Vector Meson Mixing and Charge Symmetry Violation

We discuss the consistency of the traditional vector meson dominance (VMD) model for photons coupling to matter, with the vanishing of vector meson-meson and meson-photon mixing self-energies at q^2=0. This vanishing of vector mixing has been demonstrated in the context of rho-omega mixing for a large class of effective theories. As a further constraint on such models, we here apply them to a study of photon-meson mixing and VMD. As an example we compare the predicted momentum dependence of one such model with a momentum-dependent version of VMD discussed by Sakurai in the 1960's. We find that it produces a result which is consistent with the traditional VMD phenomenology. We conclude that comparison with VMD phenomenology can provide a useful constraint on such models.Comment: 7 pages, uses epsfig.sty. Publication details added to title pag

Enhancing metabolomic data analysis with Progressive Consensus Alignment of NMR Spectra (PCANS)

<p>Abstract</p> <p>Background</p> <p>Nuclear magnetic resonance spectroscopy is one of the primary tools in metabolomics analyses, where it is used to track and quantify changes in metabolite concentrations or profiles in response to perturbation through disease, toxicants or drugs. The spectra generated through such analyses are typically confounded by noise of various types, obscuring the signals and hindering downstream statistical analysis. Such issues are becoming increasingly significant as greater numbers of large-scale systems or longitudinal studies are being performed, in which many spectra from different conditions need to be compared simultaneously.</p> <p>Results</p> <p>We describe a novel approach, termed Progressive Consensus Alignment of Nmr Spectra (PCANS), for the alignment of NMR spectra. Through the progressive integration of many pairwise comparisons, this approach generates a single consensus spectrum as an output that is then used to adjust the chemical shift positions of the peaks from the original input spectra to their final aligned positions. We characterize the performance of PCANS by aligning simulated NMR spectra, which have been provided with user-defined amounts of chemical shift variation as well as inter-group differences as would be observed in control-treatment applications. Moreover, we demonstrate how our method provides better performance than either template-based alignment or binning. Finally, we further evaluate this approach in the alignment of real mouse urine spectra and demonstrate its ability to improve downstream PCA and PLS analyses.</p> <p>Conclusions</p> <p>By avoiding the use of a template or reference spectrum, PCANS allows for the creation of a consensus spectrum that enhances the signals within the spectra while maintaining sample-specific features. This approach is of greatest benefit when complex samples are being analyzed and where it is expected that there will be spectral features unique and/or strongly different between subgroups within the samples. Furthermore, this approach can be potentially applied to the alignment of any data having spectra-like properties.</p

Metabolomic analysis of bronchoalveolar lavage fluid from cystic fibrosis patients

Metabolite profiles of bronchoalveolar lavage fluid (BALF) from pediatric patients with cystic fibrosis (CF) were correlated to the degree of airway inflammation using nuclear magnetic resonance spectroscopy-based metabolomics. BALF was collected from 11 children with CF during clinically indicated bronchoscopy. The spectra from BALF with high levels of neutrophilic airway inflammation displayed signals from numerous metabolites, whereas the spectra from subjects with low levels of inflammation were very sparse. The metabolites identified in samples taken from subjects with high inflammation include known markers of inflammation such as amino acids and lactate, as well as many novel signals. Statistical analysis highlighted the most important metabolites that distinguished the high- from the low-inflammation groups. This first demonstration of metabolomics of human BALF shows that clear distinctions in the metabolic profiles can be observed between subjects experiencing high versus low inflammation and is a first step toward the goal of discovering novel biomarkers of airway inflammation

A generalized framework unifying image registration and respiratory motion models and incorporating image reconstruction, for partial image data or full images

Surrogate-driven respiratory motion models relate the motion of the internal anatomy to easily acquired respiratory surrogate signals, such as the motion of the skin surface. They are usually built by first using image registration to determine the motion from a number of dynamic images, and then fitting a correspondence model relating the motion to the surrogate signals. In this paper we present a generalized framework that unifies the image registration and correspondence model fitting into a single optimization. This allows the use of 'partial' imaging data, such as individual slices, projections, or k-space data, where it would not be possible to determine the motion from an individual frame of data. Motion compensated image reconstruction can also be incorporated using an iterative approach, so that both the motion and a motion-free image can be estimated from the partial image data. The framework has been applied to real 4DCT, Cine CT, multi-slice CT, and multi-slice MR data, as well as simulated datasets from a computer phantom. This includes the use of a super-resolution reconstruction method for the multi-slice MR data. Good results were obtained for all datasets, including quantitative results for the 4DCT and phantom datasets where the ground truth motion was known or could be estimated

Epistasis between MicroRNAs 155 and 146a during T Cell-Mediated Antitumor Immunity

An increased understanding of antitumor immunity is necessary for improving cell-based immunotherapies against human cancers. Here, we investigated the roles of two immune system-expressed microRNAs (miRNAs), miR-155 and miR-146a, in the regulation of antitumor immune responses. Our results indicate that miR-155 promotes and miR-146a inhibits interferon γ (IFNγ) responses by T cells and reduces solid tumor growth in vivo. Using a double-knockout (DKO) mouse strain deficient in both miR-155 and miR-146a, we have also identified an epistatic relationship between these two miRNAs. DKO mice had defective T cell responses and tumor growth phenotypes similar to miR-155^(−/−) mice. Further analysis of the T cell compartment revealed that miR-155 modulates IFNγ expression through a mechanism involving repression of Ship1. Our work reveals critical roles for miRNAs in the reciprocal regulation of CD4^+ and CD8^+ T cell-mediated antitumor immunity and demonstrates the dominant nature of miR-155 during its promotion of immune responses

Effects of a prolonged standardized diet on normalizing the human metabolome

Background: Although the effects of acute dietary interventions on the human metabolome have been studied, the extent to which the metabolome can be normalized by extended dietary standardization has not yet been examined

Anemia is an independent risk for mortality after acute myocardial infarction in patients with and without diabetes

INTRODUCTION: Anemia and diabetes are risk factors for short-term mortality following an acute myocardial infarction(AMI). Anemia is more prevalent in patients with diabetes. We performed a retrospective study to assess the impact of the combination of diabetes and anemia on post-myocardial infarction outcomes. METHODS: Data relating to all consecutive patients hospitalized with AMI was obtained from a population-based disease-specific registry. Patients were divided into 4 groups: diabetes and anemia (group A, n = 716), diabetes and no anemia (group B, n = 1894), no diabetes and anemia (group C, n = 869), and no diabetes and no anemia (group D, n = 3987). Mortality at 30 days and 31 days to 36 months were the main outcome measures. RESULTS: 30-day mortality was 32.3% in group A, 16.1% in group B, 21.5% in group C, 6.6% in group D (all p < 0.001). 31-day to 36-month mortality was 47.6% in group A, 20.8% in group B, 34.3% in group C, and 10.4% in group D (all p < 0.001). Diabetes and anemia remained independent risk factors for mortality with odds ratios of 1.61 (1.41–1.85, p < 0.001) and 1.59 (1.38–1.85, p < 0.001) respectively at 36 months. Cardiovascular death from 31-days to 36-months was 43.7% of deaths in group A, 54.1% in group B, 47.0% in group C, 50.8% group D (A vs B, p < 0.05). INTERPRETATION: Patients with both diabetes and anemia have a significantly higher mortality than those with either diabetes or anemia alone. Cardiovascular death remained the most likely cause of mortality in all groups

A portable centrifugal analyser for liver function screening

Mortality rates of up to 50% have been reported after liver failure due to drug-induced hepatotoxicity and certain viral infections(Gao et al. 2008). These adverse conditions frequently affect HIV and tuberculosis patients on regular medication in resource-poor settings. Here, we report full integration of sample preparation with read-out of a 5-parameter liver assay panel (LAP) on a portable, easy-to-use, fast and cost- efficient centrifugal microfluidic analysis system (CMAS). Our unique, dissolvable-film based centrifugo- pneumatic valving was employed to provide sample-to-answer fashion automation for plasma extraction (from finger-prick of blood), metering and aliquoting into separate reaction chambers for parallelized colorimetric quantification during rotation. The entire LAP completes in less than 20 minutes while using only a tenth the reagent volumes when compared with standard hospital laboratory tests. Accuracy of in-situ liver function screening was validated by 96 separate tests with an average coefficient of variance (CV) of 7.9% compared to benchtop and hospital lab tests. Unpaired two sample statistical t-tests were used to compare the means of CMAS and benchtop reader, on one hand; and CMAS and hospital tests on the other. The results demonstrate no statistical difference between the respective means with 94% and 92% certainty of equivalence, respectively. The portable platform thus saves significant time, labour and costs compared to established technologies, and therefore comply with typical restrictions on lab infrastructure, maintenance, operator skill and costs prevalent in many field clinics of the developing world. It has been successfully deployed in a centralised lab in Nigeria

Direct CP Violation, Branching Ratios and Form Factors B→πB \to \pi, B→KB \to K in BB Decays

The $B \to \pi$ and $B \to K$ transitions involved in hadronic B decays are investigated in a phenomenological way through the framework of QCD factorization. By comparing our results with experimental branching ratios from the BELLE, BABAR and CLEO Collaborations for all the B decays including either a pion or a kaon, we propose boundaries for the transition form factors $B \to \pi$ and $B \to K$ depending on the CKM matrix element parameters $\rho$ and $\eta$. From this analysis, the form factors required to reproduce the experimental data for branching ratios are $F^{B \to \pi}= 0.31 \pm 0.12$ and $F^{B \to K}= 0.37\pm 0.13$. We calculate the direct CP violating asymmetry parameter, $a_{CP}$, for $B \to \pi^{+} \pi^{-} \pi$ and $B \to \pi^{+} \pi^{-} K$ decays, in the case where $\rho-\omega$ mixing effects are taken into account. Based on these results, we find that the direct CP asymmetry for $B^{-} \to \pi^{+} \pi^{-} \pi^{-}$, $\bar{B}^{0} \to \pi^{+} \pi^{-} \pi^{0}$, $B^{-} \to \pi^{+} \pi^{-} K^{-}$, and $\bar{B}^{0} \to \pi^{+} \pi^{-} \bar{K}^{0}$, reaches its maximum when the invariant mass $\pi^{+} \pi^{-}$ is in the vicinity of the $\omega$ meson mass. The inclusion of $\rho-\omega$ mixing provides an opportunity to erase, without ambiguity, the phase uncertainty mod$(\pi)$ in the determination of the CKM angles $\alpha$ in case of $b\to u$ and $\gamma$ in case of $b \to s$.Comment: 74 pages, 15 figures, 8 tables. A few misprints corrected, two references adde

Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection

Loss of the conserved “cryptic” plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL) in C. caviae. However, 2-deoxyglucose (2DG) treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains