Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma

BACKGROUND. Identifying factors conferring responses to therapy in cancer is critical to select the best treatment for patients. For immune checkpoint inhibition (ICI) therapy, mounting evidence suggests that the gut microbiome can determine patient treatment outcomes. However, the extent to which gut microbial features are applicable across different patient cohorts has not been extensively explored. METHODS. We performed a meta-analysis of 4 published shotgun metagenomic studies (Ntot = 130 patients) investigating differential microbiome composition and imputed metabolic function between responders and nonresponders to ICI. RESULTS. Our analysis identified both known microbial features enriched in responders, such as Faecalibacterium as the prevailing taxa, as well as additional features, including overrepresentation of Barnesiella intestinihominis and the components of vitamin B metabolism. A classifier designed to predict responders based on these features identified responders in an independent cohort of 27 patients with the area under the receiver operating characteristic curve of 0.625 (95% CI: 0.348–0.899) and was predictive of prognosis (HR = 0.35, P = 0.081). CONCLUSION. These results suggest the existence of a fecal microbiome signature inherent across responders that may be exploited for diagnostic or therapeutic purposes

Diffractive D_s production in charged current DIS

We present a perturbative QCD calculation of diffractive $D_s$ production in charged current deep inelastic scattering. In the two-gluon exchange model, we analyze the diffractive process \nu N \to \mu^- N \Ds, which may provide useful information for the gluon structure of nucleons and the diffraction mechanism in QCD. The cross section of diffractive $D_s$ production with \xBj=0.005-0.05 and $E_\nu=50$ Gev is found to be $2.7\times10^{-5}$ pb. In spite of this small cross section, the high luminosity available at the $\nu$-Factory in the future would lead to a sizable number of diffraction events.Comment: 6 pages, 5 eps figures, final version to appear in PL

Skewed Parton Distributions and F_2^D at beta -> 1

We show that the diffractive structure function is perturbatively calculable in the domain where the diffractive mass is small but still outside the resonance region. In this domain, which can be characterized by Lambda^2/Q^2 << 1-beta << (Lambda^2/Q^2)^1/2, the structure function represents a new observable, which is highly sensitive to the small-x skewed gluon distribution. Our leading order calculation and the estimate of next-to-leading order corrections are consistent with available data and demonstrate the potential of more precise data to put further constraints on skewing effects.Comment: 11 pages, LaTeX, including five PostScript figure

Quark initiated coherent diffractive production of muon pair and W boson at hadron colliders

The large transverse momentum muon pair and W boson productions in the quark initiated coherent diffractive processes at hadron colliders are discussed under the framework of the two-gluon exchange parametrization of the Pomeron model. In this approach, the production cross sections are related to the small-x off-diagonal gluon distribution and the large-x quark distribution in the proton (antiproton). By approximating the off-diagonal gluon distribution by the usual gluon distribution function, we estimate the production rates of these processes at the Fermilab Tevatron.Comment: 11pages, 6 PS figures, to appear in PR

Reduced EGFR signaling enhances cartilage destruction in a mouse osteoarthritis model

Osteoarthritis (OA) is a degenerative joint disease and a major cause of pain and disability in older adults. We have previously identified epidermal growth factor receptor (EGFR) signaling as an important regulator of cartilage matrix degradation during epiphyseal cartilage development. To study its function in OA progression, we performed surgical destabilization of the medial meniscus (DMM) to induce OA in two mouse models with reduced EGFR activity, one with genetic modification (Egfr Wa5/+ mice) and the other one with pharmacological inhibition (gefitinib treatment). Histological analyses and scoring at 3 months post-surgery revealed increased cartilage destruction and accelerated OA progression in both mouse models. TUNEL staining demonstrated that EGFR signaling protects chondrocytes from OA-induced apoptosis, which was further confirmed in primary chondrocyte culture. Immunohistochemistry showed increased aggrecan degradation in these mouse models, which coincides with elevated amounts of ADAMTS5 and matrix metalloproteinase 13 (MMP13), the principle proteinases responsible for aggrecan degradation, in the articular cartilage after DMM surgery. Furthermore, hypoxia-inducible factor 2α (HIF2α), a critical catabolic transcription factor stimulating MMP13 expression during OA, was also upregulated in mice with reduced EGFR signaling. Taken together, our findings demonstrate a primarily protective role of EGFR during OA progression by regulating chondrocyte survival and cartilage degradation

The total virtual photoabsorption cross section, deeply virtual Compton scattering and vector-meson production

Based on the two-gluon-exchange dynamical mechanism for deeply inelastic scattering at low x ~= Q^2/W^2 <<1, we stress the intimate connection between the total virtual photoabsorption cross section, deeply virtual Compton scattering and vector-meson electroproduction. A simple expression for the cross section for deeply virtual Compton scattering is derived. Parameter-free predictions are obtained for deeply-virtual Compton forward scattering and vector-meson forward production, once the parameters in the total virtual photoabsorption cross section are determined in a fit to the experimental data on deeply inelastic scattering. Our predictions are compared with the experimental data from HERA.Comment: 31 pages Latex, 10 figures and 1 tabl

A Study of Off-Forward Parton Distributions

An extensive theoretical analysis of off-forward parton distributions (OFPDs) is presented. The OFPDs and the form factors of the quark energy-momentum tensor are estimated at a low-energy scale using a bag model. Relations among the second moments of OFPDs, the form factors, and the fraction of the nucleon spin carried by quarks are discussed.Comment: 29 pages revtex, 12 postscript figures, minor corrections, references update

Diffractive light quark jet production at hadron colliders in the two-gluon exchange model

Massless quark and antiquark jet production at large transverse momentum in the coherent diffractive processes at hadron colliders is calculated in the two-gluon exchange parametrization of the Pomeron model. We use the helicity amplitude method to calculate the cross section formula. We find that for the light quark jet production the diffractive process is related to the differential off-diagonal gluon distribution function in the proton. We estimate the production rate for this process at the Fermilab Tevatron by approximating the off-diagonal gluon distribution function by the usual diagonal gluon distribution in the proton. And we find that the cross sections for the diffractive light quark jet production and the charm quark jet production are in the same order of magnitude. We also use the helicity amplitude method to calculate the diffractive charm jet production at hadron colliders, by which we reproduce the leading logarithmic approximation result of this process we previously calculated.Comment: 15 pages, 4 PS figures, Revte

Investigation of Early Protein Changes in the Urinary Bladder Following Partial Bladder Outlet Obstruction by Proteomic Approach

We investigated the pathophysiological mechanism by proteomic approach as a possible tool to detect the marker proteins to develop lower urinary tract symptoms following bladder outlet obstruction (BOO). Rats were randomized into 3 groups; control, sham operation and BOO groups. BOO group was divided into 1, 3, and 5 day-group. Conventional proteomics was performed with high resolution 2-D gel electrophoresis followed by computational image analysis and protein identification using mass spectrometry using rat urinary bladders. A comparison of bladder of BOO group with control bladder showed that three proteins of optineurin, thioredoxin and preprohaptoglobin were over-expressed in the bladder of BOO group. In addition, four proteins, such as peroxiredoxin 2, transgelin, hippocampal cholinergic neurostimulating peptide (HCNP) and beta-galactoside-binding lectin, were under-expressed in the bladder of BOO group. These data supported that down-regulation of HCNP might make detrusor muscle be supersensitive to acetylcholine, up-regulation of optineurin means the protection of nerve injury, and down-regulation of transgelin means the decreased contractility of detrusor muscle. Beside these proteins, other proteins are related to oxidative stress or have a nonspecific function in this study. However more information is needed in human bladder tissue for clinical usage

QCD dipole model and k_T factorization

It is shown that the colour dipole approach to hard scattering at high energy is fully compatible with k_T factorization at the leading logarithm approximation (in -log x_Bj). The relations between the dipole amplitudes and unintegrated diagonal and non-diagonal gluon distributions are given. It is also shown that including the exact gluon kinematics in the k_T factorization formula destroys the conservation of transverse position vectors and thus is incompatible with the dipole model for both elastic and diffractive amplitudes.Comment: 16 pages, 2 .eps figure