Miracle-dz/UniFAR-FTUs huggingface dataset:
P2 receptor antagonist PPADS inhibits mesangial cell proliferation in experimental mesangial proliferative glomerulonephritis.

BACKGROUND Although extracellular nucleotides have been shown to confer mitogenic effects in cultured rat mesangial cells through activation of purinergic P2 receptors (P2Y receptors), thus far the in vivo relevance of these findings is unclear. Virtually all cells and in particular the dense granules of platelets contain high levels of nucleotides that are released upon cell injury or platelet aggregation. In experimental mesangial proliferative glomerulonephritis in the rat (anti-Thy1 model), mesangiolysis and glomerular platelet aggregation are followed by a pronounced mesangial cell (MC) proliferative response leading to glomerular hypercellularity. Therefore, we examined the role of extracellular nucleotides and their corresponding receptors in nucleotide-stimulated cultured mesangial cells and in inflammatory glomerular disease using the P2 receptor antagonist PPADS. METHODS The effects of PPADS on nucleotide- or fetal calf serum (FCS)-stimulated proliferation of cultured MC were measured by cell counting and [3H]thymidine incorporation assay. After induction of the anti-Thy1 model, rats received injections of the P2-receptor antagonist PPADS at different doses (15, 30, 60 mg/kg BW). Proliferating mesangial and non-mesangial cells, mesangial cell activation, matrix accumulation, influx of inflammatory cells, mesangiolysis, microaneurysm formation, and renal functional parameters were assessed during anti-Thy1 disease. P2Y-mRNA and protein expression was assessed using RT-PCR and real time PCR, Northern blot analysis, in situ hybridization, and immunohistochemistry. RESULTS In cultured mesangial cells, PPADS inhibited nucleotide, but not FCS-stimulated proliferation in a dose-dependent manner. In the anti-Thy1 model, PPADS specifically and dose-dependently reduced early (day 3), but not late (day 8), glomerular mesangial cell proliferation as well as phenotypic activation of the mesangium and slightly matrix expansion. While no consistent effect was obtained in regard to the degree of mesangiolysis, influx of inflammatory cells, proteinuria or blood pressure, PPADS treatment increased serum creatinine and urea in anti-Thy1 rats. P2Y receptor expression (P2Y2 and P2Y6) was detected in cultured MC and isolated glomeruli, and demonstrated a transient marked increase during anti-Thy1 disease. CONCLUSION These data strongly suggest an in vivo role for extracellular nucleotides in mediating early MC proliferation after MC injury.
Incitants Financiers Du Dirigeant Et Niveau D'Endettement Optimal

The purpose of this paper is to highlight the link between incentive mix and financing policy. We focus on the conditional effect of pay to performance sensitivity on risk taking behavior. We focus on target debt leverage level determinants using a dynamic adjustment model. We consider US firms to validate our hypothesis on the period 1992-2005. Our data are extracted from Compustat and Execucomp database. The main result of this work is that the efficiency of risk incentive is highly dependent of CEO's performance incentive reaching a given threshold.
Hairpin ribozyme-antisense RNA constructs can act as molecular lassos

We have developed a novel class of antisense agents, RNA Lassos, which are capable of binding to and circularizing around complementary target RNAs. The RNA Lasso consists of a fixed sequence derived from the hairpin ribozyme and an antisense segment whose size and sequence can be varied to base pair with accessible sites in the target RNA. The ribozyme catalyzes self-processing of the 5′- and 3′-ends of a transcribed Lasso precursor and ligates the processed ends to produce a circular RNA. The circular and linear forms of the self-processed Lasso coexist in an equilibrium that is dependent on both the Lasso sequence and the solution conditions. Lassos form strong, noncovalent complexes with linear target RNAs and form true topological linkages with circular targets. Lasso complexes with linear RNA targets were detected by denaturing gel electrophoresis and were found to be more stable than ordinary RNA duplexes. We show that expression of a fusion mRNA consisting of a sequence from the murine tumor necrosis factor-α (TNF-α) gene linked to luciferase reporter can be specifically and efficiently blocked by an anti-TNF Lasso. We also show in cell culture experiments that Lassos directed against Fas pre-mRNA were able to induce a change in alternative splicing patterns.
The utility of web mining for epidemiological research: studying the association between parity and cancer risk

BACKGROUND The World Wide Web has emerged as a powerful data source for epidemiological studies related to infectious disease surveillance. However, its potential for cancer-related epidemiological discoveries is largely unexplored. METHODS Using advanced web crawling and tailored information extraction procedures, the authors automatically collected and analyzed the text content of 79 394 online obituary articles published between 1998 and 2014. The collected data included 51 911 cancer (27 330 breast; 9470 lung; 6496 pancreatic; 6342 ovarian; 2273 colon) and 27 483 non-cancer cases. With the derived information, the authors replicated a case-control study design to investigate the association between parity (i.e., childbearing) and cancer risk. Age-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each cancer type and compared to those reported in large-scale epidemiological studies. RESULTS Parity was found to be associated with a significantly reduced risk of breast cancer (OR = 0.78, 95% CI, 0.75-0.82), pancreatic cancer (OR = 0.78, 95% CI, 0.72-0.83), colon cancer (OR = 0.67, 95% CI, 0.60-0.74), and ovarian cancer (OR = 0.58, 95% CI, 0.54-0.62). Marginal association was found for lung cancer risk (OR = 0.87, 95% CI, 0.81-0.92). The linear trend between increased parity and reduced cancer risk was dramatically more pronounced for breast and ovarian cancer than the other cancers included in the analysis. CONCLUSION This large web-mining study on parity and cancer risk produced findings very similar to those reported with traditional observational studies. It may be used as a promising strategy to generate study hypotheses for guiding and prioritizing future epidemiological studies.
Accumulated financial strain and women's health over three decades.

OBJECTIVE Drawing from cumulative inequality theory, this research examines how accumulated financial strain affects women's self-rated health in middle and later life. METHOD Using data from the National Longitudinal Survey of Mature Women (1967-2003), we employ random-coefficient growth curve models to examine whether recurring financial strain influences women's health, above and beyond several measures of objective social status. Predicted probabilities of poor health were estimated by the frequency of financial strain. RESULTS Financial strain is associated with rapid declines in women's health during middle and later life, especially for those women who reported recurrent strain. Changes in household income and household wealth were also associated with women's health but did not eliminate the effects due to accumulated financial strain. DISCUSSION Accumulated financial strain has long-term effects on women's health during middle and later life. The findings demonstrate the importance of measuring life course exposure to stressors in studies of health trajectories.
β-catenin is Required in Odontoblasts for Tooth Root Formation

The tooth root is an important part of the tooth that works together with the surrounding periodontium to maintain the tooth in the alveolar socket. The root develops after crown morphogenesis. While the molecular and cellular mechanisms of early tooth development and crown morphogenesis have been extensively studied, little is known about the molecular mechanisms controlling tooth root formation. Here, we show that β-catenin is strongly expressed in odontoblast-lineage cells and is required for root formation. Tissue-specific inactivation of β-catenin in developing odontoblasts produced molars lacking roots and aberrantly thin incisors. At the beginning of root formation in the mutant molars, the cervical loop epithelium extended apically to form Hertwig’s epithelial root sheath (HERS), but root odontoblast differentiation was disrupted and followed by the loss of some HERS inner layer cells. However, the outer layer of the HERS extended without the root, and the mutant molars finally erupted. The periodontal tissues extensively invaded the dental pulp. These results indicate that there is a cell-autonomous requirement for Wnt/β-catenin signaling in the dental mesenchyme for root formation.
Perceived financial incentives, HMO market penetration, and physicians' practice styles and satisfaction.

OBJECTIVE To estimate the effects of physicians' personal financial incentives and other measures of involvement with HMOs on three measures of satisfaction and practice style: overall practice satisfaction, the extent to which prior expectations about professional autonomy and the ability to practice good-quality medicine are met, and several specific measures of practice style. DATA SOURCES A telephone survey conducted in 1997 of 1,549 physicians who were located in the 75 largest Metropolitan Statistical Areas in 1991. Eligible physicians were under age 52, had between 8 and 17 years of post-residency practice experience, and spent at least 20 hours per week in patient care. The response rate was 74 percent. STUDY DESIGN Multivariate binomial and multinomial ordered logistic regression models were estimated. Independent variables included physicians' self-reported financial incentives, measured by the extent to which their overall financial arrangements created an incentive to either reduce or increase services to patients, the level of HMO penetration in the market, employment setting, medical specialty, exposure to managed care while in medical training, and selected personal characteristics. PRINCIPAL FINDINGS About 15 percent of survey respondents reported a moderate or strong incentive to reduce services; 70 percent reported a neutral incentive; and 15 percent reported an incentive to increase services. Compared to physicians with a neutral incentive, physicians with an incentive to reduce services were from 1.5 to 3.5 times more likely to be very dissatisfied with their practices and were 0.2 to 0.5 times as likely to report that their expectations regarding professional autonomy and ability to practice good-quality medicine were met. They were also 0.2 to 0.6 times as likely to report having the freedom to care for patients the way they would like along several specific measures of practice style, such as sufficient time with patients, ability to hospitalize, ability to order tests and procedures, and ability to make referrals. These effects were generally reinforced by practicing in an area with a high level of HMO penetration and were offset to some extent by having had exposure to HMOs and the practice of cost-effective medicine while in medical training. CONCLUSIONS Although financial incentives to reduce services are not widespread, there is a legitimate reason to be concerned about possible adverse affects on the quality of care. More research is needed to investigate directly whether changes in patients' health are affected by their physicians' financial incentives.
Towards Sustainable Urban Spatial Structure: Does Decentralization Reduce Commuting Times?

This paper contributes to the existing debate on the co-location hypothesis, by devising a proximity measure and controlling for a set of other urban form measures. Utilizing the LEHD (Longitudinal Employer–Household Dynamics) Origin-Destination Employment Statistics (LODES) data that provide the number of jobs by a finer geography, this paper measured the degree of centralization, proximity, and job–housing mismatch. Multiple regression analysis revealed that the job–worker proximity leads to a shorter commuting time. In addition, the results focusing on suburban areas revealed that the impact of the job–worker imbalance and the impact of job–worker mismatch on the commuting time are greater in the suburb in comparison with the city center.
Testing for financial contagion: New evidence from the European debt crisis

This paper tested for a contagion effect between the foreign exchange market of the Eurozone and the markets of seven emerging and growth leading economies - EAGLEs - during the European Debt Crisis. For this purpose, we used the daily domestic currency per unit of US Dollar of seven EAGLEs countries from 01.01. 2007 to 31.12. 2012. The tranquil period was from 01.01. 2007 to 19.10. 2009 and the turmoil period was from 20.10. 2009 to 31.12. 2012. We found a contagion effect between the foreign exchange market of the Eurozone and the markets of Brazil, Mexico, and Turkey. The evidence suggests that foreign trade is likely to be the source of the contagion during the European Debt Crisis. The evidence presented in this paper is important for policy makers, international investors, and portfolio managers.
Conflicting selection on the timing of germination in a natural population of Arabidopsis thaliana

The timing of germination is a key life‐history trait that may strongly influence plant fitness and that sets the stage for selection on traits expressed later in the life cycle. In seasonal environments, the period favourable for germination and the total length of the growing season are limited. The optimal timing of germination may therefore be governed by conflicting selection through survival and fecundity. We conducted a field experiment to examine the effects of timing of germination on survival, fecundity and overall fitness in a natural population of the annual herb Arabidopsis thaliana in north‐central Sweden. Seedlings were transplanted at three different times in late summer and in autumn covering the period of seed germination in the study population. Early germination was associated with low seedling survival, but also with high survival and fecundity among established plants. The advantages of germinating early more than balanced the disadvantage and selection favoured early germination. The results suggest that low survival among early germinating seeds is the main force opposing the evolution of earlier germination and that the optimal timing of germination should vary in space and time as a function of the direction and strength of selection acting during different life‐history stages.
Estradiol administration to ovariectomized rats potentiates mephedrone-induced disruptions of nonspatial learning.

Mephedrone (4-methylmethcathinone) has been found in several over-the-counter products that are abused by humans, but very little is known about its behavioral effects and abuse liability. The present study examined the effects of mephedrone (1-10 mg/kg) on learning in female rats, as well as its interaction with the ovarian hormone estradiol. More specifically, female rats were trained to respond under a multiple schedule of repeated acquisition and performance of response sequences and then ovariectomized. Following ovariectomy, mephedrone dose-effect curves were obtained during periods of 17β-estradiol administration and periods without estradiol administration. Unlike mephedrone, which was administered acutely (i.p.) before the experimental sessions, 17β-estradiol was administered via subcutaneous Silastic capsules containing 25% 17β-estradiol and 75% cholesterol. In general, mephedrone produced dose-dependent rate-decreasing and error-increasing effects in the acquisition and performance components of the schedule in all subjects. However, when estradiol was present, three of the four rats were more sensitive to the rate-decreasing effects of mephedrone, and all of the subjects were more sensitive to its error-increasing effects. These data indicate that estradiol can potentiate the disruptive effects of mephedrone on both the acquisition and performance of complex behavior in female rats.
Association study of the 15q11‐q13 maternal expression domain in Japanese autistic patients

Chromosome 15q11‐q13 has been a focus of genetic studies of autism susceptibility, because cytogenetic abnormalities are frequently observed in this region in autistic patients. An imprinted, maternally expressed gene within the region may have a role in autistic symptomatology. In the present study, we investigated the association between autism and the maternal expression domain (MED) in the region, containing the UBE3A and ATP10C genes, and the upstream imprinting center (IC), which mediates coordinate control of imprinted expression throughout the region. We analyzed 41 single nucleotide polymorphisms (SNPs) in 166 patients with autism and 416 controls from a Japanese population. As a result, a statistically significant difference after correction for multiple testing was observed between the patients and controls in the genotypic distribution of SNP rs7164989 (SNP8 in this study) located in SNRPN, whose promoter corresponds to the IC (P = 0.018, corrected for multiple testing). In the analysis of a four‐marker haplotype located in ATP10C, a statistically significant difference after correction for multiple testing was observed in the frequency of one haplotype between male patients and controls (permutation P = 0.033, corrected for multiple testing). Thus, the present study may suggest the association between autism and the MED or the upstream IC in chromosome 15q11‐q13 in the Japanese population. © 2008 Wiley‐Liss, Inc.
Movement variability in the golf swing

Traditionally, golf biomechanics has focused upon achieving consistency in swing kinematics and kinetics, whilst variability was considered to be noise and dysfunctional. There has been a growing argument that variability is an intrinsic aspect of skilled motor performance and plays a functional role. Two types of variability are described: ‘strategic shot selection’ and ‘movement variability’. In ‘strategic shot selection’, the outcome remains consistent, but the swing kinematics/kinetics (resulting in the desired ball flight) are free to vary; ‘movement variability’ is the changes in swing kinematics and kinetics from trial to trial when the golfer attempts to hit the same shot. These changes will emerge due to constraints of the golfer's body, the environment, and the task. Biomechanical research has focused upon aspects of technique such as elite versus non-elite kinematics, kinetics, kinematic sequencing, peak angular velocities of body segments, wrist function, ground reaction forces, and electromyography, mainly in the search for greater distance and clubhead velocity. To date very little is known about the impact of variability on this complex motor skill, and it has yet to be fully researched to determine where the trade-off between functional and detrimental variability lies when in pursuit of enhanced performance outcomes.
IL-6 Is Required for the Development of Th1 Cell-Mediated Murine Colitis1

Proinflammatory cytokines have been demonstrated to play a crucial role in the pathogenesis of Crohn’s disease. Among those cytokines, strong expression of IL-6 has been repeatedly demonstrated. To examine the role for IL-6 in the pathogenesis of Crohn’s disease, we introduced anti-IL-6R mAb to a murine model of colitis. Colitis was induced in C.B-17-scid mice transferred with CD45RBhigh CD4+ T cells from BALB/c mice. Anti-IL-6R mAb or rat IgG was administered weekly after T cell transfer. ICAM-1 and VCAM-1 expression were analyzed by immunohistochemistry. Colonic cytokine expression was determined by RT-PCR. Mice treated with mAb showed normal growth, whereas controls lost weight. The average colitis score was 0.64 for mAb-treated mice and 1.80 for controls. T cell expansion in treated mice was less remarkable than in the controls. Colonic ICAM-1 and VCAM-1 expression were markedly suppressed by mAb. IFN-γ, TNF-α, and IL-1β mRNA were reduced by the treatment. The results presented here show a crucial role for IL-6 in the pathogenesis of murine colitis and suggest a therapeutic potential of anti-IL-6R mAb for treatment of human Crohn’s disease.
Stochastic supply curves and liquidity costs: estimation for brazilian equities

Market Liquidity is characterized by the easiness and freedom to trade assets at desired volumes and for prices perceived as representative of their values. When there is a scarcity of bid and ask offers at those terms, traders face the so called Market Liquidity Risk and they must offer concessions on their original offers, leading to additional costs. Approaches to model this phenomena exist in broad variety but a common component of most Market Liquidity models is an instantaneous cost component, also known as transaction/execution costs or realized/instantaneous impact. This element, here the Liquidity Cost, gives the actual trading prices faced by a trader, frequently a deviation from the unobservable “true price”, normally represented as a GBM with the mid-price as a proxy for modeling purposes. Although it is clear that Liquidity Costs are a relevant aspect of Market Liquidity Risk and it is present in many models, it is relegated to a more simplistic treatment, being though as well-behaved, deterministic, smooth and static. The main point of this work is to follow a different approach by evaluating Liquidity Costs at a microstructural level by estimating the Stochastic Supply Curve from Çetin-Jarrow-Protter Model for Brazilian equities. To do so, high-frequency-data from B3’s ftp is used and to build Limit Order Books for several stocks at intraday periods. The empirical findings support the existence of non-trivial Stochastic Supply Curves as a representation for Liquidity Costs in several equities on Brazilian Markets. Additionally, there is evidence that Liquidity Costs may behave in contrast with some of the literature, being stochastic with time-varying functional representations on the LOB and with liquidity parameters that could be represented as mean-reverting stochastic process.
mRNA Capping Enzyme Requirement forCaenorhabditis elegans Viability*

Capping of the initiated 5′ ends of RNA polymerase II products is evolutionarily and functionally conserved from yeasts to humans. The m7GpppN cap promotes RNA stability, processing, transport, and translation. Deletion of capping enzymes in yeasts was shown to be lethal due to rapid exonucleolytic degradation of uncapped transcripts or failure of capped but unmethylated RNA to initiate protein synthesis. Using RNA interference and Caenorhabditis elegans we have found that RNA capping is also essential for metazoan viability. C. elegansbifunctional capping enzyme was cloned, and capping activity by the expressed protein as well as growth complementation of yeast deletion strains missing either RNA triphosphatase or guanylyltransferase required terminal sequences not present in the previously isolatedcel-1 clone. By RNA interference analysis we show thatcel-1 is required for embryogenesis.cel-1(RNAi) embryos formed cytoplasmic granules characteristic of a phenocluster of RNA processing genes and died early in development.