Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth and development of the mammalian oocyte

The oocyte is not only the rarest and the largest cell in the body, but it also has one of the most remarkable life histories. Formed in the fetal ovary and suspended at diplotene of meiosis, it may wait for years before beginning to grow, and not until this process is complete can it resume meiosis and undergo fertilisation. Major changes in the number, morphology and distribution of cytoplasmic organelles occur during growth, and a molecular program for embryogenesis is formed. Specific yolk proteins are absent and much of the RNA and some of the protein are degraded by the cleavage stage. The zona pellucida has been intensively studied, but knowledge of oocyte‐specific genes is otherwise surprisingly patchy given the significance of this cell type and the expansion of reproductive technology. Finally, it is now clear that oocytes are not mere passengers which depend on granulosa cells for nutrition and regulation but actively promote the growth and differentiation of their follicles.
Crystal Structure of a Viral FLIP

Death receptor signaling is initiated by the assembly of the deathinducing signaling complex, which culminates in the activation of the initiator caspase, either caspase-8 or caspase-10. A family of viral and cellular proteins, known as FLIP, plays an essential role in the regulation of death receptor signaling. Viral FLIP (v-FLIP) and short cellular FLIP (c-FLIPS) inhibit apoptosis by interfering with death receptor signaling. The structure and mechanisms of v-FLIP and c-FLIPS remain largely unknown. Here we report a high resolution crystal structure of MC159, a v-FLIP derived from the molluscum contagiosum virus, which is a member of the human poxvirus family. Unexpectedly, the two tandem death effector domains (DEDs) of MC159 rigidly associate with each other through a hydrophobic interface. Structure-based sequence analysis suggests that this interface is conserved in the tandem DEDs from other v-FLIP, c-FLIPS, and caspase-8 and -10. Strikingly, the overall packing arrangement between the two DEDs of MC159 resembles that between the caspase recruitment domains of Apaf-1 and caspase-9. In addition, each DED of MC159 contains a highly conserved binding motif on the surface, to which loss-of-function mutations in MC159 map. These observations, in conjunction with published evidence, reveal significant insights into the function of v-FLIP and suggest a mechanism by which v-FLIP and c-FLIPS inhibit death receptor signaling.
Gender differences among hardcore smokers: an analysis of the tobacco use supplement of the current population survey.

BACKGROUND Despite significant declines in smoking rates in the United States, a substantial percentage of adults continue to smoke. Improved understanding of current smokers and their contact with sources of cessation support future tobacco control efforts. Recent evidence suggests that hardcore smokers, established smokers without a history of quit attempts, have less contact with cessation support. Although gender is among the major factors that influence smoking cessation, no research is available on gender differences among hardcore smokers. METHODS Demographic, environmental, and smoking-related characteristics of female hardcore smokers and male hardcore smokers and other female smokers were examined. Data from 17,777 smokers from the 2003 Current Population Survey Tobacco Use Supplement were analyzed. RESULTS Compared with female hardcore smokers, male hardcore smokers were more likely to have contact with smoking restrictions at work (OR = 1.69) and at home (OR = 1.45). Compared with female hardcore smokers, female other smokers were more likely to have seen a healthcare provider during the past year who advised them to quit smoking (OR = 1.39) and more likely to have smoking restrictions at work (OR = 1.25) and at home (OR = 2.32)). Measures of nicotine dependence suggested that female hardcore smokers were less dependent than male hardcore smokers but more dependent than other female smokers. CONCLUSIONS The sociodemographic and healthcare access variations in tobacco use identified in our analyses have significant public health implications and underscore the vital need for clinical and scientific advances in tobacco use prevention and control efforts.
Retention of oncogenicity by a Marek's disease virus mutant lacking six unique short region genes

We previously reported the construction of Marek's disease virus (MDV) strains having mutations in various genes that map to the unique short (US) region of the viral genome (J.L. Cantello, A.S. Anderson, A. Francesconi, and R.W. Morgan, J. Virol. 65:1584-1588, 1991; M.S. Parcells, A.S. Anderson, and R.W. Morgan, Virus Genes 9:5-13, 1994; M.S. Parcells, A.S. Anderson, and R.W. Morgan, J. Virol. 68:8239-8253, 1994). These strains were constructed by using a high-passage-level serotype 1 MDV strain which grew well in chicken embryo fibroblasts. Despite the growth of the parent and mutant viruses in cell culture, in vivo studies were limited by poor growth of these strains in chickens. One of the mutants studied lacked 4.5 kbp of US region DNA and contained the lacZ gene of Escherichia coli inserted at the site of the deletion. The deletion removed MDV homologs to the US1, US2, and US10 genes of herpes simplex virus type 1 as well as three MDV-specific open reading frames. We now report the construction of a mutant MDV containing a similar deletion in the US region of the highly oncogenic RB1B strain. This mutant, RB1B delta 4.5lac, had a growth impairment in established chicken embryo fibroblasts similar to that described previously for MDVs lacking a functional US1 gene. In chickens, RB1B delta 4.5lac showed decreased early cytolytic infection, mortality, tumor incidence, and horizontal transmission. Several lymphoblastoid cell lines were established from RB1B delta 4.5lac-induced tumors, and virus reactivated from these cell lines was LacZ+. These results indicate that the deleted genes are nonessential for the transformation of chicken T cells or for the establishment and maintenance of latency. On the basis of the growth impairment observed for RB1B delta 4.5lac in cell culture and in vivo, we conclude that deletion of these genes affects the lytic replication of MDV. This is the first MDV mutant constructed in the RB1B oncogenic strain, and the methodology described herein provides for the direct examination of MDV-encoded determinants of oncogenicity.
Differences in Access to Care Among Students Using School-Based Health Centers

Health care reform has changed the landscape for the nation’s health safety net, and school-based health centers (SBHCs) remain an important part of this system. However, few large-scale studies have been conducted to assess their impact on access to care. This study investigated differences in access among a nationally representative sample of adolescent SBHC users. An analysis using multivariate logistic regression examined the association between student characteristics and access to care. We found no differences based on race/ethnicity or insurance status among adolescent SBHC users; however, we did observe significant differences with regard to unmet health needs. School nurses serve as invaluable frontline staff who can facilitate equitable access to care, provide high-quality primary care, coordinate care for students with community health services, and advocate for policy and funding support of SBHCs as a critical part of the safety net for underserved adolescents.
The force—velocity relation of isolated twitch and slow muscle fibres of Xenopus laevis

1. A study has been made of the relation between force and speed of shortening, or lengthening, in isolated twitch and slow muscle fibres, dissected from the iliofibularis muscle of Xenopus laevis. Both after‐loaded and quick‐release contractions were studied. Twitch fibres were stimulated electrically to give tetanic contractions (5‐20 °C); slow fibres were activated by a rapid change to solutions with high K concentration (30‐75 m M; experiments at 21‐24 °C).
The Accuracy of Microtargeted Policy Positions

ABSTRACT Identifying voters who share policy positions with the candidates has become an important component of modern political campaigns as they rely on microtargeted estimates to guide targeting decisions. Using survey data and microtargeted estimates from the 2012 election, I conduct one of the first independent examinations of the accuracy of microtargeting. The estimates are the most accurate in Florida, a state that requests information on the race of voters when they register and has party registration. The estimates are less accurate in the other battleground states that do not collect as much information. The accuracy rates range from 36% to 82% depending on the issue and state.
Influence of psychiatric comorbidity in alcohol-dependent subjects in a representative population survey on treatment utilization and natural recovery.

BACKGROUND It is well known that only a minority of alcohol-dependent subjects seek help and that the majority of alcohol-dependent individuals recover without utilization of formal help. Psychiatric comorbidity is highly prevalent among alcohol-dependent individuals. However, no data are available on the impact of psychiatric comorbidity on natural recovery. AIMS To analyse the impact of non-psychotic psychiatric comorbid Axis I disorders on remission rate and utilization of formal help in alcohol-dependent individuals drawn from a representative general population sample in northern Germany (response rate: 70.2%, n = 4075). Psychiatric diagnoses and utilization of help were assessed in a personal interview using standardized instruments. One hundred and fifty-three life-time alcohol-dependent individuals were assessed, among whom 98 fulfilled the criteria for sustained long-term remission according to the Diagnostic and Statistical Manual version II (DSM-IV) criteria. Any coincidence of DSM-IV non-psychotic Axis I disorders with alcohol dependence was counted as comorbidity. Comorbidity rate in the whole sample was 36.1%. RESULTS The rate of individuals who remitted from alcohol dependence without formal help was 36.9% in the non-comorbid and 42.6% in the comorbid group. Utilization of formal help was unrelated to comorbidity. Dually diagnosed subjects without a history of help-seeking showed minor differences concerning reasons for not seeking help. Seeking help was not related to schooling, severity of dependence and gender. CONCLUSION Data reveal that remission without formal help is equally prevalent among non-comorbid as among comorbid alcohol-dependent individuals. Axis I comorbidity is not related directly to utilization of alcohol-related help. Negative prognoses for untreated comorbid alcohol-dependent individuals are not justified from an epidemiological point of view.
Urine Flow Is a Novel Hemodynamic Monitoring Tool for the Detection of Hypovolemia

BACKGROUND:Noticeable changes in vital signs indicating hypovolemia occur only after 15% of the blood volume is lost. More sensitive variables (e.g., cardiac output, systolic pressure variation and its &Dgr;down component) are invasive and difficult to obtain in the early phase of bleeding. Lately, a new technology for continuous optical measurements of minute-to-minute urine flow rates has become available. We performed a preliminary evaluation to determine whether urine flow can act as an early and sensitive warning of hypovolemia. METHODS:Eleven patients (ASA physical status I–II) undergoing posterior spine fusion surgery were studied prospectively. Study variables included heart rate, blood pressure (systolic and diastolic), systolic pressure variation and &Dgr;down, minute urinary flow, hemoglobin, blood and urinary sodium, and creatinine in the blood and urine. Urine flow rate was measured using URINFO 2000™ (FlowSense Medical, Misgav, Israel). After recording baseline variables, 10 mL/kg of the patient's blood was shed and a second set of variables was recorded. Subsequently, hypovolemia was reversed by infusing colloid solution (hetastarch 6%) followed by recording a third set of variables. These 3 observations were then compared. RESULTS:An average of 614 ± 143 mL (mean ± SD) of blood was shed. During phlebotomy, the mean urine flow rate decreased from 5.7 ± 8 mL/min to 1.07 ± 2.5 mL/min. Systolic blood pressure and hemoglobin also decreased. &Dgr;down increased. After rehydration, urine flow, blood pressure, and &Dgr;down values returned to baseline. The hemoglobin concentration decreased whereas other variables did not change significantly. CONCLUSION:Urine flow rate is a dynamic variable that seems to be a reliable indicator of changes in blood volume. These results justify further investigation.
Quality of government and regional competition: A spatial analysis of subnational regions in the European Union

Building on previous work on competition networks and governmental performance among British local governments, this article investigates the diffusion of government quality across subnational regions of Europe through strategic interaction with neighbouring regions or competitor regions more generally. The article demonstrates the presence of spatial interdependence using standard spatial regression models and controlling for common explanations of quality of government. In particular for regions with high levels of autonomy from the national government, there is clear adjustment in government quality to be seen in response to disparities with competitor regions. The article further investigates the intensity of this geographical effect separately in the north and south of Europe in order to estimate the potential for virtuous or vicious cycles of good governance in the two regions, respectively. It is found that while regions in the north develop relatively independently of each other but respond to competitive pressure across Europe, in the south regions demonstrate a higher level of local interdependence, increasing the possibility of virtuous cycles – but also of vicious ones.
5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside Inhibits Cancer Cell Proliferation in Vitro and in Vivo via AMP-activated Protein Kinase*

5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) is widely used as an AMP-kinase activator, which regulates energy homeostasis and response to metabolic stress. Here, we investigated the effect of AICAR, an AMPK activator, on proliferation of various cancer cells and observed that proliferation of all the examined cell lines was significantly inhibited by AICAR treatment due to arrest in S-phase accompanied with increased expression of p21, p27, and p53 proteins and inhibition of PI3K-Akt pathway. Inhibition in in vitro growth of cancer cells was mirrored in vivo with increased expression of p21, p27, and p53 and attenuation of Akt phosphorylation. Anti-proliferative effect of AICAR is mediated through activated AMP-activated protein kinase (AMPK) as iodotubericidin and dominant-negative AMPK expression vector reversed the AICAR-mediated growth arrest. Moreover, constitutive active AMPK arrested the cells in S-phase by inducing the expression of p21, p27, and p53 proteins and inhibiting Akt phosphorylation, suggesting the involvement of AMPK. AICAR inhibited proliferation in both LKB and LKB knock-out mouse embryo fibroblasts to similar extent and arrested cells at S-phase when transfected with dominant negative expression vector of LKB. Altogether, these results indicate that AICAR can be utilized as a therapeutic drug to inhibit cancer, and AMPK can be a potential target for treatment of various cancers independent of the functional tumor suppressor gene, LKB.
Increased susceptibility of splenectomized mice to infection after exposure to an aerosolized suspension of type III Streptococcus pneumoniae

Most reported experimental studies concerning the effect of splenectomy in animals have shown enhanced mortality from pneumococci injected either intravenously or intraperitoneally. We have developed a laboratory model in which mice are exposed to type III Streptococcus pneumoniae via an aerosolized atmosphere, thus closely approximating the route of human infection with this organism. Ninety-one male Swiss mice (mean weight 26 g) were divided into three approximately equal groups of control, sham-operated, and splenectomized animals. Two weeks later they were exposed for 30 min in individualized compartments within a confined chamber to an aerosolized atmosphere producing a uniform challenge of 5.9 X 10(9) colony-forming units per ml of pneumococci. A statistically significant increase (P less than 0.01) in mortality was demonstrated in the splenectomized group over the pooled sham-operated and control groups. The animal model used in these investigations can be applied to the study of infections acquired by the respiratory route in numerous experimental designs.
Payout incremental e o modelo de três fatores de Fama e French

This study aims to analyze whether the inclusion of the Payout factor on the three factors of Fama and French (1993) is relevant to an explanation of the return of the companies listed on the BM&FBOVESPA between 2004 and 2014. The Payout evaluates the level of payment of dividends. The premium of the Payout’s factor is obtained by the difference of returns among the companies that paid the dividend percentage – Incremental Payout higher than what legislation suggests – and the return of the companies that did not pay dividends. The method used in this paper is based on Fame and French (1993) model’s, which the Payout factor was added to by the market risk premium (RM-RF), an award by the factor (SMB) size and prize for the book-to-market factor (HML) creating a new model of 4 factors. The explanatory power of this model was tested in the face of the return of 12 portfolios created by orthogonalizing these factors. The results indicate that the Payout factor is significant in the model and that this factor generally has a negative relationship with the return of portfolios. The model can explain better the return of seven from twelve portfolios studied. From these portfolios stands out portfolios with little value, high value and that paid dividends, small, low-value and that paid dividends, small, low-value and that did not pay dividends, with an explanatory power of over 70%. For great portfolios, high value and that did not pay dividends, large, low-value and that did not pay dividends, small, low-value and that paid minimum dividends, small, high value and that did not pay dividends, the model explains the return in more than 50% with the variables presented. The variable Payout was not significant for small, low portfolio value and that paid dividends. Therefore, the inclusion of the Payout factor model of Fame and French (1993) has relevance to portfolio assessment studies. This study contributes to the discussion and improvement of asset pricing models in the Brazilian market.
HTLV‐1 carriers with B‐cell lymphoma of localized stage head and neck: prognosis, clinical and immunopathological features

Summary. Human T‐lymphotropic virus type I (HTLV‐I) is closely associated with T‐cell lymphoma/leukaemia, which always shows monoclonal HTLV‐1 provirus DNA integration. HTLV‐1 is not associated with B‐cell lymphoma. The relationship between B‐cell lymphoma and HTLV‐1 was analysed retrospectively in early stage B‐cell non‐Hodgkin's lymphoma (NHL) according to HTLV‐1 infection and pathological features. We analysed 198 cases of head and neck B‐cell NHL treated with radiotherapy and/or chemotherapy; 21 were seropositive and 177 were seronegative for HTLV‐1. We also immunostained 26 cases of diffuse large B‐cell lymphoma (DLBL), including 12 seropositive and 14 seronegative for HTLV‐1 respectively, for CD20, CD3, CD4, CD8, CD56, MIB‐1 and T‐cell‐restricted intracellular antigen (TIA‐1) to examine the phenotype, immunity and proliferation activity. The 5‐year overall survival rates were 78% and 49% (P = 0·007, log rank test) for HTLV‐1 seronegative and seropositive cases respectively. Infection with HTLV‐1 was significantly associated with poor survival in patients with B‐cell lymphoma by multivariate analysis. For DLBL, HTLV‐1 infection was not a significant factor, but the overall survival curve was similar to that of the 21 seropositive B‐cell lymphoma cases. Lymphoma cells were negative for TIA‐1, but the background lymphocytes were positive for this marker. The number of TIA‐1‐positive cells was higher in HTLV‐1‐negative cases than in‐positive cases. In conclusion, patients with B‐cell‐NHL (B‐NHL) who are also HTLV‐1 carriers have a poorer prognosis than non‐carriers. HTLV‐1 does not seem to be associated with lymphomagenesis of the B phenotype itself, but correlates with host immunity by reducing the number of cytotoxic T‐cells.
Aup1p, a Yeast Mitochondrial Protein Phosphatase Homolog, Is Required for Efficient Stationary Phase Mitophagy and Cell Survival*

Autophagy is a catabolic membrane-trafficking process that occurs in all eukaryotic cells and leads to the hydrolytic degradation of cytosolic material in the vacuolar or lysosomal lumen. Mitophagy, a selective form of autophagy targeting mitochondria, is poorly understood at present. Several recent reports suggest that mitophagy is a selective process that targets damaged mitochondria, whereas other studies imply a role for mitophagy in cell death processes. In a screen for protein phosphatase homologs that functionally interact with the autophagy-dedicated protein kinase Atg1p in yeast, we have identified Aup1p, encoded by Saccharomyces cerevisiae reading frame YCR079w. Aup1p is highly similar to a family of protein phosphatase homologs in animal cells that are predicted to localize to mitochondria based on sequence analysis. Interestingly, we found that Aup1p localizes to the mitochondrial intermembrane space and is required for efficient mitophagy in stationary phase cells. Viability studies demonstrate that Aup1p is required for efficient survival of cells in prolonged stationary phase cultures, implying a pro-survival role for mitophagy under our working conditions. Our data suggest that Aup1p may be part of a signal transduction mechanism that marks mitochondria for sequestration into autophagosomes.