Pion and Vector Meson Form Factors in the Kuperstein-Sonnenschein holographic model

We study phenomenological aspects of the holographic model of chiral symmetry breaking recently introduced by Kuperstein and Sonnenschein (KS). As a first step, we calculate the spectrum of vector and axial-vector mesons in the KS model. We numerically compute various coupling constants of the mesons and pions. Our analysis indicates that vector meson dominance is realized in this model. The pion, vector meson and axial-vector meson form factors are obtained and studied in detail. We find good agreement with QCD results. In particular, the pion form factor closely matches available experimental data.Comment: v1: 27 pages, 9 figures, 4 tables; v2: minor changes, added more general discussion of vector meson dominance; v3: minor changes and additions, version accepted for publication in JHE

Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx

<p>Abstract</p> <p>Background</p> <p>Prognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections.</p> <p>Objectives</p> <p>To determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease.</p> <p>Methods</p> <p>E-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance.</p> <p>Results</p> <p>pT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (<it>p </it>= 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (<it>p </it>= 0.005) in univariate and multivariate analysis.</p> <p>Conclusion</p> <p>These data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx.</p> <p><b>Level of evidence: 2b</b></p

RG-improved single-particle inclusive cross sections and forward-backward asymmetry in ttˉt\bar t production at hadron colliders

We use techniques from soft-collinear effective theory (SCET) to derive renormalization-group improved predictions for single-particle inclusive (1PI) observables in top-quark pair production at hadron colliders. In particular, we study the top-quark transverse-momentum and rapidity distributions, the forward-backward asymmetry at the Tevatron, and the total cross section at NLO+NNLL order in resummed perturbation theory and at approximate NNLO in fixed order. We also perform a detailed analysis of power corrections to the leading terms in the threshold expansion of the partonic hard-scattering kernels. We conclude that, although the threshold expansion in 1PI kinematics is susceptible to numerically significant power corrections, its predictions for the total cross section are in good agreement with those obtained by integrating the top-pair invariant-mass distribution in pair invariant-mass kinematics, as long as a certain set of subleading terms appearing naturally within the SCET formalism is included.Comment: 55 pages, 14 figures, 6 table

Elevated tumor and serum levels of the hypoxia-associated protein osteopontin are associated with prognosis for soft tissue sarcoma patients

<p>Abstract</p> <p>Background</p> <p>Osteopontin (OPN) overexpression is correlated with a poor prognosis for tumor patients. However, only a few studies investigated the prognostic impact of expression of OPN in soft tissue sarcomas (STS) yet.</p> <p>Methods</p> <p>This study is based on tumor and serum samples from 93 adult STS patients. We investigated OPN protein levels in serum (n = 86) and tumor tissue (n = 80) by ELISA and OPN mRNA levels in tumor tissue (n = 68) by quantitative real-time PCR.</p> <p>Results</p> <p>No correlation was found between OPN levels in serum and tumor tissue. Moreover, an elevated OPN protein level in the serum was significantly associated with clinical parameters such as higher stage (p = 0.004), higher grade (p = 0.003), subtype (p = 0.002) and larger tumor size (p = 0.03). OPN protein levels in the tumor tissue were associated with higher stage (p = 0.06), higher grade (p = 0.003), subtype (p = 0.07) and an increased rate of relapse (p = 0.02). In addition, using a Cox's proportional hazards regression model, we found that an elevated OPN protein level in the serum and tumor tissue extracts is a significant negative prognostic factor for patients with STS. The relative risks of tumor-related death were 2.2 (p < 0.05) and 3.7 (p = 0.01), respectively.</p> <p>Conclusion</p> <p>Our data suggest OPN protein in serum as well as in tumor tissue extracts is an important prognostic factor for soft tissue sarcoma patients.</p

Application and Validation of PFGE for Serovar Identification of Leptospira Clinical Isolates

Serovar identification of clinical isolates of Leptospira is generally not performed on a routine basis, yet the identity of an infecting serovar is valuable from both epidemiologic and public health standpoints. Only a small number of reference laboratories worldwide have the capability to perform the cross agglutinin absorption test (CAAT), the reference method for serovar identification. Pulsed-field gel electrophoresis (PFGE) is an alternative method to CAAT that facilitates rapid identification of leptospires to the serovar level. We employed PFGE to evaluate 175 isolates obtained from humans and animals submitted to the Centers for Disease Control and Prevention (CDC) between 1993 and 2007. PFGE patterns for each isolate were generated using the NotI restriction enzyme and compared to a reference database consisting of more than 200 reference strains. Of the 175 clinical isolates evaluated, 136 (78%) were identified to the serovar level by the database, and an additional 27 isolates (15%) have been identified as probable new serovars. The remaining isolates yet to be identified are either not represented in the database or require further study to determine whether or not they also represent new serovars. PFGE proved to be a useful tool for serovar identification of clinical isolates of known serovars from different geographic regions and a variety of different hosts and for recognizing potential new serovars

Genome Sequence Analysis of Dengue Virus 1 Isolated in Key West, Florida

Dengue virus (DENV) is transmitted to humans through the bite of mosquitoes. In November 2010, a dengue outbreak was reported in Monroe County in southern Florida (FL), including greater than 20 confirmed human cases. The virus collected from the human cases was verified as DENV serotype 1 (DENV-1) and one isolate was provided for sequence analysis. RNA was extracted from the DENV-1 isolate and was used in reverse transcription polymerase chain reaction (RT-PCR) to amplify PCR fragments to sequence. Nucleic acid primers were designed to generate overlapping PCR fragments that covered the entire genome. The DENV-1 isolate found in Key West (KW), FL was sequenced for whole genome characterization. Sequence assembly, Genbank searches, and recombination analyses were performed to verify the identity of the genome sequences and to determine percent similarity to known DENV-1 sequences. We show that the KW DENV-1 strain is 99% identical to Nicaraguan and Mexican DENV-1 strains. Phylogenetic and recombination analyses suggest that the DENV-1 isolated in KW originated from Nicaragua (NI) and the KW strain may circulate in KW. Also, recombination analysis results detected recombination events in the KW strain compared to DENV-1 strains from Puerto Rico. We evaluate the relative growth of KW strain of DENV-1 compared to other dengue viruses to determine whether the underlying genetics of the strain is associated with a replicative advantage, an important consideration since local transmission of DENV may result because domestic tourism can spread DENVs

Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus

Although human immunodeficiency type 1 (HIV-1) infection induces strong antibody responses to the viral envelope glycoprotein (Env) only a few of these antibodies possess the capacity to neutralize a broad range of strains. The induction of such antibodies represents an important goal in the development of a preventive vaccine against the infection. Among the broadly neutralizing monoclonal antibodies discovered so far, three (2F5, Z13 and 4E10) target the short and hidden membrane proximal external region (MPER) of the gp41 transmembrane protein. Antibody responses to MPER are rarely observed in HIV-infected individuals or after immunization with Env immunogens. To initiate antibody responses to MPER in its membrane-embedded native conformation, we generated expression plasmids encoding the membrane-anchored ectodomain of gp41 with N-terminal deletions of various sizes. Following transfection of these plasmids, the MPER domains are displayed on the cell surface and incorporated into HIV virus like particles (VLP). Transfected cells displaying MPER mutants bound as efficiently to both 2F5 and 4E10 as cells transfected with a plasmid encoding full-length Env. Mice immunized with VLPs containing the MPER mutants produced MPER-specific antibodies, the levels of which could be increased by the trimerization of the displayed proteins as well as by a DNA prime-VLP boost immunization strategy. Although 2F5 competed for binding to MPER with antibodies in sera of some of the immunized mice, neutralizing activity could not be detected. Whether this is due to inefficient binding of the induced antibodies to MPER in the context of wild type Env or whether the overall MPER-specific antibody response induced by the MPER display mutants is too low to reveal neutralizing activity, remains to be determined

Arthroscopy vs. MRI for a detailed assessment of cartilage disease in osteoarthritis: diagnostic value of MRI in clinical practice

<p>Abstract</p> <p>Background</p> <p>In patients with osteoarthritis, a detailed assessment of degenerative cartilage disease is important to recommend adequate treatment. Using a representative sample of patients, this study investigated whether MRI is reliable for a detailed cartilage assessment in patients with osteoarthritis of the knee.</p> <p>Methods</p> <p>In a cross sectional-study as a part of a retrospective case-control study, 36 patients (mean age 53.1 years) with clinically relevant osteoarthritis received standardized MRI (sag. T1-TSE, cor. STIR-TSE, trans. fat-suppressed PD-TSE, sag. fat-suppressed PD-TSE, Siemens Magnetom Avanto syngo MR B 15) on a 1.5 Tesla unit. Within a maximum of three months later, arthroscopic grading of the articular surfaces was performed. MRI grading by two blinded observers was compared to arthroscopic findings. Diagnostic values as well as intra- and inter-observer values were assessed.</p> <p>Results</p> <p>Inter-observer agreement between readers 1 and 2 was good (kappa = 0.65) within all compartments. Intra-observer agreement comparing MRI grading to arthroscopic grading showed moderate to good values for readers 1 and 2 (kappa = 0.50 and 0.62, respectively), the poorest being within the patellofemoral joint (kappa = 0.32 and 0.52). Sensitivities were relatively low at all grades, particularly for grade 3 cartilage lesions. A tendency to underestimate cartilage disorders on MR images was not noticed.</p> <p>Conclusions</p> <p>According to our results, the use of MRI for precise grading of the cartilage in osteoarthritis is limited. Even if the practical benefit of MRI in pretreatment diagnostics is unequivocal, a diagnostic arthroscopy is of outstanding value when a grading of the cartilage is crucial for a definitive decision regarding therapeutic options in patients with osteoarthritis.</p

Migration of Th1 Lymphocytes Is Regulated by CD152 (CTLA-4)-Mediated Signaling via PI3 Kinase-Dependent Akt Activation

Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response

Ligand-Induced Tyrosine Phosphorylation of Cysteinyl Leukotriene Receptor 1 Triggers Internalization and Signaling in Intestinal Epithelial Cells

Leukotriene D(4) (LTD(4)) belongs to the bioactive lipid group known as eicosanoids and has implications in pathological processes such as inflammation and cancer. Leukotriene D(4) exerts its effects mainly through two different G-protein-coupled receptors, CysLT(1) and CysLT(2). The high affinity LTD(4) receptor CysLT(1)R exhibits tumor-promoting properties by triggering cell proliferation, survival, and migration in intestinal epithelial cells. In addition, increased expression and nuclear localization of CysLT(1)R correlates with a poorer prognosis for patients with colon cancer