Miracle-dz/UniFAR-FTUs huggingface dataset:
Chloride channels: An emerging molecular picture

Chloride channels are probably found in every cell, from bacteria to mammals. Their physiological tasks range from cell volume regulation to stabilization of the membrane potential, signal transduction, transepithelial transport and acidification of intracellular organelles. These different functions require the presence of many distinct chloride channels, which are differentially expressed and regulated by various stimuli. These include various intracellular messengers (like calcium and cyclic AMP), pH, extracellular ligands and transmembrane voltage. Three major structural classes of chloride channels are known to date, but there may be others not yet identified. After an overview of the general functions of chloride channels, this review will focus on these cloned chloride channels: the CLC chloride channel family, which includes voltage‐gated chloride channels, and the cystic fibrosis transmembrane regulator (CFTR), which performs other functions in addition to being a chloride channel. Finally, a short section deals with GABA and glycine receptors. Diseases resulting from chloride channel defects will be specially emphasized, together with the somewhat limited information about how these proteins work at the molecular level.
Fatigue of insect cuticle

SUMMARY Many parts of the insect exoskeleton experience repeated cyclic loading. Although the cuticle of insects and other arthropods is the second most common natural composite material in the world, so far nothing is known about its fatigue properties, despite the fact that fatigue undoubtedly limits the durability of body parts in vivo. For the first time, we here present experimental fatigue data of insect cuticle. Using force-controlled cyclic loading, we determined the number of cycles to failure for hind legs (tibiae) and hind wings of the locust Schistocerca gregaria, as a function of the applied cyclic stress. Our results show that, although both are made from cuticle, these two body parts behave very differently. Wing samples showed a large fatigue range, failing after 100,000 cycles when we applied 46% of the stress needed for instantaneous failure [the ultimate tensile strength (UTS)]. Legs, in contrast, were able to sustain a stress of 76% of the UTS for the same number of cycles to failure. This can be explained by the difference in the composition and structure of the material, two factors that, amongst others, also affect the well-known behaviour of engineering composites. Final failure of the tibiae occurred via one of two different failure modes – crack propagation in tension or buckling in compression – indicating that the tibia is ‘optimized’ by evolution to resist both failure modes equally. These results are further discussed in relation to the evolution and normal use of these two body parts.
Mean reversion and sales

This article analyses the degree of inflation persistence in the EU15 using disaggregate HICP price indices. The results, based on a nonparametric measure proposed by Marques (2004) suggest a very moderate degree of median and mean inflation persistence. The modified treatment of sales in the Harmonised Index of Consumer Prices tends to reduce the measured degree of inflation persistence.
Biomarkers for depression: recent insights, current challenges and future prospects

A plethora of research has implicated hundreds of putative biomarkers for depression, but has not yet fully elucidated their roles in depressive illness or established what is abnormal in which patients and how biologic information can be used to enhance diagnosis, treatment and prognosis. This lack of progress is partially due to the nature and heterogeneity of depression, in conjunction with methodological heterogeneity within the research literature and the large array of biomarkers with potential, the expression of which often varies according to many factors. We review the available literature, which indicates that markers involved in inflammatory, neurotrophic and metabolic processes, as well as neurotransmitter and neuroendocrine system components, represent highly promising candidates. These may be measured through genetic and epigenetic, transcriptomic and proteomic, metabolomic and neuroimaging assessments. The use of novel approaches and systematic research programs is now required to determine whether, and which, biomarkers can be used to predict response to treatment, stratify patients to specific treatments and develop targets for new interventions. We conclude that there is much promise for reducing the burden of depression through further developing and expanding these research avenues.
Hepatitis C viral dynamics during ribavirin priming differ according to prior treatment response and HCV type

The mode of action of ribavirin is not completely understood. Ribavirin monotherapy has a measurable antiviral effect, which shows great variability. It might lead to an earlier steady state of plasma concentration and therefore enhance the effect of following combination treatment. The aim of this study was to evaluate the antiviral effect of ribavirin priming and its influence on sustained virologic response after combination treatment in a group of patients with different hepatitis C virus (HCV) types with or without prior treatment experience. Retrospective analysis of 75 patients (37 treatment naïve, 20 prior relapse, 16 prior nonresponse, genotype 1 present in 60 patients) from five centres who received ribavirin priming as part of an individual strategy in order to improve treatment outcome. All patients received ribavirin monotherapy with a mean dose of 14.5 mg kg−1 body weight for a mean of 28 days. After ribavirin priming, dual combination treatment with pegylated interferon alfa and ribavirin was started. The mean HCV RNA decline after ribavirin priming was 0.6 log10 IU mL−1 (P<.001). The initial viral decline depended on HCV type and previous treatment status being highest among prior relapsers (0.8 log10 IU mL−1; P=.002) and HCV type 2/3 (1.2 log10 IU mL−1; P=.05) and lowest among those with prior nonresponse (0.3 log10 IU mL−1, P=.01). IFNL4 (formerly IL28B) genotype for rs12979860 and IFNL3 genotype rs8099917 did not influence the initial viral decline. The study demonstrates a significant variability in the viral dynamics and antiviral efficacy of ribavirin monotherapy, which is mainly influenced by prior treatment status. The fact that the lowest response pattern was observed in prior nonresponder patients to pegylated interferon alfa plus ribavirin combination therapy can be taken as a hint that not only the individual interferon, but also the ribavirin sensitivity contributes significantly to the nonresponsive state.
Life cycle accumulation and aging risks

How to de ne the most appropriate institutional framework that could encourage to better plan retirement? The French population used to consider that the PAYG public pension system should finance pensions. The pension system being based on an insurance principle and intergenerational risk sharing, once retired, households estimate that the public system has to provide them an adequate level of pension. But in the context of pension reforms, the replacement rates provided by the PAYG pension system are going to decrease. Households will need to increase their savings rates to maintain their standard of living during retirement. We test the impact of new risks and aspects of the aging issue on retirement related asset holding behaviour. We integrate the longevity and disability risks, the impact of the public pension information system, which is a way to improve private nancial education and awareness, and psychological variables. We estimate bivariate probit models to better understand these behaviours. Our results indicate that the households change their mind and adapt their behaviour to new economic and demographic issues. The implementation of the pension information right allows them to increase their private savings for the retirement and the life expectancy at old age increases the probability to hold an annuity contract.
Modelling the transaction role of money and the essentiality of money in a hyperinflation context

This paper uses an analytical approach and the precise definition of money essentiality given by Scheinkman (1980) with the aim to establish a formal theoretical link between the possibility of hyperinflationary paths and the concept of money essentiality. In this respect the paper contributes to the understanding of the well known failure of Cagan based inflationary finance models to produce explosive hyperinflation. We consider two standard optimizing monetary models representing alternative ways of modelling the transaction role of money. The paper considers a money-in-the-utility-function model and a cash-in-advance model where representative agent’s preferences are represented by general utility functions. We show that modelling monetary hyperinflation with perfect foresight is closely linked to the concept of money essentiality as defined by Scheinkman (1980). The possibility of explosive monetary hyperinflation in a perfect foresight inflationary finance model always relies on a sufficient level of money essentiality. The main contribution of this paper is to show that, whether in a cash-in-advance or in a money-in-the-utility-function framework, this sufficient level of money essentiality does not depend on the specific way, cash-in-advance or moneyin- the-utility-function, of modelling the role of money as a medium of exchange.
Ureteral stent symptom questionnaire: development and validation of a multidimensional quality of life measure.

PURPOSE We developed the ureteral stent symptom questionnaire (USSQ), a psychometrically valid measure to evaluate symptoms and impact on quality of life of ureteral stents. MATERIALS AND METHODS A total of 309 patients were asked to participate during different phases of our study. In phase 1 a structured literature search, 9 patient interviews and studies of 90 patients using existing instruments formed the foundation for the initial draft of our new questionnaire. In phase 2 the USSQ was pilot tested, reviewed by experts and field tested in 40 patients to produce a final 38-item draft. In phase 3 formal validation studies were performed in 55 patients to assess validity, reliability and sensitivity to change. Discriminant validation was performed by administering the questionnaire to 3 groups of patients without stents. RESULTS The final draft addressed various domains of health (6 sections and 38 items) affected by stents covering urinary symptoms, pain, general health, work performance, sexual matters and additional problems. The validation studies showed the questionnaire to be internally consistent (Cronbach's alpha > 0.7) with good test-retest reliability (Pearson's coefficient > 0.84). The questionnaire demonstrated good construct validity and sensitivity to change shown by significant changes in the score with and after removal of stents. The new USSQ discriminated patients with stents from healthy controls (p < 0.001) and patients with urinary calculi without stents and lower urinary tract symptoms. CONCLUSIONS Indwelling ureteral stents have a significant impact on health related quality of life. The new USSQ is a valid and reliable instrument that is expected to become a standard outcome measure to evaluate the impact and compare different types of stents.
The impact of hypothermia on dilutional coagulopathy.

UNLABELLED The control of hemorrhage in hypothermic patients with platelet and clotting factor depletion is often impossible. Determining the cause of coagulopathic bleeding (CB) will enable physicians to appropriately focus on rewarming, clotting factor repletion, or both. OBJECTIVE To determine the contribution of hypothermia in producing CB and ascertain if simultaneous hypothermia and dilutional coagulopathy (DC) interact synergistically. METHOD Prothrombin time, partial thromboplastin time, and platelet function were determined at assay temperatures of 29 degrees to 37 degrees C on normal and critically ill, noncoagulopathic (NC) individuals. Dilutional coagulopathy was created using buffered saline and the assays repeated. RESULTS Hypothermic assay at < or = 35 degrees C significantly prolonged coagulation times. The effect of hypothermia on NC and DC samples was not different. CONCLUSION Assays performed at 37 degrees C underestimate coagulopathy in hypothermic patients. The effect of hypothermia on NC and DC is not different, indicating the lack of a synergistic effect. Normalization of clotting requires both rewarming and clotting factor repletion.
Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer

Summary Urokinase-type plasminogen activator (uPA) and its inhibitor, PAI-1, play a key role in tumor invasion and metastasis. They were the first novel tumor biological factors to be validated at the highest level of evidence (LOE I) regarding their clinical utility in breast cancer. Their antigen levels are determined in tumor tissue extracts by standardized, quality-assured immunometric assays (ELISA). Since the late 1980s, numerous independent studies have demonstrated that patients with low levels of uPA and PAI-1 in their primary tumor tissue have a significantly better survival than patients with high levels of either factor. These prognostic data have recently been validated by an EORTC (European Organization for Research and Treatment of Cancer) pooled analysis comprising more than 8,000 breast cancer patients. In addition, results from a multicenter prospective randomized therapy trial in node-negative breast cancer (“Chemo N0”) showed that node-negative breast cancer patients with low levels of uPA and PAI-1 in their primary tumor have a very good prognosis, and may thus be candidates for being spared the burden of adjuvant chemotherapy. In contrast, node-negative patients with high uPA/PAI-1 are at substantially increased risk of disease recurrence, comparable to that of patients with three or more tumor cell positive axillary lymph nodes. The “Chemo N0” trial as well as retrospective data also indicate that these high-risk patients benefit from adjuvant chemotherapy. In conclusion, over a period of about 15 years sufficient evidence has been put forward to demonstrate that determination of uPA and PAI-1 in primary breast cancer patients supports risk-adapted individualized therapy decisions, particularily in patients with node-negative disease.
The Transmission of US Business Cycles to the Canadian Economy

As the substantial share of the Canadian trade occurs with the United States, one would expect that the fluctuations in US macroeconomic aggregates are rapidly transmitted to the Canadian economy. Specifically, the transmission should occur through changes in the flow of goods and financial assets. However, the standard general equilibrium models fail to show such a relationship. In this paper, I consider a small open-economy model taking the fluctuations of US variables as given and explicitly incorporating the flows of intermediate goods and financial assets. The simulation results show that the model can reproduce the actual data reasonably well when the trade share of intermediate goods is properly calibrated and the flow of financial asset is absent. That is, transmission does occur through trade in goods but not through assets.
Randomised controlled trial of health promotion in general practice for patients at high cardiovascular risk

Abstract Objective: To assess the value of health education for patients with angina in reducing risk factors for cardiovascular disease and lessening the effect of angina on everyday activities. Design: Randomised controlled trial of personal health education given every four months. Setting: 18 general practices in the greater Belfast area. Subjects: 688 patients aged less than 75 years and known to have had angina for at least six months; 342 randomised to receive education and 346 to no education. Main outcome measures: Restriction of everyday activities, dietary habit, smoking habit, frequency of physical exercise; blood pressure, body mass index, and serum total cholesterol concentration at entry to trial and after two years. Results: 317 in the intervention group and 300 in the control group completed the trial. At the two year review more of the intervention group (140, 44%) reported taking daily physical exercise than the control group (70, 24%). The intervention group also reported eating a healthier diet than the control group and less restriction by angina in any everyday activity. No significant differences were found between the groups in smoking habit, systolic or diastolic blood pressure, cholesterol concentration, or body mass index. Conclusion: Despite having no significant effect on objective cardiovascular risk factors, personal health education of patients with angina seems to increase exercise and improve dietary habits and is effective in lessening the restriction of everyday activities.
Energy Consumption, Financial Development and Growth: Evidence from Cointegration with unknown Structural breaks in Lebanon

This paper investigates the dynamic causal relationship between financial development, energy consumption and economic growth in Lebanon over the period 1993M1-2010M12.Our findings confirm the existence of cointegration among the variables. The results indicate that financial development and energy consumption, contribute to economic growth in Lebanon. The impact of energy consumption on economic growth is positive showing the significance of energy as a main stimulant of economic growth. Financial development is also found to play a vital role in enhancing economic growth. Economic growth and financial development also add in energy consumption. The study, therefore, recommends that in short run, policy makers should put more emphasis in developing strategies that would result in achieving higher mobilization of savings in order to boost Lebanese investors’ confidence and to also attract more foreign investment in Lebanon. Furthermore, desired financial policy to encounter the rising demand for energy by enhancing the process of capitalization of the energy sector is also very desirable. Our results further cautions of the use of policy tools geared towards restricting energy consumption in short run, something that is called for as part of national energy policy, as these may result in lower economic growth. Such conservation policies should be taken gradually and carefully as to not negatively impact the growth of the economy. However, in long run, the Lebanese government should shift its focus towards achieving higher economic growth, in order to boost its financial development and to sustain a steady flow of needed energy. In this regards, policymakers should put emphasis on the development of domestic energy resources to protect the country from any undesirable external energy shock given its extensive dependence on energy imports.
The Contributions of Daniel Kahneman and Amos Tversky

The Royal Swedish Academy of Science awarded the 2002 Nobel Prize in Economics to Daniel Kahneman “for having integrated insights from psychological research into economic science, especially concerning human judgment and decision-making under uncertainty. ” Kahneman shares the prize with Vernon Smith.1 KahnemandidmuchofhisNobelPrizewinning work with Amos Tversky, a fellow psychologist, starting when both were at the Hebrew University of Jerusalem. Tversky was not eligible for the Nobel Prize since its rules prohibit posthumous awards. He was 59 when he died in 1996. The concepts of risk and return lie at the heart of finance; Kahneman and Tversky’s work provides fundamental insights into the psychology associated with both. Their work is composed of two strands, prospect theory, and heuristics and biases. Prospect theory describes how people make decisions when facing risky (or risk-free) alternatives, while heuristics and biases describe, among other things, how people assess risk. Prospect theory provides the major psychological underpinnings for the behavioral approaches to portfolio selection, while heuristics and biases provide the major psychological underpinnings for the behavioral approach to asset pricing. We describe each strand and its applications to finance.
Diverging roles for Lrp4 and Wnt signaling in neuromuscular synapse development during evolution

In this study, Remédio et al. use mice and zebrafish to show that muscle prepatterning in mammals and zebrafish is established by different mechanisms. Their findings demonstrate that Agrin/Lrp4/MuSK signaling plays an essential role in neuromuscular synapse formation in both fish and mammals, whereas Wnt signaling is dispensable.
Reduced mitochondrial density in the vastus lateralis muscle of patients with COPD

Skeletal muscle dysfunction is a well-recognised hallmark of chronic obstructive pulmonary disease (COPD) leading to exercise intolerance. The vastus lateralis of COPD patients is characterised by reduced mitochondrial enzyme activity; however, this is not the case in the tibialis anterior. It is, however, unclear whether the compromised oxidative capacity in the vastus is due to reduced mitochondrial volume density. Muscle biopsies were obtained from the vastus lateralis of six COPD patients and four healthy age-matched controls, and from the tibialis anterior of another six COPD patients and six controls. Mitochondrial number, fractional area and morphometry, as well as Z-line width (as a surrogate marker of fibre type), were analysed using transmission electron microscopy. Mitochondrial number (0.34 versus 0.63 n·µm−2) and fractional area (1.95 versus 4.25%) were reduced in the vastus of COPD patients compared with controls. Despite a reduced mitochondrial number (0.65 versus 0.88 n·µm−2), the mitochondrial fractional area was maintained in the tibialis of COPD patients compared with controls. It can be concluded that the reduced mitochondrial fractional area is likely to contribute to the decreased oxidative capacity in the vastus of chronic obstructive pulmonary disease patients, whereas the maintained mitochondrial fractional area in the tibialis may explain the normal oxidative capacity.
Identification of novel hair‐growth inducers by means of connectivity mapping

The aim of this study was to identify novel inducers of hair growth using gene expression profiling at various stages of hair‐growth induction. First, we analyzed gene expression at the onset of hair growth in mice induced by cyclosporin A (CsA), a well‐known hair‐growth inducer, using DNA microarray analysis. The results unveiled genes involved in the step‐by‐step progression of hair growth, including increases in melanin biosynthesis and decreases in immune response at d 2 and the subsequent stimulation of cell proliferation at d 4, followed by the up‐regulation of hair specific keratins at d 7 after CsA treatment. With the use of the connectivity map (Cmap), agents that had a similar “gene signature” to that of the profiles of CsA‐treated mice were identified. Several agents, including CsA, were identified by the Cmap and were evaluated for hair induction activity in vivo. One of the proposed agents, fluphenazine (from the d 2 signature) actually induced hair growth in vivo (ED50: 2 mM for single application), and the subsequent application of 5 mM iloprost (from the d 4 signature) significantly enhanced the hair‐growth effect of fluphenazine. From these results, Cmap analysis was proven to be a useful method that connects gene expression profiles of complicated biological processes, such as hair‐growth induction, to effective agents. —Ishimatsu‐Tsuji, Y. , Soma, T. , Kishimoto, J. Identification of novel hair‐growth inducers by means of connectivity mapping. FASEB J. 24, 1489–1496 (2010). www.fasebj. org