Miracle-dz/UniFAR-FTUs huggingface dataset:
An alternative form and level of the human health ozone standard

Controlled human laboratory studies have shown that there is a disproportionately greater pulmonary function response from higher hourly average ozone (O3) concentrations than from lower hourly average values and thus, a nonlinear relationship exists between O3 dose and pulmonary function (FEV1) response. The nonlinear dose–response relationship affects the efficacy of the current 8-h O3 standard to describe adequately the observed spirometric response to typical diurnal O3 exposure patterns. We have reanalyzed data from five controlled human response to O3 health laboratory experiments as reported by , Adams (), and . These investigators exposed subjects to multi-hour variable/stepwise O3 concentration profiles that mimicked typical diurnal patterns of ambient O3 concentrations. Our findings indicate a common response pattern across most of the studies that provides valuable information for the development of a lung function (FEV1)–based alternate form for the O3 standard. Based on our reanalysis of the realistic exposure profiles used in these experiments, we suggest that an alternative form of the human health standard, similar to the proposed secondary (i.e., vegetation) standard form, be considered. The suggested form is an adjusted 5-h cumulative concentration weighted O3 exposure index, which addresses both the delay associated with the onset of response (FEV1 decrement) and the nonlinearity of response (i.e., the greater effect of higher concentrations over the mid- and low-range values) on an hourly basis.
Expected time for random genetic drift of a population between stable phenotypic states.

Natural selection and random genetic drift are modeled by using diffusion equations for the mean phenotype of a quantitative (polygenic) character in a finite population with two available adaptive zones or ecological niches. When there is appreciable selection, the population is likely to spend a very long time drifting around the peak in its original adaptive zone. With the mean phenotype initially anywhere near the local optimum, the expected time until a shift between phenotypic adaptive peaks increases approximately exponentially with the effective population size. In comparison, the expected duration of intermediate forms in the actual transition between adaptive peaks is extremely short, generally below the level of resolution in the fossil record, and increases approximately logarithmically with the effective population size. The evolutionary dynamics of this model conform to the pattern of current paleontological concepts of morphological "stasis" and "punctuated equilibria. "
Super-Suppression of Mitochondrial Reactive Oxygen Species Signaling Impairs Compensatory Autophagy in Primary Mitophagic Cardiomyopathy

Rationale: Mitochondrial reactive oxygen species (ROS) are implicated in aging, chronic degenerative neurological syndromes, and myopathies. On the basis of free radical hypothesis, dietary, pharmacological, and genetic ROS suppression has been tested to minimize tissue damage, with remarkable therapeutic efficacy. The effects of mitochondrial-specific ROS suppression in primary mitophagic dysfunction are unknown. Objective: An in vivo dose-ranging analysis of ROS suppression in an experimental cardiomyopathy provoked by defective mitochondrial clearance. Methods and Results: Mice lacking mitofusin 2 (Mfn2) in hearts have impaired parkin-mediated mitophagy leading to accumulation of damaged ROS-producing organelles and progressive heart failure. As expected, cardiomyocyte-directed expression of mitochondrial-targeted catalase at modest levels normalized mitochondrial ROS production and prevented mitochondrial depolarization, respiratory impairment, and structural degeneration in Mfn2 null hearts. In contrast, catalase expression at higher levels that supersuppressed mitochondrial ROS failed to improve either mitochondrial fitness or cardiomyopathy, revealing that ROS toxicity is not the primary mechanism for cardiac degeneration. Lack of benefit from supersuppressing ROS was associated with failure to invoke secondary autophagic pathways of mitochondrial quality control, revealing a role for ROS signaling in mitochondrial clearance. Mitochondrial permeability transition pore function was normal, and genetic inhibition of mitochondrial permeability transition pore function did not alter mitochondrial or cardiac degeneration, in Mfn2 null hearts. Conclusions: Local mitochondrial ROS (1) contribute to mitochondrial degeneration and (2) activate mitochondrial quality control mechanisms. A therapeutic window for mitochondrial ROS suppression should minimize the former while retaining the latter, which we achieved by expressing lower levels of catalase.
Regulators of calcium homeostasis and bone mineral density in patients with Crohn's disease.

BACKGROUND Several papers have reported on vitamin D, parathyroid hormone (PTH), and other regulators of calcium metabolism in patients with Crohn's disease, but results have been conflicting. Bone mineral density (BMD) has been found to be reduced in several papers. A recent study from our laboratory suggested that the expected reduction in BMD disappears when the patients are compared with sex-, age-, and weight-matched healthy controls. The relationship between BMD and regulators of calcium homeostasis is not well established in patients with Crohn's disease. METHODS BMD and biochemical regulators of calcium metabolism were measured in 115 unselected patients with Crohn's disease, most of whom were in remission. RESULTS Vitamin D deficiency (25-OHD < or = 10 pg/ml) was present in 44% of patients. Secondary hyperparathyroidism was present in 2% of unoperated patients and in 18% of patients subjected to bowel operations. CONCLUSIONS 1) Vitamin D deficiency is common in patients with Crohn's disease even when the disease is in remission and regardless of the location of the disease. 2) Secondary hyperparathyroidism is most frequently seen in patients who have undergone intestinal resection(s). 3) PTH correlates with BMD in a large group of unselected patients with Crohn's disease; 25-OHD only correlates with BMD of the forearm.
Cigarette graphic warning labels and smoking prevalence in Canada: a critical examination and reformulation of the FDA regulatory impact analysis

Background The estimated effect of cigarette graphic warning labels (GWL) on smoking rates is a key input to the Food and Drug Administration's (FDA) regulatory impact analysis (RIA), required by law as part of its rule-making process. However, evidence on the impact of GWLs on smoking prevalence is scarce. Objective The goal of this paper is to critically analyse FDA's approach to estimating the impact of GWLs on smoking rates in its RIA, and to suggest a path forward to estimating the impact of the adoption of GWLs in Canada on Canadian national adult smoking prevalence. Methods A quasi-experimental methodology was employed to examine the impact of adoption of GWLs in Canada in 2000, using the USA as a control. Findings We found a statistically significant reduction in smoking rates after the adoption of GWLs in Canada in comparison with the USA. Our analyses show that implementation of GWLs in Canada reduced smoking rates by 2.87–4.68 percentage points, a relative reduction of 12.1–19.6%; 33–53 times larger than FDA’s estimates of a 0.088 percentage point reduction. We also demonstrated that FDA’s estimate of the impact was flawed because it is highly sensitive to the changes in variable selection, model specification, and the time period analysed. Conclusions Adopting GWLs on cigarette packages reduces smoking prevalence. Applying our analysis of the Canadian GWLs, we estimate that if the USA had adopted GWLs in 2012, the number of adult smokers in the USA would have decreased by 5.3–8.6 million in 2013. Our analysis demonstrates that FDA’s approach to estimating the impact of GWLs on smoking rates is flawed. Rectifying these problems before this approach becomes the norm is critical for FDA’s effective regulation of tobacco products.
Noise robust exemplar-based connected digit recognition

This paper proposes a noise robust exemplar-based speech recognition system where noisy speech is modeled as a linear combination of a set of speech and noise exemplars. The method works by finding a small number of labeled exemplars in a very large collection of speech and noise exemplars that jointly approximate the observed speech signal. We represent the exemplars using melenergies, which allows modeling the summation of speech and noise, and estimate the activations of the exemplars by minimizing the generalized Kullback-Leibler divergence between the observations and the model. The activations of the speech exemplars are directly being used for recognition. This approach proves to be promising, achieving up to 55.8% accuracy at signal-to-noise ratio −5 dB on the AURORA-2 connected digit recognition task.
Effects of tadalafil on erectile dysfunction in men with diabetes.

OBJECTIVE To evaluate the efficacy and safety of tadalafil taken as needed before sexual activity by men with diabetes and erectile dysfunction (ED). RESEARCH DESIGN AND METHODS Men with type 1 or type 2 diabetes and a minimum 3-month history of ED were randomly allocated to one of three groups: placebo (n = 71), tadalafil 10 mg (n = 73), or tadalafil 20 mg (n = 72) taken up to once daily for 12 weeks. Changes from baseline in mean scores on the erectile function domain of the International Index of Erectile Function (IIEF) and changes from baseline in the proportion of "yes" responses to question 2, "Were you able to penetrate? ," and 3, "Were you able to complete intercourse? ," of the Sexual Encounter Profile were coprimary outcome measures. RESULTS A total of 191 (88%) of 216 patients completed the study. Treatment with tadalafil significantly improved all primary efficacy variables, regardless of baseline HbA(1c) level. Therapy with tadalafil also significantly improved a number of secondary outcome measures, including changes in other IIEF domains, individual IIEF questions, and percentage of positive responses to a global assessment question measuring erection improvement. Treatment with tadalafil did not alter mean HbA(1c) levels. Tadalafil was well tolerated, with headache and dyspepsia being the most frequent adverse events with active treatment. CONCLUSIONS Tadalafil therapy significantly enhanced erectile function and was well tolerated by men with diabetes and ED.
Simple model for multistability and domain formation in semiconductor superlattices.

Negative differential conductivity is a well-known effect in semiconductor superlattices if a voltage is applied perpendicular to the layer structure. For highly doped superlattices, the appearance of electric-field domains has been found experimentally [H. T. Grahn et al., Phys. Rev. Lett. 67, 1618 (1991)]. In this paper we present a theoretical model which can explain these effects quantitatively. The model considers the lowest two subbands of the single quantum wells and includes resonant tunneling between adjacent wells, miniband conduction, and intersubband relaxation within each well. We obtain multistability of the current-voltage characteristic and various hysteretic transitions which arise upon sweeping the applied voltage, and which are associated with changes in the domain size.
The Social and Learning Environments Experienced by Underrepresented Minority Medical Students: A Narrative Review

Purpose To review the literature on the social and learning environments experienced by underrepresented minority (URM) medical students to determine what type of interventions are needed to eliminate potential barriers to enrolling and retaining URM students. Method The authors searched MEDLINE, PubMed, Ovid HealthStar, and Web of Science, and the reference lists of included studies, published between January 1, 1980, and September 15, 2012. Studies of the learning and social environments and of students’ satisfaction, experiences with discrimination or unfair practices, and academic performance or progress, as well as assessments of programs or interventions to improve URM students’ academic performance, were eligible for inclusion. Results The authors identified 28 studies (27 unique data sets) meeting the inclusion criteria. The results of the included studies indicated that URM students experienced less supportive social and less positive learning environments, were subjected to discrimination and racial harassment, and were more likely to see their race as having a negative impact on their medical school experiences than non-URM students. Academic performance on standardized exams was worse, progress less timely, and attrition higher for URM students as well. Conclusions For URM students, an adverse climate may be decreasing the attractiveness of careers in medicine, impairing their academic performance, and increasing attrition. Improvements to the social and learning environments experienced by URM students are needed to make medicine a more inclusive profession. The current environment of health care reform creates an opportunity for institutions to implement strategies to achieve this goal.
Protective role of urinary trypsin inhibitor in lung expression of proinflammatory cytokines accompanied by lethal liver injury in mice

Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used for patients with inflammatory disorders including disseminated intravascular coagulation, shock, and pancreatitis in Japan, since it reportedly exhibits anti-inflammatory properties aside from its blocking of the protease pathway both in vitro and in vivo. In accordance with other reports, our previous studies using UTI-null (–/–) mice showed that UTI protects against systemic inflammatory responses in vivo. Recently, we also revealed the protective role of UTI against lethal liver injury induced by lipopolysaccharide and D-galactosamine (LPS/D-GalN). However, the anti-inflammatory role of UTI has not been sufficiently clarified using the model. The present study determined the effects of endogenous UTI on lung inflammation accompanied by lethal liver injury induced by LPS/D-GalN in the context of the lung expression of proinflammatory cytokines. After LPS/D-GalN challenge, protein levels of interleukin-1β, tumor necrosis factor-α, macrophage inflammatory protein-1α, and macrophage chemoattractant protein-1 in the lung homogenates were elevated in both genotypes, but to a greater extent in UTI (–/–) than in WT mice (P < 0.05 for TNF-α). The IFN-γ level was also significantly greater in LPS/D-GalN challenged UTI (–/–) mice than in other mice (P < 0.01). These results suggest that UTI protects against the local inflammatory response accompanied by severe liver injury, which supports its anti-inflammatory properties in vivo.
Development of HIV-1 Rectal-Specific Microbicides and Colonic Tissue Evaluation

The gastrointestinal tract is structurally and functionally different from the vagina. Thus, the paradigm of topical microbicide development and evaluation has evolved to include rectal microbicides (RMs). Our interest was to create unique RM formulations to safely and effectively deliver antiretroviral drugs to mucosal tissue. RMs were designed to include those that spread and coat all surfaces of the rectum and distal colon rapidly (liquid) and those that create a deformable, erodible barrier and remain localized at the administration site (gel). Tenofovir (TFV) (1%) was formulated as an aqueous thermoreversible fluid and a carbopol-based aqueous hydrogel. Lipid-based liquid and gel formulations were prepared for UC781 (0.1%) using isopropyl myristate and GTCC (Caprylic/Capric Triglycerides), respectively. Formulations were characterized for pH, viscosity, osmolality, and drug content. Pre-clinical testing incorporated ex vivo colonic tissue obtained through surgical resections and flexible sigmoidoscopy (flex sig). As this was the first time using tissue from both sources side-by-side, the ability to replicate HIV-1 was compared. Efficacy of the RM formulations was tested by applying the products with HIV-1 directly to polarized colonic tissue and following viral replication. Safety of the formulations was determined by MTT assay and histology. All products had a neutral pH and were isoosmolar. While HIV-1BaL and HIV-1JR-CSF alone and in the presence of semen had similar replication trends between surgically resected and flex sig tissues, the magnitude of viral replication was significantly better in flex sig tissues. Both TFV and UC781 formulations protected the colonic tissue, regardless of tissue source, from HIV-1 and retained tissue viability and architecture. Our in vitro and ex vivo results show successful formulation of unique RMs. Moreover, the results of flex sig and surgically resected tissues were comparable suggesting the incorporation of both in pre-clinical testing algorithms.
Relationship between perceived stress and personality traits in emergency medical personnel

Introduction: Emergency Medical Personnel (EMP) perform their duties to take care of critically-ill patients in stressful situations. It is not clear what kind of personality traits have negative relationships with perceived stress. The aim of this study is to identify paramedics who are able to maintain their work performances at high levels despite facing stressful situations. Materials and Methods: This study was conducted on emergency medical personnel from March to September 2015. This was a correlational study in which the convenience sampling method was used to select 120 men as the sample. Research instrument included demographic form, NEO Five-Factor Inventory and Cohenâ��s Perceived Stress Scale were employed to collect data which were then analyzed via descriptive and inferential statistics (correlation and regression) in SPSS software version 16.0. Results:The results revealed that Neuroticism (N) was significantly and positively correlated with perceived stress. However, extraversion (E), agreeableness (A), conscientiousness (C) were negatively correlated with the perceived stress scale (P<0.001). Moreover, neuroticism (N), openness to experience (O), agreeableness (A) and conscientiousness (C) included 59.5 of variances in perceived stress. Conclusion: It seems that among emergency medical personnel, those who were more emotionally stable, more responsible and more willing to help people have lower perceived stress and they perform their duties more efficiently.
Whole cell mechanics of contractile fibroblasts: relations between effective cellular and extracellular matrix moduli

While much is known about the subcellular structures responsible for the mechanical functioning of a contractile fibroblast, debate exists about how these components combine to endow a cell with its form and mechanical function. We present an analysis of mechanical characterization experiments performed on bio-artificial tissue constructs, which we believe serve as a more realistic testing environment than two-dimensional cell culture. These model tissues capture many features of real tissues with the advantage that they can be engineered to model different physiological and pathological characteristics. We study here a model tissue consisting of reconstituted type I collagen and varying concentrations of activated contractile fibroblasts that is relevant to modelling different stages of wound healing. We applied this system to assess how cell and extracellular matrix (ECM) mechanics vary with cell concentration. Short-term and long-term moduli of the ECM were estimated through analytical and numerical analysis of two-phase elastic solids containing cell-shaped voids. The relative properties of cells were then deduced from the results of numerical analyses of two-phase elastic solids containing mechanically isotropic cells of varying modulus. With increasing cell concentration, the short-term and long-term tangent moduli of the reconstituted collagen ECM increased sharply from a baseline value, while those of the cells decreased monotonically.
Exercise as a Healthy Lifestyle Choice: A Review and Avenues for Future Research

The health benefits of exercising and the prevalent sedentary lifestyle give a strong reason for the research into the determinants of exercise behaviour. The present paper reviews several health-related behavioural theories and models that have been applied to understand the factors influencing physical activity or exercise participation and suggest avenues for future research. In particular, a review of literature provides strong empirical support for the theory of planned behaviour, yet several theoretical issues need to be resolved to aid in the development of a more comprehensive health-related model that can explain and predict exercise behaviour. The present paper highlights that there is a need to develop and empirically test a more integrative model of exercise behaviour from consumer behaviour perspective. Besides, the conceptualisation of TPB measures and sufficiency issues related to the model need to be addressed prior to the adoption of the TPB model.
Elevation of the cytosolic free [Ca2+] is indispensable for the transduction of the Nod factor signal in alfalfa.

In root hairs of alfalfa (Medicago sativa), the requirement of Ca(2+) for Nod factor signaling has been investigated by means of ion-selective microelectrodes. Measured 50 to 100 microm behind the growing tip, 0.1 microM NodRm-IV(C16:2,S) increased the cytosolic free [Ca2+] by about 0.2 pCa, while the same concentration of chitotetraose, the nonactive glucosamine backbone, had no effect. We demonstrate that NodRm-IV(C16:2,S) still depolarized the plasma membrane at external Ca(2+) concentrations below cytosolic values if the free EGTA concentration remained low (</=0.01 mM). Externally added Sr(2+) was able to replace Ca(2+), and to some extent even enhanced the Nod-factor-induced depolarization, whereas with Mg(2+) it was decreased. This suggests that the Nod factor response is triggered by Ca(2+) from external stores. The addition of the endomembrane Ca(2+)-ATPase inhibitor 2,5-di(t-butyl)-1, 4-benzohydroquinone, which presumably mobilizes Ca(2+) from Ins(1,4, 5)P(3)-sensitive stores, mimicked the Nod factor response, i.e. increased the cytosolic free [Ca2+], triggered Cl(-)-efflux, depolarized the plasma membrane, and alkalized the root hair space. In all cases a refractory state toward Nod factor perception was produced, indicating a shortcut of Nod factor signal transduction by releasing Ca(2+) from internal stores. These latter results strongly support the idea that an elevation of cytosolic free [Ca2+] is indispensable for the transduction of the Nod factor signal, which is consistent with the role of Ca(2+) as a second messenger.