to increase T cell hyperplasia and development of spontaneous T cell lymphomas. Within 1 year, >90% of these mice had developed thymic T cell lymphomas. This high penetrance contrasts with a one year incidence of <5% of thymic lymphoma in Lck-Bcl-2 or p27 −/− mice alone. In contrast, p27 deficiency had no effect on tumor formation in Lck-Bax38/1 transgenic mice, another model of T cell lymphoma. Histologically the lymphomas in p27 −/− Lck-Bcl-2 mice are lymphoblastic and frequently involve multiple organs suggesting an aggressive phenotype. Interestingly, in mature splenic T cells, Bcl-2 largely retains its anti-proliferative function even in the absence of p27. T cells from p27 −/− Lck-Bcl-2 mice show delayed kinetics of CDK2 Thr-160 phosphorylation. This delay is associated with a delay in the up regulation of both Cyclin D2 and D3. These data demonstrate a complex relationship between the Bcl-2 family, cellular proliferation, and oncogenesis and demonstrate that p27 up-regulation is not singularly important in the proliferative delay observed in T cells expressing Bcl-2 family members. Nonetheless, the results indicate that p27 is a critical tumor suppressor in the context of Bcl-2 expression

Transfusion-transmitted infections

Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens

Current clinical applications of spectral tissue Doppler echocardiography (E/E' ratio) as a noninvasive surrogate for left ventricular diastolic pressures in the diagnosis of heart failure with preserved left ventricular systolic function

Congestive heart failure with preserved left ventricular systolic function has emerged as a growing epidemic medical syndrome in developed countries, which is characterized by high morbidity and mortality rates. Rapid and accurate diagnosis of this condition is essential for optimizing the therapeutic management. The diagnosis of congestive heart failure is challenging in patients presenting without obvious left ventricular systolic dysfunction and additional diagnostic information is most commonly required in this setting. Comprehensive Doppler echocardiography is the single most useful diagnostic test recommended by the ESC and ACC/AHA guidelines for assessing left ventricular ejection fraction and cardiac abnormalities in patients with suspected congestive heart failure, and non-invasively determined basal or exercise-induced pulmonary capillary hypertension is likely to become a hallmark of congestive heart failure in symptomatic patients with preserved left ventricular systolic function. The present review will focus on the current clinical applications of spectral tissue Doppler echocardiography used as a reliable noninvasive surrogate for left ventricular diastolic pressures at rest as well as during exercise in the diagnosis of heart failure with preserved left ventricular systolic function. Chronic congestive heart failure, a disease of exercise, and acute heart failure syndromes are characterized by specific pathophysiologic and diagnostic issues, and these two clinical presentations will be discussed separately

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis

Precision Measurement of the Helium Flux in Primary Cosmic Rays of Rigidities 1.9 GV to 3 TV with the Alpha Magnetic Spectrometer on the International Space Station

Knowledge of the precise rigidity dependence of the helium flux is important in understanding the origin, acceleration, and propagation of cosmic rays. A precise measurement of the helium flux in primary cosmic rays with rigidity (momentum/charge) from 1.9 GV to 3 TV based on 50 million events is presented and compared to the proton flux. The detailed variation with rigidity of the helium flux spectral index is presented for the first time. The spectral index progressively hardens at rigidities larger than 100 GV. The rigidity dependence of the helium flux spectral index is similar to that of the proton spectral index though the magnitudes are different. Remarkably, the spectral index of the proton to helium flux ratio increases with rigidity up to 45 GV and then becomes constant; the flux ratio above 45 GV is well described by a single power law.</p

A modified QuickDASH-9 provides a valid outcome instrument for upper limb function

Background. The 30-item Disabilities Arm Shoulder and Hand (DASH) questionnaire was introduced to facilitate assessment of upper limb functional limitations. To improve practicality and eliminate item redundancy a modified instrument was needed. The 11-item QuickDASH was developed to fulfil these requirements and translated into several languages. However, prospective investigations of psychometric and practical characteristics are limited. No published study investigated readability or used concurrent validation with a standardized upper limb criterion measure. The validity of the QuickDASH has been questioned as the results for factor structure are conflicting, and the English-language version has not yet had factor structure reported. A shortened 9-item version, the QuickDASH-9, that addresses these issues is proposed. Methods. This two-stage observational study assessed the psychometric and practical characteristics of the QuickDASH and the extracted QuickDASH-9. The Upper Limb Functional Index (ULFI) was the criterion standard in both stages. Stage 1, calibration, reanalyzed extracted QuickDASH and QuickDASH-9 responses from a previous prospective study, by the authors, of the 30-item DASH (n = 137). Stage 2, prospective validation, investigated the QuickDASH through repeated measures in consecutive upper limb musculoskeletal participants' consulting for physical therapy in Australia (n = 67). The QuickDASH and extracted QuickDASH-9 data from both stages was analyzed and compared for psychometric properties, practical characteristics and factor structure. Results. The proposed QuickDASH-9 had a unidimensional structure, high reliability (ICC 2:1, r = 0.92), internal consistency (alpha = 0.93) and responsiveness (ES = 1.05). It correlated highly with both the DASH (r = 0.97), QuickDASH (r = 0.99) and ULFI criterion (r = 0.85). QuickDASH-9 missing responses reduced to 3.5% from 26% in the QuickDASH. Completion and scoring time was 134 ± 56 seconds and required a computational aid. The QuickDASH demonstrated a bidimensional structure making it invalid. The QuickDASH-9 summary performance was measured on the 'Measurement of Outcome Measures' at 88% and on the 'Bot' clinimetric scale at 75%. Conclusions. The proposed QuickDASH-9 had a unidimensional structure and similar psychometric precision to the full-length DASH with improved practicality and completion time. The QuickDASH was invalid as its bidimensional structure made a single summated score inappropriate. The QuickDASH-9 offers a future direction for ongoing use of the QuickDASH concept. © 2009 Gabel et al; licensee BioMed Central Ltd