Miracle-dz/UniFAR-FTUs huggingface dataset:
The coral-derived natural products eleutherobin and sarcodictyins A and B: effects on the assembly of purified tubulin with and without microtubule-associated proteins and binding at the polymer taxoid site.

We examined interactions with purified tubulin of synthetic sarcodictyins A and B and eleutherobin (coral-derived antimitotic agents) and of compound 1, an analogue of sarcodictyin A methylated at the C-3 oxygen atom (i.e., the methyl ketal analogue of sarcodictyin A and thus structurally similar to eleutherobin but lacking the C-3 sugar moiety). Eleutherobin was much more active than sarcodictyins A and B, which were somewhat more active than compound 1. Effects of eleutherobin did not differ greatly from those of paclitaxel and epothilone A. Eleutherobin and epothilone A were competitive inhibitors of the binding of radiolabeled paclitaxel to tubulin polymer (apparent Ki values of 2.1 and 2.6 microM, respectively). Tubulin assembly reactions induced by all compounds were similar to the paclitaxel-driven reactions in being enhanced by the addition of microtubule-associated proteins and/or GTP to the reaction mixture and by progressively higher reaction temperatures. Antiproliferative activity was studied in six human cancer cell lines, including two paclitaxel-resistant lines with point mutations in a beta-tubulin gene. Except for compound 1, effects on cell growth were generally in accord with effects on purified tubulin. Thus, sarcodictyins A and B had IC50 values in the 200-500 nM range; paclitaxel, <10 nM (except in the resistant lines); and eleutherobin and epothilone A, 10-40 nM. The antiproliferative activity of compound 1 was more comparable to that of eleutherobin than sarcodictyin A, despite its weak interaction with tubulin. The activities of the sarcodictyins, eleutherobin, and compound 1 in the mutant ovarian lines were similar to their activities in the parental line.
Student Engagement with a Flipped Classroom Teaching Design Affects Pharmacology Examination Performance in a Manner Dependent on Question Type

Objective: To investigate the relationship between student engagement with the key elements of a flipped classroom approach (preparation and attendance), their attitudes to learning, including strategy development, and their performance on two types of examination questions (knowledge recall and providing rational predictions when faced with novel scenarios). Methods. This study correlated student engagement with the flipped classroom and student disposition to learning with student ability to solve novel scenarios in examinations. Results. Students who both prepared for and attended classes performed significantly better on examination questions that required analysis of novel scenarios compared to students who did not prepare and missed classes. However, there was no difference for both groups of students on examination questions that required knowledge and comprehension. Student motivation and use of strategies correlated with higher examination scores on questions requiring novel scenario analysis. Conclusion. There is a synergistic relationship between class preparation and attendance. The combination of preparation and attendance was positively correlated to assessment type; the relationship was apparent for questions requiring students to solve novel problems but not for questions requiring knowledge or comprehension.
Complication Rates in Posterior Lumbar Interbody Fusion (PLIF) Surgery With Human Bone Morphogenetic Protein 2: Medicare Population

Study Design: Retrospective cohort study among Medicare beneficiaries who underwent posterior lumbar interbody fusion (PLIF) surgery. Objective: To identify the complication rates associated with the use of bone morphogenetic protein 2 (BMP2) in PLIF. Human BMP2 is commonly used in the “off-label” manner for various types of spine fusion procedures, including PLIF. However, recent studies have reported potential complications associated with the recombinant human BMP2 (rhBMP2) use in the posterior approach. Methods: Medicare records within the PearlDiver database were queried for patients undergoing PLIF procedure with and without rhBMP2 between 2005 and 2010. We evaluated complications within 1 year postoperatively. Chi-square was used to compare the complication rates between the 2 groups. Results: A total of 8609 patients underwent PLIF procedure with or without rhBMP2. Individual complication rates in the rhBMP2 group ranged from 0.45% to 7.68% compared with 0.65% to 10.99 in the non-rhBMP2 group. Complication rates for cardiac, pulmonary, lumbosacral neuritis, infection, wound, and urinary tract (include acute kidney failure and post-operative complications) were significantly lower in the rhBMP2 group (P < .05). There was no difference in the rates of central nervous system complications or radiculitis between the 2 groups. Conclusion: Our data showed that the patients who received rhBMP2 had lower complication rates compared to the non-rhBMP2 group. However, use of rhBMP2 was associated with a higher rate of pseudarthrosis. We did not observe any difference in radiculitis and central nervous system complications between the groups.
Outcomes Assessment for Chronic Otitis Media: The Chronic Ear Survey

Analysis of outcomes in chronic otitis media has in the past been limited to audiological measurement or physical examination. The Chronic Ear Survey (CES) is an instrument to measure the impact of chronic otitis media and its treatment. The survey provides information regarding total ear‐specific health, as well as subscore information regarding activity restriction, symptoms, and medical resource usage attributable to chronic otitis media. Application of the CES to a prospective, nonrandomized series of 147 patients revealed that patients with chronic otitis media have significantly decreased CES scores compared with unaffected controls and that surgical intervention provides a significant improvement in ear‐specific outcomes.
Electro-thermal aging behaviour of thermoplastic compounds

Improved recyclability and cost pressure encourage the use of thermoplastics as electrical insulation material for demanding electrical applications. Besides their basic mechanical, thermal and electrical properties it is of interest to study the aging behavior of these thermoplastic materials. In this paper a non-standard test method is presented, where rod-rod shaped test samples have been exposed to electro-thermal stress. The samples have been aged at elevated temperature under alternating current (AC) field until breakdown occurred. Several thermoplastic materials were tested and differences in performance due to fillers and additives were investigated.
Alcohol consumption and cardiovascular disease: differential effects in France and Northern Ireland. The PRIME study

Background The effects of wine and other alcoholic beverages on coronary heart disease (CHD) have seldom been studied in several countries using a common methodology. Design Five-year prospective study conducted among 9750 men (7352 in France and 2398 in Northern Ireland) free of CHD at entry. Outcomes were angina pectoris, myocardial infarction or CHD death. Results In all, 90% of subjects in France reported drinking at least once per week, versus 61% in Northern Ireland. In France, after adjusting for other CHD risk factors, subjects in the highest quartile of alcohol consumption had a significantly lower risk of developing angina pectoris relative to non-drinkers. For myocardial infarction and all CHD events, the risk also decreased from the first to the fourth quartile (P for trend = 0.02). Conversely, in Northern Ireland, no significant relationship was found between alcohol consumption and the incidence of angina pectoris or all CHD events, although alcohol consumption appeared to decrease the risk for myocardial infarction. Similar findings were obtained when the 5% higher alcohol consumers were excluded from the analysis. Finally, splitting the alcohol consumption into wine, beer and spirits did not improve the relationships, the three types of beverage exerting comparable effects on CHD events. Conclusions Alcohol consumption patterns exert differential effects on CHD risk in middle-aged men from France and Northern Ireland. Further, the amount of alcohol consumption, rather than the type of alcoholic beverage, is related to both angina pectoris and myocardial infarction in France, whereas no relationship was found in Northern Ireland.
Long-term prognosis in patients with severe late radiation enteropathy: a prospective cohort study.

AIM To assess persistent symptoms and mortality in a cohort of patients with severe (grade 3-4) radiation enteropathy, 59 patients were followed up after 15-18 years. METHODS Fifty-nine patients were prospectively enrolled by twelve surgical departments. Primary malignant disease, radiation therapy and surgical management were recorded at inclusion. The cause of death or persistence of symptoms was examined in public death records or by interview of survivors. RESULTS Thirty-nine patients had received radiation therapy for gynaecological cancers, twelve for urological cancers, four for gastrointestinal cancers and four for other malignancies. Forty-five patients (76%) required surgical intervention. Complications occurred in 11 (25%) operated patients. Forty-seven patients had died at the time of follow-up, seven (12%) died as a direct result of radiation enteropathy, while radiation enteropathy contributed to death in an additional seven patients. Four of the twelve surviving patients suffered from chronic debilitating symptoms of radiation enteropathy, while three had moderate symptoms. CONCLUSION Patients with severe delayed radiation enteropathy have a high risk of persistence of symptoms after surgery. At least one in ten patients dies from radiation-induced bowel injury.
A long-term follow-up of stroke patients.

BACKGROUND AND PURPOSE Two hundred ninety-one residents of southeast London, younger than 75 years, suffered their first stroke in 1989/1990. The objectives of this study were to determine the long-term outcome of this cohort of stroke patients in terms of impairment, disability, handicap, and quality of life and their use of services and prevention measures subsequent to their stroke. METHODS The survivors and their identified caregivers were traced and completed a structured interview questionnaire that included the Barthel Index, modified Rankin Scale, Hospital Anxiety and Depression Scale (HAD), Mini-Mental State Examination, Frenchay Activities Index, and Caregiver Strain Index. RESULTS One hundred twenty-three people (42%) were alive, of whom 106 were interviewed. The mean interval between the stroke and the long-term follow-up was 4.9 years. Thirty-one of the survivors (29%) were severely or moderately disabled, 39 (37%) were mildly disabled, and 36 (34%) were functionally independent. Of the 96 people who completed the HAD, 35 (36%) had scores suggesting that they were depressed or had borderline depression. The most likely nontherapy services to have been provided were chiropody and district nursing. Five people had received respite care. Of the 104 subjects for whom information about their home was available, 53 (51%) had had an adaptation. Seventy-five people (71%) had an aid or appliance. Sixty-five people (61%) were on aspirin, and an additional 14 (13%) were on warfarin. Fifty subjects (47%) identified a main caregiver. No one with a moderate or more severe disability was living at home without an identified caregiver. CONCLUSIONS The levels of both health and social service provision are likely to be inadequate for this population. The use of prevention measures is encouraging. There is a clear need for a coordinated policy to guide assessment and management across sectors.
Measuring both systems of reasoning: a study of the predictive capacity of a new version of the Rational-Experiential Inventory

Previous research on the Rational-Experiential Inventory (REI; Epstein, Pacini, Denes-Raj and Heier, 1996) has produced inconsistent results concerning its predictive validity with specific reasoning tasks. To evaluate the predictive capacity of the REI in greater detail we used ten tasks requiring different types of reasoning (e.g., deductive and probabilistic). The latest version of the REI (Pacini and Epstein, 1999) was adapted to Spanish and answered by 120 participants. Findings suggest that thinking styles of processing as measured by the REI reflect the existence of individual differences, but that its predictive capacity is limited to some particular reasoning tasks. Some explanations for these limitations are discussed within the context of dual-reasoning theories.
Three-Dimensional Compressed Sensing-Based Millimeter-Wave Imaging

An extension of compressed sensing (CS)-based millimeter-wave imaging techniques from two- to three-dimensional (2-D to 3-D) is presented. The idea is to study the reduction in the minimum number of receivers with respect to standard synthetic aperture radar (SAR) imaging to accurately recover the geometry of the object-under-test. 3-D CS main drawback is the increased calculation time with respect to standard SAR algorithms. To overcome this limitation, a novel technique consisting in splitting a large problem as a combination of small ones is proposed. These small problems can be solved via parallelized 3-D CS, resulting in calculation time savings. Moreover, practical implementation of a 3-D CS-based millimeter-wave imaging system is discussed. Validation with simulations and measurements is presented.
Role of melatonin in mucosal gastroprotection against aspirin‐induced gastric lesions in humans

Abstract: Melatonin and its precursor, l‐tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l‐tryptophan on ASA‐induced gastric mucosal damage, gastric microbleeding, mucosal generation of prostaglandin E2, and plasma melatonin, and gastrin levels. Three groups of healthy male volunteers (n = 30) with intact gastric mucosa received daily for 11 days either ASA alone or that combined with melatonin or tryptophan. Gastric blood loss and mucosal damage were evaluated at 3rd, 7th, and 11th days of ASA administration by endoscopy using Lanza score. ASA alone caused a marked rise of gastric damage and gastric blood loss, mainly at day 3rd and 7th, but they were significantly reduced at 11th day. Pretreatment with melatonin or tryptophan remarkably reduced ASA‐induced gastric lesions and microbleeding. Gastric mucosal generation of PGE2 was suppressed by about 90% in all subjects treated with ASA alone without or with addition of melatonin or tryptophan. Plasma melatonin was markedly increased after treatment with melatonin or tryptophan plus ASA, but it was also raised significantly after application of ASA alone. Plasma gastrin levels were raised in subjects given melatonin or tryptophan plus ASA, but not in those with ASA alone. We conclude that melatonin and its precursor tryptophan given orally significantly reduce gastric lesions induced by ASA possibly due to (a) direct gastroprotective action of exogenous melatonin or that generated from tryptophan and (b) gastrin released from the gastric mucosa by melatonin or tryptophan.
Cell-Free Human Immunodeficiency Virus Type 1 Transcytosis through Primary Genital Epithelial Cells

ABSTRACT Although the transport of human immunodeficiency virus type 1 (HIV-1) through the epithelium is critical for HIV-1 colonization, the mechanisms controlling this process remain obscure. In the present study, we investigated the transcellular migration of HIV-1 as a cell-free virus through primary genital epithelial cells (PGECs). The absence of CD4 on PGECs implicates an unusual entry pathway for HIV-1. We found that syndecans are abundantly expressed on PGECs and promote the initial attachment and subsequent entry of HIV-1 through PGECs. Although CXCR4 and CCR5 do not contribute to HIV-1 attachment, they enhance viral entry and transcytosis through PGECs. Importantly, HIV-1 exploits both syndecans and chemokine receptors to ensure successful cell-free transport through the genital epithelium. HIV-1-syndecan interactions rely on specific residues in the V3 of gp120 and specific sulfations within syndecans. We found no obvious correlation between coreceptor usage and the capacity of the virus to transcytose. Since viruses isolated after sexual transmission are mainly R5 viruses, this suggests that the properties conferring virus replication after transmission are distinct from those conferring cell-free virus transcytosis through the genital epithelium. Although we found that cell-free HIV-1 crosses PGECs as infectious particles, the efficiency of transcytosis is extremely poor (less than 0.02% of the initial inoculum). This demonstrates that the genital epithelium serves as a major barrier against HIV-1. Although one cannot exclude the possibility that limited passage of cell-free HIV-1 transcytosis through an intact genital epithelium occurs in vivo, it is likely that the establishment of infection via cell-free HIV-1 transmigration is a rare event.
Effects of stimulation parameters and electrode location on thresholds for epidural stimulation of cat motor cortex

Epidural electrical stimulation (ECS) of the motor cortex is a developing therapy for neurological disorders. Both placement and programming of ECS systems may affect the therapeutic outcome, but the treatment parameters that will maximize therapeutic outcomes and minimize side effects are not known. We delivered ECS to the motor cortex of anesthetized cats and investigated the effects of electrode placement and stimulation parameters on thresholds for evoking motor responses in the contralateral forelimb. Thresholds were inversely related to stimulation frequency and the number of pulses per stimulus train. Thresholds were lower over the forelimb representation in motor cortex (primary site) than surrounding sites (secondary sites), and thresholds at sites <4 mm away from the primary site were significantly lower than at sites >4 mm away. Electrode location and montage influenced the effects of polarity on thresholds: monopolar anodic and cathodic thresholds were not significantly different over the primary site, cathodic thresholds were significantly lower than anodic thresholds over secondary sites and bipolar thresholds were significantly lower with the anode over the primary site than with the cathode over the primary site. A majority of bipolar thresholds were either between or equal to the respective monopolar thresholds, but several bipolar thresholds were greater than or less than the monopolar thresholds of both the anode and cathode. During bipolar stimulation, thresholds were influenced by both electric field superposition and indirect, synaptically mediated interactions. These results demonstrate the influence of stimulation parameters and electrode location during cortical stimulation, and these effects should be considered during the programming of systems for therapeutic cortical stimulation.
Cryptanalysis of smart‐card‐based password authenticated key agreement protocol for session initiation protocol of Zhang et al.

As the core signaling protocol for multimedia services, such as voice over internet protocol, the session initiation protocol (SIP) is receiving much attention and its security is becoming increasingly important. It is critical to develop a roust user authentication protocol for SIP. The original authentication protocol is not strong enough to provide acceptable security level, and a number of authentication protocols have been proposed to strengthen the security. Recently, Zhang et al. proposed an efficient and flexible smart‐card‐based password authenticated key agreement protocol for SIP. They claimed that the protocol enjoys many unique properties and can withstand various attacks. However, we demonstrate that the scheme by Zhang et al. is insecure against the malicious insider impersonation attack. Specifically, a malicious user can impersonate other users registered with the same server. We also proposed an effective fix to remedy the flaw, which remedies the security flaw without sacrificing the efficiency. The lesson learned is that the authenticators must be closely coupled with the identity, and we should prevent the identity from being separated from the authenticators in the future design of two‐factor authentication protocols. Copyright © 2014 John Wiley & Sons, Ltd.
Does the metabolic syndrome improve identification of individuals at risk of type 2 diabetes and/or cardiovascular disease?

OBJECTIVE The metabolic syndrome has been promoted as a method for identifying high-risk individuals for type 2 diabetes and cardiovascular disease (CVD). We therefore sought to compare this syndrome, as defined by the National Cholesterol Education Program, to the Diabetes Predicting Model and the Framingham Risk Score as predictors of type 2 diabetes and CVD, respectively. RESEARCH DESIGN AND METHODS A population-based sample of 1,709 initially nondiabetic San Antonio Heart Study (SAHS) participants were followed for 7.5 years, 195 of whom developed type 2 diabetes. Over the same time interval, 156 of 2,570 SAHS participants experienced a cardiovascular event. A population-based sample of 1,353 initially nondiabetic Mexico City Diabetes Study (MCDS) participants were followed for 6.5 years, 125 of whom developed type 2 diabetes. Baseline measurements included medical history, age, sex, ethnicity, smoking status, BMI, blood pressure, fasting and 2-h plasma glucose levels, and fasting serum total and HDL cholesterol and triglycerides. RESULTS The sensitivities for predicting diabetes with the metabolic syndrome were 66.2 and 62.4% in the SAHS and the MCDS, respectively, and the false-positive rates were 27.8 and 38.7%, respectively. The sensitivity and false-positive rates for predicting CVD with the metabolic syndrome in the SAHS were 67.3 and 34.2%, respectively. At corresponding false-positive rates, the two predicting models had significantly higher sensitivities and, at corresponding sensitivities, significantly lower false-positive rates than the metabolic syndrome for both end points. Combining the metabolic syndrome with either predicting model did not improve the prediction of either end point. CONCLUSIONS The metabolic syndrome is inferior to established predicting models for either type 2 diabetes or CVD.
Pseudo-invariant H2 multi variable robust control of a flexible beam

We present the principle of pseudo-invariant controls devoted to robustness with respect to uncertainties of the model under consideration. Trough the concept of diffusive representation of pseudo-differential time-operators, implementable control strategies can then be elaborated. We apply this concept to robust multivariable feedback control of a flexible beam with an unknown mass attached at the controlled end.