Major Histocompatibility Complex Class I- And II-Deficient Knock-Out Mice Are Resistant to Primary but Susceptible to Secondary Eimeria Papillata Infections

Two distinct mechanisms seem to function in reducing oocyst output during Eimeria papillata infections in mice. For naive mice, immunity was afforded by a T-cell-independent gamma-interferon (IFN-γ) response mediated by natural killer (NK) cells. On reinfection, resistance was associated with T-cells and, to a lesser extent, perforin. To determine if antigen presentation with major histocompatibility complex (MHC) molecules was required to control oocyst production by NK cells during primary infection or by T-cells during secondary infection, mutant mice that lacked H2-IAβb (Aβb(-/-)) or β2-microglobulin (β2m(-/-)) were used. Since MHC molecules are required for the maturation of αβ T-cells, Aβb(-/-) and β2m(-/-) mutant mice are also deficient in functional αβ+ CD4+ or αβ+ CD8+ T-cells, respectively. As compared with wild-type control mice, oocyst output by mutant mice was not significantly affected during primary infection, suggesting that the ability of NK cells to control parasite replication is not dependent on the expression of MHC molecules. On reinfection, differences were observed for mutant mice as compared with controls. Aβb(-/-) mice were found to be more susceptible than β2m(-/-) mice, suggesting that the αβ+ CD4+ T-cell subset plays a greater role in resistance to reinfection than does the αβ+ CD8+ T-cell subset. The mechanism of resistance depends on the immune status of the host and requires the coordinated interaction of both αβ+ T-cell, subsets for optimal parasite control during subsequent infections

Codes and standards on computational wind engineering for structural design: State of art and recent trends

This paper first provides a wide overview about the design codes and standards covering the use of Computational Wind Engineering / Computational Fluid Dynamics (CWE/CFD) for wind-sensitive structures and built environment. Second, the paper sets out the basic assumptions and underlying concepts of the new Annex T "Simulations by Computational Fluid Dynamics (CFD/CWE)" of the revised version "Guide for the assessment of wind actions and effects on structures" issued by the Advisory Committee on Technical Recommendations for Constructions of the Italian National Research Council in February 2019 and drafted by the members of the Special Interest Group on Computational Wind Engineering of the Italian Association for Wind Engineering (ANIV-CWE). The same group is currently advising UNI CT021/SC1 in supporting the drafting of the new Annex K - "Derivation of design parameters from wind tunnel tests and numerical simulations" of the revised Eurocode 1: Actions on structures - Part 1-4: General actions - Wind actions. Finally, the paper outlines the subjects most open to development at the technical and applicative level

Raman spectral shifts in naturally faulted rocks

Acknowledgements. We thank Colin Taylor at UoA for help in sample preparation.This study was supported by the School of Geosciences at the University of Aberdeen and in part by the NERC Centre for Doctoral Training in Oil & Gas (Grant Number: NE/R01051x/1).Peer reviewedPublisher PD

Forced expiratory volume in one second: A novel predictor of work disability in subjects with suspected obstructive sleep apnea

Whether the association of work disability with obstructive sleep apnea (OSA) is mainly due to the disease, i.e. the number and frequency of apneas-hypoapneas, or to coexisting factors independent from the disease, is not well-established. In this study, we aim to evaluate work ability in a group of subjects undergoing OSA workup and to identify the major contributors of impaired work ability. In a cross-sectional study, we enrolled 146 consecutive subjects who have been working for the last five years and referred to the sleep disorders outpatients’ clinic of the University-Hospital of Ferrara, Italy, with suspected OSA. After completing an interview in which the Work Ability Index (WAI) and the Epworth Sleepiness Scale (ESS) questionnaires were administered to assess work ability and excessive daytime sleepiness, respectively, subjects underwent overnight polysomnography for OSA diagnosing and spirometry. Of the 146 subjects, 140 (96%) completed the tests and questionnaires and, of these, 66 exhibited work disability (WAI < 37). OSA was diagnosed (apnea-hypopnea index 5) in 45 (68%) of the 66 subjects. After controlling for confounders, a lower level of forced expiratory volume at 1 second (FEV1), [odds ratio 0.97 (95% CI 0.95–1.00)], older age [1.09 (95% CI 1.03–1.15)], excessive daytime sleepiness [3.16 (95% CI 1.20–8.34)] and a worse quality of life [0.96 (95% CI 0.94–1.00)], but not OSA [1.04 (95% CI 0.41–2.62)], were associated with work disability. Patients with a higher number of diseases, in which OSA was not included, and a lower quality of life had an increased probability of absenteeism in the previous 12 months. In subjects with suspected OSA, FEV1 can be an important predictor of work disability

Hypoxia-inducible Factor-dependent Breast Cancer-mesenchymal Stem Cell Bidirectional Signaling Promotes Metastasis.

published_or_final_versio

Aberrant methylation of N-methyl-D-aspartate receptor type 2B (NMDAR2B) in non-small cell carcinoma

<p>Abstract</p> <p>Background</p> <p>N-methyl-D-aspartate receptors (NMDAR) act as tumor suppressors of digestive malignancies. The expression and genetic methylation patterns of <it>NMDAR2B </it>in non-small cell lung cancer (NSCLC) are unknown.</p> <p>Methods</p> <p>The relationship between gene methylation and expression of <it>NMDAR2B </it>was analyzed in NSCLC cell lines (N = 9) and clinical tissues (N = 216). The cell lines were studied using RT-PCR and 5-aza-2'-deoxycytidine treatment, while the clinical tissues were examined by methylation specific real-time quantitative PCR and immunohistochemistry. Retrospective investigation of patient records was used to determine the clinical significance of <it>NMDAR2B </it>methylation.</p> <p>Results</p> <p><it>NMDAR2B </it>was silenced in five of the nine cell lines; 5-aza-2'-deoxycytidine treatment restored expression, and was inversely correlated with methylation. Aberrant methylation of <it>NMDAR2B</it>, detected in 61% (131/216) of clinical NSCLC tissues, was inversely correlated with the status of protein expression in 20 randomly examined tumors. Aberrant methylation was not associated with clinical factors such as gender, age, histological type, or TNM stage. However, aberrant methylation was an independent prognostic factor in squamous cell carcinoma cases.</p> <p>Conclusions</p> <p>Aberrant methylation of the <it>NMDAR2B </it>gene is a common event in NSCLC. The prognosis was significantly better for cases of squamous cell carcinoma in which <it>NMDAR2B </it>was methylated. It may have different roles in different histological types.</p

Blind test comparison on the wake behind a yawed wind turbine

This article summarizes the results of the Blind test 5 workshop, which was held in Visby, Sweden, in May 2017. This study compares the numerical predictions of the wake flow behind a model wind turbine operated in yaw to experimental wind tunnel results. Prior to the workshop, research groups were invited to predict the turbine performance and wake flow properties using computational fluid dynamics (CFD) methods. For this purpose, the power, thrust, and yaw moments for a 30° yawed model turbine, as well as the wake's mean and turbulent streamwise and vertical flow components, were measured in the wind tunnel at the Norwegian University of Science and Technology (NTNU). In order to increase the complexity, a non-yawed downstream turbine was added in a second test case, while a third test case challenged the modelers with a new rotor and turbine geometry.Four participants submitted predictions using different flow solvers, three of which were based on large eddy simulations (LES) while another one used an improved delayed detached eddy simulation (IDDES) model. The performance of a single yawed turbine was fairly well predicted by all simulations, both in the first and third test cases. The scatter in the downstream turbine performance predictions in the second test case, however, was found to be significantly larger. The complex asymmetric shape of the mean streamwise and vertical velocities was generally well predicted by all the simulations for all test cases. The largest improvement with respect to previous blind tests is the good prediction of the levels of TKE in the wake, even for the complex case of yaw misalignment. These very promising results confirm the mature development stage of LES/DES simulations for wind turbine wake modeling, while competitive advantages might be obtained by faster computational methods.</p

Toward New Therapeutics for Skin and Soft Tissue Infections: Propargyl-Linked Antifolates Are Potent Inhibitors of MRSA and Streptococcus pyogenes

Hospital- and community-acquired, complicated skin and soft tissue infections, often attributed to Staphylococcus aureus and Streptococcus pyogenes, present a significant health burden that is associated with increased health care costs and mortality. As these two species are difficult to discern on diagnosis and are associated with differential profiles of drug resistance, the development of an efficacious antibacterial agent that targets both organisms is a high priority. Herein we describe a structure-based drug development effort that has produced highly potent inhibitors of dihydrofolate reductase from both species. Optimized propargyl-linked antifolates containing a key pyridyl substituent display antibacterial activity against both methicillin-resistant S. aureus and S. pyogenes at MIC values below 0.1 µg/mL and minimal cytotoxicity against mammalian cells. Further evaluation against a panel of clinical isolates shows good efficacy against a range of important phenotypes such as hospital- and community-acquired strains as well as strains resistant to vancomycin