Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted Sos1 deletion reveals its critical role in early T-cell development

Activation of the small G protein Ras is required for thymocyte differentiation. In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1. We report the development of a floxed allele of sos1 to assess the role of Sos1 during thymocyte development. Sos1 was required for pre–T-cell receptor (pre-TCR)– but not TCR-stimulated developmental signals. Sos1 deletion led to a partial block at the DN-to-DP transition. Sos1-deficient thymocytes showed reduced pre-TCR–stimulated proliferation, differentiation, and ERK phosphorylation. In contrast, TCR-stimulated positive selection, and negative selection under strong stimulatory conditions, remained intact in Sos1-deficient mice. Comparison of RasGEF expression at different developmental stages showed that relative to Sos2 and RasGRP1, Sos1 is most abundant in DN thymocytes, but least abundant in DP thymocytes. These data reveal that Sos1 is uniquely positioned to affect signal transduction early in thymocyte development.
Cross-sectional study of the isokinetic muscle trunk strength among school children.

Our surveys have shown lifetime prevalence of L.BP. over 30% among schoolchildren. The purpose of this study was to evaluate the relationship between back and isokinetic trunk strength, anthropometric parameters, and sports activities. One hundred and seventeen healthy children aged 10-16 years were included. All these volunteers had semi-structured interview, anthropometric and dynamic strength measurements. Lifetime prevalence of back pain was 44.5% and point prevalence was 13%. In this cross-sectional study, anthropometric and strength profiles were significantly related to age and gender. Non specific low back pain was not correlated to trunk muscle strength and/or sports activities.
Incidence of leukemia in atomic bomb survivors belonging to a fixed cohort in Hiroshima and Nagasaki, 1950--71. Radiation dose, years after exposure, age at exposure, and type of leukemia.

Department of Hematology, Atomic Disease Institute, Nagasaki University School of Medicine 2Department of Epidemiology and Statistics, Radiation Effects Research Foundation, Hiroshima, Department of Epidemiology, Faculty of Medicine, Tokyo University 3Division of Medicine, The Community Health Center Danbury Hospital, U.S.A.the former Chief of Department of Medicine, Atomic Bomb Casualty Commission, Hiroshima (Received January 23, 1978; Revised version received July 17, 1978)
The Social Antecedents of Anger Proneness in Young Adulthood

Anger has been shown to be an important factor in occupational maladjustment, family conflict, physical and sexual assault, criminal behavior, and substance abuse. It has also been linked with such adverse health outcomes as hypertension, heart disease, and cancer. Focusing on anger proneness, conceptualized as a relatively enduring propensity to experience and express anger, this article examines both early and recent antecedent factors that predict and may condition levels of anger proneness. The roles of both prospectively and retrospectively assessed factors are considered. Data from an ethnically diverse and representative sample of young adults reveals clear gender differences and, at least for short-tempered anger, decreasing levels of anger with increasing socioeconomic status. Prior exposure to violent events, prior exposure to other forms of social stress, and certain personal attributes were found to be significant antecedents of both hostility and short-tempered forms of anger proneness.
Protective Effects of Volatile Agents against Methacholine-induced Bronchoconstriction in Rats

BackgroundThe protective properties of common volatile agents against generalized lung constriction have previously been addressed only via estimations of parameters that combine airway and tissue mechanics. Their effectiveness in preventing airway constriction have not been compared systematically. Therefore, the authors investigated the abilities of halothane, isoflurane, sevoflurane, and desflurane to provide protection against airway constriction induced by methacholine. MethodsLow-frequency pulmonary impedance data were collected in open-chest rats under baseline conditions and during three consecutive intravenous infusions of methacholine (32 &mgr;g · kg−1 · min−1) while the animals were anesthetized with intravenous pentobarbital (control group). Methacholine challenges were performed in four other groups of rats, first during intravenous anesthesia and then repeated during the inhalation of halothane, isoflurane, sevoflurane, or desflurane at concentrations of 1 and 2 minimum alveolar concentration (MAC). Airway resistance and inertance, parenchymal damping, and elastance were estimated from the impedance data by model fitting. ResultsThe methacholine-induced increases in airway resistance during intravenous pentobarbital anesthesia (204 ± 53%) were markedly and significantly (P < 0.005) reduced by 1-MAC doses of halothane (80 ± 48%), isoflurane (112 ± 59%), sevoflurane (68 ± 34%), and desflurane (96 ± 34%), with no significant difference between the gases applied. Increasing the concentration to 2 MAC did not lead to any significant further protection against the increase in airway resistance. ConclusionsThese data demonstrate that isoflurane, sevoflurane, and desflurane are as effective as the widely accepted halothane in protecting against methacholine-induced airway constriction.
Peripheral Autoimmune Regulator Induces Exhaustion of CD4+ and CD8+ Effector T Cells to Attenuate Autoimmune Diabetes in Non-Obese Diabetic Mice

Autoimmune regulator (Aire) is one of the most crucial genes expressed in the thymus, where it orchestrates the promiscuous expression and presentation of tissue-specific antigens during thymocyte selection. The presence of Aire-expressing cells outside the thymus points toward its plausible extrathymic functions; however, the relative contribution of Aire-expressing cells of hematopoietic origin and their role in the modulation of autoimmune diseases are still obscure. Here, we report that non-obese diabetic mice with transgenic Aire expression under the control of the CD11c (integrin alpha X) promoter were significantly protected from autoimmune diabetes compared with their non-transgenic littermates. The protective effect of Aire transgene was mediated primarily by an increase in the “exhausted” populations of CD4+ and CD8+ T cells, both demonstrating poor expressions of interferon-γ and tumor necrosis factor-α. Both CD4+ and CD8+ effector T cells in transgenic mice displayed distinctive and differential expression of T-bet and Eomesodermin, respectively, in conjunction with high expression of programmed cell death protein-1 and other exhaustion-associated markers. Importantly, transgenic Aire expression did not result in any detectable changes in the population of Foxp3+ regulatory T (Treg) cells. Co-transfer experiments also demonstrated that Aire transgenic dendritic cells, as a “stand-alone” cell population, had the potential to suppress effector T cells in vivo without the support of Treg cells, but eventually failed to prevent the diabetogenesis in recipient mice. In conclusion, our study suggests that apart from its role in clonal deletion of autoreactive T cells or clonal diversion to Treg lineage, Aire can also contribute to tolerance by forcing effector T cells into a state of exhaustion with poor effector functions, thereby effectively containing autoimmune diseases.
Variation beneath the surface: Quantifying complex thermal environments on coral reefs in the Caribbean, Bahamas and Florida

Analysis of in situ temperature records collected on six coral reefs in the Caribbean, Bahamas, and Florida Keys reveal significant variability across a range of temporal and spatial scales from minutes to seasons, across depths, and among sites. Subsurface variability occurring at daily and faster frequencies is prevalent across the region, likely driven by combinations of diurnal heating and cooling, wind driven advection, and internal waves at tidal and faster frequencies. This high frequency variability is not detected in records of remotely-sensed sea surface temperature alone. Diurnal variability likely caused by diurnal solar heating and cooling and possibly by advection associated with diurnal winds (daily sea breeze) was significant at all sites and showed greatest magnitude of variation at shallowest depths. Temperature fluctuations at tidal and faster frequencies were common at 5 out of the 6 sites. The magnitude of this variability is not well explained by measured vertical temperature stratification combined with oscillations of the water column associated with barotropic surface tides. Rather, the magnitude and nature of the temperature changes point to the presence of internal waves generated at tidal and faster frequencies. Power spectra calculated seasonally show greatest variability within both diurnal and semi-diurnal frequency bands in Spring and Summer at Florida, Bahamas, Jamaica, and St. Croix. Variability within the semi-diurnal frequency band at Belize and Bonaire was greatest in Winter. Warming in Summer estimated as degree-hours per day above 29.0°C increased with increasing latitude and varied significantly among sites and depths in a manner not predictable from remotely sensed SST data alone. Site latitude was directly related to the amplitude of the seasonal thermal variability, but was not tightly related to variability at daily and faster frequencies which was greatest at the highest and lowest latitude sites. The interactions of depth, site, and season across the study region are associated with distinct signals of thermal variability, and have significant implications for the physiology and ecology of corals and other reef organisms.
Escherichia coli O104:H4 outbreak in Germany.

To the Editor: In their article on last year’s outbreak of Escherichia coli O104:H4 in Germany, Frank et al. (Nov. 10 issue)1 report some striking features. Nearly 90% of patients were adults (median age, 42 years), with an overrepresentation of women (68%). In pediatric series, girls also predominate over boys but not to such a marked degree.2 Moreover, the attack rate of the hemolytic–uremic syndrome associated with diarrhea (845 of 3816 cases, or 22%) in Germany exceeded the rate of 5 to 15% in most previous reports of outbreaks. In children, the administration of antibiotics to empirically treat the prodromal enteritis has been associated with a significantly increased risk of progression to the hemolytic– uremic syndrome.3,4 This finding is supported by preclinical data in the infection model in the gnotobiotic piglet.5 The pattern of antibiotic use to treat bloody diarrhea may differ between children and adults. This may explain the high proportion of patients with the hemolytic–uremic syndrome in the German outbreak, independent of the pathogenicity of the unusual bacterial strain. Clarification of antibiotic use to treat the antecedent enteritis may shed light on this particular outbreak and help guide the prescription of antibiotics in patients with gastroenteritis and bloody diarrhea. Howard Trachtman, M.D.
Snail1 is over‐expressed in prostate cancer

Transcription factor Snail1 is a mediator of cell migration and survival, and expression is elevated in several cancer types. The Snail1 gene is reportedly amplified in prostate cancer (PC), and we investigated Snail1 expression in PC. Immunohistochemical Snail1 staining was determined on a tissue microarray which includes 327 specimens of PC, 30 specimens from patients with benign prostatic hyperplasia (BPH), benign tissue from 30 PC patients and 15 high‐grade prostate intraepithelial neoplasia (high‐grade PIN) specimens. Clinicopathological and follow‐up data were available for all patients. No BPH specimen and only 21% of benign tissue from PC patients showed high expression of Snail1. Only 7% of high‐grade PIN patients expressed a high level of Snail1. In contrast, approximately 50% of PC tissue from patients with PC showed marked nuclear immunostaining. Snail1 immunostaining was significantly associated with Gleason score (p<0.05). Snail1 expression was not correlated to T stage, metastasis at time of diagnosis, risk of or time to recurrence. Snail1 expression was significantly increased in PC with a positive correlation to dedifferentiation, but not to cancer progression or prognosis. The presented data indicate that Snail1 expression is upregulated from the early stages of PC.
The eating disorder examination-questionnaire 8: A brief measure of eating disorder psychopathology (EDE-Q8).

OBJECTIVE The aim of this study was to develop, evaluate, and standardize a short form of the well-established Eating Disorder Examination-Questionnaire (EDE-Q). The newly developed EDE-Q8 was required to reflect the originally postulated structure of the EDE-Q. METHOD Data were drawn from two nationwide representative population surveys in Germany: a survey conducted to develop the EDE-Q8 in 2009 (N = 2,520); and a survey conducted in 2013 (N = 2,508) for the evaluation and calculation of EDE-Q8 percentiles. RESULTS The EDE-Q8 had excellent item characteristics, very good reliability and a very good model fit for the postulated second-order factorial structure. Furthermore, a strong correlation between the EDE-Q8 and a 13 item short form of the Eating Attitudes Test was observed. DISCUSSION The EDE-Q8 appears to be particularly suitable in epidemiological research, when an economical assessment of global eating disorder psychopathology is required. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:613-616).
A Finite Element Model of the Human Buttocks for Prediction of Seat Pressure Distributions

Seating comfort is becoming increasingly important for the automotive industry. Car manufacturers use seating comfort to distinguish their products from those of competitors. However, the development and design of a new, more comfortable seat is time consuming and costly. The introduction of computer models of human and seat will accelerate this process. The contact interaction between human and seat is an important factor in the comfort sensation of subjects. This paper presents a finite element (FE) model of the human buttocks, able to predict the pressure distribution between human and seating surface by its detailed and realistic geometric description. A validation study based on volunteer experiments shows reasonable correlation in pressure distributions between the buttocks model and the volunteers. Both for simulations on a rigid and a soft cushion, the model predicts realistic seat pressure distributions. A parameter study shows that a pressure distribution at the interface between human and seat strongly depends on variations in human flesh and seat cushion properties.
Time-Randomized Stopping Problems for a Family of Utility Functions

This paper studies stopping problems of the form $V=\inf_{0 \leq \tau \leq T} \mathbb{E}[U(\frac{\max_{0\le s \le T} Z_s }{Z_\tau})]$ for strictly concave or convex utility functions U in a family of increasing functions satisfying certain conditions, where Z is a geometric Brownian motion and T is the time of the nth jump of a Poisson process independent of Z. We obtain some properties of $V$ and offer solutions for the optimal strategies to follow. This provides us with a technique to build numerical approximations of stopping boundaries for the fixed terminal time optimal stopping problem presented in [J. Du Toit and G. Peskir, Ann. Appl. Probab. , 19 (2009), pp. 983--1014].
In Vivo Studies of an Implantable Energy Convertor for Skeletal Muscle Powered Cardiac Assist

A device that harnesses the mechanical energy of skeletal muscle contracting in a linear configuration has been implanted in goats. This energy convertor transforms muscle work to hydraulic energy that could drive a variety of cardiac assist devices. The device is mounted with a rib clamp and plate affixed to the sternum by cortical bone screws. A transcutaneous hydraulic line carries a silicon based working fluid to an external system that controls the muscle load. In 60 to 70 kg goats, the latissimus dorsi insertion was reattached to the energy convertor. A Telectronics myostimulator with intramuscular electrodes stimulated the latissimus dorsi. In acute implants, hydraulic pressures in excess of 150 psi were obtained. Chronic implantation of the device allowed system evaluation in the conscious unanesthetized animal. Two weeks after implant, hydraulic pressures in excess of 200 psi were obtained and energy transferred to the external loading system exceeded 1 J per contraction. Six weeks after implant, the device continued to cycle freely. These initial results are very promising and suggest an implantable energy convertor is feasible. Development of an energy convertor is an important step toward tether-free skeletal muscle powered cardiac assist devices.
Beta-d-Glucan Detection as a Diagnostic Test for Invasive Aspergillosis in Immunocompromised Critically Ill Patients with Symptoms of Respiratory Infection: an Autopsy-Based Study

ABSTRACT Beta-(1,3)-d-glucan (BG) detection is an emerging tool to diagnose invasive fungal infections (IFIs). Invasive aspergillosis (IA) is the second most common IFI in immunocompromised intensive care unit (ICU) patients. We retrospectively analyzed the serum BG concentration (Fungitell; Associates of Cape Cod) in immunocompromised ICU patients with proven IA and in immunocompromised ICU patients in whom autopsy failed to show IFI. The study was performed in a 17-bed medical ICU in a 1,900-bed referral hospital. Patients at risk for IA were eligible for inclusion when at least two additional clinical signs were present. Patients with other IFIs were excluded. Fourteen patients with IA and 33 patients who had no IFI were eligible for inclusion. Serum BG levels were significantly higher in patients with IA than patients without an IFI (P < 0.01). Using a cutoff of 140 pg/ml, the sensitivity and specificity were 85.7 and 69.7%, respectively; the positive and negative predictive values were 54.5 and 92.0%, respectively. The positive and negative likelihood ratios were 2.83 and 0.21, respectively. Although serum BG concentrations were higher in immunocompromised ICU patients with IA than in patients with the same risk factors who did not have IFI on autopsy, the moderate performance characteristics of this test limit its use as a diagnostic test for IA in this population.
Investigation on the Ability of an Ultrasound Bubble Detector to Deliver Size Measurements of Gaseous Bubbles in Fluid Lines by Using a Glass Bead Model

Detectors based on ultrasonic principles are today’s state of the art devices to detect gaseous bubbles that may be present in extracorporeal circuits (ECC) for various reasons. Referring to theoretical considerations and other studies, it also seems possible to use this technology to measure the size of detected bubbles, thus offering the chance to evaluate their potential hazardous effect if introduced into a patient’s circulation. Based on these considerations, a commercially available ultrasound bubble detector has been developed by Hatteland Instrumentering, Norway, to deliver bubble size measurements by means of supplementary software. This device consists of an ultrasound sensor that can be clamped onto the ECC tubing, and the necessary electronic equipment to amplify and rectify the received signals. It is supplemented by software that processes these signals and presents them as specific data. On the basis of our knowledge and experience with bubble detection by ultrasound technology, we believe it is particularly difficult to meet all the requirements for size measurements, especially if these are to be achieved by using a mathematical procedure rather than exact devices. Therefore, we tried to evaluate the quality of the offered bubble detector in measuring bubble sizes. After establishing a standardized test stand, including a roller pump and a temperature sensor, we performed several sets of experiments using the manufacturers software and a program specifically designed at our department for this purpose. The first set revealed that the manufacturer’s recommended calibration material did not meet essential requirements as established by other authors. Having solved that problem, we could actually demonstrate that the ultrasonic field, as generated by the bubble detector, has been correctly calculated by the manufacturer. Simply, it is a field having the strongest reflecting region in the center, subsequently losing strength toward the ECC tubing’s edge. The following set of experiments revealed that the supplementary software not only does not compensate for the ultrasonic field’s inhomogeneity, but, furthermore, delivers results that are inappropriate to the applied calibration material. In the last set of experiments, we were able to demonstrate that the signals as recorded by the bubble detector heavily depend upon the circulating fluid’s temperature, a fact that the manufacturer does not address. Therefore, it seems impossible to resolve all these sensor related problems by ever-increasing mathematical intervention. We believe it is more appropriate to develop a new kind of ultrasound device, free of these shortcomings. This seems to be particularly useful, because the problem of determining the size of gaseous bubbles in ECC is not yet solved.
Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS)

Transgenic overexpression of Cu+2/Zn+2 superoxide dismutase 1 (SOD1) harboring an amyotrophic lateral sclerosis (ALS)-linked familial genetic mutation (SOD1G93A) in a Sprague–Dawley rat results in ALS-like motor neuron disease. Motor neuron disease in these rats depended on high levels of mutant SOD1 expression, increasing from 8-fold over endogenous SOD1 in the spinal cord of young presymptomatic rats to 16-fold in end-stage animals. Disease onset in these rats was early, ≈115 days, and disease progression was very rapid thereafter with affected rats reaching end stage on average within 11 days. Pathological abnormalities included vacuoles initially in the lumbar spinal cord and subsequently in more cervical areas, along with inclusion bodies that stained for SOD1, Hsp70, neurofilaments, and ubiquitin. Vacuolization and gliosis were evident before clinical onset of disease and before motor neuron death in the spinal cord and brainstem. Focal loss of the EAAT2 glutamate transporter in the ventral horn of the spinal cord coincided with gliosis, but appeared before motor neuron/axon degeneration. At end-stage disease, gliosis increased and EAAT2 loss in the ventral horn exceeded 90%, suggesting a role for this protein in the events leading to cell death in ALS. These transgenic rats provide a valuable resource to pursue experimentation and therapeutic development, currently difficult or impossible to perform with existing ALS transgenic mice.