Miracle-dz/UniFAR-FTUs huggingface dataset:
An investigation of new toxicity test method performance in validation studies: 1. toxicity test methods that have predictive capacity no greater than chance

An approach commonly used to measure new toxicity test method (NTM) performance in validation studies is to divide toxicity results into positive and negative classifications, and then identify true positive (TP), true negative (TN), false positive (FP) and false negative (FN) results. After this step is completed, the contingent probability statistics (CPS), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) are calculated. Although these statistics are widely used and often the only statistics used to assess the performance of toxicity test methods, there is little specific guidance in the validation literature on what values for these statistics indicate adequate performance. The purpose of this study was to begin developing data-based answers to this question by characterizing the CPS obtained from an NTM whose data have a completely random association with a reference test method (RTM). Determining the CPS of this worst-case scenario is useful because it provides a lower baseline from which the performance of an NTM can be judged in future validation studies. It also provides an indication of relationships in the CPS that help identify random or near-random relationships in the data. The results from this study of randomly associated tests show that the values obtained for the statistics vary significantly depending on the cut-offs chosen, that high values can be obtained for individual statistics, and that the different measures cannot be considered independently when evaluating the performance of an NTM. When the association between results of an NTM and RTM is random the sum of the complementary pairs of statistics (sensitivity+ specificity, NPV+PPV) is approximately 1, and the prevalence (i.e., the proportion of toxic chemicals in the population of chemicals) and PPV are equal. Given that combinations of high sensitivity–low specificity or low specificity–high sensitivity (i.e., the sum of the sensitivity and specificity equal to approximately 1) indicate lack of predictive capacity, an NTM having these performance characteristics should be considered no better for predicting toxicity than by chance alone.
Knowledge about Glaucoma in the Unselected Population: A German Survey

PurposeTo determine the general population's knowledge about glaucoma. Materials and MethodsA representative survey of the German population was conducted in which 2,742 men and women were interviewed face to face. The sample was matched with the German population for age, sex, education, income, and other factors. Questions were asked concerning the nature, occurrence, possible risk factors, and course of glaucoma. ResultsFifty-one percent of the population had an active knowledge of the term “glaucoma” and 75% had a passive knowledge of the term. Of those interviewees with a passive knowledge, glaucoma was thought to be associated with raised intraocular pressure (IOP) by 28% and loss of visual field (14%) but also with corneal (14%) or lens disease (10%). Only 8.4% correctly recognized a basic glaucoma definition. Suspected symptoms were blurred vision (39%), pain (28%), or reading difficulties (22%). Twenty-nine percent of respondents believed that one is able to feel increased IOP. Prevention of visual loss was believed to be possible by reading (16%) or smoking less (11%). Therapeutic measures known were surgery (63%), laser treatment (26%), and medical treatment (23%). Information about glaucoma was mainly obtained from friends (44%), and less often from doctors (13%). ConclusionsIn a large representative sample of the population, knowledge about glaucoma, its signs and symptoms, risk factors, treatment, and possible outcome is poor. Lack of knowledge in the general population may be an important cause for failure to detect glaucoma and may result in blindness from the disease.
2 Role of Insulin‐Like Growth Factor‐I in the Regulation of Skeletal Muscle Adaptation to Increased Loading

Adaptations in muscle mass stimulated by changes in muscle loading state entail alternations in the synthesis and degradation of myofiber proteins and the modulation of myonuclear number such that the ratio between the number of myonuclei and the size of the myofibers remains relatively constant. As depicted schematically in Figure 2.6, the literature regarding the role of IGF-in mediating muscle adaptation to alterations in loading state suggests the following conclusions: During periods of increased loading, myofibers upregulate the expression and secretion of IGF-I. Acting as an autocrine and/or paracrine growth factor, IGF-I stimulates myofiber anabolic processes. Acting as a paracrine growth factor, IGF-I also stimulates adjacent satellite cells to enter the cell cycle and proliferate. Continued myofiber production of IGF-I stimulates some satellite cells to differentiate and then fuse with myofibers, thus providing additional myonuclei in order to maintain or reestablish the myonucleus to myofiber size ratios of the enlarged myofibers.
Bacterial Lipopolysaccharide Signaling Through Toll-Like Receptor 4 Suppresses Asthma-Like Responses Via Nitric Oxide Synthase 2 Activity1

Asthma results from an intrapulmonary allergen-driven Th2 response and is characterized by intermittent airway obstruction, airway hyperreactivity, and airway inflammation. An inverse association between allergic asthma and microbial infections has been observed. Microbial infections could prevent allergic responses by inducing the secretion of the type 1 cytokines, IL-12 and IFN-γ. In this study, we examined whether administration of bacterial LPS, a prototypic bacterial product that activates innate immune cells via the Toll-like receptor 4 (TLR4) could suppress early and late allergic responses in a murine model of asthma. We report that LPS administration suppresses the IgE-mediated and mast cell-dependent passive cutaneous anaphylaxis, pulmonary inflammation, airway eosinophilia, mucus production, and airway hyperactivity. The suppression of asthma-like responses was not due to Th1 shift as it persisted in IL-12−/− or IFN-γ−/− mice. However, the suppressive effect of LPS was not observed in TLR4- or NO synthase 2-deficient mice. Our findings demonstrate, for the first time, that LPS suppresses Th2 responses in vivo via the TLR4-dependent pathway that triggers NO synthase 2 activity.
Advances in auditory prostheses.

PURPOSE OF REVIEW Auditory prostheses use electric currents on multiple electrodes to stimulate auditory neurons and recreate auditory sensations in deaf people. Cochlear implants have restored hearing in more than 200 000 deaf adults and children to a level that allows most to understand speech. Here we review the reasons underlying these results and describe new directions in restoring hearing to additional patient populations and the design of new devices. RECENT FINDINGS From their early development about 50 years ago, cochlear implants have been well received and beneficial to people who had lost their hearing. Although those first implants did not allow high levels of speech understanding, they provided auditory information that worked synergistically with lip reading to improve communication. Present day cochlear implants provide excellent speech understanding in children and in postlingually deafened adults. Research is focused on improved signal processing and new electrode designs. Electric stimulation of the auditory brainstem can also produce excellent hearing in some children and adults. SUMMARY Auditory prostheses, both at the level of the sensory nerve and at the brainstem, can restore patterns of neural activation that are sufficient for high levels of speech understanding. These prostheses are not only clinically successful but also important tools for understanding sensory processing in the brain.
Hyperalgesia and blunted morphine analgesia in G protein-gated potassium channel subunit knockout mice

Our aim was to determine whether G protein-gated potassium (Kir3) channels contribute to thermonociception and morphine analgesia. Western blotting was used to probe for the presence of Kir3.1, Kir3.2, Kir3.3, and Kir3.4 subunits in the mouse brain and spinal cord. Hot-plate paw-lick latencies for wild-type, Kir3.2 knockout, Kir3.3 knockout, and Kir3.4 knockout mice were measured at 52°C and 55°C, following the s.c. injection of either saline or 10 mg/kg morphine. Paw-lick latencies for Kir3.4 knockout mice were similar to those of wild-type mice, consistent with the restricted expression pattern of Kir3.4 subunit in the mouse brain. In contrast, Kir3.2 knockout and Kir3.3 knockout mice displayed hyperalgesia at both temperatures tested, and both Kir3.2 knockout and Kir3.3 knockout mice displayed shorter paw-lick latencies following morphine administration, with Kir3.2 knockout mice exhibiting the more dramatic phenotype. Kir3.2/Kir3.3 double knockout mice displayed a greater degree of hyperalgesia than either the Kir3.2 knockout or Kir3.3 knockout mice, while performing similarly to Kir3.2 knockout mice following morphine administration. We conclude that G protein-gated potassium channels containing Kir3.2 and/or Kir3.3 play a significant role in responses to moderate thermal stimuli. Furthermore, the activation of Kir3 channels containing the Kir3.2 subunit contributes to the analgesia evoked by a moderate dose of morphine. As such, receptor-independent Kir3 channel agonists may represent a novel and selective class of analgesic agent.
Broadening of CD8+ cell responses in vaccine-based simian immunodeficiency virus controllers

Objective:In our prior study on a prophylactic T-cell-based vaccine, some vaccinated macaques controlled a simian immunodeficiency virus (SIV) challenge. These animals allowed viremia in the acute phase but showed persistent viral control after the setpoint. Here, we examined the breadth of postchallenge virus-specific cellular immune responses in these SIV controllers. Design:We previously reported that in a group of Burmese rhesus macaques possessing the MHC haplotype 90-120-Ia, immunization with a Gag-expressing vaccine results in nonsterile control of a challenge with SIVmac239 but not a mutant SIV carrying multiple cytotoxic T lymphocyte (CTL) escape gag mutations. In the present study, we investigated whether broader cellular immune responses effective against the mutant SIV replication are induced after challenge in those vaccinees that maintained wild-type SIVmac239 control. Methods:We analyzed cellular immune responses in these SIV controllers (n = 8). Results:These controllers elicited CTL responses directed against SIV non-Gag antigens as well as Gag in the chronic phase. Postvaccinated, prechallenge CD8+ cells obtained from these animals suppressed wild-type SIV replication in vitro, but mostly had no suppressive effect on the mutant SIV replication, whereas CD8+ cells in the chronic phase after challenge showed efficient antimutant SIV efficacy. The levels of in-vitro antimutant SIV efficacy of CD8+ cells correlated with Vif-specific CD8+ T-cell frequencies. Plasma viremia was kept undetectable even after the mutant SIV superchallenge in the chronic phase. Conclusion:These results suggest that vaccine-based wild-type SIV controllers can acquire CD8+ cells with the potential to suppress replication of SIV variants carrying CTL escape mutations.
Infant weight gain and childhood overweight status in a multicenter, cohort study.

OBJECTIVE To determine whether a rapid rate of weight gain in early infancy is associated with overweight status in childhood. DESIGN Prospective, cohort study from birth to age 7 years. SETTING Twelve sites across the United States. PARTICIPANTS Twenty-seven thousand, eight hundred ninety-nine (27 899) eligible participants born at full term between 1959 and 1965. MAIN OUTCOME MEASURE Overweight status at age 7 years, defined by a body mass index above the 95th percentile of the Centers for Disease Control and Prevention reference data. RESULTS In the 19 397 participants with complete data (69.6%), the prevalence of overweight status at age 7 years was 5.4%. The rate of weight gain during the first 4 months of life (as 100 g/month) was associated with being overweight at age 7 years, after adjustment for several confounding factors: odds ratio: 1.38; 95% confidence interval: 1.32-1.44. This association was present in each birth weight quintile, and remained significant after adjustment for the weight attained at age 1 year (odds ratio: 1.17; 95% confidence interval: 1.11-1.24). CONCLUSIONS A pattern of rapid weight gain during the first 4 months of life was associated with an increased risk of overweight status at age 7 years, independent of birth weight and weight attained at age 1 year. These findings may lead to new hypotheses regarding the cause of childhood obesity, which may contribute to our understanding of this increasing public health problem in the United States.
Effect of Drug Alprazolam on Restrained Stress Induced Alteration of Serum Cortisol and Antioxidant Vitamins (Vitamin C and E) in Male Albino Rats.

INTRODUCTION Stress can cause harmful effects in the body that induce a wide range of biochemical and behavioural changes. As anti-stress drugs are routinely used to combat stress hence study is needed to assess the contraindication of these drugs in the physiological systems. AIM To investigate the effect of alprazolam on restrained stress induced alteration of serum cortisol, and antioxidant vitamin levels in male albino rats. MATERIALS AND METHODS Adult male albino rats (body weight 175-225g) were divided into four groups of six animals in each. Group I (control), kept undisturbed in the metabolic cage throughout the 42 days experimental period. Group II (stress) rats were kept in a wire mesh restrainer for 6 hr/day for 42 days. Group III (stress+ withdrawal) rats were stressed for 21 days and withdrawal of stress for remaining 21 days (total 42 days). Group IV (stress + alprazolam) rats were only stressed for 21 days and treated with drug alprazolam (5mg/kg body weight, intraperitoneal) in continuation with stress for remaining 21 days (total period is 42 days). At the end of 42 days all the rats were sacrificed and serum cortisol, vitamin C and E levels were estimated. RESULTS Group II (stressed) showed a significant increase in serum cortisol level with concomitant decrease of serum vitamin C and E levels. Group III (withdrawal) and Group IV (+alprazolam) rats showed significant reduction of serum cortisol along with subsequent increase of serum vitamin C and E concentrations. CONCLUSION Results indicate a possible antioxidant effect of alprazolam on restrained stress induced alteration of serum cortisol and antioxidant vitamin levels.
BLAST OBSERVATIONS OF THE SOUTH ECLIPTIC POLE FIELD: NUMBER COUNTS AND SOURCE CATALOGS

We present results from a survey carried out by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST) on a 9 deg2 field near the South Ecliptic Pole at 250, 350, and 500 μm. The median 1σ depths of the maps are 36.0, 26.4, and 18.4 mJy, respectively. We apply a statistical method to estimate submillimeter galaxy number counts and find that they are in agreement with other measurements made with the same instrument and with the more recent results from Herschel/SPIRE. Thanks to the large field observed, the new measurements give additional constraints on the bright end of the counts. We identify 132, 89, and 61 sources with S/N ⩾4 at 250, 350, 500 μm, respectively and provide a multi-wavelength combined catalog of 232 sources with a significance ⩾4σ in at least one BLAST band. The new BLAST maps and catalogs are available publicly at http://blastexperiment.info.
Regulation of lung surfactant secretion by intracellular pH.

We investigated secretion of lung surfactant phosphatidylcholine (PC) using isolated perfused rat lung preparation after labeling the lung lipids in vitro with [methyl-3H]choline. The perfusion medium was Krebs-Ringer bicarbonate buffer (pH 7.4) containing 10 mM glucose and 3% fatty acid-poor bovine serum albumin. After ventilation of lungs with air containing 5% CO2 (control) for 1 h, 0.91% +/- 0.04 (mean +/- SE, n = 6) of total lung lipid radioactivity (greater than 95% in PC) was recovered in the cell-free lavage fluid. The secretion of PC was increased with terbutaline (50 microM), 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP, 100 microM), phorbol L2-myristate 13-acetate (30 ng/ml), and ATP (1 mM), in each case by approximately 150%. Secretion of PC was also increased by 160% if the lungs were ventilated with air containing 0% CO2. The low CO2-mediated PC secretion was time and concentration dependent. The dose-response curve for 0-10% CO2 was S-shaped. The low CO2-induced increase in PC secretion could be largely reversed with diffusible weak acids (25 mM, acetate or butyrate) in the perfusion medium. An increase (70%) in secretion was also induced with 10 mM NH4Cl, suggesting a role for intracellular alkalosis. These observations suggest that intracellular alkalosis stimulates lung surfactant secretion. Alkalosis-stimulated secretion of PC was additive with that with terbutaline (5 X 10(-7) to 5 X 10(-4) M) or 10(-4) M 8-BrcAMP, suggesting that alkalosis effect was not mediated through the beta-adrenergic pathway of surfactant secretion. (ABSTRACT TRUNCATED AT 250 WORDS)
Creating Domain-Specific Sentiment Lexicons via Text Mining

Sentiment analysis aims to identify and categorize customer’s opinion and judgments using either traditional supervised learning techniques or unsupervised approaches. Traditionally, Sentiment Analysis is performed using machine learning techniques such as a naive Bayes classification or support vector machines (SVM), or could make use of a sentiment lexicon, that is, a list of words that are mapped to a sentiment score. Our work focuses on generating a domain-specific lexicon using probabilities and information theoretic techniques. By employing text mining, we overcome the poor performance of transferred supervised machine learning techniques and remove the need to adapt an existing lexicon while maintaining accuracy. We show that text mining techniques performs as well as traditional approaches and we demonstrate that domain specific lexicons perform better than general lexicons in a sentiment analysis task. We further review and compare the generated lexicons.
Virulence Attenuation and Live Vaccine Potential of aroA, crp cdt cya, and Plasmid-Cured Mutants of Salmonella enterica Serovar Abortusovis in Mice and Sheep

ABSTRACT Three live vaccine candidates of Salmonella enterica subspecies I serotype Abortusovis (aroA, cya crp cdt, and plasmid-cured strains) have been developed, and their efficacies in inducing humoral antibodies and protecting against abortion after challenge with wild-type strain SS44 were evaluated in sheep. Following estrus synchronization, animals were immunized 3 weeks after fertilization and boosted once 3 weeks later. Following challenge with wild-type SS44, pregnancy failure of vaccinated ewes was reduced compared to that of nonimmunized controls. Attenuation of each vaccine was also assessed in challenge experiments with nonimmunized pregnant ewes and in BALB/c mice. All three vaccine candidates appear to be safe for use in sheep and provide a model for the development of live vaccine candidates against naturally occurring ovine salmonellosis.
Blockade of angiotensin II provides additional benefits in hypertension- and ageing-related cardiac and vascular dysfunctions beyond its blood pressure-lowering effects

Objectives To assess the blockade of the renin–angiotensin system (RAS) or blood pressure-lowering on cardiovascular functions in hypertensive and ageing animals. Methods Male spontaneously hypertensive rats (SHR) and their normotensive counterparts, Wistar–Kyoto rats (WKY), at the ages of 3–4 (young), 34–35 (adult) and 74–75 (old) weeks were treated with an angiotensin II type 1 receptor antagonist, losartan (25 mg/kg) or a combination of a smooth muscle relaxant and a diuretic [H/H, hydralazine (50 mg/kg) plus hydrochlorothiazide (7.5 mg/kg), respectively] for 8 weeks. Each experimental group contained 10 SHR and 10 WKY, where equal numbers of untreated animals served as controls. Results Compared to age-matched WKY groups, SHR groups possessed, on average, 48 ± 7 mmHg and 57 ± 16 mmHg (P < 0.05) higher systolic blood pressure and left ventricular developed pressures, respectively. The values of these parameters were significantly lowered in both strains by both treatment regimens. SHR had higher heart rates, which were increased by H/H treatment selectively in adult and old animal groups of both strains. Both treatment regimens enhanced KCl-mediated, that is, receptor-independent, aortic contractile responses and bradykinin-mediated coronary vasodilatation in adult and old WKY and SHR age-groups. Although both therapies augmented endothelium-dependent and endothelium-independent relaxant responses in young and adult, but not in old, SHR aortas to the levels observed in age-matched WKY, these beneficial effects were more prominent with losartan. Moreover, losartan reduced heart to body weight ratio in all SHR age groups, and selectively in the old WKY group. Conclusions Blockade of RAS provides a better protective effect on cardiovascular function compared to sole reduction of blood pressure, and the efficacy of antihypertensive treatment is dictated by age and the hypertensive stage of the animals.
Measurement Characteristics of a Force-Displacement Curve for Chronic Patellar Instability

Objective:The clinical diagnosis of patellar instability is subjective, depending on the patient's apprehension. We hypothesized that a subjective diagnosis could be supported by a numerical evaluation of the slope, or compliance, of the early phase of a force-displacement curve. Design:Cross-sectional control group comparison. Setting:A university-based sports clinic. Participants:Healthy volunteers (n = 21; 16-40 years old) and patients (n = 21; 15-34 years old) who had a clearly definable diagnosis of unilateral dislocation, followed by chronic anterior knee pain, and positive apprehension signs for more than 6 months, without patella alta or abnormal limb alignment. Intervention:Lateral displacement and reactive forces were measured with a Patella Stability Tester. Main Outcome Measures:Sensitivity in detecting injured knees was defined, with the 95% confidence interval of healthy subjects determined as the normal range. Results:Compliance at 5 mm in displacement showed the highest reproducibility (plot difference of 4.7%) and the highest sensitivity (95%). Among injured knees, compliance was significantly correlated with the activity-related symptoms of the Kujala score (correlation coefficient, −0.61; P = 0.004). Compliance at 5 mm of displacement showed the highest sensitivity (95%) and significant correlation with the activity-related symptoms of the Kujala score among injured knees (coefficient of determination, 0.37; P = 0.004). Conclusions:It is a novel finding that early compliance at 5 mm of displacement showed a correlation with the subjective diagnosis and symptoms.