Barrier-to-autointegration factor 1 protects against a basal cGAS-STING response

Although the pathogen recognition receptor pathways that activate cell-intrinsic antiviral responses are well delineated, less is known about how the host regulates this response to prevent sustained signaling and possible immune-mediated damage. Using a genome-wide CRISPR-Cas9 screening approach to identify host factors that modulate interferon-stimulated gene (ISG) expression, we identified the DNA binding protein Barrier-to-autointegration factor 1 (Banf1), a previously described inhibitor of retrovirus integration, as a modulator of basal cell-intrinsic immunity. Ablation of Banf1 by gene editing resulted in chromatin activation near host defense genes with associated increased expression of ISGs, includin

Cumulative fatigue damage of stress below the fatigue limit in weldment steel under block loading

To investigate the cumulative fatigue damage below the fatigue limit of multipass weldment martensitic stainless steel, and to clarify the effect of cycle ratios and high‐stress level in the statement, fatigue tests were conducted under constant and combined high‐ and low‐stress amplitude relative to stress above and below the fatigue limit. The outcomes indicate that neither modified Miner's nor Haibach's approach provided accurate evaluation under repeated two‐step amplitude loading. Moreover, effect of cycle ratios has been determined. Additionally, the cumulative fatigue damage saturated model is established and validated. Cumulative fatigue damage contributed by low‐stress below the fatigue limit in high stress of 700 MPa is higher than that with 650 MPa at identical conditions (fatigue limit 575 MPa). Thus, high stress affects fatigue damage behaviour below the fatigue limit. A new predicted approach has been proposed based on Corten‐Dolan law, whose accuracy and applicability have been proven

Investigating in-service failures of water pipes from a multiaxial notch fatigue point of view: A conceptual study

Many mechanisms and processes can cause deterioration and ultimately failure of water distribution pipes during in-service operation, amongst these is damage caused by metal fatigue. This paper summarises an attempt at formalising a novel methodology suitable for estimating the number of years taken for a through thickness fatigue crack to form in this complex scenario. The devised method is based on the so-called modified Wo¨hler curve method and can be applied to estimate fatigue damage of water pipes independently from the degree of multiaxiality and non-proportionality of the load history. The computational approach of the proposed fatigue life estimation technique makes full use of an incremental procedure: fatigue damage is evaluated year by year by assuming that all variable involved in the process can change over time. The detrimental effect of corrosion pits is directly accounted for by treating them as conventional notches whose size increases with time. Finally, by taking as reference information the number of years for a blowout hole to form, the proposed approach is used to show how the lifetime of grey cast iron pipes can be remarkably shortened by fatigue

Proportional/non-proportional constant/variable amplitude multiaxial notch fatigue: cyclic plasticity, non-zero mean stresses, and critical distance/plane

This paper deals with the formulation and experimental validation of a novel fatigue lifetime estimation technique suitable for assessing the extent of damage in notched metallic materials subjected to in‐service proportional/nonproportional constant/variable amplitude multiaxial load histories. The methodology being formulated makes use of the Modified Manson‐Coffin Curve Method, the Shear Strain–Maximum Variance Method, and the elasto‐plastic Theory of Critical Distances, with the latter theory being applied in the form of the Point Method. The accuracy and reliability of our novel fatigue lifetime estimation technique were checked against a large number of experimental results we generated by testing, under proportional/nonproportional constant/variable amplitude axial‐torsional loading, V‐notched cylindrical specimens made of unalloyed medium‐carbon steel En8 (080M40). Specific experimental trials were run to investigate also the effect of non‐zero mean stresses as well as of different frequencies between the axial and torsional stress/strain components. This systematic validation exercise allowed us to demonstrate that our novel multiaxial fatigue assessment methodology is remarkably accurate, with the estimates falling within an error factor of 2. By modelling the cyclic elasto‐plastic behaviour of metals explicitly, the design methodology being formulated and validated in the present paper offers a complete solution to the problem of estimating multiaxial fatigue lifetime of notched metallic materials, with this holding true independently of sharpness of the stress/strain raiser and complexity of the load history

An improved critical plane and cycle counting method to assess damage under variable amplitude multiaxial fatigue loading

The plane with the maximum variance of the resolved shear stress is taken as the critical plane. Two algorithms are used along with the maximum variance method (MVM) to determine the orientation of the critical plane. The maximum variance of the normal stress on the potential critical planes is calculated to determine the one experiencing the maximum extent of fatigue damage. A new multiaxial cycle counting method is proposed to count cycles on the critical plane. The modified Wöhler curve method is used to assess fatigue damage. About 200 experimental results were collected from the technical literature to validate the approaches being proposed. The results show that the improved design technique being proposed is successful in assessing fatigue damage under variable amplitude multiaxial cyclic loading

Exacerbation of Bloody Diarrhea as a Side Effect of Mesalamine Treatment of Active Ulcerative Colitis

Mesalamine has been used as the first-line therapy for the treatment of ulcerative colitis (UC) because of its efficacy and fewer side effects. However, earlier study showed that mesalamine occasionally causes diarrhea. We are presenting a patient with active UC in whom bloody diarrhea accompanied by abdominal pain and fever occurred and the symptoms were aggravated after administration of mesalamine. In order to clarify the reason of symptoms aggravation, drug lymphocyte stimulation test and rechallenge trial with mesalamine were performed. The results indicated the possibility that aggravation was related to allergic reaction and was dose-dependent. Furthermore, we examined colonoscopic views but there was no remarkable change in before and after rechallenge trial. Based on the above result, the patient was diagnosed with mesalamine intolerance. In order to differentiate whether the exacerbation of bloody diarrhea is due to the side effects of the mesalamine or a true relapse of UC, taking careful history before and after increasing mesalamine dosage as well as being aware of side effects of mesalamine are required. Clinicians should be aware of diarrhea as a side effect of mesalamine particularly after onset of mesalamine formulation, change in mesalamine formulation, or change in mesalamine dose

Stress induced polarization of immune-neuroendocrine phenotypes in Gallus gallus

Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals’ interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.Fil: Nazar, Franco Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Estevez, Inma. Centro de Investigación. Neiker - Tecnalia; EspañaFil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Marin, Raul Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Effect of 12 months of testosterone replacement therapy on metabolic syndrome components in hypogonadal men: data from the Testim Registry in the US (TRiUS)

<p>Abstract</p> <p>Background</p> <p>Recent evidence suggests that there may be a bidirectional, physiological link between hypogonadism and metabolic syndrome (MetS), and testosterone replacement therapy (TRT) has been shown to improve some symptoms of MetS in small patient populations. We examined the effect of 12 months of TRT on MetS components in a large cohort of hypogonadal men.</p> <p>Methods</p> <p>Data were obtained from TRiUS (Testim^®Registry in the United States), a 12-month, multicenter, prospective observational registry (N = 849) of hypogonadal men prescribed Testim 1% testosterone gel (5-10 g/day). Data analyzed included age, total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), and MetS components: waist circumference, blood pressure, fasting blood glucose, plasma triglycerides, and HDL cholesterol.</p> <p>Results</p> <p>Of evaluable patients (581/849) at baseline, 37% were MetS+ (n = 213) and 63% were MetS- (n = 368). MetS+ patients had significantly lower TT (p < 0.0001) and SHBG (p = 0.01) levels. Patients with the lowest quartile TT levels (<206 ng/dL [<7.1 nmol/L]) had a significantly increased risk of MetS+ classification vs those with highest quartile TT levels (≥331 ng/dL [≥11.5 nmol/L]) (odds ratio 2.66; 95% CI, 1.60 to 4.43). After 12 months of TRT, TT levels significantly increased in all patients (p < 0.005). Despite having similar TT levels after TRT, only MetS+ patients demonstrated significant decreases in waist circumference, fasting blood glucose levels, and blood pressure; lowest TT quartile patients demonstrated significant decreases in waist circumference and fasting blood glucose. Neither HDL cholesterol nor triglyceride levels changed significantly in either patient population.</p> <p>Conclusion</p> <p>Hypogonadal MetS+ patients were more likely than their MetS- counterparts to have lower baseline TT levels and present with more comorbid conditions. MetS+ patients and those in the lowest TT quartile showed improvement in some metabolic syndrome components after 12 months of TRT. While it is currently unclear if further cardiometabolic benefit can be seen with longer TRT use in this population, testing for low testosterone may be warranted in MetS+ men with hypogonadal symptoms.</p

Estimation of Steam Turbine Shafts Fatigue Damage Caused by Torsional Vibrations

В Україні 74 енергоблоки потужністю 150-800 МВт теплових електростанцій із 102 перебувають на межі перевищення паркового ресурсу (220 тис. Годин). З них 17 енергоблоків наближаються до кінця ресурсу парку, а 11 енергоблоків досягли передбачуваного ресурсу (100 тис. Годин). Статистика аварій на електростанціях у різних країнах показує, що більшість з них спричинені тривалим накопиченням збитків від втоми. Серед основних причин пошкодження втоми - пульсація високотемпературних потоків пари в циліндрах турбіни, поперечні та крутильні коливання валів при тривалій експлуатації тощо. Це обумовлює розробку обчислювальних та експериментальних методів визначення втомних пошкоджень вали турбінних установок при динамічних навантаженнях. Оцінка втомних пошкоджень вала парової турбіни К-200-130 базується на 3D-моделі кінцевих елементів. Розрахунки враховують експериментально визначені втомні властивості роторної сталі. Розраховано втомну пошкодження в результаті крутильних коливань валу турбіни, спричинених аномальною роботою турбінного генератора. Зони концентрації напружень в обертових елементах парової турбіни типу К-200-130 встановлені для різних режимів роботи. Запропоновано процедуру прогнозування впливу втоми від пошкоджень на розрахунковий ресурс турбінного агрегату.In Ukraine, 74 power units with a capacity of 150-800 MW of thermal power plants out of 102 are on the verge of exceeding the park resource (220 thousand hours). Of these, 17 power units are close to the end the park resource, and 11 units have reached their estimated resource (100 thousand hours). Statistics of power plants accidents in different countries indicates that most of them are caused by the long term accumulation of fatigue damage. Among the main causes of fatigue damage are the pulsating of high-temperature steam flows in the turbine cylinders, transverse and torsional vibrations of shafts during long-term operation etc. This causes the development of computational and experimental methods for the determination of fatigue damage of turbine units’ shafts under dynamic loads. The evaluation of fatigue damage of steam turbine K-200-130 shaft is based on the 3D finite element model. The calculations take into account experimentally determined fatigue properties of rotor steel. The fatigue damage as a result of torsional vibrations of turbine shaft caused by the abnormal operation of turbine generator is calculated. Zones of stress concentration in the rotating elements of the steam turbine type K-200-130 are established for various operating modes. The procedure to predict the effect of fatigue damage on the estimated resource of turbine unit is proposed.В Украине 74 энергоблока мощностью 150-800 МВт тепловых электростанций из 102 находятся на грани превышения ресурса парка (220 тыс. Часов). Из них 17 энергоблоков близки к исчерпанию ресурса парка, а 11 энергоблоков вышли на расчетный ресурс (100 тыс. Часов). Статистика аварий на электростанциях в разных странах показывает, что большинство из них вызвано длительным накоплением усталостных повреждений. Среди основных причин усталостных повреждений - пульсации высокотемпературных потоков пара в цилиндрах турбины, поперечные и крутильные колебания валов при длительной эксплуатации и т. Д. Это вызывает развитие расчетных и экспериментальных методов определения усталостных повреждений. валы турбоагрегатов при динамических нагрузках. Оценка усталостных повреждений вала паровой турбины К-200-130 проводится на основе трехмерной конечно-элементной модели. В расчетах учтены экспериментально определенные усталостные свойства роторной стали. Рассчитано усталостное повреждение в результате крутильных колебаний вала турбины, вызванных ненормальной работой турбогенератора. Установлены зоны концентрации напряжений во вращающихся элементах паровой турбины типа К-200-130 для различных режимов работы. Предложена методика прогнозирования влияния усталостных повреждений на расчетный ресурс турбоагрегата