Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure of the voltage-gated K+ channel Eag1 reveals an alternative voltage sensing mechanism

A different gate design The voltage-gated potassium channel Eag1 is overexpressed in tumor cells from a range of cancers, and inhibiting Eag1 reduces tumor growth. Whicher and Mackinnon determined the structure of a mammalian Eag1 bound to the inhibitor calmodulin at 3.78 Å resolution (see the Perspective by Toombes and Swartz). The organization of the voltage-sensing and pore domains differs from that of other potassium channels, indicating that the gating mechanism is distinct. The structure also shows how the channel can be closed by a ligand, independently of the position of the voltage sensor. Science, this issue p. 664; see also p. 646 Structure of a potassium channel reveals the mechanism of the interplay between voltage-dependent and ligand gating. Voltage-gated potassium (Kv) channels are gated by the movement of the transmembrane voltage sensor, which is coupled, through the helical S4-S5 linker, to the potassium pore. We determined the single-particle cryo–electron microscopy structure of mammalian Kv10.1, or Eag1, bound to the channel inhibitor calmodulin, at 3.78 angstrom resolution. Unlike previous Kv structures, the S4-S5 linker of Eag1 is a five-residue loop and the transmembrane segments are not domain swapped, which suggest an alternative mechanism of voltage-dependent gating. Additionally, the structure and position of the S4-S5 linker allow calmodulin to bind to the intracellular domains and to close the potassium pore, independent of voltage-sensor position. The structure reveals an alternative gating mechanism for Kv channels and provides a template to further understand the gating properties of Eag1 and related channels.
Health Education in Patients with a Recent Stroke or Transient Ischaemic Attack: A Comprehensive Review

Health education aims at the acquisition of skills and attitudes to modify behaviour that influences health, leads to a modification of risk factors and ultimately to a decrease in disability and case fatality from stroke. Health education is an underdeveloped but important aspect of stroke care. Health education could promote compliance and healthy behaviour, improve patients' understanding of their health status and treatment options and facilitate communication. We reviewed the effect of health education in stroke and transient ischaemic attack patients, aiming at feasibility, effectiveness at the level of knowledge, attitude and skills, health behaviour changes and stroke outcome. We also describe the current status of health education for patients with recent coronary artery disease and public health education in stroke. Basic knowledge of stroke and transient ischaemic attack patients of their disease and associated risk factors is not sufficient. This is also observed in patients with coronary artery disease and in the general population. A beneficial effect of health education in stroke and transient ischaemic attack patients on health behaviour, risk reduction or stroke outcome has not been proven. Trials in patients with coronary artery disease, however, have shown that health education could result in a change of lifestyle. No specific method is superior, although the individualised, repetitive and active methods appear more successful. More intervention studies of health education in stroke and transient ischaemic attack patients are needed. Future trials should be large, have a long follow-up, should use an intensive and repetitive approach and involve patients' relatives to induce and maintain a healthy lifestyle.
Contributions to accelerating atmospheric CO2 growth from economic activity, carbon intensity, and efficiency of natural sinks

The growth rate of atmospheric carbon dioxide (CO2), the largest human contributor to human-induced climate change, is increasing rapidly. Three processes contribute to this rapid increase. Two of these processes concern emissions. Recent growth of the world economy combined with an increase in its carbon intensity have led to rapid growth in fossil fuel CO2 emissions since 2000: comparing the 1990s with 2000–2006, the emissions growth rate increased from 1.3% to 3.3% y−1. The third process is indicated by increasing evidence (P = 0.89) for a long-term (50-year) increase in the airborne fraction (AF) of CO2 emissions, implying a decline in the efficiency of CO2 sinks on land and oceans in absorbing anthropogenic emissions. Since 2000, the contributions of these three factors to the increase in the atmospheric CO2 growth rate have been ≈65 ± 16% from increasing global economic activity, 17 ± 6% from the increasing carbon intensity of the global economy, and 18 ± 15% from the increase in AF. An increasing AF is consistent with results of climate–carbon cycle models, but the magnitude of the observed signal appears larger than that estimated by models. All of these changes characterize a carbon cycle that is generating stronger-than-expected and sooner-than-expected climate forcing.
Protocol for the provision of amplification within the Ontario Infant hearing program

Abstract This document describes the protocol for the provision of amplification to infants and preschool children registered with the Ontario infant hearing program (OIHP) in Canada. The provision of amplification includes the prescription and dispensing of hearing instruments to infants and preschool children identified with permanent childhood hearing impairment (PCHI) in the province of Ontario. The first section deals with the structure and processes of the program, while the second section specifies the clinical procedures that are applied in providing hearing instruments to infants and young children with hearing impairment. Sumario Este documento describe el protocolo para el suministro de amplificación a niños y preescolares registrados en el programa de audición infantil de Ontario (OIHP) en Canadá. El suministro de amplificación incluye la prescripción y entrega de instrumentos auditivos a niños y a preescolares identificados con discapacidad infantil auditiva permanente (PCHI) en la provincia de Ontario. La primera sección trata sobre la estructura y los procesos del programa, mientras que la segunda sección, especifica los procedimientos clínicos que se aplican para suministrar instrumentos auditivos a bebes y ninos pequeños con discapacidad auditiva.
Trajectories Of Aging: Imagined Pathways In Later Life

The model of aging that people construct influences interpretations of and responses to actual situations when they occur, as well as preparatory actions that people take. Thus the question of what people foresee for themselves and the process by which they construct and revise this subjective aging trajectory has implications for such issues as health behavior, retirement planning, migration and residential moves, and advance directives, as well as for overall well-being in old age. This exploratory, hypothesis-generating study found that informants referred frequently to the course of aging and the events they envisioned in their own futures. The analysis delineates 1) types of events that older people see as part of aging in general and their own aging in particular, 2) factors and processes that enter into the construction of the subjective trajectory of aging, and 3) feeling and behavioral responses to the imagined future.
Sorafenib in combination with transarterial chemoembolization in Chinese patients with hepatocellular carcinoma: a subgroup interim analysis of the START trial.

AIM The third interim results of the START trial showed encouraging safety and efficacy profiles, with a median time to progression of 9 months. This subgroup analysis presents results in Chinese patients enrolled in the START trial. MATERIALS & METHODS Sixty two Chinese patients (median age 52 years) with unresectable hepatocellular carcinoma had transarterial chemoembolization (TACE) performed with an emulsion of Lipiodol(®) (Guerbet, Paris, France) and doxorubicin (30-60 mg) followed by embolization with absorbable particles. Sorafenib (400 mg twice-daily) was administered continuously with dose holidays 4 days prior to and post TACE procedures. TACE was performed every 6-8 weeks and responses were assessed after 4-6 weeks and then every 3 months if no further TACE was indicated. Patients continued receiving sorafenib until disease progression or unacceptable toxicity occurred. RESULTS Thirty seven patients (59.68%) received no more than two TACE procedures. During sorafenib treatment (median duration 6.4 months; mean daily dose 787.6 mg), 75.8% of patients experienced adverse events, most commonly pyrexia (37.1%), diarrhea (27.4%), skin reactions (22.6%), alopecia (19.4%) and abnormal hepatic function (16.1%). The most common grade 3-4 adverse events were abnormal hepatic function (6.5%) and diarrhea (3.2%). The median time to progression and overall survival were 10.6 and 16.5 months, respectively, and the objective response and stable disease rates were 44.3 and 42.6%, respectively. CONCLUSION The combination of the TACE and sorafenib proved both safe and effective in the treatment of Chinese patients with unresectable hepatocellular carcinoma.
The compilation of the Vercelli Book

The Vercelli Book, as is well known, is a codex of the late tenth century containing a selection of religious prose and verse in Old English. Of the manuscript's twenty-nine items (some of which are defective owing to loss of leaves), six are alliterative poems and the rest prose homilies. There seems little doubt that one scribe (henceforth referred to as V) was responsible for writing the whole of the codex, even though the size of the writing changes considerably at various points, particularly towards the end of the volume where the lineation also changes. As the earliest of the four extant poetic codices and the earliest surviving collection of homilies in the vernacular, the book is potentially a most important source of knowledge of tenth-century English; most linguistic studies which range over Old English as a whole have included some reference to it. Yet the language of the manuscript is a relatively neglected subject of study, the place of its composition has not been established and the circumstances of its compilation have not been fully explained. This paper seeks to learn more of the book's origin in two ways: firstly, by examining its make-up in an attempt to determine the number and the nature of the sources that V used, and, secondly, by considering the distribution of distinctive linguistic forms in the manuscript in order to find out more about the nature of V's exemplars and about his background and training as displayed in his attitude to the language of his exemplars.
Photoluminescence and thermal stability of Mn2+-doped CdSe/CdS/ZnS quantum dots

Colloidal Manganese-doped cadmium selenium quantum dots (Mn-doped CdSe QDs) and Mn-doped CdSe/CdS/ZnS core/multishell QDs were successfully synthesized via non-trioctylphosphine (non-TOP) green route. The TEM image reveals that the CdSe QDs are almost spherical in shape and have a good monodispersion. The optical properties of Mn-doped CdSe QDs were investigatedusing ultraviolet-visible and photoluminescence spectroscopy. The absorption spectra exhibit a red-shift with increasing QDs size, which is attributed to the quantum confinement effect. The PL spectra exhibit a first blue-shift to a later red-shiftwith increasing QDs size, which is attributed to the combined effect of Mn-doping and quantum confinement effect. Quantum confinement allows tuning of the CdSebandgap energy across the Mnexcited-state energies. Temperature-dependent (300–500 K) PL data suggest that Mn-doped CdSe/CdS/ZnS core/multishell QDs with enhanced thermal stabilities could be realized by blocking the nonradiative recombination centers with thick CdS/ZnS shells.
Separation of concerns: experiences of the crowd

Separation of concerns is an important concept to define meaningful artifacts of a system. For software product lines (SPLs), concerns are described as features---that can be reused to configure and automatically derive variants of the system. Despite being extensively investigated, several fundamental questions regarding SPLs can only be answered vaguely. In particular, when and how developers separate a feature from a system. We aim to investigate this question by employing community question-answering (CQA) systems, which allow developers to share their experiences.
Freshwater snails and schistosomiasis mansoni in the State of Rio de Janeiro, Brazil: I-- Metropolitan mesoregion.

In order to elaborate a planorbid chart of the State of Rio de Janeiro a survey of freshwater gastropods in the Metropolitan Mesoregion of this State was performed and revealed the occurrence of 20 species: Antillorbis nordestensis (Lucena, 1954); Biomphalaria glabrata (Say, 1818); Biomphalaria schrammi (Crosse, 1864); Biomphalaria straminea (Dunker, 1848); Biomphalaria tenagophila (Orbigny, 1835); Burnupia sp. ; Drepanotrema anatinum (Orbigny, 1835); Drepanotrema cimex (Moricand, 1839); Drepanotrema lucidum (Pfeiffer, 1839); Ferrissia sp. ; Gundlachia ticaga (Marcus & Marcus, 1962); Heleobia davisi Silva & Thomé, 1985; Lymnaea columella Say, 1817; Melanoides tuberculatus (Müller, 1774); Physa cubensis Pfeiffer, 1839; Physa marmorata Guilding, 1828; Pomacea sp. ; Pomacea canaliculata (Lamarck, 1822); Pomacea lineata (Spix, 1827) and Pomacea sordida (Swainson, 1823). Among the planorbid species B. tenagophila was the most frequent, occurring in all municipalities surveyed. The present study extends the distribution of B. straminea in the State of Rio de Janeiro and reports new records for A. nordestensis, B. schrammi, G. ticaga, H. davisi and the genera Burnupia and Ferrissia. An account about the current transmission areas of schistosomiasis mansoni in this Mesoregion is presented as well.
Role of Biomarkers in the Study and Management of Inflammatory Bowel Disease: A “Nonsystematic” Review

A tool cannot be evaluated unless its purpose is known. This axiom is as applicable to the study of biomarkers as to any other instrument. In the case of inflammatory bowel disease (IBD), biomarkers are typically used by clinicians to serve any of 3 principal functions: diagnosis, interval assessment, or prognosis. The intense interest in biomarkers has been prompted largely by the failure of purely “clinical” indices to fulfill these purposes consistently and reliably. In this IOIBD Task Force White Paper, I shall review the data concerning the relative utility of 3 of the oldest, simplest, and most widely used biomarkers, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and orosomucoid (alpha-1 acid glycoprotein), as well as newer fecal markers (primarily calprotectin and lactoferrin) to fulfill each of these functions in the management of patients with IBD. It is the intent of this review to focus on fluctuating biomarkers that are reflective of the ongoing state of inflammatory activity, rather than the familiar and emerging serologic antibodies like ASCA, ANCA, anti-cBir1, and the like, a whole subject in itself.
Molecular Determinants for Competitive Inhibition of α4β2 Nicotinic Acetylcholine Receptors

The Erythrina alkaloids erysodine and dihydro-β-erythroidine (DHβE) are potent and selective competitive inhibitors of α4β2 nicotinic acetylcholine receptors (nAChRs), but little is known about the molecular determinants of the sensitivity of this receptor subtype to inhibition by this class of antagonists. We addressed this issue by examining the effects of DHβE and a range of aromatic Erythrina alkaloids on [3H]cytisine binding and receptor function in conjunction with homology models of the α4β2 nAChR, mutagenesis, and functional assays. The lactone group of DHβE and a hydroxyl group at position C-16 in aromatic Erythrina alkaloids were identified as major determinants of potency, which was decreased when the conserved residue Tyr126 in loop A of the α4 subunit was substituted by alanine. Sensitivity to inhibition was also decreased by substituting the conserved aromatic residues α4Trp182 (loop B), α4Tyr230 (loop C), and β2Trp82 (loop D) and the nonconserved β2Thr84; however, only α4Trp182 was predicted to contact bound antagonist, suggesting α4Tyr230, β2Trp82, and β2Thr84 contribute allosterically to the closed state elicited by bound antagonist. In addition, homology modeling predicted strong ionic interactions between the ammonium center of the Erythrina alkaloids and β2Asp196, leading to the uncapping of loop C. Consistent with this, β2D196A abolished sensitivity to inhibition by DHβE or erysodine but not by epierythratidine, which is not predicted to form ionic bonds with β2Asp196. This residue is not conserved in subunits that comprise nAChRs with low sensitivity to inhibition by DHβE or erysodine, which highlights β2Asp196 as a major determinant of the receptor selectivity of Erythrina alkaloids.
A Constraint-based intrusion detection system

The expressiveness of constraints has a potential to define network behavior and defend against complex network intrusions. This potential can be an integral part of an Intrusion Detection System (IDS) for defending networks against various attacks. The existing approaches of constraint logic programming have limitations when it comes to solving the network constraints in the presence of the continuous, constantly changing stream of network data. In this paper, we propose two variations of a tree-based constraint satisfaction technique to evaluate network constraints on continuous network data. A Domain Specific Language (DSL) is developed so that the IDS users can specify different intrusions related to their networks. We also present a prototype implementation of these techniques. We evaluate the performance and effectiveness of our approach against the network traffic data generated from an experimental network.
External Evaluation of Population Pharmacokinetic Models of Vancomycin in Neonates: The transferability of published models to different clinical settings.

BACKGROUND Vancomycin is one of the most evaluated antibiotics in neonates using modeling and simulation approaches. However no clear consensus on optimal dosing has been achieved. The objective of the present study was to perform an external evaluation of published models, in order to test their predictive performances in an independent dataset and to identify the possible study-related factors influencing the transferability of pharmacokinetic models to different clinical settings. METHOD Published neonatal vancomycin pharmacokinetic models were screened from the literature. The predictive performance of 6 models was evaluated using an independent dataset (112 concentrations from 78 neonates). The evaluation procedures used simulation-based diagnostics (visual predictive check [VPC] and normalized prediction distribution errors [NPDE]). RESULTS Differences in predictive performances of models for vancomycin pharmacokinetics in neonates were found. The mean of NPDE for 6 evaluated models were 1.35, -0.22, -0.36, 0.24, 0.66, 0.48, respectively. These differences were explained, at least partly, by taking into account the method used to measure serum creatinine concentrations. The adult conversion factor of 1.3 (enzymatic to Jaffé) was tested with an improvement in the VPC and NPDE, but it still need to be evaluated and validated in neonates. Differences were also identified between analytical methods for vancomycin. CONCLUSION The importance of analytical techniques for serum creatinine concentrations and vancomycin as a predictor of vancomycin concentrations in neonates has been confirmed. Dosage individualisation of vancomycin in neonates should consider not only patients' characteristics and clinical conditions, but also the methods used to measure serum creatinine and vancomycin.
Feeding and socioeconomic characteristics of nursing caries children in a Saudi population.

N ursing caries is a frustrating condition that is difficult to treat in infants and very young children. It may retard the child’s health, development, and speech. It can be painful, is infectious, and results in impairment of nutrition and esthetics with accompanying psychological problems. 1 The risk factors for nursing caries vary from population to population, and some additional factors may be present in a population due the sociocultural differences in different geographical locations. The aim of this investigation was to study characteristics of nursing caries children in central Saudi Arabia by obtaining information about their socioeconomic status, feeding practices, use of sweetened pacifiers, and other relevant information mentioned in the literature by various researchers, 2 5 by using a self-administered questionnaire. Such a profile may help identify high-risk groups, which in turn may help target preventive measures to children at high risk for nursing caries.
Refined X-ray crystallographic structure of the poliovirus 3C gene product.

The X-ray crystallographic structure of the recombinant poliovirus 3C gene product (Mahoney strain) has been determined by single isomorphous replacement and non-crystallographic symmetry averaging and refined at 2.1 A resolution. Poliovirus 3C is comprised of two six-stranded antiparallel beta-barrel domains and is structurally similar to the chymotrypsin-like serine proteinases. The shallow active site cleft is located at the junction of the two beta-barrel domains and contains a His40, Glu71, Cys147 catalytic triad. The polypeptide loop preceding Cys147 is flexible and likely undergoes a conformational change upon substrate binding. The specificity pockets for poliovirus 3C are well-defined and modeling studies account for the known substrate specificity of this proteinase. Poliovirus 3C also participates in the formation of the viral replicative initiation complex where it specifically recognizes and binds the RNA stem-loop structure in the 5' non-translated region of its own genome. The RNA recognition site of 3C is located on the opposite side of the molecule in relation to its proteolytic active site and is centered about the conserved KFRDIR sequence of the domain linker. The recognition site is well-defined and also includes residues from the amino and carboxy-terminal helices. The two molecules in the asymmetric unit are related by an approximate 2-fold, non-crystallographic symmetry and form an intermolecular antiparallel beta-sheet at their interface.
Platelet‐neutrophil complex formation—a detailed in vitro analysis of murine and human blood samples

Platelets form complexes with neutrophils during inflammatory processes. These aggregates migrate into affected tissues and also circulate within the organism. Several studies have evaluated platelet‐neutrophil complexes as a marker of cardiovascular diseases in human and mouse. Although multiple publications have reported platelet‐neutrophil complex counts, we noticed that different methods were used to analyze platelet‐neutrophil complex formation, resulting in significant differences, even in baseline values. We established a protocol for platelet‐neutrophil complex measurement with flow cytometry in murine and human whole blood samples. In vitro platelet‐neutrophil complex formation was stimulated with ADP or PMA. We tested the effect of different sample preparation steps and cytometer settings on platelet‐neutrophil complex detection and noticed false‐positive counts with increasing acquisition speed. Platelet‐neutrophil complex formation depends on platelet P‐selectin expression, and antibody blocking of P‐selectin consequently prevented ADP‐induced platelet‐neutrophil complex formation. These findings may help generating more comparable data among different research groups that examine platelet‐neutrophil complexes as a marker for cardiovascular disease and novel therapeutic interventions.