Miracle-dz/UniFAR-FTUs huggingface dataset:
Extensive Positive Selection Drives the Evolution of Nonstructural Proteins in Lineage C Betacoronaviruses

ABSTRACT Middle East respiratory syndrome-related coronavirus (MERS-CoV) spreads to humans via zoonotic transmission from camels. MERS-CoV belongs to lineage C of betacoronaviruses (betaCoVs), which also includes viruses isolated from bats and hedgehogs. A large portion of the betaCoV genome consists of two open reading frames (ORF1a and ORF1b) that are translated into polyproteins. These are cleaved by viral proteases to generate 16 nonstructural proteins (nsp1 to nsp16) which compose the viral replication-transcription complex. We investigated the evolution of ORF1a and ORF1b in lineage C betaCoVs. Results indicated widespread positive selection, acting mostly on ORF1a. The proportion of positively selected sites in ORF1a was much higher than that previously reported for the surface-exposed spike protein. Selected sites were unevenly distributed, with nsp3 representing the preferential target. Several pairs of coevolving sites were also detected, possibly indicating epistatic interactions; most of these were located in nsp3. Adaptive evolution at nsp3 is ongoing in MERS-CoV strains, and two selected sites (G720 and R911) were detected in the protease domain. While position 720 is variable in camel-derived viruses, suggesting that the selective event does not represent a specific adaptation to humans, the R911C substitution was observed only in human-derived MERS-CoV isolates, including the viral strain responsible for the recent South Korean outbreak. It will be extremely important to assess whether these changes affect host range or other viral phenotypes. More generally, data herein indicate that CoV nsp3 represents a major selection target and that nsp3 sequencing should be envisaged in monitoring programs and field surveys. IMPORTANCE Both severe acute respiratory syndrome coronavirus (SARS-CoV) and MERS-CoV originated in bats and spread to humans via an intermediate host. This clearly highlights the potential for coronavirus host shifting and the relevance of understanding the molecular events underlying the adaptation to new host species. We investigated the evolution of ORF1a and ORF1b in lineage C betaCoVs and in 87 sequenced MERS-CoV isolates. Results indicated widespread positive selection, stronger in ORF1a than in ORF1b. Several selected sites were found to be located in functionally relevant protein regions, and some of them corresponded to functional mutations in other coronaviruses. The proportion of selected sites we identified in ORF1a is much higher than that for the surface-exposed spike protein. This observation suggests that adaptive evolution in ORF1a might contribute to host shifts or immune evasion. Data herein also indicate that genetic diversity at nonstructural proteins should be taken into account when antiviral compounds are developed.
Switching from Payroll Taxes to Corporate Income Taxes: Firms’ Employment and Wages after the 2012 Colombian Tax Reform

ABSTRACT: The 2012 Colombian tax reform reduced payroll taxes and employer contributions to health insurance by 13.5 percent, while also increasing corporate income taxes and leaving untouched the benefits to workers financed through these taxes. Shifting taxation from formal employment to other business activities is a policy recipe under heated discussion in Latin America. The reform offers an ideal laboratory for studying empirically the potential distortions against formal employment associated with payroll taxes in contrast to other taxes on firms. We analyze the impact of the reform on employment and wages using monthly firm-level data on all formal employment in nonpublic firms in the country and a difference-in-differences approach that takes advantage of the fact that a few sectors were exempt from the 2012 tax reform. We find a positive average effect of 4.3 percent on employment and 2.7 percent on average firm wages, for the average firm. The employment effect is found only for micro and small firms, whereas the bulk of the employment is concentrated in medium and large firms, which show no significant effect. According to these estimates, about 145,000 new jobs were created between January and May of 2015 by virtue of the reform. These results are generally supportive of efforts to reduce payroll taxes, though our findings on employment are less robust than those on wages, and large firms do not seem to have benefitted. The apparent lack of effect for medium and large employers is also a source of concern. We speculate that it may be due to these firms’ being more sensitive to the increase in corporate taxation that financed the reduction in payroll taxes, but lack of access to the relevant data prevents us from offering solid evidence regarding this hypothesis.
Suppressors of Cytokine Signaling Modulate JAK/STAT-Mediated Cell Responses During Atherosclerosis

Objective—Suppressors of cytokine signaling (SOCS) proteins are intracellular regulators of receptor signal transduction, mainly Janus kinase/signal transducers and activators of transcription (JAK/STAT). We investigated the effects of SOCS modulation on the JAK/STAT-dependent responses in vascular cells, and their implication in atherosclerotic plaque development. Methods and Results—Immunohistochemistry in human plaques revealed a high expression of SOCS1 and SOCS3 by vascular smooth muscle cells (VSMCs) and macrophages in the inflammatory region of the shoulders, when compared to the fibrous area. SOCS were also increased in aortic lesions from apoE−/− mice. In cultured VSMCs, endothelial cells, and monocytes, SOCS1 and SOCS3 were transiently induced by proinflammatory cytokines, proatherogenic lipoproteins, and immune molecules. Furthermore, overexpression of SOCS suppressed STAT activation and reduced inflammatory gene expression and cell growth, whereas SOCS knockdown increased these cell responses. In vivo, antisense oligodeoxynucleotides targeting SOCS3 exacerbated the atherosclerotic process in apoE−/− mice by increasing the size, leukocyte content, and chemokine expression in the lesions. Conclusions—SOCS expressed in atherosclerotic lesions are key regulators of vascular cell responses. Activation of this endogenous antiinflammatory pathway might be of interest in the treatment of atherosclerosis.
Comparative analysis of serum proteomes of degenerative scoliosis

Degenerative scoliosis (DS) is an important degenerative lumbar disease causing spinal dysfunction and affecting the quality of life of the elderly, and is associated not only with severe back or leg pain but also with complicated surgical outcomes. The pathogenesis of DS is still unknown. Therefore, it is very important to ascertain the etiology of degenerative scoliosis and establish related molecular markers predicting and controlling the scoliosis. For the first time, we used two‐dimensional fluorescence DIGE to compare the serum proteome profiles of 12 DS patients and controls. Proteins found to be differentially expressed were identified by MALDI‐TOF mass spectrometric analysis, coupled with database interrogation. Eleven spots that were differentially expressed in the sera of DS patients were found, and eight gene products were identified among these spots. Clusterin, CLU cDNA FLJ57622, ALB cDNA FLJ50830, Hypothetical short protein, HLA‐A MHC class 1 antigen. (Fragment), ALB 23 kDa protein, Isoform 1 of G protein‐regulated inducer of neurite outgrowth 1 (GPRIN I)and Ficolin‐3 were down‐regulated in the sera of DS patients. The decreased levels of Clusterin and Ficolin‐3 were confirmed by Western blot. The information obtained with this proteomic analysis will be very useful in understanding the pathophysiology of DS as well as in finding candidates as drug targets of DS. These results may provide a novel approach for the pathogenesis study of DS. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1896–1903, 2011
Melatonin Production in Healthy Infants: Evidence for Seasonal Variations

The objective of this study was to determine the normal range of nocturnal urinary excretion of the major melatonin metabolite, 6-sulfatoxymelatonin (6SMT) in a large sample of healthy full-term infants (8 and 16 wk old) and assess whether the endogenous production of melatonin changes with season. 6SMT was assessed in urine samples extracted from disposable diapers removed from full-term, 8- (n = 317) and 16-wk-old (n = 93) infants over the nocturnal period (19:00–08:00 h). In addition, 6SMT was assessed in 8-wk-old (n = 35) healthy infants over the entire 24-h period. 6SMT was determined by an ELISA assay. 6SMT excretion at 8 wk of age exhibited diurnal variations with (mean ± SD) 61 ± 18% of the daily production excreted during the nocturnal period regardless of season. The nocturnal 6SMT values in the entire cohort (at 8 as well as 16 wk of age) were found to significantly depart from normal distribution (Kolmogorov-Smirnov test). A normal distribution was obtained using a natural base logarithmic (ln) transformation of the data. The normal range (2.5–97.5 percentile of the ln 6SMT excretion per night) was thus defined as 4.66–8.64 (106–5646 ng/night) for 8-wk-old and 5.19–9.67 (180–15,820 ng/night) for 16-wk-old infants. A significant effect of the month of birth on 6SMT production at the age of 8 wk was found (ANOVA, p < 0.002) with maximal levels produced by infants born in June (summer solstice) and minimal excretion in infants born in December (winter solstice). Short-photoperiod-born infants excreted on average about threefold less 6SMT compared with long-photoperiod-born infants (t test, p = 0.01). The seasonal variations were no longer present at 16 wk of age. No effect of breast-feeding at the time of sampling on seasonality of 6SMT was found. Normal ranges for the nocturnal urinary excretion of 6SMT in full-term infants at 8 and 16 wk of age are defined. This enables the evaluation of nocturnal 6SMT excretion as a prognostic and diagnostic factor for child development. The strong effect of season on the normal excretion of nocturnal 6SMT at 8 but not 16 wk of age suggests prenatal influence of the photoperiod on the ontogeny of melatonin.
The Relative Skill Demand of Superstar Firms and Aggregate Implications

This paper proposes a new reason for why the relative demand for skilled workers has increased over past decades. I suggest that increases in market concentration and the rise of superstar firms may be important causes for the rise in demand for skill. I use detailed employer-employee data for the Swedish manufacturing sector between 1997 and 2014 to validate my hypothesis. My analysis demonstrates a strong correlation between firm size and the skilled share of a firm’s worker mix. The slope of this relationship is at its steepest in the right tail of the size distribution. I also, as Autor et al. (2017b), find a substantial rise in market concentration in Swedish manufacturing, both in the aggregate and across sub-sectors. The rise in market concentration is strongly correlated with a rise in the relative usage of skilled workers. Furthermore, a majority of the change in skill usage is due to between-firm variation, a reallocation of production across firms. This supports the notion that market concentration, rather than a general skill upgrading across all firms, has caused the rise in skill demand. Finally, the reallocation of production was most pronounced in industries characterized by large increases in market concentration. I estimate that about a tenth of the rise in the usage of skilled labor in Swedish manufacturing is due to the increasing importance of the largest firms.
Temperature–density hysteresis in X-ray CT during HIFU thermal ablation: Heating and cooling phantom study

Abstract Purpose: This paper investigated the effects of thermal ablation treatment on imaged X-ray computed tomography (CT) Hounsfield units (HU), for the purpose of monitoring tissue denaturation and coagulation. Materials and methods: Eight phantoms of water, oil, and chicken serum albumin as well as 15 ex vivo tissue samples were heated by applying high intensity focused ultrasound (HIFU) for 10 to 29 min to obtain denaturation temperatures, (i.e. >50 °C). X-ray CT scanning was performed simultaneously during heating and post-ablation cooling stages, and the HU at the focal zone were registered. The temperature profile versus time was also monitored under similar conditions using a thermocouple probe. The results were plotted and correlated as curves of HU versus temperature. Results: In all specimens studied, HU values depicted an exponential curve as a function of temperature during the heating stage. However, linear behaviour was observed during the cool-down stage for both chicken serum albumin and ex vivo bovine liver. Thus, a hysteresis phenomenon occurred only when the thermal conditions induced irreversible changes in the sample with quantification demonstrating high correlation with the maximal temperature reached during treatment (R2 > 0.9) for the chicken serum albumin. Conclusions: Our results demonstrate a HU–temperature hysteresis phenomenon for HIFU ablation, which is detectible by X-ray CT. This hysteresis is related to the amount of heat induced into the tissue and could potentially indicate irreversible tissue damage. Accordingly, this measurable phenomenon can be utilised as a quantitative method for non-invasive monitoring of thermal ablation.
Factors Influencing Beliefs Formation towards the Adoption of Social Commerce in SME Travel Agencies

The purpose of this study is to investigate the factors that influence beliefs formation towards the adoption of social commerce in SME travel agencies. Accordingly, a distal-proximal model is developed to study CEOs’ beliefs towards the usefulness of social commerce. Data were collected through a questionnaire survey of travel agencies’ CEOs in Isfahan, Iran. With 180 collected data from respondents, the Partial Least Squares-Structural Equation Modeling approach was taken to assess both measurement and structural models of the study. The results revealed that CEOs’ innovativeness and attitude towards IT as individual factors, and organizational resources as institutional factor were significantly explained beliefs formation of respondents towards the usefulness of social commerce. However, it was found that the influences of CEOs’ IT knowledge, subjective norms (professional peers, employees) and firm size on perceived usefulness were found insignificant. Implications of the study are further discussed.
Plasma Gonadotropins and Estrogens in Girls with Idiopathic Precocious Puberty

Summary: Luteinizing hormone (LH), follicle-stimulating hormone (FSH) estrone, and estradiol were measured radioimmunologically in more than 60 plasma specimens of 34 girls suffering from idiopathic precocious puberty. Although the median values of both gonadotropins in the plasma of the patients (LH = 1.0 ng/ml; FSH = 1.6 ng/ml) were higher than those from healthy prepubertal girls (LH = 0.6 ng/ml; FSH = 0.5 ng/ml), only 23 out of 64 LH levels and 30 out of 64 FSH levels exceeded the upper normal limit for age. While the median value of plasma estrone (13 pg/ml) was found to lie within the normal range for prepubertal girls (7–29 pg/ml) and only 13 out of 75 estrone values were pathologically elevated, the median value of plasma estradiol (22 pg/ml) was nearly 3 times higher than the normal median for prepuberty (8 pg/ml). Of 75 estradiol levels, 35 were above normal for age. Grouping the values according to the stage of sexual development revealed considerably lower gonadotropin and estrogen levels in the patients than in normally maturing girls of the same developmental stage. However, patients who were examined repeatedly at short intervals over a 1-month period showed an almost cyclic sequence of their estradiol levels similar to the pattern observed in healthy pubertal girls.Speculation: The findings that plasma estrogens are relatively low in idiopathic precocious puberty in spite of well advanced sexual development suggest that the symptoms of this disturbance do not depend on estrogen concentrations alone. Other factors, such as enhanced receptor sensitivity or changes in the concentration of sexual hormone-binding globulin, must also be taken into consideration.
How Large is the Potential Economic Benefit of Agricultural Adaptation to Climate Change

Although climate change may severely impact agriculture, farmers can mitigate it by adapting to their new climates. Using US data, we estimate the amount of potential loss in agricultural profits, due to climate change, that can be reduced by agricultural adaptation. We propose two panel frameworks that differ only in their fixed effects specifications, where this difference allows us to estimate the climate change impact on agricultural profits with or without adaptation taken into account. Comparing these estimates, we find that adaptation has the potential to offset about two-thirds of the end-of-this-century loss in agricultural profits potentially resulting from climate chang Acknowledgement :
The contribution of financial entities to the sustainable development through the reporting of corporate social responsibility information

This paper aims at examining the relationship between board composition and corporate social responsibility (CSR) of a sample of listed financial entities, discussing the driving reasons of these entities to disclose CSR information. We hypothesize that there is a positive association between outside (institutional and independent directors) and female directors and CSR disclosure and a negative relationship between inside directors and CSR reporting. Our findings provide evidence that the proportions of independent directors and female directors on boards encourage CSR disclosure. Moreover, the results also show that the proportions of inside directors and institutional directors on boards do not have influence on CSR reporting. Thus, our evidence suggests that board attributes such as independent and female directors encourage financial entities to report CSR matters, showing the effectiveness of these two corporate governance mechanisms. The paper shed light on the influence of board structure of financial entities on CSR disclosure. Therefore, this study contributes to past research by providing an index to measure CSR disclosure of financial entities and the importance of the distinction between outside and inside directors.
Socio-Political Unrest in Pakistan: A Perception of University Students in The Province of Balochistan, Pakistan

Pakistan has been suffering from issues of socio-political, economic and provincialism despite having a democratic federal form of government. The issue of provincialism has made Balochistan one of the volatile places regarding social unrest and instability. Therefore the present study was conducted to know the perspective of youth regarding social unrest in Balochistan. Questionnaire used as a survey instrument for data collection. Population of the study was students studying in various universities of Balochistan. A sample of 200 respondents was selected randomly from three universities of Quetta a province of Balochistan. Majority of the respondents agreed that economic deprivation, security issues, federal dominancy over Balochistan province and lack of political will on the part of local politicians were the major reasons. According to the studies suggested that this province has large amount of minerals reserves and whole country is getting benefits from it, whereas on the other side the present study concluded that lack of access to basic public facilities further aggravates the already volatile security situation in the province due to nationalistic feelings among youth. A few suggested measures are providing more educational opportunities, provision of justice and state willingness to exert proper governance, law and order.
Extrauterine Epithelioid Trophoblastic Tumor Arising in the Ovary With Multiple Metastases

Epithelioid trophoblastic tumor is a neoplasm of the chorionic-type intermediate trophoblasts. It is considered a rare gestational trophoblastic disease and is frequently misdiagnosed as carcinoma. Extrauterine epithelioid trophoblastic tumor has been reported in multiple anatomical sites. We report a case of a 50-year-old woman who presented with abdominal pain and distension. Her initial β-human chorionic gonatotropin level was 806.7 IU/L. Imaging showed a large complex ovarian mass with peritoneal and subcapsular hepatic deposits as well as pulmonary nodules. Morphological features of the tumor and its immunohistochemical reactivity to CK8/18, CK7, p63, and CD10 were consistent with the diagnosis of an extrauterine epithelioid trophoblastic tumor arising from the ovary. The differential diagnoses, including other ovarian tumors, were ruled out on the basis of morphology and negative immunostaining to a relatively extended panel of antibodies. A prolonged follow up of these cases and the recognition of such rare tumors in unusual sites are crucial to the diagnosing pathologist and treating physician.
Colonization of Rhodnius prolixus gut by Trypanosoma cruzi involves an extensive parasite killing

SUMMARY Trypanosoma cruzi, the etiological agent of Chagas disease, is ingested by triatomines during their bloodmeal on an infected mammal. Aiming to investigate the development and differentiation of T. cruzi inside the intestinal tract of Rhodnius prolixus at the beginning of infection we fed insects with cultured epimastigotes and blood trypomastigotes from infected mice to determine the amount of recovered parasites after ingestion. Approximately 20% of the ingested parasites was found in the insect anterior midgut (AM) 3 h after feeding. Interestingly, a significant reduction (80%) in the numbers of trypomastigotes was observed after 24 h of infection suggesting that parasites were killed in the AM. Moreover, few parasites were found in that intestinal portion after 96 h of infection. The evaluation of the numbers of parasites in the posterior midgut (PM) at the same periods showed a reduced parasite load, indicating that parasites were not moving from the AM. Additionally, incubation of blood trypomastigotes with extracts from R. prolixus AMs revealed that components of this tissue could induce significant death of T. cruzi. Finally, we observed that differentiation from trypomastigotes to epimastigotes is not completed in the AM; instead we suggest that trypomastigotes change to intermediary forms before their migration to the PM, where differentiation to epimastigotes takes place. The present work clarifies controversial points concerning T. cruzi development in insect vector, showing that parasite suffers a drastic decrease in population size before epimastigonesis accomplishment in PM.
Estimating the Returns to Professional Certifications and Licenses in the U.S. Manufacturing Sector

This study uses recently released Current Population Survey microdata to estimate the earnings premium associated with professional certification and licenses. The author finds that full-time manufacturing workers with a certification or license earn close to $200 more in median weekly earnings compared to those without. However, this does not account for differences in pay that are associated with worker endowments, such as education and gender. A Blinder–Oaxaca decomposition is used to distinguish the portion of the earnings gap that is attributable to the credential from the portion associated with endowments. Endowments explain 62% of the total earnings gap, meaning that the actual returns to a certification or license are closer to $70 per week. The author also finds that workers with no high school or college education receive a relatively larger increase in weekly earnings, compared to those with more advanced degrees.