Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural and functional differences in PHOX2B frameshift mutations underlie isolated or syndromic congenital central hypoventilation syndrome

Heterozygous mutations in the PHOX2B gene are causative of congenital central hypoventilation syndrome (CCHS), a neurocristopathy characterized by defective autonomic control of breathing due to the impaired differentiation of neural crest cells. Among PHOX2B mutations, polyalanine (polyAla) expansions are almost exclusively associated with isolated CCHS, whereas frameshift variants, although less frequent, are often more severe than polyAla expansions and identified in syndromic CCHS. This article provides a complete review of all the frameshift mutations identified in cases of isolated and syndromic CCHS reported in the literature as well as those identified by us and not yet published. These were considered in terms of both their structure, whether the underlying indels induced frameshifts of either 1 or 2 steps (“frame 2” and “frame 3” mutations respectively), and clinical associations. Furthermore, we evaluated the structural and functional effects of one “frame 3” mutation identified in a patient with isolated CCHS, and one “frame 2” mutation identified in a patient with syndromic CCHS, also affected with Hirschsprung's disease and neuroblastoma. The data thus obtained confirm that the type of translational frame affects the severity of the transcriptional dysfunction and the predisposition to isolated or syndromic CCHS.
Innovation : The trade-off between speculation and innovation performance

The research in this study looks at the effectiveness of an online stock market for innovation (SMI) implemented inside a large multinational firm. Alike financial stock markets, the SMI is prone to speculation. We describe this initiative and study the association between participants’ speculative behavior and their innovation performance by looking at the actual transactional history of their participation in the market (N=6,067 participants). Moreover, we supplement our analysis with individual level data derived from a survey of a sample of the employee population participating in the initiative (N=403 respondents). On the one hand, our findings indicate that some speculation activities are positively associated with better innovation performance. On the other hand, controlling for strict speculative behavior, we find that it significantly and negatively impacts innovative performance. This evidence suggests that while contributors speculating in the SMI innovate by doing so, strict speculative behavior could be potentially detrimental. The speculative nature of this crowdsourcing innovation initiative provides novel insights about this alternate approach to internal knowledge markets. Our findings contribute to the innovation management literature by shedding light on a stock market model of distributed innovation allowing the firm to leverage upon its existing workforce to expand its ability to innovate.
Nonlytic Lymphocytes Engineered to Express Virus-Specific T-Cell Receptors Limit HBV Infection by Activating APOBEC3.

BACKGROUND & AIMS Strategies to develop virus-specific T cells against hepatic viral infections have been hindered by safety concerns. We engineered nonlytic human T cells to suppress replication of hepatitis B virus (HBV) and hepatitis C virus (HCV) without overt hepatotoxicity and investigated their antiviral activity. METHODS We electroporated resting T cells or T cells activated by anti-CD3 with mRNAs encoding HBV or HCV-specific T-cell receptors (TCRs) to create 2 populations of TCR-reprogrammed T cells. We tested their ability to suppress HBV or HCV replication without lysis in 2-dimensional and 3-dimensional cultures of HepG2.2. 15 cells and HBV-infected HepG2-hNTCP cells. We also injected TCR-reprogrammed resting and activated T cells into HBV-infected urokinase-type plasminogen activator/severe combined immunodeficiency disease/interleukin 2γ mice with humanized livers and measured levels of intrahepatic and serological viral parameters and serum alanine aminotransferase. Livers were collected for analysis of gene expression patterns to determine effects of the TCR-reprogrammed T cells. RESULTS TCR-reprogrammed resting T cells produced comparable levels of interferon gamma but lower levels of perforin and granzyme than activated T cells and did not lyse HCV- or HBV-infected hepatoma cells. Although T-cell secretion of interferon gamma was required to inhibit HCV replication, the HBV-specific TCR-reprogrammed resting T cells reduced HBV replication also through intracellular activation of apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3). The mechanism of APOBEC3 intracellular activation involved temporal expression of lymphotoxin-β receptor ligands on resting T cells after TCR-mediated antigen recognition and activation of lymphotoxin-β receptor in infected cells. CONCLUSIONS We developed TCR-reprogrammed nonlytic T cells capable of activating APOBEC3 in hepatoma cells and in HBV-infected human hepatocytes in mice, limiting viral infection. These cells with limited hepatotoxicity might be developed for treatment of chronic HBV infection.
Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial--lipid-lowering arm (ASCOT-LLA).

OBJECTIVE This study aims to establish the benefits of lowering cholesterol in diabetic patients with well-controlled hypertension and average/below-average cholesterol concentrations, but without established coronary disease. RESEARCH DESIGN AND METHODS In the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA), 10,305 hypertensive patients with no history of coronary heart disease (CHD) but at least three cardiovascular risk factors were randomly assigned to receive 10 mg atorvastatin or placebo. Effects on total cardiovascular outcomes in 2,532 patients who had type 2 diabetes at randomization were compared. RESULTS During a median follow-up of 3.3 years, concentrations of total and LDL cholesterol among diabetic participants included in ASCOT-LLA were approximately 1 mmol/l lower in those allocated atorvastatin compared with placebo. There were 116 (9.2%) major cardiovascular events or procedures in the atorvastatin group and 151 (11.9%) events in the placebo group (hazard ratio 0.77, 95% CI 0.61-0.98; P = 0.036). For the individual components of this composite end point, the number of events occurring in the diabetes subgroup was small. Therefore, although fewer coronary events (0.84, 0.55-1.29; P = 0.14) and strokes (0.67, 0.41-1.09; P = 0.66) were observed among the patients allocated atorvastatin, these reductions were not statistically significant. CONCLUSIONS Atorvastatin significantly reduced the risk of major cardiovascular events and procedures among diabetic patients with well-controlled hypertension and without a history of CHD or markedly elevated cholesterol concentrations. The proportional reduction in risk was similar to that among participants who did not have diagnosed diabetes. Allocation to atorvastatin prevented approximately 9 diabetic participants from suffering a first major cardiovascular event or procedure for every 1,000 treated for 1 year.
Screening of nutritional, phytochemical, antioxidant and antibacterial activity of Chenopodium album (Bathua)

Chenopodium album (L.), Bathua is a fast-growing weedy annual plant in the genus Chenopodium. In the present work, we have attempted to study different characteristics of bathua in different solvents (petroleum ether, dichloromethane, ethyl acetate, methanol, distilled water, and the mixture of all solvents in equal proportion), to understand its health benefits. Various studies were done to estimate phytochemicals like alkaloids, saponins, total flavonoids and total phenolics. Nutritional analysis proved it to be a potential source of energy, proteins, carbohydrates; ascorbic acid and beta carotene and minerals; potassium, sodium, calcium, phosphorous, magnesium, iron and zinc. The petroleum ether extract, methanol extract and aqueous extract of C. album revealed good antioxidant potential of ABTS and FRAP which proves them as potent electron and hydrogen donors. The methanol extract of C. album was found to be most active among all other extracts and inhibited Staphylococcus epidermidis, Bacillus subtilis, Staphylococcus aureus, Escherichia coli. The extract of a mixture of solvents was also found to be effective in inhibiting Staphylococcus aureus.
Radiological Findings in Pulmonary Tuberculosis among HIV Infected and Uninfected Adult Patients inYenagoa, Nigeria

Background: Tuberculosis is one of the most serious public healthproblem globally and its pulmonary form is the most common clinical presentation. This study, undertaken in a tertiary hospital in the Niger Delta region of Nigeria, retrospectively examined the radiology features of pulmonary tuberculosis in all HIV infected and unaffected adult patients attending its pulmonary tuberculosis clinic. Method: The chest radiography and case notes of the patients treated in the chest clinic between January 2012 and December 2013 were retrieved and evaluated according to radiological features. Results: Of the total of 307 chest radiography studied, 156 (53.7%) were male and 142 (46.3%) were female, showing a male preponderance of 1.2:1. PTB/HIV co-infection was in 116 (37.8%) of the cohorts studied. The commonest radiological feature observed were cavitory lesions (63.8%), patchy opacities (43.9%), and hilar opacities (38.1%). Bilateral cavitory lesions, patchy opacities and hilar opacities were commonest than on either right or left side. Bilateral chest disease was commoner in the cohorts with PTB/HIV co-infection. Perihilar patchy opacities were seen in 18.9%, consolidation in 5.2% and pleuraleffusion in 4.6% of the cohort. Conclusion: The chest radiography, though nonspecific, still remains a sensitive tool in the diagnosis of pulmonary tuberculosis and will continue to provide essential guidance in the management and follow up of patients especially in our setting.
Transaction Costs and Environmental Policy: An Assessment Framework and Literature Review

This article develops a framework for environmental policy analysis based on an encompassing assessment of transaction costs. This approach emphasizes the ex ante costs of establishing environmental entitlements, and the ex post costs of administrating, monitoring, and enforcing them. The framework is used to organize a literature review which addresses policy design and instrument choice, as well as optimal environmental policy-making and benefit-cost analysis. The review also considers the empirical literature on transaction costs associated with environmental policy-making, and current practices to record some categories of transaction costs in regulatory impact assessments. The article concludes with a discussion of the implications for environmental policy analysis.
Structural, super-resolution microscopy analysis of paraspeckle nuclear body organization

Paraspeckles are nuclear bodies built on the long noncoding RNA Neat1. Using structural illumination microscopy, West et al. analyze the organization of paraspeckles at the submicron scale and show that paraspeckle proteins are arranged around bundles of Neat1, forming core-shell spheroidal structures dependent on the RNA binding protein Fus.
Separate and Unequal: Residential Segregation and Estimated Cancer Risks Associated with Ambient Air Toxics in U.S. Metropolitan Areas

This study examines links between racial residential segregation and estimated ambient air toxics exposures and their associated cancer risks using modeled concentration estimates from the U.S. Environmental Protection Agency’s National Air Toxics Assessment. We combined pollutant concentration estimates with potencies to calculate cancer risks by census tract for 309 metropolitan areas in the United States. This information was combined with socioeconomic status (SES) measures from the 1990 Census. Estimated cancer risks associated with ambient air toxics were highest in tracts located in metropolitan areas that were highly segregated. Disparities between racial/ethnic groups were also wider in more segregated metropolitan areas. Multivariate modeling showed that, after controlling for tract-level SES measures, increasing segregation amplified the cancer risks associated with ambient air toxics for all racial groups combined [highly segregated areas: relative cancer risk (RCR) = 1.04; 95% confidence interval (CI), 1.01–107; extremely segregated areas: RCR = 1.32; 95% CI, 1.28–1.36]. This segregation effect was strongest for Hispanics (highly segregated areas: RCR = 1.09; 95% CI, 1.01–1.17; extremely segregated areas: RCR = 1.74; 95% CI, 1.61–1.88) and weaker among whites (highly segregated areas: RCR = 1.04; 95% CI, 1.01–1.08; extremely segregated areas: RCR = 1.28; 95% CI, 1.24–1.33), African Americans (highly segregated areas: RCR = 1.09; 95% CI, 0.98–1.21; extremely segregated areas: RCR = 1.38; 95% CI, 1.24–1.53), and Asians (highly segregated areas: RCR = 1.10; 95% CI, 0.97–1.24; extremely segregated areas: RCR = 1.32; 95% CI, 1.16–1.51). Results suggest that disparities associated with ambient air toxics are affected by segregation and that these exposures may have health significance for populations across racial lines.
MiR-99a suppress proliferation, migration and invasion through regulating insulin-like growth factor 1 receptor in breast cancer.

OBJECTIVE Breast cancer is one of the most common malignant tumors in women. Despite the advances made in treatments of breast cancer, the incidence and death rates of breast cancer are still on the rise. Therefore, it is essential for us to explore the potential mechanism accounting for the malignancy of breast cancer. MATERIALS AND METHODS A lentiviral vector over-expressing miR-99a in MDA-MB-231 breast cancer cells was constructed. Cell proliferation was detected by MTT assay. Migration and invasion were measured by Scratch-wound assay and transwell assay. Direct target of miR-99a in MDA-MB-231 breast cancer cells was examined using bioinformatics and luciferase assay. The expression of endogenous insulin-like growth factor 1 receptor was quantified by qRT-PCR and Western blotting. RESULTS In our study, we found that miR-99a could suppress the proliferation, migration and invasion of MDA-MB-231 cell in vitro and inhibited the growth of xeno-transplant tumor in vivo. We also found that insulin-like growth factor 1 receptor (IGF-1R) was a direct target of miR-99a. Furthermore, knockdown of endogenous IGF-1R by siRNA could mimic the effect of miR-99a over-expression. CONCLUSIONS Our findings demonstrated that miR-99a could inhibit the malignancy of breast cancer cell by directly down-regulation of IGF-1R. These results indicated that miR-99a may be an important biomarker for prognosis and anticancer therapy in breast cancer in the future.
Branching effect and morphology control in electrospun PbZr_0.52Ti_0.48O_3 nanofibers

Utilization of PbZr_xTi_1− x O_3 (PZT) nanofibers as functional flexible fillers in sensing and energy harvesting applications requires uniform, submicrometer fibers with a large aspect ratio. Previous studies concentrated on the rheological effects on the fiber’s diameter and morphology. However, reports on the effect of electric field on these fiber properties are still scarce. In this paper, the effects of surface charge and electric field on the fiber branching are decoupled. We show unequivocally that the external electric field governs this phenomenon. Low viscosity (∼0.12 Pa s) PZT sols yielded a sharp step-like transition from a large to a small diameter regime at electric fields above 0.8 kV/cm. On the other hand, high viscosity sols (∼0.74 Pa s) yielded a transition from a single to a bimodal distribution at the same electric field, due to the branching effect. An ability to obtain a single or bimodal diameter distribution in the range of 100–800 nm was demonstrated.
Strong association between parasitism and phenotypic variation in a supralittoral amphipod

Phenotypic variation is common among conspecifics from the same population, but its causes are not always clear. Parasites may often play a role, as their ability to induce phenotypic changes in their hosts is well established, though not widely acknowledged among marine ecologists. Here, we tested for a possible role of parasites as determinants of marked colour polymorphism, as well as variation in several distinct behavioural traits in the supralittoral amphipod Transorchestia chiliensis (Talitridae). Our results indicate that the juvenile stages of 2 parasites, the acanthocephalan Plagiorhynchus allisonae and a dilepidid cestode, are disproportionately common in certain colour morphs (i.e. green and dark grey in the case of acanthocephalans and green and blue in the case of cestodes) relative to other colour morphs. In addition, amphipods preferring light over dark background substrate were more likely to harbour acanthocephalans, whereas amphipods that either stayed at the surface or did not burrow very deeply harboured more cestodes than those that burrowed deep into the sediment. Our findings also indicate that later developmental stages of P. allisonae are associated with more pronounced host phenotypic variation, suggesting that phenotypic changes escalate in parallel with parasite growth within the host. Furthermore, the 2 parasite species tend not to co-occur in the same individual hosts; thus, their distinct phenotypic effects apply to different subsets of the host population. We suggest that the role of parasitism in inducing and maintaining phenotypic variation within populations of marine invertebrates is probably more important than currently recognised.
Comparison of sedation method in pediatrics cardiac catheterization.

OBJECTIVE Purpose of this study is to compare the effects of various anaesthetic combinations on hemodynamics, sedation level, recovery period and complications in the patients which undergo pediatric cardiac catheterization. PATIENTS AND METHODS Four groups of anaesthetic combinations was created. The groups are classified as propofol-ketamine (group 1), propofol-dexmedetomidine (group 2), dexmedetomidine-ketamine (group 3), midazolam-ketamine (group 4) (for each group n=20). Baseline heart rate (HR), mean arterial blood pressure (MAP), respiratory rate (RR), peripheral oxygen saturation (SpO2) were recorded. This parameters values were recorded at 0. , 5. , 10. , 15. , 20. , 25. , 30. minutes; and the groups were compared according to these measurements data. RESULTS For heart rate, Group 2 and 3 reduce the HR more than the drugs of Group 1 and 4 (p < 0.05). The SpO2 values of Group 1 were measured to have 5% further reduction compared to the Group 2 and 3; and Group 4 has the same SpO2 recordings compared to the Group 3 (p < 0.05). Comparing the recovery times; Group 4 was found to have the highest recovery time compared to the other drug groups. It is found that additional doses are needed for recovery in Group 4 (p < 0.008). Side effects were lowest for Group 3 and highest for Group 4. CONCLUSIONS Considering the complication rates, it is concluded that Group 3 is spotted as the better sedation method among the other groups. In terms of additional propofol dose, Group 1 would be the better choice. Thus, the clinician should choose the suitable methods for the patient.
Multi-Period Corporate Default Prediction with Stochastic Covariates

We provide maximum likelihood estimators of term structures of conditional probabilities of corporate default, incorporating the dynamics of firm-specific and m acroeconomic covariates. For U.S. Industrial firms, based on over 390,000 firm-months of data spanning 1979 to 2004, the level and shape of the estimated term structure of conditional future default probabilities depends on a firm's distance to default (a volatility-adjusted measure of leverage), on the firm's trailing stock return, on trailing S& P 500 returns, and on U.S. interest rates, among other covariates. Variation in a firm's distance to default has a substantially greater effection the term structure of future default hazard rates than does a comparatively significant change in any of the other covariates. Default intensities are estimated to be lower with higher short-term interest rates. Theout-of-sample predictive performance of the model is an improvement over that of other available models.
Does director trading change the information environment?

Investigating ASX300 firms for the period 2002–2010, we find that the information content of director trading has a negative relationship with post-trade information asymmetry, but a positive relationship with information efficiency. These results are mainly driven by director purchases rather than their sales, and are stronger in non-executive director trading. Our results are robust to the adoption of IFRS in 2005 and the global financial crisis in 2008. These findings back the claims of insider trading proponents, by showing that director trading plays a crucial role in reducing information asymmetry and in improving information efficiency for stock market participants.
Factors influencing the intention to use information service mashups: An empirical study of digital libraries in China

This study aims to examine the factors influencing the adoption intention of information service mashup in digital library (DL). The study is an empirical study on DLs in China. ,This paper employs the theory of information service mashup as its theoretical background and applies it to the field of DL to develop the measurement model which is based on technology acceptance model (TAM). A structured questionnaire was developed including the demographic information, the advantages of information service mashup in DL and the Likert evaluation of each construct. As a result, of 303 questionnaires distributed among DL users, 281 were remained as acceptable answers. The data were processed and analyzed with the aid of the SPSS 20.0 and SmartPLS 2.0. ,The results show that beyond perceived usefulness and perceived ease of use, both perceived integration and perceived risk have direct impacts on user’s intention to adopt information service mashup in DL. Perceived integration has the dramatic positive effects, while perceived risk negatively correlates to adoption intention. Moreover, perceived integration and individualization have positive impacts on perceived ease of use, while network externality positively influences perceived usefulness. ,Information service mashup is still a relatively new technology in DL. There were few theoretical and empirical studies that examine the user adoption behaviour of the service. This study contributes to existing information service mashup application studies by modifying and extending TAM. The results would help the DL gain a deeper understanding of the factors affecting DL user adoption of information service mashup.