Miracle-dz/UniFAR-FTUs huggingface dataset:
Human U4/U6.U5 and U4atac/U6atac.U5 Tri-snRNPs Exhibit Similar Protein Compositions

ABSTRACT In the U12-dependent spliceosome, the U4atac/U6atac snRNP represents the functional analogue of the major U4/U6 snRNP. Little information is available presently regarding the protein composition of the former snRNP and its association with other snRNPs. In this report we show that human U4atac/U6atac di-snRNPs associate with U5 snRNPs to form a 25S U4atac/U6atac.U5 trimeric particle. Comparative analysis of minor and major tri-snRNPs by using immunoprecipitation experiments revealed that their protein compositions are very similar, if not identical. Not only U5-specific proteins but, surprisingly, all tested U4/U6- and major tri-snRNP-specific proteins were detected in the minor tri-snRNP complex. Significantly, the major tri-snRNP-specific proteins 65K and 110K, which are required for integration of the major tri-snRNP into the U2-dependent spliceosome, were among those proteins detected in the minor tri-snRNP, raising an interesting question as to how the specificity of addition of tri-snRNP to the corresponding spliceosome is maintained. Moreover, immunodepletion studies demonstrated that the U4/U6-specific 61K protein, which is involved in the formation of major tri-snRNPs, is essential for the association of the U4atac/U6atac di-snRNP with U5 to form the U4atac/U6atac.U5 tri-snRNP. Subsequent immunoprecipitation studies demonstrated that those proteins detected in the minor tri-snRNP complex are also incorporated into U12-dependent spliceosomes. This remarkable conservation of polypeptides between minor and major spliceosomes, coupled with the absence of significant sequence similarity between the functionally analogous snRNAs, supports an evolutionary model in which most major and minor spliceosomal proteins, but not snRNAs, are derived from a common ancestor.
Stem Cells of the Breast and Cancer Therapy

Breast cancer remains a significant public health problem despite advances in the understanding of the molecular and cellular events that underlie the disease. Crucial pathways regulating the cell cycle, proliferation and survival of breast cancer cells have been investigated and aberrant components of these pathways have been exploited as new drug targets. However, the mortality from breast cancer is only slowly declining. Recently, a model has been proposed that might explain the heterogeneous biological features of breast cancer cell populations and their differential response to therapeutic agents, which has interesting implications for further progress in therapy. This model links the emergence of breast cancer cells to stem cells and progenitors, an observation originally made in other cancer entities. It hypothesizes that the tumors originate from a small population of undifferentiated cells. These cells can undergo self-renewal and are able to generate a large number of partially differentiated cells, which constitute the bulk of the tumor. These cancer stem cells resemble adult stem and progenitor cells found in the normal breast, but are deregulated in their patterns of proliferation and differentiation. They could originate from normal stem cells or from more differentiated progenitors and lose their normal growth restraints through a series of oncogenic mutations that deregulate a small number of central signaling pathways. If breast cancer really is a stem and progenitor cell disease, this will have important implications for the understanding of the emergence of cancer cells. A combination of the cell-type of origin, stem cells, early or late progenitors and the particular oncogenic mutations acquired could provide a new classification of the different types of breast cancer. These parameters might determine the mechanisms of cancer progression and the responsiveness of patients to drug treatment. Stem cell-specific features could possibly be exploited as innovative drug targets.
The ChEMBL bioactivity database: an update

ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 Nucleic Acids Research Database Issue. Since then, a variety of new data sources and improvements in functionality have contributed to the growth and utility of the resource. In particular, more comprehensive tracking of compounds from research stages through clinical development to market is provided through the inclusion of data from United States Adopted Name applications; a new richer data model for representing drug targets has been developed; and a number of methods have been put in place to allow users to more easily identify reliable data. Finally, access to ChEMBL is now available via a new Resource Description Framework format, in addition to the web-based interface, data downloads and web services.
Mechanosensory Neurons With Bend- and Osmo-sensitivity in Mouthpart Setae From the Spiny Lobster Panulirus argus

The mouthparts of the spiny lobster Panulirus argus hold primarily two types of setae—simple setae and cuspidate setae. Mechanosensory neurons from these setae were examined by electrophysiological recordings. The population of simple setae contained two types of mechanosensory neurons: displacement-sensitive neurons, which responded to deflection at the setal base; and bend-sensitive neurons, which responded to bending of the setal shaft. Displacement-sensitive neurons, in general, responded phasically and only during actual displacement. Typically, their response changed with alteration of the direction, amplitude, and velocity/acceleration of the mechanical stimulus. Bend-sensitive neurons, in general, responded phaso-tonically and carried information on the direction and region of bending. This is the first experimental demonstration of bend sensitivity for arthropod setae. Cuspidate setae contain highly sensitive mechanosensory neurons; however, due to the rigid nature of these setae, whether they were bend sensitive or displacement sensitive could not be determined, and they were thus called “tactile neurons. ” Bend-sensitive neurons, but not displacement-sensitive neurons or tactile neurons, showed graded responses to changes in osmolarity. The osmosensitivity of these neurons could mediate behavioral responses to changes in the osmolarity of seawater or food.
A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis

BACKGROUND The pharmacological inhibition of exocrine pancreatic secretion with the somatostatin analogue octreotide has been advocated as a specific treatment of acute pancreatitis. AIM To investigate the efficacy of octreotide in acute pancreatitis in a randomised, placebo controlled trial. METHODS 302 patients from 32 hospitals, fulfilling the criteria for moderate to severe acute pancreatitis within 96 hours of the onset of symptoms, were randomly assigned to one of three treatment groups: group P (n=103) received placebo, while groups O1 (n=98) and O2 (n=101) received 100 and 200 μg of octreotide, respectively, by subcutaneous injection three times daily for seven days. The primary outcome variable was a score composed of mortality and 15 typical complications of acute pancreatitis. RESULTS The three groups were well matched with respect to pretreatment characteristics. An intent to treat analysis of all 302 patients revealed no significant differences among treatment groups with respect to mortality (P: 16%; O1: 15%; O2: 12%), the rate of newly developed complications, the duration of pain, surgical interventions, or the length of the hospital stay. A valid for efficacy analysis (251 patients) also revealed no significant differences. CONCLUSIONS This trial shows no benefit of octreotide in the treatment of acute pancreatitis.
The transmission of spirochaeta duttoni Novy & Knapp by Pediculus humanus corporis de Geer

1. Cyclical development of Spirochaeta duttoni in lice was observed in seven experiments. In the last four, the same strain was transmitted through four successive batches. 2. The resultant infections in animals behaved exactly like S. duttoni even after the fourth transmission through the abnormal host.
Automated population of causal models for improved software risk assessment

Recent work in applying causal modeling (Bayesian networks) to software engineering has resulted in improved decision support systems for software project managers. Once the causal models are built there are commercial tools that can run them. However, data to populate the models is typically entered manually and this is an impediment to their more widespread use. Hence, here we present a prototype tool for automatically extracting a range of relevant software metrics from popular project management and CASE tools. This information is used to populate Bayesian networks with the aim of providing better real world predictions of the risks associated with software costs, timescales and reliability.
Fetal pulse oximetry for fetal assessment in labour.

BACKGROUND Fetal pulse oximetry (FPO) may contribute to the evaluation of fetal well-being during labour. OBJECTIVES To compare the effectiveness and safety of FPO with conventional surveillance techniques, using the results of randomised controlled trials. SEARCH STRATEGY We searched the Cochrane Pregnancy and Childbirth Group trials register (31 July 2004) and conducted a systematic literature search of MEDLINE (1994 to July 2004), EMBASE (1994 to July 2004) and Current Contents (1994 to July 2004). SELECTION CRITERIA All published and unpublished randomised controlled trials (RCTs) that compared maternal and fetal/neonatal/infant outcomes when FPO was used in labour, with or without concurrent use of conventional fetal surveillance, compared with using cardiotocography (CTG) alone. DATA COLLECTION AND ANALYSIS Two independent reviewers performed data extraction. Analyses were performed on an intention-to-treat basis. We sought additional information from the investigators of the one reported trial. MAIN RESULTS One published RCT (comparing FPO and CTG with CTG alone) was included; and two ongoing RCTs were identified. The single included RCT reported on 1010 cases. Unpublished pilot data were available for some outcomes to give a total of 1190 cases. There was no difference in the overall caesarean section rate between the two groups (relative risk (RR) 1.12, 95% confidence interval (CI) 0.91 to 1.37). There were less caesarean sections for nonreassuring fetal status in the FPO plus CTG group compared with the CTG only group (RR 0.45, 95% CI 0.28 to 0.72). The only reported neonatal seizure occurred in the CTG only group (RR 0.29 95% CI 0.01 to 7.08). Use of FPO with CTG decreased operative delivery (caesarean section, forceps, vacuum) for nonreassuring fetal status (RR 0.71, 95% CI 0.55 to 0.93) compared with CTG alone. No differences were seen for overall operative deliveries, endometritis, intrapartum or postpartum haemorrhage, uterine rupture, low Apgar scores, umbilical arterial pH or base excess, admission to the neonatal intensive care unit or fetal/neonatal death. REVIEWERS' CONCLUSIONS The one published RCT reported that FPO decreased the caesarean section rate and operative delivery rates for nonreassuring fetal status, without adversely affecting maternal or fetal/neonatal outcomes. However, no difference was seen in the overall caesarean section (CS) or operative delivery rates because more CS were performed for dystocia in the FPO group. Further RCTs may address dystocia in labours monitored with FPO, maternal satisfaction with fetal monitoring and labour, long-term neurodevelopmental outcome of infants who exhibited nonreassuring fetal status in labour and costs of FPO.
Detection of Small Hypervascular Hepatocellular Carcinomas in Cirrhotic Patients: Comparison of Superparamagnetic Iron Oxide-Enhanced MR Imaging with Dual-Phase Spiral CT

Objective To compare the performance of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging at 1.5T and dual-phase spiral computed tomography (CT) for the depiction of small hypervascular hepatocellular carcinomas (HCCs). Materials and Methods Forty-three patients with 70 small nodular HCCs (5-20 mm; mean, 13.7 mm) were examined. Diagnosis was based on the results of surgical biopsy in 22 patients and by the combined assessment of MR imaging, lipiodol CT, alpha feto-protein levels, and angiographic findings in 21. MR imaging consisted of respiratory-triggered turbo spin-echo T2-weighted imaging, T1-weighted fast low-angle shot, and T2*-weighted fast imaging with steady-state precession imaging before and after SPIO enhancement. CT imaging was performed with 5-mm collimation and 1:1.4 pitch, and began 30 and 65 secs after the injection of 150 mL of contrast medium at a rate of 3 mL/sec. Two blinded observers reviewed all images independently on a segment-by-segment basis. Diagnostic accuracy was evaluated using receiver operating characteristics (ROC) analysis. Results The mean areas (Az) under the ROC curves were 0.85 for SPIO-enhanced MR imaging and 0.79 for dual-phase spiral CT (p < .05). The mean sensitivity of SPIO-enhanced MR imaging was significantly higher than that of CT (p < .05), i.e. 70.6% for MR imaging and 58.1% for CT. MR imaging had higher false-positive rates than dual-phase spiral CT, but the difference was not statistically significant (3.7% vs 3.3%) (p > .05). Conclusion SPIO-enhanced MR imaging is more sensitive than dual-phase spiral CT for the depiction of small hypervascular hepatocellular carcinomas.
Individual Differences and Their Impact on the Safety and the Efficiency of Human-Wheelchair Systems

Objective: The extent to which individual differences in fine motor abilities affect indoor safety and efficiency of human-wheelchair systems was examined. Background: To reduce the currently large number of indoor wheelchair accidents, assistance systems with a high level of automation were developed. It was proposed to adapt the wheelchair’s level of automation to the user’s ability to steer the device to avoid drawbacks of highly automated wheelchairs. The state of the art, however, lacks an empirical identification of those abilities. Method: A study with 23 participants is described. The participants drove through various sections of a course with a powered wheelchair. Repeatedly measured criteria were safety (numbers of collisions) and efficiency (times required for reaching goals). As covariates, the participants’ fine motor abilities were assessed. Results: A random coefficient modeling approach was conducted to analyze the data, which were available on two levels as course sections were nested within participants. The participants’ aiming, precision, and arm–hand speed contributed significantly to both criteria: Participants with lower fine motor abilities had more collisions and required more time for reaching goals. Conclusion: Adapting the wheelchair’s level of automation to these fine motor abilities can improve indoor safety and efficiency. In addition, the results highlight the need to further examine the impact of individual differences on the design of automation features for powered wheelchairs as well as other applications of automation. Application: The results facilitate the improvement of current wheelchair technology.
Productive infection of primary cultures of endothelial cells from the cat liver sinusoid with the feline immunodeficiency virus

Given the similarities between the two viruses, the feline immunodeficiency virus (FIV) is becoming an interesting animal model for human immunodeficiency virus (HIV) studies. To explore the still controversial role of the liver in the development of HIV infection, sinusoidal endothelial cells (SEC) were isolated, and primary cultures were infected with the FIV Villefranche IFFA strain. The isolated cells were characterized by their typical fenestrations, the presence of von Willebrand factor (vWf), and their ability to take up acetylated low‐density lipoproteins and denatured collagen. Two weeks after infection, significant amounts of FIV p24 antigen were detected by immunofluorescence in both multinucleated giant and single cells and by enzyme‐linked immunosorbent assay in the culture medium. High amounts of viral particles were observed together with different steps of budding at the plasma membrane or at the membrane of intracytoplasmic vacuoles. The released viral particles were shown to be infectious for a permissive cell line. During the first 3 weeks of infection, the only cytopathic effect of FIV was syncytia formation. No noticeable impairment of the pattern of fenestrations and the modulation of their number by a cytoskeleton‐mediated process occurred. The productive infection of SEC may contribute to the progression of the infection.
Flexible, Task-Dependent Use of Sensory Feedback to Control Hand Movements

We tested whether changing accuracy demands for simple pointing movements leads humans to adjust the feedback control laws that map sensory signals from the moving hand to motor commands. Subjects made repeated pointing movements in a virtual environment to touch a button whose shape varied randomly from trial to trial—between squares, rectangles oriented perpendicular to the movement path, and rectangles oriented parallel to the movement path. Subjects performed the task on a horizontal table but saw the target configuration and a virtual rendering of their pointing finger through a mirror mounted between a monitor and the table. On one-third of trials, the position of the virtual finger was perturbed by ±1 cm either in the movement direction or perpendicular to the movement direction when the finger passed behind an occluder. Subjects corrected quickly for the perturbations despite not consciously noticing them; however, they corrected almost twice as much for perturbations aligned with the narrow dimension of a target than for perturbations aligned with the long dimension. These changes in apparent feedback gain appeared in the kinematic trajectories soon after the time of the perturbations, indicating that they reflect differences in the feedback control law used throughout the duration of movements. The results indicate that the brain adjusts its feedback control law for individual movements “on demand” to fit task demands. Simulations of optimal control laws for a two-joint arm show that accuracy demands alone, coupled with signal-dependent noise, lead to qualitatively the same behavior.
Infinitely Dilute Partial Molar Properties of Proteins from Computer Simulation

A detailed understanding of temperature and pressure effects on an infinitely dilute protein’s conformational equilibrium requires knowledge of the corresponding infinitely dilute partial molar properties. Established molecular dynamics methodologies generally have not provided a way to calculate these properties without either a loss of thermodynamic rigor, the introduction of nonunique parameters, or a loss of information about which solute conformations specifically contributed to the output values. Here we implement a simple method that is thermodynamically rigorous and possesses none of the above disadvantages, and we report on the method’s feasibility and computational demands. We calculate infinitely dilute partial molar properties for two proteins and attempt to distinguish the thermodynamic differences between a native and a denatured conformation of a designed miniprotein. We conclude that simple ensemble average properties can be calculated with very reasonable amounts of computational power. In contrast, properties corresponding to fluctuating quantities are computationally demanding to calculate precisely, although they can be obtained more easily by following the temperature and/or pressure dependence of the corresponding ensemble averages.
ÖĞRENİLMİŞ GÜÇLÜLÜK, KIDEM VE MEDENİ DURUMUN DUYGUSAL TÜKENMEDEKİ ROLÜ: KAYNAKLARIN KORUNMASI TEORİSİ KAPSAMINDA BİR ANALİZ

Bu arastirmanin amaci ogretmenlerin ogrenilmis gucluluk duzeyleri, medeni durumlari ve kidemlerinin duygusal tukenme duzeylerine etkilerini analiz etmektir. Arastirmaya Yalova’da calisan 350 ogretmen katilmis, olcum araci olarak Rosenbaum Ogrenilmis Gucluluk Olcegi ve Maslach Tukenmislik Olcegi-Duygusal Tukenme alt olcegi kullanilmistir. Elde edilen sonuclara gore ogrenilmis gucluluk, ogretmenlerin duygusal tukenme duzeylerini etkilemektedir. Bunun yani sira ogretmenlerin mesleki kidemleri artikca duygusal tukenme duzeyi de artmaktadir. Son olarak bu arastirmada ogretmenlerin medeni durumlari ile duygusal tukenme duzeyleri arasinda anlamli bir iliski bulunamamistir. Bu arastirmada ogretmenlerin ogrenilmis gucluluk duzeylerinin duygusal tukenme duzeylerine etkisi Kaynaklarin Korunmasi Teorisi kapsaminda ele alinmis ve konuya ampirik destek saglanmistir.
Use of complementary and alternative medicine for weight control in the United States.

OBJECTIVES The purpose was to assess the prevalence and correlates of complementary and alternative medicine use for weight control. DESIGN A list-assisted random-digit-dialed telephone survey of adults was conducted in the fall of 2002 (n = 11,211). The focus of the study was complementary and alternative medicine (CAM) use, other than dietary supplements, in the previous 12 months. SETTINGS/LOCATION The sample of respondents was drawn from the total noninstitutionalized U.S. adult population residing in telephone-equipped locations. SUBJECTS The sampling procedures were designed to obtain adequate representation of Hispanic and non-Hispanic black respondents. Data from the total sample of 11,211 were weighted to achieve an estimate of the U.S. population. Analyses focused on 372 people who had used CAM within the previous 12 months. RESULTS Of the total, 3.3% (n = 372) had used a CAM therapy in the previous 12 months. Higher adjusted odds ratios for CAM use were found among respondents who were exercising for weight control; using a lower carbohydrate, higher protein diet; using a nonprescription weight-loss product(s); overweight; physically active; and not satisfied with one's body (adjusted for age, race, gender, education, and city size). The most often used therapies were yoga (57.4%), meditation (8.2%), acupuncture (7.7%), massage (7.5%), and Eastern martial arts (5.9%). CAM users used CAM therapies on their own (62.6%), in a group setting (26.8%) or with a CAM practitioner (10.6%). CONCLUSIONS The use of CAM therapies other than dietary supplements for weight loss was relatively low. The most popular therapy was yoga, and the majority of CAM users used CAM therapies on their own. Persons who had used other weight loss methods had greater odds for using CAM in the previous 12 months, suggesting that CAM use is often added to other weight-loss strategies.
Blind reverberation time estimation based on Laplace distribution

We propose an algorithm for the estimation of reverberation time (RT) from the reverberant speech signal by using a maximum likelihood (ML) estimator. Based on the analysis of an existing RT estimation method, which models the reverberation decay as a Gaussian random process modulated by a deterministic envelope, a Laplacian distribution based decay model is proposed in which an efficient procedure for locating free decay from reverberant speech is also incorporated. Then the RT is estimated from the free decays by the ML estimator. The method was motivated by our observation that the distribution pattern for temporal decay of the reverberant hand clap is much closer to the Laplace distribution. The estimation accuracy of the proposed method is evaluated using the experimental results and is in good agreement with the RT values measured from room impulse responses.