This current and comprehensive book provides an updated treatment of molecular gas dynamics topics for aerospace engineers, or anyone researching high-temperature gas flows for hypersonic vehicles ...and propulsion systems. It demonstrates how the areas of quantum mechanics, kinetic theory, and statistical mechanics can combine in order to facilitate the study of nonequilibrium processes of internal energy relaxation and chemistry. All of these theoretical ideas are used to explain the direct simulation Monte Carlo (DSMC) method, a numerical technique based on molecular simulation. Because this text provides comprehensive coverage of the physical models available for use in the DSMC method, in addition to the equations and algorithms required to implement the DSMC numerical method, readers will learn to solve nonequilibrium flow problems and perform computer simulations, and obtain a more complete understanding of various physical modeling options for DSMC than is available in other texts.
The 100 mm visual analog scale (VAS) score is widely used to measure pain intensity after surgery. Despite this widespread use, it is unclear what constitutes the minimal clinically important ...difference (MCID); that is, what minimal change in score would indicate a meaningful change in a patient's pain status.
We enrolled a sequential, unselected cohort of patients recovering from surgery and used a VAS to quantify pain intensity. We compared changes in the VAS with a global rating-of-change questionnaire using an anchor-based method and three distribution-based methods (0.3 sd, standard error of the measurement, and 5% range). We then averaged the change estimates to determine the MCID for the pain VAS. The patient acceptable symptom state (PASS) was defined as the 25th centile of the VAS corresponding to a positive patient response to having made a good recovery from surgery.
We enrolled 224 patients at the first postoperative visit, and 219 of these were available for a second interview. The VAS scores improved significantly between the first two interviews. Triangulation of distribution and anchor-based methods resulted in an MCID of 9.9 for the pain VAS, and a PASS of 33.
Analgesic interventions that provide a change of 10 for the 100 mm pain VAS signify a clinically important improvement or deterioration, and a VAS of 33 or less signifies acceptable pain control (i.e. a responder), after surgery.
Autophagy constitutes a major cell-protective mechanism that eliminates damaged components and maintains energy homeostasis via recycling nutrients under normal/stressed conditions. Although the ...core components of autophagy have been well studied, regulation of autophagy at the transcriptional level is poorly understood. Herein, we establish ZKSCAN3, a zinc finger family DNA-binding protein, as a transcriptional repressor of autophagy. Silencing of ZKSCAN3 induced autophagy and increased lysosome biogenesis. Importantly, we show that ZKSCAN3 represses transcription of a large gene set (>60) integral to, or regulatory for, autophagy and lysosome biogenesis/function and that a subset of these genes, including Map1lC3b and Wipi2, represent direct targets. Interestingly, ZKSCAN3 and TFEB are oppositely regulated by starvation and in turn oppositely regulate lysosomal biogenesis and autophagy, suggesting that they act in conjunction. Altogether, our study uncovers an autophagy master switch regulating the expression of a transcriptional network of genes integral to autophagy and lysosome biogenesis/function.
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► Silencing of ZKSCAN3 induces autophagy and lysosome biogenesis ► ZKSCAN3 transcriptionally regulates an extensive set of genes involved in autophagy ► ZKSCAN3 nuclear localization is regulated by nutrient availability ► ZKSCAN3 and TFEB regulate autophagy in opposite directions
Abstract Several nerve guidance conduits (NGCs) and nerve protectant wraps are approved by the US Food and Drug Administration (FDA) for clinical use in peripheral nerve repair. These devices cover a ...wide range of natural and synthetic materials, which may or may not be resorbable. This review consolidates the data pertaining to all FDA approved materials into a single reference, which emphasizes material composition alongside pre-clinical and clinical safety and efficacy (where possible). This article also summarizes the key advantages and limitations for each material as noted in the literature (with respect to the indication considered). In this context, this review provides a comprehensive reference for clinicians which may facilitate optimal material/device selection for peripheral nerve repair. For materials scientists, this review highlights predicate devices and evaluation methodologies, offering an insight into current deficiencies associated with state-of-the-art materials and may help direct new technology developments and evaluation methodologies thereof.
The effects of ambient atmospheric conditions, air temperature, and density on rotor harmonic noise radiation are characterized using theoretical models and experimental measurements of helicopter ...noise collected at three different test sites at elevations ranging from sea level to 7000 ft above sea level. Significant changes in the thickness, loading, and blade–vortex interaction noise levels and radiation directions are observed across the different test sites for an AS350 helicopter flying at the same indicated airspeed and gross weight. However, the radiated noise is shown to scale with ambient pressure when the flight condition of the helicopter is defined in nondimensional terms. Although the effective tip Mach number is identified as the primary governing parameter for thickness noise, the nondimensional weight coefficient also impacts lower harmonic loading noise levels, which contribute strongly to low-frequency harmonic noise radiation both in and out of the plane of the horizon. Strategies for maintaining the same nondimensional rotor operating condition under different ambient conditions are developed using an analytical model of single main rotor helicopter trim and confirmed using a CAMRAD II model of the AS350 helicopter. The ability of the Fundamental Rotorcraft Acoustics Modeling from Experiments (FRAME) technique to generalize noise measurements made under one set of ambient conditions to make accurate noise predictions under other ambient conditions is also validated.
Ingestion of innocuous antigens, including food proteins, normally results in local and systemic immune nonresponsiveness in a process termed oral tolerance. Oral tolerance to food proteins is likely ...to be intimately linked to mechanisms that are responsible for gastrointestinal tolerance to large numbers of commensal microbes. Here we review our current understanding of the immune mechanisms responsible for oral tolerance and how perturbations in these mechanisms might promote the loss of oral tolerance and development of food allergies. Roles for the commensal microbiome in promoting oral tolerance and the association of intestinal dysbiosis with food allergy are discussed. Growing evidence supports cutaneous sensitization to food antigens as one possible mechanism leading to the failure to develop or loss of oral tolerance. A goal of immunotherapy for food allergies is to induce sustained desensitization or even true long-term oral tolerance to food allergens through mechanisms that might in part overlap with those associated with the development of natural oral tolerance.
In Pseudomonas fluorescens Pf0-1 the availability of inorganic phosphate (Pi) is an environmental signal that controls biofilm formation through a cyclic dimeric GMP (c-di-GMP) signaling pathway. In ...low Pi conditions, a c-di-GMP phosphodiesterase (PDE) RapA is expressed, depleting cellular c-di-GMP and causing the loss of a critical outer-membrane adhesin LapA from the cell surface. This response involves an inner membrane protein LapD, which binds c-di-GMP in the cytoplasm and exerts a periplasmic output promoting LapA maintenance on the cell surface. Here we report how LapD differentially controls maintenance and release of LapA: c-di-GMP binding to LapD promotes interaction with and inhibition of the periplasmic protease LapG, which targets the N-terminus of LapA. We identify conserved amino acids in LapA required for cleavage by LapG. Mutating these residues in chromosomal lapA inhibits LapG activity in vivo, leading to retention of the adhesin on the cell surface. Mutations with defined effects on LapD's ability to control LapA localization in vivo show concomitant effects on c-di-GMP-dependent LapG inhibition in vitro. To establish the physiological importance of the LapD-LapG effector system, we track cell attachment and LapA protein localization during Pi starvation. Under this condition, the LapA adhesin is released from the surface of cells and biofilms detach from the substratum. This response requires c-di-GMP depletion by RapA, signaling through LapD, and proteolytic cleavage of LapA by LapG. These data, in combination with the companion study by Navarro et al. presenting a structural analysis of LapD's signaling mechanism, give a detailed description of a complete c-di-GMP control circuit--from environmental signal to molecular output. They describe a novel paradigm in bacterial signal transduction: regulation of a periplasmic enzyme by an inner membrane signaling protein that binds a cytoplasmic second messenger.
T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe of foreign antigens, is generated in the first two decades of life in the thymus and then persists to an ...unknown extent through life via homeostatic proliferation of naïve T cells. We have used next-generation sequencing and nonparametric statistical analysis to estimate a lower bound for the total number of different TCR beta (TCRB) sequences in human repertoires. We arrived at surprisingly high minimal estimates of 100 million unique TCRB sequences in naïve CD4 and CD8 T-cell repertoires of young adults. Naïve repertoire richness modestly declined two-to fivefold in healthy elderly. Repertoire richness contraction with age was even less pronounced for memory CD4 and CD8 T cells. In contrast, age had a major impact on the inequality of donai sizes, as estimated by a modified Gini-Simpson index clonality score. In particular, large naïve T-cell clones that were distinct from memory clones were found in the repertoires of elderly individuals, indicating uneven homeostatic proliferation without development of a memory cell phenotype. Our results suggest that a highly diverse repertoire is maintained despite thymic involution; however, peripheral fitness selection of T cells leads to repertoire perturbations that can influence the immune response in the elderly.
► Heat treatments produce two distinct TRIP microstructures: equiaxed and lamellar. ► 100
s bainite hold time produces highest level of retained austenite and strain at UTS. ► Lamellar microstructure ...has higher sustained work hardening rate in uniaxial tension. ► Sustained work hardening directly related to higher retained austenite stability.
Retained austenite is a metastable phase in transformation induced plasticity (TRIP) steels that transforms into martensite under local stress and strain. This transformation improves sheet formability, allowing this class of higher strength steels to be used for applications such as automotive structural components. The current work studies two distinct TRIP steel microstructures, i.e. equiaxed versus lamellar, and how microstructure affects the austenite transformation during uniaxial tensile loading. Different heat treatments were employed to obtain the two microstructures, and the bainite hold times of the treatments were varied to change the volume fraction of retained austenite. Based on uniaxial tensile response and magnetic saturation measurements, the bainite hold time of 100
s was determined to produce the best results in terms of largest strain at the ultimate tensile strength and highest volume fraction of retained austenite. The work hardening of the samples with a 100
s bainite hold was evaluated by calculating the instantaneous
n value as a function of strain. It was found that the lamellar microstructure has a lower maximum instantaneous
n value than the equiaxed microstructure, but has higher work hardening values for strain levels greater than 0.05 and up to the ultimate tensile strength. This difference in work hardening behaviour corresponds directly to the transformation rate of retained austenite in the two microstructures. The slower rate of transformation in the lamellar microstructure allows for work hardening to persist at high strains where the transformation effect has already been exhausted in the equiaxed microstructure. The different rates of transformation can be attributed to the location, carbon content, and size of the retained austenite grains in the respective TRIP microstructures.
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