Miracle-dz/UniFAR-FTUs huggingface dataset:
Reflections on the history of pre-mRNA processing and highlights of current knowledge: a unified picture.

Several strong conclusions emerge concerning pre-mRNA processing from both old and newer experiments. The RNAPII complex is involved with pre-mRNA processing through binding of processing proteins to the CTD (carboxyl terminal domain) of the largest RNAPII subunit. These interactions are necessary for efficient processing, but whether factor binding to the CTD and delivery to splicing sites is obligatory or facilitatory is unsettled. Capping, addition of an m(7)Gppp residue (cap) to the initial transcribed residue of a pre-mRNA, occurs within seconds. Splicing of pre-mRNA by spliceosomes at particular sites is most likely committed during transcription by the binding of initiating processing factors and ∼50% of the time is completed in mammalian cells before completion of the primary transcript. This fact has led to an outpouring in the literature about "cotranscriptional splicing. " However splicing requires several minutes for completion and can take longer. The RNAPII complex moves through very long introns and also through regions dense with alternating exons and introns at an average rate of ∼3 kb per min and is, therefore, not likely detained at each splice site for more than a few seconds, if at all. Cleavage of the primary transcript at the 3' end and polyadenylation occurs within 30 sec or less at recognized polyA sites, and the majority of newly polyadenylated pre-mRNA molecules are much larger than the average mRNA. Finally, it seems quite likely that the nascent RNA most often remains associated with the chromosomal locus being transcribed until processing is complete, possibly acquiring factors related to the transport of the new mRNA to the cytoplasm.
Disentangling the effects of psychological and physical work demands on sleep, recovery and maladaptive chronic stress outcomes within a large sample of Australian nurses.

AIM This paper reports a study to determine if different types of work strain experienced by nurses, particularly those of an essentially psychological nature, such as emotional demand, mental effort and problems with peers and/or supervisors, have a differential impact on sleep quality and overall recovery from work strain, compared with physical work strains, and lead to higher maladaptive chronic fatigue outcomes. BACKGROUND Various studies have shown that the dominant work-demand strain associated with nursing work can vary between different areas of nursing. For example, whereas emotional strain is reported to be the principal strain associated with work in areas such as oncology, haematology and renal units, medical and surgical unit nurses report work pace and staffing issues as the dominant work strain. Purely physical strain seems to be less commonly reported as a concern. METHOD A large sample (n = 760) of Australian nurses working in a large metropolitan hospital completed questionnaires on their work demands, sleep quality, fatigue, and recovery between shifts in January 2004. FINDINGS A high work pace exacerbates the psychological rather than the physical strain demands of nursing. Psychological strain affects sleep quality and impairs recovery from overall work strain between shifts. This combination is highly predictive of serious maladaptive stress/fatigue outcomes among nurses. CONCLUSION Coping with psychological stressors adequately is an important requirement for nurses in order to avoid adverse health effects and maintain a long-term career in nursing. Appropriate training of undergraduate nursing students in managing the stresses they are likely to encounter would seem to be an essential requirement for the 21st century. Such training might constitute an important long-term component in overcoming the chronic nurse shortages evident in many countries.
Kinematics and Electromyography of Landing Preparation in Vertical Stop-Jump

Background Biomechanical analysis of stop-jump tasks has demonstrated gender differences during landing and a potential increase in risk of noncontact anterior cruciate ligament injury for female athletes. Analysis of landing preparation could advance our understanding of neuromuscular control in movement patterns and be applied to the development of prevention strategies for noncontact anterior cruciate ligament injury. Hypothesis There are differences in the lower extremity joint angles and electromyography of male and female recreational athletes during the landing preparation of a stop-jump task. Study Design Controlled laboratory study. Methods Three-dimensional videographic and electromyographic data were collected for 36 recreational athletes (17 men and 19 women) performing vertical stop-jump tasks. Knee and hip angular motion patterns were determined during the flight phase before landing. Results Knee and hip motion patterns and quadriceps and hamstring activation patterns exhibited significant gender differences. Female subjects generally exhibited decreased knee flexion (P = .001), hip flexion (P = .001), hip abduction (P = .001), and hip external rotation (P = .03); increased knee internal rotation (P = .001); and increased quadriceps activation (P = .001) compared with male subjects. Female subjects also exhibited increased hamstring activation before landing but a trend of decreased hamstring activation after landing compared with male subjects (P = .001). Conclusion Lower extremity motion patterns during landing of the stop-jump task are preprogrammed before landing. Female subjects prepared for landing with decreased hip and knee flexion at landing, increased quadriceps activation, and decreased hamstring activation, which may result in increased anterior cruciate ligament loading during the landing of the stop-jump task and the risk for noncontact ACL injury.
Topical application of slow-release simvastatin as a bone substitute in bone defects in the rat tibia: a pilot study.

PURPOSE It is hypothesized that local application of statins positively affects bone formation. The aim of this study was to evaluate the potential effect of topical slow-release simvastatin as a bone substitute on the healing of bone defects in rat tibia. MATERIALS AND METHODS Granules of slow-releasing hydroxypropyl methylcellulose, with or without simvastatin, were inserted into critical-size defects in the tibiae of 16 rats (8 in the study group, 8 in the control group). Bone static and dynamic histomorphometric variables were examined at 2, 4, 6, and 8 weeks postsurgery. RESULTS All indices examined in the study group indicated improved healing relative to the control group, although statistical significance was not demonstrated for all variables. In the static histomorphometric analysis, osteoid thickness and volume were significantly higher in the study group, but the fraction of trabecular surface covered with active osteoblasts, the fraction of trabecular surface covered with osteoid, and total calcified bone volume were not significantly higher in the experimental group. In the dynamic histomorphometric analysis, the mineral apposition rate, determined by time-repeated calcein labeling, was significantly higher in the study group than in the control group. Experimental time and dosage effects were observed for most bone values in the study group. CONCLUSION The findings indicate that topical application of simvastatin for the treatment of bone defects enhances the process of healing. Dosage and the methodology of administration require further calibration.
QT interval prolongation and arrhythmia: an unbreakable connection?

QT interval prolongation is incontrovertibly linked to increased risk of arrhythmias but, paradoxically, QT interval prolongation can also be an effective antiarrhythmic strategy and is in fact the goal of class III antiarrhythmic drugs. This discussion examines the cellular effects of QT interval prolongation and proposes that calmodulin kinase II (CaMKII) is a specific cellular proarrhythmic signal that is activated downstream to QT interval prolongation. Inhibition of CaMKII can prevent cellular arrhythmia surrogates and in vivo arrhythmias linked to excessive action potential prolongation, suggesting that QT interval prolongation alone does not fully account for proarrhythmia. This reasoning points to the conclusion that QT interval modulation and prolongation not only grades cellular Ca2+ entry for cardiac contraction but also has the potential to recruit Ca2+‐activated signalling molecules. CaMKII is one of these molecules and CaMKII activity is at least partially responsible for the proarrhythmic consequences of excessive QT interval prolongation.
Down-regulation of 20-HETE synthesis and signaling inhibits renal adenocarcinoma cell proliferation and tumor growth.

BACKGROUND We examined the ability of inhibitors of the synthesis or actions of 20-HETE, metabolite of arachidonic acid, to inhibit proliferation of human renal carcinoma cell lines. MATERIALS AND METHODS 786-O and 769-P cells were exposed to either 10 microM HET0016 (selective inhibitor of 20-HETE synthesis), 10 microM WIT002 (20-HETE antagonist), or vehicle. Subsequently, we assessed the effect of WIT002 on tumor growth in vivo using an ectopic mouse model of clear-cell renal carcinoma. RESULTS Addition of HET0016 and WIT002 inhibited the proliferation of 786-O and 769-P human renal cell carcinoma lines. HET0016 and WIT002 had little effect on the proliferation of primary cultures of normal human proximal tubule epithelial cells. WIT002 (10 mg/kg, s.c.) administered daily to athymic nude mice implanted subcutaneously with 786-O cells reduced the growth of the tumors by 84 % compared to vehicle (p<0.001). CONCLUSION 20-HETE is required for proliferation of human renal epithelial cancer.
Chronotype and personality factors of predisposition to seasonal affective disorder

The study aimed to recognize the personality factors of a predisposition to seasonal mood fluctuations in a non-clinical sample. A group of 101 subjects (57 women, 44 men; mean age 26.4 ± 6.5 years) completed a battery of tests comprising a Seasonal Pattern Assessment Questionnaire (SPAQ), Chronotype Questionnaire (ChQ), a NEO-Five Factor Inventory and a Coping Inventory for Stressful Situations (CISS). A smaller sample (n = 44) completed a Winter Blues Scale (WBS). Women scored significantly higher than men in seasonality (p = 0.014), neuroticism (p = 0.049), agreeableness (p = 0.010), and avoidance-oriented coping style (p = 0.041). Subjects with seasonal affective disorder (SAD) (n = 41) or sub-SAD (n = 33), as diagnosed with SPAQ, exhibited higher levels of neuroticism (p = 0.017) and openness (p = 0.016) in comparison to non-SAD individuals. The latter declared a less frequent avoidance coping style. Both measures of seasonality, i.e. the SPAQ Global Seasonality Score and WBS, correlated significantly (r = 0.28 and 0.44, respectively) with the subjective amplitude of the circadian rhythm, as described with the “distinctness” scale of ChQ. Female gender, neuroticism and openness were confirmed as factors linked to seasonal mood variability. Additionally, the study revealed an association between susceptibility to mild winter depression and an avoidance-oriented coping style. The avoidance coping style was correlated positively with all the aspects of seasonality described by SPAQ (correlation coefficients from 0.21 to 0.34). Both sub-types of avoidance-oriented style, i.e. distraction and social diversion, were associated with marked subjective seasonal changes in sleep length, mood and the energy level. While the subjective amplitude of circadian rhythm proved to be connected with seasonality, the subjective acrophase of the rhythm (morningness–eveningness preference) did not. It may be hypothesized that sensitivity to natural environmental conditions/synchronizers is a separate individual trait shaping the subject’s proneness to energy and mood changes both in diurnal and year scale, i.e. circadian and seasonal mood variations.
NEURO-OPHTHALMOLOGIC EVALUATION OF OCULOMOTOR NERVE PARALYSIS.

Paralysis of the oculomotor nerve as a clinical sign has been well known to both the neurologist and the ophthalmologist. In recent years its relationship to underlying, potentially remediable, intracranial aneurysms has been described and emphasized.1-11Also described and becoming more recognized has been the relationship between oculomotor nerve paralysis and the relatively common metabolic disorder of diabetes mellitus.12-25 A series of 130 consecutive patients with isolated oculomotor nerve paralysis has been examined in the Neurology Clinic of the Wills Eye Hospital during the past 20 years and serves as the basis for this study. Such a series of patients would be comparable to patients who might present themselves first to an ophthalmologist. Excluded from our series have been all patients initially showing any signs referable to the nervous system other than an isolated oculomotor nerve paralysis. Present Study This survey consists of 130 patients with oculomotor nerve paralysis
Dumping Determination Discretions Analysis: Through Lenses of Relevant Accounting Principles

Antidumping (AD) law and policy is concerned with fair trading among World Trade Organisation. However, it has been known to be used as protection policy. Article II of Agreement on implementation of Article VI of GATT 1994 provides significant discretions to national investigating authorities in investigating AD actions. Positive outcome of AD cases is predictable. The current paper contributes to AD literature by investigating the discretions provided in accounting principles point of view. The findings indicate that there is a great range of accounting principles relevant to the computation of exported price, normal value and dumping-margin. Each of the accounting principles identified provides a different product cost.
Improved least squares MR image reconstruction using estimates of k‐Space data consistency

This study describes a new approach to reconstruct data that has been corrupted by unfavorable magnetization evolution. In this new framework, images are reconstructed in a weighted least squares fashion using all available data and a measure of consistency determined from the data itself. The reconstruction scheme optimally balances uncertainties from noise error with those from data inconsistency, is compatible with methods that model signal corruption, and may be advantageous for more accurate and precise reconstruction with many least squares‐based image estimation techniques including parallel imaging and constrained reconstruction/compressed sensing applications. Performance of the several variants of the algorithm tailored for fast spin echo and self‐gated respiratory gating applications was evaluated in simulations, phantom experiments, and in vivo scans. The data consistency weighting technique substantially improved image quality and reduced noise as compared to traditional reconstruction approaches. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
Attitudes and Perceptions Regarding Alzheimer's Disease in Greece

The Facing Dementia Survey was conducted across Europe to assess awareness and behaviors regarding Alzheimer's disease. A similar survey was undertaken in Greece. Interviews were conducted with the general public, primary caretakers, and physicians involved with Alzheimer's disease patients. Results indicated that the general public is not able to recognize the early symptoms of the disease and seek help resulting in a delay in the diagnosis. The principal cause was attributing the symptoms as part of the normal ageing process and ignorance regarding the disease. In addition, the survey indicated that only a small proportion of the physicians and the primary caretakers believed that there is an effective treatment for Alzheimer's disease but agreed on the goals of treatment. In addition there was a consensus among all respondents that the government should take a more active role as far as informing the public, supporting the caregivers, and treating the patients.
Real‐time visualization of oxidative stress in a floating macrophyte Lemna minor L. exposed to cadmium, copper, menadione, and AAPH

An ultra‐sensitive digital imaging system was employed to visualize oxidative stress in intact L. minor plants exposed to Cd, Cu, menadione, AAPH, and ascorbate in real time. The increase of ROS production was assessed by measuring the rate of fluorescence intensity increases of the test medium supplemented with a fluorescing probe (dichlorofluorescein diacetate). The addition of 100 μM CdCl2 or 100 μM CuSO4 to the growth medium resulted in a significant increase of medium fluorescence. Additionally, CuSO4 caused a significantly higher fluorescence intensity than CdCl2 did. A strong positive correlation (R2 = 0.99) between menadione concentration and fluorescence intensity was observed. The positive correlation between AAPH concentration and fluorescence intensity was not as strong as in the case of menadione (R2 = 0.81). Menadione induced a stronger oxidative stress than similar concentration of AAPH. The addition of 100 μM ascorbate to L. minor treated with 50 μM menadione significantly reduced the fluorescence intensity increase. A linear trend of the fluorescence increase was observed in all treatments, indicating that chemical‐induced oxidative stress is a gradual process and that the applied concentrations of the chemicals caused a constant increased production of ROS with different intensities, depending on the treatment. This is the combined result of a gradual diminishing of antioxidant reserves and accumulating oxidative damage. The observed rates of ROS production were slower than those in the studies using cell cultures. © 2009 Wiley Periodicals, Inc. Environ Toxicol 25: 573–580, 2010.
Genetic association and gene-gene interaction analyses in African American dialysis patients with nondiabetic nephropathy.

BACKGROUND African Americans have increased susceptibility to nondiabetic nephropathy relative to European Americans. STUDY DESIGN Follow-up of a pooled genome-wide association study (GWAS) in African American dialysis patients with nondiabetic nephropathy; novel gene-gene interaction analyses. SETTING & PARTICIPANTS Wake Forest sample: 962 African American nondiabetic nephropathy cases, 931 non-nephropathy controls. Replication sample: 668 Family Investigation of Nephropathy and Diabetes (FIND) African American nondiabetic nephropathy cases, 804 non-nephropathy controls. PREDICTORS Individual genotyping of top 1,420 pooled GWAS-associated single-nucleotide polymorphisms (SNPs) and 54 SNPs in 6 nephropathy susceptibility genes. OUTCOMES APOL1 genetic association and additional candidate susceptibility loci interacting with or independently from APOL1. RESULTS The strongest GWAS associations included 2 noncoding APOL1 SNPs, rs2239785 (OR, 0.33; dominant; P = 5.9 × 10(-24)) and rs136148 (OR, 0.54; additive; P = 1.1 × 10(-7)) with replication in FIND (P = 5.0 × 10(-21) and 1.9 × 10(-05), respectively). rs2239785 remained associated significantly after controlling for the APOL1 G1 and G2 coding variants. Additional top hits included a CFH SNP (OR from meta-analysis in the 3,367 African American cases and controls, 0.81; additive; P = 6.8 × 10(-4)). The 1,420 SNPs were tested for interaction with APOL1 G1 and G2 variants. Several interactive SNPs were detected; the most significant was rs16854341 in the podocin gene (NPHS2; P = 0.0001). LIMITATIONS Nonpooled GWASs have not been performed in African American patients with nondiabetic nephropathy. CONCLUSIONS This follow-up of a pooled GWAS provides additional and independent evidence that APOL1 variants contribute to nondiabetic nephropathy in African Americans and identified additional associated and interactive nondiabetic nephropathy susceptibility genes.
Is DBS-STN appropriate to treat severe Parkinson disease in an elderly population?

Objective: To assess the role of age in the results of bilateral deep brain stimulation in the subthalamic nucleus (DBS-STN), we carried out a study of two groups of patients regarding age at time of surgery. Methods: We compared, up to 2 years after surgery, the clinical effects, safety, and quality of life in parkinsonian patients younger than 65 years old (young patients) vs parkinsonian patients 65 years old or older (old patients). Results: The mean age was 57.4 ± 4.9 years (n = 53) in young patients and 68.8 ± 2.8 years (n = 34) in old patients. A dramatic improvement in motor complications was equally observed in both groups of patients. There was no significant difference between the groups regarding acute effects of DBS-STN on the motor score of the Unified Parkinson's Disease Rating Scale part III (UPDRS III). Time course evolution of UPDRS the motor score (p < 0.0001) and axial score (p = 0.0001) assessed postoperatively in “on” medication and “on” stimulation conditions appeared worse in old patients as compared to young patients. Improvement in the Schwab and England Scale score was better in young patients in “on” (p < 0.0003) and “off” state (p < 0.001). Quality of life assessed with the 39-item Parkinson's Disease Questionnaire showed an improvement in subscales evaluating mobility (p < 0.0001), activities of daily life (p < 0.0001), emotion and stigma (p = 0.0004), cognition (p < 0.0074), and communication (p = 0.0029) in young patients as compared to old patients. Side effects were similar in the two groups. Conclusions: Although deep brain stimulation in the subthalamic nucleus reduces motor complications equally in both groups of patients, postoperative quality of life improved only in young patients.
Increasing spectrum capacity for ad hoc networks using cognitive radios: an analytical model

In this letter, an analytical model to evaluate the performance of ad hoc devices equipped with cognitive radio capabilities, is investigated. By applying cognitive radio technology, the ad hoc devices will utilize the unused spectrum of the existing legacy systems in an opportunistic manner in addition to using the unlicensed spectrum. Therefore, the network throughput will be increased. The results show that the performance is improved in terms of blocking and dropping probabilities.
Profile of Cognitive Impairment in Parkinson's Disease

Cognitive impairment (CI) is a common nonmotor complication of Parkinson's disease (PD), and is associated with significant disability for patients and burden for caregivers. Similar to motor symptoms, the characteristics of CI in PD can be quite variable, both in terms of what cognitive domains are impaired, and the timing of onset and rate of progression. This review will examine the profile of cognitive domain impairments observed in PD, with a focus on early CI (without dementia). We will also discuss possible relationships between specific cognitive domain impairments in PD and pathological processes such as Lewy‐related pathology and Alzheimer's disease. It is our hypothesis that the specific characteristics of CI observed in individual PD patients provide clues to the underlying pathological processes, and that understanding the biological basis of this clinical phenomenon will assist in directing disease‐specific treatments. Given the high lifetime risk for CI in PD, it is imperative that we improve our understanding and treatments for this common and disabling problem in PD.
The newly identified yeast GRD genes are required for retention of late-Golgi membrane proteins

Processing of A-ALP, a late-Golgi membrane protein constructed by fusing the cytosolic domain of dipeptidyl aminopeptidase A to the transmembrane and lumenal domains of alkaline phosphatase (ALP), serves as a convenient assay for loss of retention of late-Golgi membrane proteins in Saccharomyces cerevisiae. In this study, a large group of novel grd (for Golgi retention defective) yeast mutants, representing 18 complementation groups, were identified on the basis of their mislocalization of A-ALP to the vacuole, where it was proteolytically processed and thus became enzymatically activated. All of the grd mutants exhibited significant mislocalization of A-ALP, as measured by determining the kinetics of A-ALP processing and by analyzing its