Miracle-dz/UniFAR-FTUs huggingface dataset:
Algorithms for protein comparative modelling and some evolutionary implications

Protein comparative modelling (CM) is a predictive technique to build an atomic model for a polypeptide chain, based on the experimentally determined structures of related proteins (templates). It is widely used in Structural Biology, with applications ranging from mutation analysis, protein and drug design to function prediction and analysis, particularly when there are no experimental structures of the protein of interest. Therefore, CM is an important tool to process the amount of data generated by genomic projects. Several problems affect the performance of CM and therefore solutions for them are needed to increase its applicability. In this work different algorithms and approaches were tested with this aim, particularly to help in template selection and alignment, and some useful insights were obtained. First, this work describes the development of DomainFishing, a tool to split protein sequences into functionally and structurally defined domains and to align each of them to the available templates. The performance of our approach is benchmarked and some problems and possible developments are identified. When comparing different alignment procedures none of them is found to be consistently superior, suggesting that a combination of several could be an advantage. Driven by these ideas and the fact that selecting templates can be a difficult problem, a new modelling approach is designed and tested. This algorithm uses crossover, mutation and selection within populations of protein models generated from different templates and alignments to obtain recombinant structures optimised in terms of fitness. Despite our simple definition of fitness, the procedure is shown to be robust to some alignment errors while simplifying the task of selecting templates, making it a good candidate for automatic building of reliable protein models. In-house benchmarks of the method show its strengths and limitations. The method was also benchmarked during the fifth Critical Assessment of techniques for protein Structure Prediction (CASP5), in which its perfomance was encouraging both for comparative modelling and fold recognition targets, among the top 20 predictors. Finally, we present some data to support a possible evolutionary feedback mechanism between protein structure and gene structure, using human and murine genomic data, structural data from the Protein Data Bank and the protein recombination methodology. This may have some implications for understanding protein evolution and protein design, which are discussed.
Negative and Positive Visual Hypnotic Hallucinations: Attending Inside and Out

Hypnotic perceptual alteration affects brain function. Those hypnotic instructions that reduce perception by creating an illusory obstruction to it reduce brain response to perception in the cognate sensory cortex, as measured by event-related potential (ERP) amplitude and regional blood flow (PET). Those hypnotic instructions that affect the subject’s reaction to perception activate the anterior attentional system, especially the anterior cingulate cortex in PET studies. Hypnosis involves activation without arousal and may be particularly mediated via dopaminergic pathways. Hypnotic alteration of perception is accompanied by measurable changes in both perceptual and attentional function of those specific regions of the brain that process these activities, modulated by the nature of the specific hypnotic instruction. Positive obstructive hallucinations seem to allow for a hypnotic focus inward, activating the functioning of attentional neural systems and reducing perceptual ones.
Surgical Management of Subungual Melanoma: Mayo Clinic Experience of 124 Cases

BackgroundOptimal surgical management of subungual malignant melanoma (SMM) has been debated. MethodsOur tumor registry was reviewed for surgically treated cases of SMM from 1914 to 2010. Resection levels were compared with outcome. ResultsDuring a 96-year period, 124 cases of SMM were identified (65 men and 59 women). Mean age at diagnosis was 58 years. Mean length of symptoms before diagnosis was 2.2 years. Lesions occurred on the hand (n = 79) and foot (n = 45). The thumb (33.8%) and hallux (25.0%) were affected most. At diagnosis, most had local (83.9%) and regional nodal involvement (12.9%). Mean follow-up was 9.4 years.Mean Breslow depth was 3.1 mm. Amputations were most commonly performed on the thumb at the proximal phalanx or metacarpophalangeal joint (43.9%), and on the hallux at the proximal phalanx or metatarsophalangeal joint (69.0%). Disease progression occurred in 61 (49.2%) patients, and most commonly occurred as regional nodal (62.3%) and distant metastasis (42.6%). Disease progression–free survival rates at 5, 10, and 15 years were 57.1%, 49.9%, and 47.0%, respectively. Fifty-three patients died of melanoma-related causes. Disease-specific survival rates at 5, 10, and 15 years after surgery were 59.3%, 49.3%, and 45.2%. Overall survival rates at 5, 10, and 15 years were 60.5%, 43.8%, and 33.1%. In 116 patients who underwent amputation, resection level outcome analysis with univariate and multivariate analysis adjusting for tumor depth and clinical involvement demonstrated that level of resection was not significantly associated with progression-free, overall, or disease-specific survival. ConclusionsDiagnosis of subungual melanoma is often delayed and carries a poor prognosis. Conservative resections are warranted as resection level does not influence outcome when histologically free margins are obtained. Amputation through the proximal phalanx or the metatarsophalangeal joint is required in the hallux and toes. Fingers require resection through the distal interphalangeal joint. For the thumb, although resection through the interphalangeal joint proved adequate, secondary efforts should be directed toward maximizing function and quality of life. Function-preserving resections in the thumb with nail removal, partial distal phalanx resection, and volar flap reconstruction are easily performed and preserve length, maximize joint and sensory function, and improve cosmesis.
Glutamatergic fine tuning with ADX-10059: a novel therapeutic approach for migraine?

Importance of the field: Migraine is an episodic, substantially inherited brain disorder affecting 15% of adults in Western Europe and North America, and is one of the commonest reasons for patients to see their physicians. While the World Health Organization considers that severe migraine can be as disabling as quadriplegia, unfortunately the condition remains undertreated. Until the 1990s, specific migraine therapies were limited to ergot derivatives. Areas covered in this review: The triptans, serotonin 5-HT1B/1D receptor agonists, revolutionized the acute management of migraine patients. However, although the triptans are generally effective and safe, not all patients can take them and many do not respond especially to oral therapies. Recently, progress has been made on the therapeutic front, particularly with new acute treatments. This review will focus on the therapeutic potential of ADX10059, a metabotropic glutamate receptor 5, negative allosteric modulator (mGluR5 NAM), in migraine. Data from a proof-of-concept study in episodic migraineurs demonstrated a significant improvement following acute treatment. A large European multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study is currently investigating the efficacy, safety and tolerability of the compound for migraine prevention. What the reader will gain: The reader will have the basic principles of migraine management and the potential for glutamate-targeted approaches. Take home message: Targeting glutamatergic transmission in migraine may provide a novel preventive therapy that is effective and well-tolerated.
Design of the Basic Building Block of a High-Speed Flexible and Modular Pipelined ADC

This paper presents the design procedure and performance of the basic building block of a flexible/modular pipelined ADC. We report the advantages of adopting a flexible ADC approach (Zanikopoulos et al., 2005) and we comment on the performance range that can be covered by this. Targeting a sampling frequency range from 50MS/s to 500MS/s and an accuracy range from 8b to 12b, we present and justify our design decisions leading to the implementation of the adjustable basic building block. The principle idea is the use of circuitries that can fully benefit from the speed-power consumption trade-off, while maintaining the desired accuracy. We employ dynamic circuitry and furthermore propose a fully adjustable open-loop amplifier suitable for flexible ADC realizations. Finally, we present the accuracy results and power consumption estimations along with the size of the building block implemented in a CMOS 0.18mum technology.
Empirical Study on the Career Development Stages of Chinese Employee

With consideration of Chinese traditional culture and social context and by conducting a research on the life cycle theories, this paper first finds the turning points in Chinese employee career which is validated by the statistical analysis based on the career development theories. Besides the two conclusions, this paper also analyzes how the education system affects the employee's career development. With these achievements, this paper builds a development model of Chinese employee career and divides their career into four stages: establishing stage, developing stage, crisis stage and maintaining stage, characteristics of which are respectively discussed. An empirical research is then conducted to prove that the division of the Chinese employee career is reasonable.
Data journals: A survey

Data occupy a key role in our information society. However, although the amount of published data continues to grow and terms such as data deluge and big data today characterize numerous (research) initiatives, much work is still needed in the direction of publishing data in order to make them effectively discoverable, available, and reusable by others. Several barriers hinder data publishing, from lack of attribution and rewards, vague citation practices, and quality issues to a rather general lack of a data‐sharing culture. Lately, data journals have overcome some of these barriers. In this study of more than 100 currently existing data journals, we describe the approaches they promote for data set description, availability, citation, quality, and open access. We close by identifying ways to expand and strengthen the data journals approach as a means to promote data set access and exploitation.
Cardiovascular autonomic function in poststroke patients

Background: Autonomic dysregulation is frequent in acute ischemic stroke. Several studies concluded that imbalance between sympathetic and parasympathetic cardiovascular function predisposes to malignant cardiac arrhythmia. However, there are few data on cardiovascular autonomic function in post–acute stroke patients. Objective: To study cardiovascular autonomic function 18 to 43 months after lacunar stroke. Patients and Methods: We continuously monitored R-R intervals (RRint), mean blood pressure (BPmean), and respiration in 15 patients (8 women, aged 43 to 73 years) after right-sided stroke, in 13 patients (7 women, aged 50 to 75 years) after left-sided stroke, and in 21 age- and sex-matched controls at rest. We used autoregressive spectral analysis to assess sympathetic and parasympathetic modulation as powers of RRint and BPmean oscillations in the low-frequency (LF: 0.04 to 0.15 Hz) and high-frequency bands (HF: 0.15 to 0.5 Hz). Results: Mean values of RRint, BPmean, and respiratory frequency did not differ between patients after right- or left-sided stroke and controls (p > 0.05). Patients after right-sided stroke showed a trend toward elevated LF power of RRint as compared with patients after left-sided stroke and controls (p < 0.10). HF powers of RRint were reduced in patients after right- and left-sided stroke as compared with controls (p < 0.05). LF/HF ratio of RRint was elevated in patients after right-sided stroke as compared with patients after left-sided stroke and controls (p < 0.05). Conclusion: Irrespective of the side of the ischemia, post–acute stroke patients showed a parasympathetic cardiac deficit. Additionally, sympathetic cardiovascular modulation was increased in patients after right-sided stroke. Post–acute stroke patients might be at an increased risk for cardiac arrhythmia after unopposed sympathetic stimulation.
Tilburg University Political diversity in social and personality psychology

A lack of political diversity in psychology is said to lead to a number of pernicious outcomes, including biased research and active discrimination against conservatives. We surveyed a large number (combined N = 800) of social and personality psychologists and discovered several interesting facts. First, although only 6% described themselves as conservative “overall,” there was more diversity of political opinion on economic issues and foreign policy. Second, respondents significantly underestimated the proportion of conservatives among their colleagues. Third, conservatives fear negative consequences of revealing their political beliefs to their colleagues. Finally, they are right to do so: In decisions ranging from paper reviews to hiring, many social and personality psychologists said that they would discriminate against openly conservative colleagues. The more liberal respondents were, the more they said they would discriminate.
Epidemiology of playground equipment injuries resulting in hospitalization

Abstract Preparation of the New Zealand Playground Standard was seriously hampered by a lack of published information on the incidence, nature, and circumstances of playground equipment‐related injuries. The present study was aimed at redressing this lack of information. Examination of all discharges from New Zealand public hospitals for 1984 identified 1125 children less than 15 years of age who had been admitted for the treatment of playground equipment‐related injury. This gave an incidence rate of 137/100000 children per year. The mean age was 7.2 years. The commonest injury was fracture of the upper limb (48%), followed by intracranial injury (26%). One‐third occurred at school, climbing apparatus (40%) was most often involved, and the great majority involved falls (93%). With this study it has been possible for the first time in any country to report an incidence rate for all causes of playground equipment‐related injuries resulting in hospitalization, based on data for an entire population. The findings support the emphasis placed on falls in the Standard.
CD133 marks a stem cell population that drives human primary myelofibrosis

Primary myelofibrosis is a myeloproliferative neoplasm characterized by bone marrow fibrosis, megakaryocyte atypia, extramedullary hematopoiesis, and transformation to acute myeloid leukemia. To date the stem cell that undergoes the spatial and temporal chain of events during the development of this disease has not been identified. Here we describe a CD133+ stem cell population that drives the pathogenesis of primary myelofibrosis. Patient-derived circulating CD133+ but not CD34+CD133− cells, with a variable burden for JAK2V617F mutation, had multipotent cloning capacity in vitro. CD133+ cells engrafted for up to 10 months in immunocompromised mice and differentiated into JAK2-V617F+ myeloid but not lymphoid progenitors. We observed the persistence of human, atypical JAK2-V617F+ megakaryocytes, the initiation of a prefibrotic state, bone marrow/splenic fibrosis and transition to acute myeloid leukemia. Leukemic cells arose from a subset of CD133+ cells harboring EZH2D265H but lacking a secondary JAK2V617F mutation, consistent with the hypothesis that deregulation of EZH2 activity drives clonal growth and increases the risk of acute myeloid leukemia. This is the first characterization of a patient-derived stem cell population that drives disease resembling both chronic and acute phases of primary myelofibrosis in mice. These results reveal the importance of the CD133 antigen in deciphering the neoplastic clone in primary myelofibrosis and indicate a new therapeutic target for myeloproliferative neoplasms.
Extracellular nucleotides, cartilage stress, and calcium crystal formation

&NA; Nucleotides are released by chondrocytes at rest and in response to mechanical stimulation. Extracellular nucleotides are metabolized by a variety of ectoenzymes, producing free phosphate (Pi) or pyrophosphate (PPi) and promoting matrix mineralization. Ectoenzymes are differentially localized in cartilage and may be co‐released with nucleotides during mechanical stimulation. Extracellular nucleotides can also serve as substrates and/or modulators of enzymes such as tissue transglutaminase and ecto‐protein kinases that modify matrix proteins and regulate crystal deposition or growth. Understanding the evolution of osteoarthritis and calcium crystal deposition diseases will require clearer knowledge of the functions of nucleotides and ectoenzymes in the cartilage extracellular matrix.
Automated office blood pressure measurement in primary care.

OBJECTIVE To provide FPs with detailed knowledge of automated office blood pressure (AOBP) measurement, its potential role in primary care, and its proper use in the diagnosis and management of hypertension. SOURCES OF INFORMATION Comprehensive monitoring and collection of scientific articles on AOBP by the authors since its introduction. MAIN MESSAGE Automated office blood pressure measurement maintains a role for blood pressure (BP) readings taken in the office setting. Clinical research studies have reported a substantially stronger relationship between awake ambulatory BP measurement and AOBP measurement compared with manual BP recorded during routine visits to the patient's physician. Automated office blood pressure measurement produces mean BP values comparable to awake ambulatory BP and home BP values. Compared with routine manual office BP measurement, AOBP correlates more strongly with awake ambulatory BP measurement, shows less digit preference, is more consistent from visit to visit, is similar both within and outside of the physician's office, virtually eliminates office-induced hypertension, and is associated with less masked hypertension. It is estimated that more than 25% of Canadian primary care physicians are now using AOBP measurement in their office practices. The use of AOBP to diagnose hypertension has been recommended by the Canadian Hypertension Education Program since 2010. CONCLUSION There is now sufficient evidence to incorporate AOBP measurement into primary care as an alternative to manual BP measurement.
The New Modeling for Semantic Representation of Moving Objects in Video

There are many researches about video retrieval using spatio-temporal relations. Most of them studied simple trajectory or content-based retrieval but without semantic motion. Therefore, in this paper, we propose a new modeling for semantic representation of moving object using new topological relations, directional relations. Especially, we described directional relations based on TSR for measuring and storing similarity of object's direction. Also, we built hierarchical structure by combining motions with motion verbs to describe semantic relations of moving objects. In the future work, we'll build knowledge base such as motion ontology and apply it for automatic summarization or annotation system.
Taxanes Synergize with the Bispecific Antibody MDXH447 to Enhance Antibody-Dependent Cell-Mediated Cytotoxicity

Abstract The interaction between antibody based therapy and cytotoxic chemotherapy is complex. To explore these interactions we investigated, in vitro, the effects of IC20 growth inhibitory concentrations of taxanes on bispecific antibody-mediated tumor cell cytotoxicity. MDXH447 is a bispecific antibody with specificity for the high affinity IgG receptor (CD64) and the type I epidermal growth factor receptor type (EGF-R). A431 cells, an epidermoid carcinoma cell line that over expresses EGF-R, were exposed to a range of IC20 growth inhibitory concentrations of paclitaxel or docetaxel. Interferon gamma activated monocytes were armed with MDXH447 and a standard chromium release antibody-dependent cell-mediated cytotoxicity (ADCC) assay was performed. Using the Chou and Talalay median effect analysis, we found that MDXH447-mediated ADCC was enhanced when A431 target cells were pretreated with paclitaxel or docetaxel. Median effect analysis of these interactions supported a synergistic interaction (CI < 1). Pretreatment of A431 cells with taxanes did not increase EGF-R expression compared to untreated controls. A431 epidermoid carcinoma cells pretreated with IC20 growth inhibitory concentrations of taxanes enhanced interferon gamma activated monocyte mediated ADCC killing through MDXH447.
Effects of resistance training on insulin sensitivity in overweight Latino adolescent males.

PURPOSE Insulin resistance is thought to be a core defect in the pathophysiology of obesity-related comorbidities in children, such as type 2 diabetes. Exercise training is known to improve insulin resistance and reduce the risk of type 2 diabetes in adults. However, very little is known regarding the effects of exercise on insulin resistance in youth. Therefore, we examined the effects of a 16-wk resistance training exercise intervention on insulin sensitivity in youth at high risk for developing type 2 diabetes. METHODS Twenty-two overweight Latino adolescent males were randomly assigned to either a twice-per-week resistance training group (RT=11) or a nonexercising control group (C=11) for 16 wk. Strength was assessed by one-repetition maximum, body composition was quantified by dual-energy x-ray absorptiometry, and insulin sensitivity was determined by the frequently sampled intravenous glucose tolerance test with minimal modeling. RESULTS Significant increases in upper- and lower-body strength were observed in the RT compared with the C group. The RT group significantly increased insulin sensitivity compared with the C group (P<0.05), and this increase remained significant after adjustment for changes in total fat mass and total lean tissue mass (P<0.05). Compared with baseline values, insulin sensitivity increased 45.1+/-7.3% in the RT group versus -0.9+/-12.9% in controls (P<0.01). CONCLUSION A twice-per-week 16-wk resistance training program can significantly increase insulin sensitivity in overweight Latino adolescent males independent of changes in body composition.
MnDPDP enhancement characteristics and differentiation between cirrhotic and noncirrhotic livers.

RATIONALE AND OBJECTIVES The objective was to analyze if liver enhancement with mangafodipir trisodium was influenced by liver cirrhosis. METHODS Eighty patients (49 with cirrhotic and 31 with noncirrhotic livers) were studied with spin-echo and spoiled gradient-echo T1-weighted images, before and after administration of mangafodipir trisodium. Hepatic insufficiency was assessed using the Child classification. Image analysis was performed both qualitatively and quantitatively. RESULTS Noncirrhotic livers enhanced homogeneously but 37% of cirrhotic livers did not; the difference was significant. Areas corresponding to collapsed fibrous zones enhanced less than the rest of the parenchyma; areas of regenerating nodular zones enhanced more. Signal-to-noise ratios were significantly less for cirrhotic livers on postcontrast spoiled gradient-echo images. Cirrhotic livers had significantly lower relative enhancement ratios than noncirrhotic ones. The Child index and aspartate aminotransferase values were statistically related to the enhancement ratio. CONCLUSIONS Mangafodipir trisodium enhancement in cirrhotic livers is related to necrosis and regeneration of the hepatocytes. Cirrhotic livers enhanced less than noncirrhotic ones.