Beta defensin-2 is reduced in central but not in distal airways of smoker COPD patients

Background: Altered pulmonary defenses in chronic obstructive pulmonary disease (COPD) may promote distal airways bacterial colonization. The expression/activation of Toll Like receptors (TLR) and beta 2 defensin (HBD2) release by epithelial cells crucially affect pulmonary defence mechanisms. Methods: The epithelial expression of TLR4 and of HBD2 was assessed in surgical specimens from current smokers COPD (s-COPD; n = 17), ex-smokers COPD (ex-s-COPD; n = 8), smokers without COPD (S; n = 12), and from non-smoker non-COPD subjects (C; n = 13). Results: In distal airways, s-COPD highly expressed TLR4 and HBD2. In central airways, S and s-COPD showed increased TLR4 expression. Lower HBD2 expression was observed in central airways of s-COPD when compared to S and to ex-s-COPD. s-COPD had a reduced HBD2 gene expression as demonstrated by real-time PCR on micro-dissected bronchial epithelial cells. Furthermore, HBD2 expression positively correlated with FEV1/FVC ratio and inversely correlated with the cigarette smoke exposure. In a bronchial epithelial cell line (16 HBE) IL-1β significantly induced the HBD2 mRNA expression and cigarette smoke extracts significantly counteracted this IL-1 mediated effect reducing both the activation of NFkB pathway and the interaction between NFkB and HBD2 promoter. Conclusions: This study provides new insights on the possible mechanisms involved in the alteration of innate immunity mechanisms in COPD. © 2012 Pace et al

Universal continuous-variable quantum computation: Requirement of optical nonlinearity for photon counting

Although universal continuous-variable quantum computation cannot be achieved via linear optics (including squeezing), homodyne detection and feed-forward, inclusion of ideal photon counting measurements overcomes this obstacle. These measurements are sometimes described by arrays of beam splitters to distribute the photons across several modes. We show that such a scheme cannot be used to implement ideal photon counting and that such measurements necessarily involve nonlinear evolution. However, this requirement of nonlinearity can be moved "off-line," thereby permitting universal continuous-variable quantum computation with linear optics.Comment: 6 pages, no figures, replaced with published versio

Therapeutic vaccination following early antiretroviral therapy elicits highly functional T cell responses against conserved HIV-1 regions

'Kick and kill' cure strategies aim to induce HIV protein expression in latently infected cells (kick), and thus trigger their elimination by cytolytic T cells (kill). In the Research in Viral Eradication of HIV Reservoirs trial (NCT02336074), people diagnosed with primary HIV infection received immediate antiretroviral therapy (ART) and were randomised 24 weeks later to either a latency-reversing agent, vorinostat, together with ChAdV63.HIVconsv and MVA.HIVconsv vaccines, or ART alone. This intervention conferred no reduction in HIV-1 reservoir size over ART alone, despite boosting virus-specific CD4+ and CD8+ T cells. The effects of the intervention were examined at the cellular level in the two trial arms using unbiased computational analysis of polyfunctional scores. This showed that the frequency and polyfunctionality of virus-specific CD4+ and CD8+ T cell populations were significantly increased over 12 weeks post-vaccination, compared to the ART-only arm. HIV-specific IL-2-secreting CD8+ T cells also expanded significantly in the intervention arm and were correlated with antiviral activity against heterologous HIV in vitro. Therapeutic vaccination during ART commenced in primary infection can induce functional T cell responses that are phenotypically similar to those of HIV controllers. Analytical therapy interruption may help determine their ability to control HIV in vivo

FAD binding, cobinamide binding and active site communication in the corrin reductase (CobR)

Adenosylcobalamin, the coenzyme form of vitamin B12, is one Nature's most complex coenzyme whose de novo biogenesis proceeds along either an anaerobic or aerobic metabolic pathway. The aerobic synthesis involves reduction of the centrally chelated cobalt metal ion of the corrin ring from Co(II) to Co(I) before adenosylation can take place. A corrin reductase (CobR) enzyme has been identified as the likely agent to catalyse this reduction of the metal ion. Herein, we reveal how Brucella melitensis CobR binds its coenzyme FAD (flavin dinucleotide) and we also show that the enzyme can bind a corrin substrate consistent with its role in reduction of the cobalt of the corrin ring. Stopped-flow kinetics and EPR reveal a mechanistic asymmetry in CobR dimer that provides a potential link between the two electron reduction by NADH to the single electron reduction of Co(II) to Co(I)

Delta excitation in K^+-nucleus collisions

We present calculations for \Delta excitation in the (K^+,K^+) reaction in nuclei. The background from quasielastic K^+ scattering in the \Delta region is also evaluated and shown to be quite small in some kinematical regions, so as to allow for a clean identification of the \Delta excitation strength. Nuclear effects tied to the \Delta renormalization in the nucleus are considered and the reaction is shown to provide new elements to enrich our knowledge of the \Delta properties in a nuclear medium.Comment: 11 pages, 6 figures, LaTe

Development of a novel classification system for anatomical variants of the puboprostatic ligaments with expert validation

Introduction: We propose a novel classification system with a validation study to help clinicians identify and typify commonly seen variants of the puboprostatic ligaments (PPL). Methods: A preliminary dissection of 6 male cadavers and a prospective dataset of over 300 robotic-assisted laparoscopic radical prostatectomies (RARP) recorded on video were used to identify 4 distinct ligament types. Then the prospectively collected database of surgical videos was used to isolate images of the PPL from RARP. Over 300 surgical videos were reviewed and classified with 1 to 5 pictures saved for reference of the type of PPL. To validate the new classification system, we selected 5 independent, blinded expert robotic surgeons to classify 100 ligaments based on morphology into a 4-type system: parallel, V-shaped, inverted V-shape, and fused. One week later, a subset of 25 photographs was sent to the same experts and classified. Statistical analyses were performed to determine both the intra-rater and inter-rater reliability of the proposed system. Results: Inverted V-shaped ligaments were noted most frequently (29.97%), parallel and V-shaped ligaments were found at 19.19% and 11.11%, respectively and fused ligaments were noted less frequently (6.06%). There was good intra-rater agreement (ê = 0.66) and inter-rater agreement (ê = 0.67) for the classification system. Conclusions: This classification system provided standardized descriptions of ligament variations that could be adopted universally to help clinicians categorize the variants. The system, validated by several blinded expert surgeons, demonstrated that surgeons were able to learn and correctly classify the variants. The system may be useful in helping to predict peri- and postoperative outcomes; however, this will require further study

Treewilder

Treewilder is an exhibition of site responsive interventions, sculptures and video work set in Barnwell Country park aiming to encourage visitors to explore the woodland space throughout autumn and winter aspart of the two year Xylophobia season

Measuring the value of air quality: application of the spatial hedonic model

This study applies a hedonic model to assess the economic benefits of air quality improvement following the 1990 Clean Air Act Amendment at the county level in the lower 48 United States. An instrumental variable approach that combines geographically weighted regression and spatial autoregression methods (GWR-SEM) is adopted to simultaneously account for spatial heterogeneity and spatial autocorrelation. SEM mitigates spatial dependency while GWR addresses spatial heterogeneity by allowing response coefficients to vary across observations. Positive amenity values of improved air quality are found in four major clusters: (1) in East Kentucky and most of Georgia around the Southern Appalachian area; (2) in a few counties in Illinois; (3) on the border of Oklahoma and Kansas, on the border of Kansas and Nebraska, and in east Texas; and (4) in a few counties in Montana. Clusters of significant positive amenity values may exist because of a combination of intense air pollution and consumer awareness of diminishing air quality

Distorted wave impulse approximation analysis for spin observables in nucleon quasi-elastic scattering and enhancement of the spin-longitudinal response

We present a formalism of distorted wave impulse approximation (DWIA) for analyzing spin observables in nucleon inelastic and charge exchange reactions leading to the continuum. It utilizes response functions calculated by the continuum random phase approximation (RPA), which include the effective mass, the spreading widths and the \Delta degrees of freedom. The Fermi motion is treated by the optimal factorization, and the non-locality of the nucleon-nucleon t-matrix by an averaged reaction plane approximation. By using the formalism we calculated the spin-longitudinal and the spin-transverse cross sections, ID_q and ID_p, of 12C, 40Ca (\vec{p},\vec{n}) at 494 and 346 MeV. The calculation reasonably reproduced the observed ID_q, which is consistent with the predicted enhancement of the spin-longitudinal response function R_L. However, the observed ID_p is much larger than the calculated one, which was consistent with neither the predicted quenching nor the spin-transverse response function R_T obtained by the (e,e') scattering. The Landau-Migdal parameter g'_N\Delta for the N\Delta transition interaction and the effective mass at the nuclear center m^*(r=0) are treated as adjustable parameters. The present analysis indicates that the smaller g'_{N\Delta}(\approx 0.3) and m^*(0) \approx 0.7 m are preferable. We also investigate the validity of the plane wave impulse approximation (PWIA) with the effective nucleon number approximation for the absorption, by means of which R_L and R_T have conventionally been extracted.Comment: RevTex 3, 29 pages, 2 tables, 8 figure

Incidental Thyroid Carcinoma by FDG-PET/CT: A Study of Clinicopathological Characteristics

BACKGROUND: The rising incidence of incidental thyroid carcinoma (ITC) detected during fluoro-2-deoxy-D: -glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scanning poses a challenge to clinicians. The present study aims to critically evaluate the clinicopathological characteristics of ITC detected by FDG-PET/CT. METHODS: Among the 557 patients managed at our institution, 40 (7.2%) patients were identified as having ITC. Of these, 22 patients had their tumor detected by FDG-PET/CT (PET group) and 11 by ultrasonography (USG group). Additional bedside ultrasonography +/- fine-needle aspiration (FNA) was done in all patients at their clinic visit. The clinicopathological characteristics were compared between the PET and USG groups. RESULTS: The PET group had significantly more patients with history of nonthyroidal malignancy (P < 0.001). Papillary carcinoma was the most common histological type in both groups. Despite having similar histological and prognostic features including tumor size, tumor multifocality, capsular invasion, extrathyroidal extension, and lymph node metastases, tumor bilaterality (or presence of contralateral tumor focus) was significantly more frequent in the PET than the USG group (P = 0.04). The tumors were also more advanced by the tumor-node-metastasis (TNM) staging system in the PET group (P = 0.021). None of the contralateral tumor foci were evident preoperatively. One patient in the USG group developed metastatic thyroid carcinoma in neck lymph nodes 28 months after thyroid resection. CONCLUSION: ITC by FDG-PET/CT had higher incidence of tumor bilaterality than those detected by ultrasonography. Total thyroidectomy should be considered for ITC detected by FDG-PET/CT even for tumor size <10 mm.published_or_final_versionSpringer Open Choice, 31 May 201