Direct evidence for thymic function in adult humans.

The understanding of human thymic function and evaluation of its contribution to T cell homeostasis are matters of great importance. Here we report the development of a novel assay to quantitate the frequency and diversity of recent thymic emigrants (RTEs) in the peripheral blood of humans. Such cells were defined by the presence of T cell receptor (TCR) rearrangement deletion circles (DCs), episomal byproducts of TCR-beta V(D)J rearrangement. DCs were detected in T cells in the thymus, cord blood, and adult peripheral blood. In the peripheral blood of adults aged 22 to 76 years, their frequency was highest in the CD4(+)CD45RA(+) CD62L(+) subpopulation of naive T cells. TCR DCs were also observed in other subpopulations of peripheral blood T cells, including those with the CD4(+)CD45RO(-)CD62L(+) and CD4(+)CD45RO(+)CD62L(+) phenotypes. RTEs were observed to have more than one Vbeta rearrangement, suggesting that replenishment of the repertoire in the adult is at least oligoclonal. These results demonstrate that the normal adult thymus continues to contribute, even in older individuals, a diverse set of new T cells to the peripheral circulation

Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells

Loss of insulin-secreting β-cells in diabetes may be either due to apoptosis or dedifferentiation of β-cell mass. The ubiquitin-proteasome system comprising E3 ligase and deubiquitinases (DUBs) controls several aspects of β-cell functions. In this study, screening for key DUBs identified USP1 to be specifically involved in dedifferentiation process. Inhibition of USP1 either by genetic intervention or small-molecule inhibitor ML323 restored epithelial phenotype of β-cells, but not with inhibition of other DUBs. In absence of dedifferentiation cues, overexpression of USP1 was sufficient to induce dedifferentiation in β-cells; mechanistic insight showed USP1 to mediate its effect via modulating the expression of inhibitor of differentiation (ID) 2. In an in vivo streptozotocin (STZ)-induced dedifferentiation mouse model system, administering ML323 alleviated hyperglycemic state. Overall, this study identifies USP1 to be involved in dedifferentiation of β-cells and its inhibition may have a therapeutic application of reducing β-cell loss during diabetes

Toward a better understanding of tool wear effect through a comparison between experiments and SPH numerical modelling of machining hard materials

The aim of this study is to improve the general understanding of tungsten carbide (WC–Co) tool wear under dry machining of the hard-to-cut titanium alloy Ti6Al4V. The chosen approach includes experimental and numerical tests. The experimental part is designed to identify wear mechanisms using cutting force measurements, scanning electron microscope observations and optical profilometer analysis. Machining tests were conducted in the orthogonal cutting framework and showed a strong evolution of the cutting forces and the chip profiles with tool wear. Then, a numerical method has been used in order to model the machining process with both new and worn tools. The use of smoothed particle hydrodynamics model (SPH model) as a numerical tool for a better understanding of the chip formation with worn tools is a key aspect of this work. The redicted chip morphology and the cutting force evolution with respect to the tool wear are qualitatively compared with experimental trends. The chip formation mechanisms during dry cutting process are shown to be quite dependent from the worn tool geometry. These mechanisms explain the high variation of the experimental and numerical feed force between new and worn tools

Voltage-programmable liquid optical interface

Recently, there has been intense interest in photonic devices based on microfluidics, including displays and refractive tunable microlenses and optical beamsteerers, that work using the principle of electrowetting. Here, we report a novel approach to optical devices in which static wrinkles are produced at the surface of a thin film of oil as a result of dielectrophoretic forces. We have demonstrated this voltage-programmable surface wrinkling effect in periodic devices with pitch lengths of between 20 and 240 µm and with response times of less than 40 µs. By a careful choice of oils, it is possible to optimize either for high-amplitude sinusoidal wrinkles at micrometre-scale pitches or more complex non-sinusoidal profiles with higher Fourier components at longer pitches. This opens up the possibility of developing rapidly responsive voltage-programmable, polarization-insensitive transmission and reflection diffraction devices and arbitrary surface profile optical devices

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Immune Dysregulation and Pathobiology Working Group Report

Immune reconstitution after hematopoietic stem cell transplantation (HCT) beyond 1 year is not completely understood. Many transplant recipients who are free of graft-versus-host disease (GVHD) and not receiving any immunosuppression more than 1 year after transplantation seem to be able to mount appropriate immune responses to common pathogens and respond adequately to immunizations. However, 2 large registry studies over the last 2 decades seem to indicate that infection is a significant cause of late mortality in some patients, even in the absence of concomitant GVHD. Research on this topic is particularly challenging for several reasons. First, there are not enough long-term follow-up clinics able to measure even basic immune parameters late after HCT. Second, the correlation between laboratory measurements of immune function and infections is not well known. Third, accurate documentation of infectious episodes is notoriously difficult. Finally, it is unclear what measures can be implemented to improve the immune response in a clinically relevant way. A combination of long-term multicenter prospective studies that collect detailed infectious data and store samples as well as a national or multinational registry of clinically significant infections (eg, vaccine-preventable severe infections, opportunistic infections) could begin to address our knowledge gaps. Obtaining samples for laboratory evaluation of the immune system should be both calendar and eventdriven. Attention to detail and standardization of practices regarding prophylaxis, diagnosis, and definitions of infections would be of paramount importance to obtain clean reliable data. Laboratory studies should specifically address the neogenesis, maturation, and exhaustion of the adaptive immune system and, in particular, how these are influenced by persistent alloreactivity, inflammation, and viral infection. Ideally, some of these long-term prospective studies would collect information on long-term changes in the gut microbiome and their influence on immunity. Regarding enhancement of immune function, prospective measurement of the response to vaccines late after HCT in a variety of clinical settings should be undertaken to better understand the benefits as well as the limitations of immunizations. The role of intravenous immunoglobulin is still not well defined, and studies to address it should be encouraged

Ti alloy with enhanced machinability in UAT turning

Metastable β-titanium alloys such as Ti 15V 3Al 3Cr 3Sn are of great technological interest thanks to their high fatigue strength-to-density ratio. However, their high hardness and poor machinability increase machining costs. Additionally, formation of undesirable long chips increases the machining time. To address those issues, a metastable β-titanium alloy (Ti 15V 3Al 3Cr 2Zr 0.9La) with enhanced machinability was developed to produce short chips even at low cutting speeds. A hybrid ultrasonically assisted machining technique, known to reduce cutting forces, was employed in this study. Cutting force components and surface quality of the finished work-pieces were analyzed for a range of cutting speeds in comparison with those for more traditional Ti 15V 3Al 3Cr 3Sn. The novel alloy demonstrated slightly improved machining characteristics at higher cutting speeds and is now ready for industrial applications

Simple Nudges for Better Password Creation

Recent security breaches have highlighted the consequences of reusing passwords across online accounts. Recent guidance on password policies by the UK government recommend an emphasis on password length over an extended character set for generating secure but memorable passwords without cognitive overload. This paper explores the role of three nudges in creating website-specific passwords: financial incentive (present vs absent), length instruction (long password vs no instruction) and stimulus (picture present vs not present). Mechanical Turk workers were asked to create a password in one of these conditions and the resulting passwords were evaluated based on character length, resistance to automated guessing attacks, and time taken to create the password. We found that users created longer passwords when asked to do so or when given a financial incentive and these longer passwords were harder to guess than passwords created with no instruction. Using a picture nudge to support password creation did not lead to passwords that were either longer or more resistant to attacks but did lead to account-specific passwords

Исследовательская деятельность эколого-биологической направленности в НОУ "Эврика" - эффективное средство профессиональной ориентации учащихся

В статье научно-исследовательская деятельность эколого-биологической направленности старшеклассников НОУ "Эврика" г. Нижнего Новгорода рассматривается как одна из значимых инновационных форм профессионального самоопределения. Материалом исследования послужил анализ программ конференции городского научного общества учащихся "Эврика" и судьбы выпускников данного общества. Отмечена тенденция роста популярности эколого-биологических исследований среди старшеклассников г. Нижнего Новгорода и успешное вхождение в профессию выпускников научного общества учащихся.In the article, the research activity of the ecology and biology of senior pupils of the scientific society of the pupils "Eureka" in Nizhny Novgorod is considered as one of the significant innovative forms of professional self-determination. The material of the study was the analysis of the programs of the conference of the city scientific society of the students "Eureka" and the fate of the graduates of this society. The tendency of growth of popularity of ecological and biological researches among senior pupils of Nizhny Novgorod and successful entry into the profession of graduates of the scientific society of students is noted

Molecular Dynamics Simulations of the Roller Nanoimprint Process: Adhesion and Other Mechanical Characteristics

Molecular dynamics simulations using tight-binding many body potential are carried out to study the roller imprint process of a gold single crystal. The effect of the roller tooth’s taper angle, imprint depth, imprint temperature, and imprint direction on the imprint force, adhesion, stress distribution, and strain are investigated. A two-stage roller imprint process was obtained from an imprint force curve. The two-stage imprint process included the imprint forming with a rapid increase of imprint force and the unloading stage combined with the adhesion stage. The results show that the imprint force and adhesion rapidly increase with decreasing taper angle and increasing imprint depth. The magnitude of the maximum imprint force and the time at which this maximum occurs are proportional to the imprint depth, but independent of the taper angle. In a comparison of the imprint mechanisms with a vertical imprint case, while high stress and strain regions are concentrated below the mold for vertical imprint, they also occur around the mold in the case of roller imprint. The regions were only concentrated on the substrate atoms underneath the mold in vertical imprint. Plastic flow increased with increasing imprint temperature

Performance measures for upper gastrointestinal endoscopy:A European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative

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