Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Dynamics Simulations of the Apo-, Holo-, and Acyl-forms of Escherichia coli Acyl Carrier Protein*

Acyl carrier protein (ACP) is an essential co-factor protein in fatty acid biosynthesis that shuttles covalently bound fatty acyl intermediates in its hydrophobic pocket to various enzyme partners. To characterize acyl chain-ACP interactions and their influence on enzyme interactions, we performed 19 molecular dynamics (MD) simulations of Escherichia coli apo-, holo-, and acyl-ACPs. The simulations were started with the acyl chain in either a solvent-exposed or a buried conformation. All four short-chain (≤C10) and one long-chain (C16) unbiased acyl-ACP MD simulation show the transition of the solvent-exposed acyl chain into the hydrophobic pocket of ACP, revealing its pathway of acyl chain binding. Although the acyl chain resides inside the pocket, Thr-39 and Glu-60 at the entrance stabilize the phosphopantetheine linker through hydrogen bonding. Comparisons of the different ACP forms indicate that the loop region between helices II and III and the prosthetic linker may aid in substrate recognition by enzymes of fatty acid synthase systems. The MD simulations consistently show that the hydrophobic binding pocket of ACP is best suited to accommodate an octanoyl group and is capable of adjusting in size to accommodate chain lengths as long as decanoic acid. The simulations also reveal a second, novel binding mode of the acyl chains inside the hydrophobic binding pocket directed toward helix I. This study provides a detailed dynamic picture of acyl-ACPs that is in excellent agreement with available experimental data and, thereby, provides a new understanding of enzyme-ACP interactions.
The Vocabularies of Academia

It has been demonstrated that humanists are far more likely to use filled pauses (“uh,” “ah,” or “um”) during their lectures than are social or natural scientists This finding has been interpreted in terms of the hypothesis that filled pauses indicate time out while the speaker searches for the next word or phrase Based on the assumption that the more options at a choice point, the more likely a speaker will say “uh,” it is hypothesized that the humanities are characterized by richer vocabularies (i e, more synonyms) than are the sciences An analysis of the number of different words used in lectures and in professional publications indicates that this is indeed the case Scientists consistently use fewer different words than do humanists Further, the number of different words correlates positively with the frequency of saying “uh” during lectures These findings are not restricted to academics, for in newspaper accounts, journalists use fewer different words in stories about science than in stories about the arts
A Map of Protein-Protein Contacts within the Small Nuclear RNA-activating Protein Complex SNAPc *

The nucleation of RNA polymerases I–III transcription complexes is usually directed by distinct multisubunit factors. In the case of the human RNA polymerase II and III small nuclear RNA (snRNA) genes, whose core promoters consist of a proximal sequence element (PSE) and a PSE combined with a TATA box, respectively, the same multisubunit complex is involved in the establishment of RNA polymerase II and III initiation complexes. This factor, the snRNA-activating protein complex or SNAPc, binds to the PSE of both types of promoters and contains five types of subunits, SNAP190, SNAP50, SNAP45, SNAP43, and SNAP19. SNAPc binds cooperatively with both Oct-1, an activator of snRNA promoters, and in the RNA polymerase III snRNA promoters, with TATA-binding protein, which binds to the TATA box located downstream of the PSE. Here we have defined subunit domains required for SNAPc subunit-subunit association, and we show that complexes containing little more than the domains mapped here as required for subunit-subunit contacts bind specifically to the PSE. These data provide a detailed map of the subunit-subunit interactions within a multifunctional basal transcription complex.
Use of unlicensed medication in palliative medicine

We were interested to read the paper by Atkinson and Kirkham1 on the use of unlicensed medication in their palliative care unit, as we have just completed a similar study on the inpatient palliative care unit at the Royal Marsden Hospital, Sutton. The methodology of our study was very similar to that employed in the paper. However, we classified our drugs as either having a product licence for the specific indication (PLI), having a product licence for an alternative indication (PLNI), having a clinical trial exemption certificate (CTX) or doctors’ and dentists’ exemption certificate (DDX). We also classified the drugs as either having a product licence for the route of use, or no product licence for the route of use. Our study was carried out over a 6-month period between October 1998 and April 1999, and involved 120 consecutive admissions to the palliative care unit. Of the 1004 drugs prescribed, 146 (14.5%) did not have a PLI, but did have a PLNI. These results are remarkably similar to those reported by Atkinson and Kirkham. A further 19 (2%) of drugs were being used under a CTX or DDX. We also observed that 115 (11.5%) of the drugs were given by an unlicensed route. The main differences between our results and those reported in the paper are the routes of use (20% of the drugs in our study were given subcutaneously, as compared to 36% in the earlier study), and the type of drugs used — co-analgesics were prescribed more frequently in our study. These differences may reflect different populations of patients with cancer, or different patterns of clinical practice. Although we agree that clinical trials can be difficult in patients with advanced cancer, we feel that it is essential to confirm the efficacy (and tolerability) of drugs in this group of patients. This is especially true of drugs that do not have a PLI. In view of the regulations governing the licensing of drugs, the onus of performing such clinical trials is likely to remain with clinicians.
Anger Expression and Blood Pressure in Adolescents

The clinical significance of childhood hypertension is important as elevated pressures during childhood are found to follow a progressively increasing track into adulthood. Little work has been done to examine the relationship of emotions and emotional behavioral factors to the development of hypertension in children. Using the Roy Adaptation Model as a guide, this study investigated the relationship of anger expression and blood pressure (BP) among adolescents 16–18 years of age. Participants were 63 urban high school seniors. Measurements included the Anger Expression Inventory, a Demographic Questionnaire, and measures of systolic and diastolic blood pressure. Analysis revealed significant positive relationships between anger expression with blood pressure, and a significant inverse relationship between blood pressure and the control of anger for girls. No significant relationships between anger expression and blood pressure were noted for boys. The majority of students (53%) were found to have high normal or hypertensive blood pressure readings, putting them at increased cardiovascular risk.
A shift from underweight to overweight and obesity in Asian children and adolescents with congenital heart disease.

BACKGROUND In Western countries, obesity is a common problem in children with congenital heart disease (CHD). However, this problem may have racial difference, and little is known about the shift of this trend as patients grow up. The present study sought to investigate the prevalence and trends of being underweight, overweight and obesity in an Asian CHD cohort using a 5-year citywide school survey database. METHODS Patient group consisted of 705 first grade elementary school students (children) and 219 first grade senior high school students (adolescents), while 18753 healthy children and 15014 healthy adolescents served as controls. Body mass index (BMI) percentile was calculated to define underweight (BMI < 15(th) percentile) and overweight (BMI 85(th) -95(th) percentile)/obesity (BMI ≥ 95(th) percentile). RESULTS In CHD children, the prevalence of underweight and overweight/obesity was 21.0% (control 16%, P < 0.001) and 14.5% (control 19.8%, P < 0.001), respectively. Children with moderate to severe CHD, especially cyanotic CHD, were more underweight and less overweight/obese than children with non-cyanotic CHD. The prevalence of underweight (23.3%) and overweight/obesity (26.5%) in CHD adolescents became close to that in controls. From childhood to adolescence, different shifts in BMI distribution were noted; controls became more underweight and overweight/obese for males and more underweight and less overweight/obese for females, while CHD patients became more overweight/obese for both genders, including cyanotic CHD. CONCLUSIONS In this Asian CHD cohort, we demonstrates a shift of BMI distribution from more underweight and less overweight/obese compared with healthy children, to a pattern similar to that in healthy adolescents.
Activity of Megazol, a Trypanocidal Nitroimidazole, Is Associated with DNA Damage

ABSTRACT DNA damage associated with the trypanocidal activity of megazol [2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazole] was shown in experiments in which DNA repair-deficient RAD51−/−Trypanosoma brucei mutants were found to be hypersensitive to the drug. Parasites resistant to megazol were selected and showed modest cross-resistance to other trypanocides, although neither drug efflux nor changes to intracellular thiols correlated with resistance.
High‐resolution analysis of acquired genomic imbalances in bone marrow samples from chronic myeloid leukemia patients by use of multiple short DNA probes

Chronic myeloid leukemia (CML) is a biphasic hematopoietic malignancy associated with a single cytogenetic aberration, the Philadelphia translocation t(9;22)(q34;q11), resulting in the BCR‐ABL1 fusion oncogene. Molecular heterogeneity was recently demonstrated in the form of extensive deletion of chromosomes 9 and 22 material from the der(9)t(9;22) in 15% of CML patients. The deletions were associated with a worse disease prognosis. Further genetic heterogeneity is seen during the terminal blast crisis stage of CML, in the form of additional non‐random chromosome abnormalities. These include most frequently an extra copy of the Ph chromosome, trisomy 8, and isochromosome 17q. We used the genetic heterogeneity of CML as a framework to explore a new technique for high‐throughput assessment of locus copy number in malignancy. Multiplex amplifiable probe hybridization (MAPH) relies on the ability of numerous short (100–300 bp) DNA probes to be recovered quantitatively by use of a common primer pair after hybridization to genomic DNA. Derivative chromosome 9 deletions were successfully mapped in a CML cell line (MC3) and nine patient bone marrow samples by simultaneous hybridization of 10 MAPH probes. All results were confirmed by fluorescence in situ hybridization. MAPH was found to be informative in the presence of up to 50% of normal cells, thus establishing the sensitivity of the technique in clonal tumor cell populations. MAPH was performed effectively on DNA samples extracted from fresh or methanol/acetic acid–fixed clonal cell populations. Amplifications of BCR‐ABL1 were also detected and quantified in four CML cell lines by use of MAPH probes specific for ABL1 exon 11 and BCR exon 1. Our results demonstrate that MAPH is a reproducible high‐throughput method suitable for the assessment of genomic imbalances of multiple loci in tumor DNA samples with heterogeneous cell populations at a resolution of 100–300 bp. © 2003 Wiley‐Liss, Inc.
A Relational Perspective on the Development of Psychosis

Background: Whether childhood adversity affects the likelihood of poor social functioning in people who later develop psychosis remains unclear. The aim of this systematic review was to synthesise the existing literature exploring the relationship between adverse childhood experiences and social functioning of adults with experiences of psychosis, in comparison to clinical and non-clinical control groups without adverse childhood experiences. Method: Five databases (PubMed, Medline, PsycINFO, Scopus, and CINAHL plus) were searched up to May 2018 for relevant terms and only included English language peerreviewed journal articles. Ten studies were identified and were of observational design. Methodological quality of studies was assessed using a modified Newcastle-Ottawa Scale. Results: Six of the studies showed significant negative associations between childhood adversity and premorbid social functioning (particularly during adolescence) within firstepisode psychosis samples. Two of the studies showed no significant associations between sexual and/or physical abuse and current social functioning in chronic psychosis samples. Nine of the studies used different measures to assess for current social functioning, yielding mixed and non-comparable findings. Depression, neuroticism, insecure attachment, and age at exposure were identified as potential mediators. Effect sizes ranged from small to large. Conclusions: This review provided initial evidence that childhood adversity can be associated with premorbid social functioning impairments during adolescence, which may persist into adulthood for some people with experiences of psychosis. However, methodological limitations precluded a causal inference. More robust longitudinal studies are needed. Clinicians ought to consider a history of interpersonal trauma and social functioning difficulties when working clinically with this population.
Parents’ Education and Children's Achievement: The Role of Personality

The reasons for the positive association between families’ background variables, such as parents’ education, and children's academic achievement have not fully been clarified yet. The present study investigates children's intelligence and personality as potential mediators. A sample of 580 German high school students (mean age: M = 17.0; SD = 0.7) indicated the highest education of their parents and completed measures assessing their own personality and intelligence. Children's academic achievement was operationalized by grade point average. Children's intelligence, openness to experience and, marginally, conscientiousness partially mediated the association between parents’ education and children's academic achievement. Even after controlling for children's intelligence, the mediating effects of those personality traits held. Results are discussed with regard to potential underlying processes. Copyright © 2010 John Wiley & Sons, Ltd.
The effect of two different interval-training programmes on physiological and performance indices

Abstract The aim of the present study was to compare the effect of an increasing-distance, interval-training programme and a decreasing-distance, interval-training programme, matched for total distance, on aerobic and anaerobic physiological indices. Forty physical education students were randomly assigned to either the increasing- or decreasing-distance, interval-training group (ITG and DTG), and completed two similar relevant sets of tests before and after six weeks of training. One training programme consisted of increasing-distance interval-training (100–200–300–400–500 m) and the other decreasing-distance interval training (500–400–300–200–100 m). While both training programmes led to a significant improvement in VO2 max (ES = 0.83–1.25), the improvement in the DTG was significantly greater than in the ITG (14.5 ± 3.6 vs. 7.8 ± 3.2%, p < .05). In addition, while both training programmes led to a significant improvement in all anaerobic indices (ES = 0.83–1.63), the improvements in peak power (15.7 ± 7.8 vs. 8.9 ± 4.7), mean power (10.6 ± 5.4 vs. 6.8 ± 4.4), and fatigue index (18.2 ± 10.9 vs. 7.0 ± 14.2) were significantly greater in the DTG compared to the ITG (p < .05). The main finding of the present study was that beyond the significant positive effects of both training programmes on aerobic and anaerobic fitness, the DTG showed significant superiority over the ITG in improving aerobic and anaerobic performance capabilities. Coaches and athletes should therefore be aware that, in spite of identical total work, an interval-training programme might induce different physiological impacts if the order of intervals is not identical.
Suppression of Hepatic CYP3A1/2 and CYP2C11 by Cyclosporine Is Not Mediated by Altering Growth Hormone Levels

Cyclosporine (CsA) suppresses drug metabolism by decreasing cytochrome P450 (P450) enzyme levels in rat liver. Growth hormone (GH) is known to pretranslationally regulate P450 expression. Thus, the suppression of P450 by CsA may involve GH as an intermediate. To address this question, we examined the effects of administering exogenous GH via twice daily subcutaneous injections and in conjunction with chronic subcutaneous CsA administration for 14 days on hepatic P450 expression. CsA alone decreased CYP3A1/2 and CYP2C11 significantly, in a manner similar to that previously found. When administered in the absence of CsA, GH also suppressed CYP3A1/2 and CYP2C11 protein levels as compared with GH vehicle. In the presence of CsA, GH did not cause further suppression of either CYP3A1/2 or CYP2C11 expression when compared with CsA treatment with GH vehicle. Testosterone in vitro catalytic assays confirmed that CsA and GH separately cause significant decreases in activity levels. Also, the concomitant administration of GH and CsA caused lowered production of 16α-, 2α-, 6β-, and 2β-hydroxytestosterone as compared with the administration of GH with CsA vehicle and as compared with the administration of GH vehicle with CsA. This study shows that GH is a dominating factor over CsA in determining hepatic P450 expression and activity. In addition, CsA does not seem to alter GH levels as a mediating event in suppressing P450 expression and activity. Since CsA given in combination with GH further suppressed P450 activity as compared with CsA given in combination with vehicle, this suggests that changes in hormonal status are likely to be one of the many factors that is responsible for the lack of a clear association between cyclosporine dosing and markers of toxicity.
Quality of life and symptom severity for individuals with chronic fatigue syndrome: findings from a randomized clinical trial.

OBJECTIVE Chronic fatigue syndrome is a profoundly disabling condition characterized by severe, unrelenting fatigue and a number of other physical and cognitive symptoms. Currently, there is no cure or widely accepted treatment for chronic fatigue syndrome, and few rehabilitation programs exist to address quality of life issues in chronic fatigue syndrome. In the present randomized clinical trial, the effects of an integrative, consumer-driven rehabilitation program on quality of life and symptom severity for individuals with chronic fatigue syndrome were examined. METHOD Forty-seven participants were randomly assigned to either an immediate program group (n = 23) or a delayed program control group (n = 24) and assessed with the Chronic Fatigue Syndrome Symptom Rating Scale and the Quality of Life Index before the program, after program participants completed the group phase, and after program participants completed the one-on-one phase. It was hypothesized that the program would lead to improvements in quality of life and an overall reduction in symptom severity. RESULTS Linear growth models were estimated comparing program and control conditions over time using random-effects regression analyses. Significant condition by time interactions were observed for the main outcomes of symptom severity and overall quality of life. Effect sizes for these interactions involving symptom severity (Cohen's d = 0.71) and overall quality of life (Cohen's d = .66) were moderate. CONCLUSIONS Findings indicate that consumer driven programs such as this one can have a positive impact on symptom severity and quality of life over time for individuals with chronic fatigue syndrome.
The Bishop Score as a Predictor of Labor Induction Success: A Systematic Review

Abstract Objective To assess the ability of the Bishop score to predict the mode of delivery in women scheduled for induction of labor at term. Study Design We performed a systematic literature search of electronic databases from inception to July 2009. Studies reporting on both the Bishop score and the outcome of labor in women scheduled for induction of labor at term were eligible. We used a bivariate model to estimate a summary receiver operating characteristic (sROC) curve for the outcome cesarean delivery. Results We included 40 primary articles reporting on 13,757 women. Study quality was mediocre. The sROC curve of the Bishop score in the prediction of cesarean delivery indicated a poor predictive capacity. For the prediction of cesarean delivery, the sensitivity-specificity combinations were 47%-75%, 61%-53% and 78%-44% for the Bishop scores of 4, 5, and 6, respectively. For a Bishop score below 9, the sensitivity-specificity combination was 95%-30%. Conclusion The Bishop score is a poor predictor for the outcome of induced labor at term and should not be used to decide whether to induce labor or not.
Cardiovascular disease and risk factors in three Alaskan Eskimo populations: the Alaska-Siberia project

Abstract Objectives. To determine the prevalence of CVD and to identify and characterize associated risk factors in three distinct Eskimo populations. Study Design. Cross-sectional. Methods. A slightly modified Strong Heart Study protocol was followed to examine 454 participants, aged 25–91, from four villages. Results. Overall, 6% of the participants under 55 years of age and 26% of those ≥ 55 years of age showed evidence of CHD by ECG, or in patient records. The prevalence of “definite coronary heart disease” (CHD) in women with glucose intolerance (GI) was 21.0%, compared to 2.4% in those with normal glucose tolerance (NGT). Men had comparable values of 26.7% and 6.3%. In addition, comparable values for “possible CHD” were 29.7% vs 6.0% for women and 21.4% vs 8.0% for men. GI was associated with relatively higher prevalences of CHD in women than in men (prevalence ratio = 8.5 vs 4.3). CHD was significantly related to age, glucose intolerance and insulin. Hypertension and obesity were significantly associated with CHD only in some ethnic groups. The prevalence of current smokers was 56%. Conclusions. Recent changes in lifestyle and diet of Alaskan Eskimos, leading to obesity, hypertension, insulin resistance and DM, contribute to an increased risk for cardiovascular disease. (Int J Circumpolar Health 2005; 64(4):365–386)
The Effect of Microwave Duty Cycle on The Electrical Conductivity of Reduced Graphene Oxide (rGO)

Graphene is a 2D material which has attracted a lot of attention due to its various fascinating properties. The most straightforward and facile synthesis method to produce graphene is chemical exfoliation method, which is conducted by reducing the graphene oxide. In this paper, we investigated the effect of microwave duty cycles on the electrical conductivity properties of rGO. The microwave was set at a different variation of duty cycles and reduction times. The reduction process with microwave-assisted was done under nitrogen conditions. The samples were characterized using Fourier transforms infrared spectrometry (FTIR), Scanning electron microscopy (SEM), and four-point probes. The highest conductivity of 18.10 S/cm was observed from rGO samples prepared by the reduction process using hydrazine as reducing agent and treated by high microwave irradiation mode for 3 min under N2 conditions.