Age is not just a number: Naive T cells increase their ability to persist in the circulation over time

The processes regulating peripheral naive T-cell numbers and clonal diversity remain poorly understood. Conceptually, homeostatic mechanisms must fall into the broad categories of neutral (simple random birth-death models), competition (regulation of cell numbers through quorum-sensing, perhaps via limiting shared resources), adaptation (involving cell-intrinsic changes in homeostatic fitness, defined as net growth rate over time), or selection (involving the loss or outgrowth of cell populations deriving from intercellular variation in fitness). There may also be stably maintained heterogeneity within the naive T-cell pool. To distinguish between these mechanisms, we confront very general models of these processes with an array of experimental data, both new and published. While reduced competition for homeostatic stimuli may impact cell survival or proliferation in neonates or under moderate to severe lymphopenia, we show that the only mechanism capable of explaining multiple, independent experimental studies of naive CD4+ and CD8+ T-cell homeostasis in mice from young adulthood into old age is one of adaptation, in which cells act independently and accrue a survival or proliferative advantage continuously with their post-thymic age. However, aged naive T cells may also be functionally impaired, and so the accumulation of older cells via 'conditioning through experience' may contribute to reduced immune responsiveness in the elderly

Evaluation of voglibose on body weight in rats

Background: As of 2018, 2.1 billion people nearly 30% of the world’s population are either obese or overweight. Worldwide obesity has nearly tripled since 1975. It is an emerging health problem with major adverse effects on health. It is a risk factor for many chronic diseases but is best known for its role in metabolic syndrome, which can lead to type 2 diabetes mellitus as well as cardiovascular diseases. Anti-obesity drugs are available but have many side effects. Voglibose, an antidiabetic drug, is an alpha glucosidase inhibitor which shows promising results in the reduction of body weight with minimal side effects.Methods: Voglibose (7 mg/kg) was administered to rats fed with normal laboratory chows and high fat diet to see its effect on body weight, body mass index, abdominal and thoracic circumference, and lipid profile at the end of 12 weeks.Results: Administration of voglibose significantly reduced food consumption, feed efficiency and increase in body weight induced by high fat diet in rats. Rats fed on normal diet also showed reductions in the same parameters, suggesting its weight lowering effect. Reductions in the anthropometric measurements, hypolipidemic effects and glucose lowering effects were also observed.Conclusions: Voglibose prevented high fat diet-induced obesity and improvement in metabolic profile, which ultimately has systemic effects on body weight in rats. Further studies are needed to see its potential therapeutic use in obese patients with type 2 diabetes mellitus, and related complications

Two-photon microscopy-guided femtosecond-laser photoablation of avian cardiogenesis: Noninvasive creation of localized heart defects

Yalçın, Hüseyin Çağatay (Dogus Author)Embryonic heart formation is driven by complex feedback between genetic and hemodynamic stimuli. Clinical congenital heart defects (CHD), however, often manifest as localized microtissue malformations with no underlying genetic mutation, suggesting that altered hemodynamics during embryonic development may play a role. An investigation of this relationship has been impaired by a lack of experimental tools that can create locally targeted cardiac perturbations. Here we have developed noninvasive optical techniques that can modulate avian cardiogenesis to dissect relationships between alterations in mechanical signaling and CHD. We used two-photon excited fluorescence microscopy to monitor cushion and ventricular dynamics and femtosecond pulsed laser photoablation to target micrometer-sized volumes inside the beating chick hearts. We selectively photoablated a small (∼100 μm radius) region of the superior atrioventricular (AV) cushion in Hamburger-Hamilton 24 chick embryos. We quantified via ultrasound that the disruption causes AV regurgitation, which resulted in a venous pooling of blood and severe arterial constriction. At 48 h postablation, quantitative X-ray microcomputed tomography imaging demonstrated stunted ventricular growth and pronounced left atrial dilation. A histological analysis demonstrated that the laser ablation produced defects localized to the superior AV cushion: a small quasispherical region of cushion tissue was completely obliterated, and the area adjacent to the myocardial wall was less cellularized. Both cushions and myocardium were significantly smaller than sham-operated controls. Our results highlight that two-photon excited fluorescence coupled with femtosecond pulsed laser photoablation should be considered a powerful tool for studying hemodynamic signaling in cardiac morphogenesis through the creation of localized microscale defects that may mimic clinical CHD

Ease of use and accuracy of a perinatal measuring device (Episiometer) to ensure correct angle and length of a mediolateral episiotomy: a mixed methods study

Introduction: To guide clinicians in performing mediolateral episiotomies (MLEs) at 60‐degrees, a new clinical innovation called the 'Episiometer' was developed. The aim of this study was to assess the usability and accuracy of the Episiometer in guiding clinicians to perform a safe episiotomy in both low‐ and high‐resource settings. Design: A prospective, multi‐site Phase‐I clinical trial was conducted between January 2017 and July 2018, involving three international study sites: Australia; Papua New Guinea; and India. The study design was mixed‐methods, incorporating an explanatory sequential design using surveys, clinician interviews and patient chart review to determine the usability and accuracy of the Episiometer. The patient chart review and results of this are discussed in an accompanying article. Methods: The Episiometer is the clinical innovation designed to attain an episiotomy cutting angle of 60‐degrees. The instrument is designed to assist clinicians to make an accurate and consistent episiotomy cutting angle within a 'safe' green zone between 45–60 degrees and length of at least 4 cm. The instrument also improves the visibility of the 60‐degree line to clinicians, and provides an exact measurement for length (located on the 60‐degree angle line). Clinicians from all three sites were recruited to provide feedback and measurements of incisions performed using the Episiometer (n = 135) following attendance at a minimum of at least one training session with site coordinators. Twenty of these clinicians were then recruited randomly from the sample who responded in the surveys and interviewed face‐to‐face. Patients were followed up 6‐weeks postpartum to monitor potential complications (n = 120). Results: Overall, the Episiometer was well received by clinicians – particularly by more junior staff members who were significantly more likely to report the Episiometer as being beneficial in guiding a safe MLE compared to their more senior counterparts (P = 0.003 and P = 0.011, respectively). In addition, 89% of incisions (107/120) were within the 'safe zone' between 45‐60 degrees, and 40% (48/120) were made at exactly 60‐degrees. No patient had any degree of perineal tear at follow up. Conclusion: The Episiometer is a well‐received clinical innovation in both high‐resource and lower resource settings. When used as directed, the Episiometer produces an accurate and safe incision, and reduces variation in clinicians' performance of episiotomy

Systematic engineering design approach for improvement of oil-free twin-screw compressors

Twin-screw compressors are widely used in industry, especially in compressed air, refrigeration, air-conditioning and process gas which consume a significant part of the world's energy. Nowadays, oil-injected compressors represent the majority of twin-screw compressors in the market due to their high efficiency and reliability. The oil-free compressor is potentially a better solution in the context of the net-zero CO2 target in 2050. However, due to its high thermal deformation and small clearances, this technology still suffers from reliability issues. To remedy this problem disruptive innovative solutions are required. In this purpose, the present study uses a systematic engineering design process to develop new concepts for the improvement of the oil-free twin-screw compressor. The paper is focused on the first two phases of the design process which are the definition of problem and the conceptual design. In the problem definition, main objectives are expressed and are divided into sub-objectives and weighed using an objective tree decomposition. Moreover, a thorough functional model of the oil-free compressor is detailed with a focus on the leakage paths and heat transfers. For the conceptual design, engineering characteristics extracted from the functional analysis have been assessed against the most important objectives using Quality Function Deployment matrices (QFD). Based on the developed problem definition, new concepts have been generated and three distinct concept categories have been further explored: Secondary flow; Surface features; Clearance control and monitoring. The evaluation, embodiment and detailed designs of the concepts, using experimental and numerical analyses will follow

In Vivo Conditional Pax4 Overexpression in Mature Islet β-Cells Prevents Stress-Induced Hyperglycemia in Mice

OBJECTIVE To establish the role of the transcription factor Pax4 in pancreatic islet expansion and survival in response to physiological stress and its impact on glucose metabolism, we generated transgenic mice conditionally and selectively overexpressing Pax4 or a diabetes-linked mutant variant (Pax4R129 W) in β-cells. RESEARCH DESIGN AND METHODS Glucose homeostasis and β-cell death and proliferation were assessed in Pax4- or Pax4R129 W-overexpressing transgenic animals challenged with or without streptozotocin. Isolated transgenic islets were also exposed to cytokines, and apoptosis was evaluated by DNA fragmentation or cytochrome C release. The expression profiles of proliferation and apoptotic genes and β-cell markers were studied by immunohistochemistry and quantitative RT-PCR. RESULTS Pax4 but not Pax4R129 W protected animals against streptozotocin-induced hyperglycemia and isolated islets from cytokine-mediated β-cell apoptosis. Cytochrome C release was abrogated in Pax4 islets treated with cytokines. Interleukin-1β transcript levels were suppressed in Pax4 islets, whereas they were increased along with NOS2 in Pax4R129 W islets. Bcl-2, Cdk4, and c-myc expression levels were increased in Pax4 islets while MafA, insulin, and GLUT2 transcript levels were suppressed in both animal models. Long-term Pax4 expression promoted proliferation of a Pdx1-positive cell subpopulation while impeding insulin secretion. Suppression of Pax4 rescued this defect with a concomitant increase in pancreatic insulin content. CONCLUSIONS Pax4 protects adult islets from stress-induced apoptosis by suppressing selective nuclear factor-κB target genes while increasing Bcl-2 levels. Furthermore, it promotes dedifferentiation and proliferation of β-cells through MafA repression, with a concomitant increase in Cdk4 and c-myc expression

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum