Miracle-dz/UniFAR-FTUs huggingface dataset:
Biased probability Monte Carlo conformational searches and electrostatic calculations for peptides and proteins.

Two major components are required for a successful prediction of the three-dimensional structure of peptides and proteins: an efficient global optimization procedure which is capable of finding an appropriate local minimum for the strongly anisotropic function of hundreds of variables, and a set of free energy components for a protein molecule in solution which are computationally inexpensive enough to be used in the search procedure, yet sufficiently accurate to ensure the uniqueness of the native conformation. We here found an efficient way to make a random step in a Monte Carlo procedure given knowledge of the energy or statistical properties of conformational subspaces (e.g. phi-psi zones or side-chain torsion angles). This biased probability Monte Carlo (BPMC) procedure randomly selects the subspace first, then makes a step to a new random position independent of the previous position, but according to the predefined continuous probability distribution. The random step is followed by a local minimization in torsion angle space. The positions, sizes and preferences for high-probability zones on phi-psi maps and chi-angle maps were calculated for different residue types from the representative set of 191 and 161 protein 3D-structures, respectively. A fast and precise method to evaluate the electrostatic energy of a protein in solution is developed and combined with the BPMC procedure. The method is based on the modified spherical image charge approximation, efficiently projected onto a molecule of arbitrary shape. Comparison with the finite-difference solutions of the Poisson-Boltzmann equation shows high accuracy for our approach. The BPMC procedure is applied successfully to the structure prediction of 12- and 16-residue synthetic peptides and the determination of protein structure from NMR data, with the immunoglobulin binding domain of streptococcal protein G as an example. The BPMC runs display much better convergence properties than the non-biased simulations. The advantage of a true global optimization procedure for NMR structure determination is its ability to cope with local minima originating from data errors and ambiguities in NMR data.
Computing Long-Term Market Inflation Expectations for Countries Without Inflation Expectation Markets

We derive daily market‐based domestic long‐term inflation expectations for eight countries without inflation swap markets. To do so, we use foreign inflation swaps together with (1) foreign and domestic interest rate swaps assuming that purchasing power parity (PPP) and uncovered interest rate parity (UIP) hold or together with (2) spot and forward exchange rates assuming that PPP, UIP and covered interest rate parity (CIP) hold. We confirm the plausibility of our PPP‐UIP and PPP‐UIC‐CIP measures by also applying these methods for countries with inflation swap markets. We moreover illustrate how the data can be used to answer such questions as whether inflation reacts to long‐term inflation expectations, whether these expectations are well‐anchored and how long‐term real interest rates have moved over the past decade.
Interbank Payments and the Daily Federal Funds Rate

This paper develops a model of bank reserve management and federal funds rate determination that incorporates the role of interbank payments. In the model, uncertainty in the receipt of payments generates a precautionary demand for bank reserves as banks face both reserve requirements and penalties for overnight overdrafts. Days with higher payment volume are assumed to create more uncertainty in a bank's reserve account that accentuates this precautionary motive. As a result, upward pressure is placed on the equilibrium funds rate. Implications of the model are then estimated using a panel of large banking institutions. Using the parameter estimates, simulations of the model suggest that patterns in payment activity explain many intra-maintenance period movements in both the level and volatility of the federal funds rate.
Migraine Without Aura and Migraine with Aura are Inherited Disorders

The familial occurrence and mode of inheritance were analysed in families with migraine without aura (MO) and migraine with aura (MA). The probands were found among 4000 persons from the general population. All persons with MA were included as probands, and an equivalent number of probands with MO was selected as a random sample among those with MO. Spouses and first-degree relatives were blindly interviewed. All interviews were performed by one neurological research fellow. The distinct familial patterns indicate that MO and MA have a different aetiology. Compared with the general population, the first-degree relatives of probands with MO had a 1.9-fold increased risk of MO while spouses had a 1.5-fold increased risk of MO, indicating that both genetic and environmental factors are important in MO. The first-degree relatives of probands with MA had a four-fold increased risk of MA while spouses had no increased risk of MA, indicating that MA is determined largely by genetic factors. The complex segregation analysis indicate that both MO and MA have multifactorial inheritance without generational difference.
Potential of nanoparticles for allergen-specific immunotherapy – use of silica nanoparticles as vaccination platform

ABSTRACT Introduction: Allergen-specific immunotherapy is the only curative approach for the treatment of allergies. There is an urgent need for improved therapies, which increase both, efficacy and patient compliance. Novel routes of immunization and the use of more advanced vaccine platforms have gained heightened interest in this field. Areas covered: The current status of allergen-specific immunotherapy is summarized and novel routes of immunization and their challenges in the clinics are critically discussed. The use of nanoparticles as novel delivery system for allergy vaccines is comprehensively reviewed. Specifically, the advantages of silica nanoparticles as vaccine carriers and adjuvants are summarized. Expert opinion: Future allergen-specific immunotherapy will combine engineered hypoallergenic vaccines with novel routes of administration, such as the skin. Due to their biodegradability, and the easiness to introduce surface modifications, silica nanoparticles are promising candidates for tailor-made vaccines. By covalently linking allergens and polysaccharides to silica nanoparticles, a versatile vaccination platform can be designed to specifically target antigen-presenting cells, render the formulation hypoallergenic, and introduce immunomodulatory functions. Combining potent skin vaccination methods, such as fractional laser ablation, with nanoparticle-based vaccines addresses all the requirements for safe and efficient therapy of allergic diseases.
Relative weight and disability retirement: a prospective cohort study.

OBJECTIVES The aims of this study were to examine (i) the association of relative weight with subsequent disability retirement due to any diagnosis and also in two major diagnostic groups (ie, musculoskeletal diseases and mental disorders) and (ii) whether diagnosed diseases, physical and mental functioning, and working conditions explain these associations. METHODS This prospective study comprised a cohort of 6542 middle-aged employees of the City of Helsinki, Finland. Questionnaire data were linked with register data on disability retirements, with a mean follow-up time of 7.8 years. RESULTS Adjusting for age, body mass index (BMI) was associated with all-cause disability retirement among men and women, the highest risk being for the severely obese and the obese [hazard ratio (HR) 3.45, 95% confidence interval (95% CI) 2.53-4.69; HR 1.94, 95% CI 1.52-2.46, respectively]. Adjusting for age, relative weight was also strongly associated with the main retirement diagnoses, especially musculoskeletal diseases among the severely obese (HR 4.76, 95% CI 3.06-7.40) and obese (HR 2.35, 95% CI 1.62-3.39). The association was attenuated when adjusting for self-reported diseases and physical and mental functioning at baseline. Working conditions had negligible effects on the associations. CONCLUSIONS Maintenance of normal weight is likely to reduce the risk of disability retirement. Among obese employees, the focus should be on the improvement of physical functioning and the effective treatment of obesity and its co-morbidities to counteract the heightened risk of disability retirement.
Forecasting USD-BRL Currency Rate Volatility using Realized and Implied Volatilities Data

Abstract This article assesses the impact of exogenous variables in GARCH models, when applied to volatility forecasts for the Brazilian USD-BRL currency market. As exogenous variables, we used the realized variance, based on high frequency data, and the FXVol index, based on market implied volatility data. This is the first study to use the FXVol index and to investigate its effects on Brazilian foreign exchange volatility. The results indicate statistical significance of the superiority of the extended models when predicting volatility. We conclude that high frequency data and market implied volatility contain relevant information with respect to USD-BRL currency volatility. These find ings are relevant for hedgers, speculators and practitioners in general.
Decrease in PSCA expression caused by Helicobacter pylori infection may promote progression to severe gastritis

SNP rs2294008 in Prostate Stem Cell Antigen (PSCA) and decreased PSCA expression are associated with gastric cancer. The objective of this study is to investigate the role of rs2294008 and PSCA expression in the gastritis-gastric cancer carcinogenic pathway. We conducted a case-control association study of H. pylori-infected gastritis and gastric cancer. rs2294008 was associated with the progression to chronic active gastritis (P = 9.4 × 10–5; odds ratio = 3.88, TT + TC vs CC genotype), but not with H. pylori infection per se nor with the progression from active gastritis to gastric cancer. We also assessed the association of rs2294008 with PSCA mRNA expression in the gastric mucosa at various disease stages and found that rs2294008 was associated with PSCA expression (P = 1.3 × 10–12). H. pylori infection (P = 5.1 × 10–8) and eradication therapy (P < 1 × 10–11) resulted in the reduced and increased PSCA expression, respectively, indicating negative regulation of PSCA expression by H. pylori infection. PSCA expression was decreased in severe gastritis compared with mild gastritis only among T allele carriers. Our findings revealed the regulation of PSCA expression by host genetic variation and bacterial infection might contribute to gastritis progression after H. pylori infection.
The impact of early menopause on risk of coronary artery disease (PREmature Coronary Artery Disease In Women – PRECADIW case-control study)

Background: Despite improved understanding of atherothrombosis pathophysiology, risk factors associated with premature coronary artery disease (CAD) in women are poorly recognized. Design and methods: A single-centre, case-control study comprised 323 women (less than 55 years) with established CAD, enrolled between April 2005 and January 2008, and 347 age-matched healthy women selected from the Multi-Center All-Polish Health Survey. We aimed to assess the relationship of menopause and premature CAD. Results: In multivariate analysis smoking, parental history of premature CVD, diabetes, menopause and hypertension were the strongest risk markers for premature CAD with ORs (95% CI): 3.83 (2.52–5.82); 3.08 (1.85–5.14); 2.89 (1.59–5.23); 2.82 (1.91–4.19); 2.39 (1.16–3.54). The most significant association was found for early postmenopause in a model including the early and late stage of postmenopause (≤ and >3 years of its onset), with OR 4.55 (95% CI 2.82–7.35), higher than other risk factors. The receiver operating characteristic (ROC) curves area revealed a significant increase from 0.81 in that model that included traditional risk factors and parental premature CVD to 0.85 after addition of the early and late stage of postmenopause. Conclusions: We have shown that smoking and early postmenopausal stage (≤3years) are the most important determinants of premature CAD followed by parental CVD, diabetes and hypertension.
Health-related quality of life after surgery for hip fracture: a multicentric study in Mexican population.

INTRODUCTION Hip fractures are an important cause of morbidity and mortality and one of the main causes of disability in the older population. The lifetime risk for any type of osteoporotic fracture is very high and falls within the range of 40-50% in women and 13-22% for men. In Mexico, the lifetime likelihood of having a hip fracture at 50 years of age is 8.5% in Mexican women and 3.8% in Mexican men, but this is expected to rise in upcoming years. AIM This study aims to report the Health-Related Quality of Life over the first six months after a hip fracture in two public and two private tertiary care hospitals in Mexico City. METHOD Changes over time were evaluated through visual observation of each patients development trajectory using the graphic representation of the EQ-5D global score. The trajectories were grouped by affinity into five levels of progress according to clinical course. The identified descriptive options were analyzed using the multinomial logistic regression model (LR). RESULTS One-hundred-and-thirty-six (136) patients with a hip fracture were followed after surgery. Their mean age was 77 ± 10 years. During the first month, mobility, daily activities, and self-care were the most affected. The group aged between 80 and 84 years reported extreme problems regarding anxiety and depression (21%), and those aged between 50 and 74 years described having issues concerning pain and discomfort (27%). At the 6-month follow-up, only those aged > 85 years of age showed worsening of their condition, a high proportion of these ranking at level 3 in mobility, self-care, and anxiety/depression. Toward the end of the follow-up period, this last group reported having extreme problems (being unable to carry out everyday activities) and worsening of their mobility (9.2%) (inability to walk about) (LR test, p = 0.06). DISCUSSION Patients with hip fracture showed difficulties in different areas during the first month after surgery, with steady recuperation up to month six. Age was an important factor in the recovery of all evaluated domains. This graphical tool facilitates classification, identification, and monitoring Health-Related Quality of Life in patients with hip fractures.
Characterization of the p53-Dependent Postmitotic Checkpoint following Spindle Disruption

ABSTRACT The p53 tumor suppressor gene product is known to act as part of a cell cycle checkpoint in G1 following DNA damage. In order to investigate a proposed novel role for p53 as a checkpoint at mitosis following disruption of the mitotic spindle, we have used time-lapse videomicroscopy to show that both p53+/+ and p53−/− murine fibroblasts treated with the spindle drug nocodazole undergo transient arrest at mitosis for the same length of time. Thus, p53 does not participate in checkpoint function at mitosis. However, p53 does play a critical role in nocodazole-treated cells which have exited mitotic arrest without undergoing cytokinesis and have thereby adapted. We have determined that in nocodazole-treated, adapted cells, p53 is required during a specific time window to prevent cells from reentering the cell cycle and initiating another round of DNA synthesis. Despite having 4N DNA content, adapted cells are similar to G1 cells in that they have upregulated cyclin E expression and hypophosphorylated Rb protein. The mechanism of the p53-dependent arrest in nocodazole-treated adapted cells requires the cyclin-dependent kinase inhibitor p21, as p21−/−fibroblasts fail to arrest in response to nocodazole treatment and become polyploid. Moreover, p21 is required to a similar extent to maintain cell cycle arrest after either nocodazole treatment or irradiation. Thus, the p53-dependent checkpoint following spindle disruption functionally overlaps with the p53-dependent checkpoint following DNA damage.
Measurement of the three‐dimensional microscope point spread function using a Shack–Hartmann wavefront sensor

We present a technique to measure the wavefront in the exit pupil of a microscope to determine the microscope’s three‐dimensional point spread function (PSF) experimentally. The wavefront yields the microscope PSF through a Fourier transform that models propagation of light from the exit pupil to the image plane. A Shack–Hartmann wavefront sensor is used to measure the wavefront shape by recording lateral displacements of a grid of focused spots created by a lenslet array. The displacement of each spot is related to the local wavefront slope. Thus, with appropriate sampling across the exit pupil, the entire wavefront can be reconstructed. This technique does not require the use of a sub‐resolution object to obtain the three‐dimensional microscope PSF. Consequently, larger, brighter fluorescent objects may be imaged, thereby reducing the requirements for detector sensitivity and leading to a three‐fold increase in the axial range over which the PSF is measured. The Shack–Hartmann technique results in a description of the PSF as a continuous function whose sampling is not dependent on the size of the CCD pixels. The Shack–Hartmann sensor is not limited by the numerical aperture of the objective and can easily be calibrated to measure the PSF at any wavelength.
The impact of information technology on the performance of clinical pharmacy services

Electronic patient records are now being developed to assist in the clinical management of patients within secondary care. This paper reviews how various types of information technology used in these electronic patient records can improve the performance of clinical pharmacy services. The different levels of information technology support for some of the main aspects of clinical pharmacy services are described. How the impact and outcome of information technology support for these services should be evaluated are discussed. The human and technological factors that must be considered to ensure that the implementation succeeds and the potential benefits are realized are examined.
Taiwan's high rate of cesarean births: impacts of national health insurance and fetal gender preference.

BACKGROUND Taiwan has a high rate of cesarean section, approximately 33 percent in the past decade. This study investigates and discusses 2 possible factors that may encourage the practice, one of which is fetal gender difference and the other is Taiwan's recently implemented National Health Insurance (NHI). METHODS A logistic regression model was used with the 1989 and 1996 National Maternal and Infant Health Survey and with the 2001 to 2003 NHI Research Databases. RESULTS Using survey data, we found a statistically significant 0.3 percent gender difference in parental choice for cesarean section. However, no statistically significant difference was found in the rate of cesarean section before and after NHI implementation. CONCLUSIONS Taiwan's high cesarean section rate is not directly related to financial incentives under NHI, indicating that adjusting policy to lower financial incentives from NHI would have only limited effect. Likewise, focusing effort on the small gender difference is unlikely to have much impact. Effective campaigns by health authorities might be conducted to educate the general population about risks associated with cesarean section and the benefits of vaginal birth to the child, mother, and society.
Comparison of the modulatory influence of maize and olive oils and butter on metabolic responses to endotoxin in rats.

1. n-3 polyunsaturated fatty acids decrease responses to cytokines and inflammatory agents. The present study examines how different intakes of n-6 and n-9 fatty acids influence the metabolic response to endotoxin in Wistar rats. 2. Weanling male rats were, for 4 weeks, fed diets containing 50, 100 or 200 g/kg fat in the form of maize oil (rich in linoleic acid), butter (poor in linoleic acid, rich in oleic acid) or olive oil (adequate in linoleic acid, rich in oleic acid) or standard laboratory chow. All butter and olive oil diets included 10 g/kg maize oil, in total fat, to avoid essential fatty acid deficiency. 3. Rats subsequently received 800 micrograms/kg Escherichia coli endotoxin or sterile saline subcutaneously. Twenty-four hours after injection, the rate of tissue protein synthesis was measured in liver, lung, kidney, tibialis muscle and spleen by the 'flooding dose' method. Protein and zinc concentrations were assayed in all tissues and serum albumin and caeruloplasmin measured. 4. In animals fed chow, protein synthetic rate increased by 18%, 29% and 27% in liver, lung and kidney respectively. Tissue zinc concentrations increased by 33% in kidney, and tissue protein increased by 17%, 23% and 17% in liver, lung and kidney respectively. Serum caeruloplasmin increased by 60% and albumin concentration fell by 14%. 5. In animals consuming the 50 g/kg maize oil diet, protein synthetic rate increased by 56%, 36% and 34% in liver, lung and kidney respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
Rheumatoid Arthritis Does Not Increase Risk of Short-term Adverse Events after Total Knee Arthroplasty: A Retrospective Case-control Study

Objective. More adverse events (AE) are reported after total knee arthroplasty (TKA) for patients with rheumatoid arthritis (RA) than for patients with osteoarthritis (OA). This study evaluates 6-month postoperative AE in a high-volume center in a contemporary RA cohort. Methods. Patients with RA in an institutional registry (2007–2010) were studied. AE were identified by self-report and review of office and hospital charts. Subjects with RA were matched to 2 with OA by age, sex, and procedure. RA-specific surgical volume was determined. Baseline characteristics and AE were compared and analyzed. Results. There were 159 RA TKA and 318 OA. Of the patients with RA, 88.0% were women, 24.5% received corticosteroids, 41.5% received biologics, and 67% received nonbiologic disease-modifying antirheumatic drugs (DMARD). There was no difference in comorbidities. RA-specific surgical volume was high; 64% of cases were performed by surgeons with ≥ 20 RA cases during the study period. Patients with RA had worse baseline pain and function and lower perceived health status (EQ-5D 0.59 vs 0.65, p < 0.01). There were no deep infections in either group and no difference in superficial infection (9.4% RA vs 10.1% OA, p = 0.82), myocardial infarction (0.7% RA vs 0% OA, p = 0.33), or thromboembolism (1.3% RA vs 0.6% OA, p = 0.60). Conclusion. In a high-volume center, with high RA-specific experience, RA does not increase postoperative AE. Despite worse preoperative function and high steroid and DMARD use, complications were not increased. However, further study to determine generalizability is needed.