Miracle-dz/UniFAR-FTUs huggingface dataset:
Taxol binds to polymerized tubulin in vitro

Taxol, a natural plant product that enhances the rate and extent of microtubule assembly in vitro and stabilizes microtubules in vitro and in cells, was labeled with tritium by catalytic exchange with (3)H(2)O. The binding of [(3)H]taxol to microtubule protein was studied by a sedimentation assay. Microtubules assembled in the presence of [(3)H]taxol bind drug specifically with an apparent binding constant, K(app), of 8.7 x 19(-7) M and binding saturates with a calculated maximal binding ration, B(max), of 0.6 mol taxol bound/mol tubulin dimer. [(3)H]Taxol also binds and assembles phosphocellulose-purified tubulin, and we suggest that taxol stabilizes interactions between dimers that lead to microtubule polymer formation. With both microtubule protein and phosphocellulose- purified tubulin, binding saturation occurs at approximate stoichiometry with the tubulin dimmer concentration. Under assembly conditions, podophyllotoxin and vinblastine inhibit the binding of [(3)H]taxol to microtubule protein in a complex manner which we believe reflects a competition between these drugs, not for a single binding site, but for different forms (dimer and polymer) of tubulin. Steady-state microtubules assembled with GTP or with 5’-guanylyl-α,β-methylene diphosphonate (GPCPP), a GTP analog reported to inhibit microtubule treadmilling (I.V. Sandoval and K. Weber. 1980. J. Biol. Chem. 255:6966-6974), bind [(3)H]taxol with approximately the same stoichiometry as microtubules assembled in the presence of [(3)H]taxol. Such data indicate that a taxol binding site exists on the intact microtubule. Unlabeled taxol competitively displaces [(3)H]taxol from microtubules, while podophyllotoxin, vinblastine, and CaCl(2) do not. Podophyllotoxin and vinblastine, however, reduce the mass of sedimented taxol-stabilized microtubules, but the specific activity of bound [(3)H]taxol in the pellet remains constant. We conclude that taxol binds specifically and reversibly to a polymerized form of tubulin with a stoichiometry approaching unity.
Stopping Behavior of Systems Analysts During Information Requirements Elicitation

Understanding the cognitive activities of analysts during information requirements determination (IRD) has been recognized as a key indicator of IRD success. The research presented here examines one such cognitive activity: analysts' determination of the sufficiency of information gathered during the elicitation of requirements. Research in behavioral decision-making has identified various heuristics, or stopping rules, that are used to gauge the sufficiency of the information obtained and to terminate information acquisition. Despite the fact that analysts undoubtedly employ such stopping rules in requirements elicitation, no research has studied this phenomenon. In the present research, we present a classification of stopping rules appropriate for information gathering problems. Stopping-rule use was identified for 54 practicing systems analysts participating in a requirements determination problem in a laboratory setting. Results indicated that analyst experience influences the application of specific cognitive stopping rules, and that the use of these stopping rules has an impact on requirements determination outcomes. In addition, the use of certain stopping rules resulted in greater quantity and completeness of requirements elicited from users. Theoretical implications for the elicitation of information and practical implications for the training of systems analysts are discussed.
Building a dictionary on constituent structure of Chinese compounds

This paper presents an approach of building a contemporary Chinese dictionary on constituent structure of compounds. Manual tagging and three automatic tagging methods, including bi-direction parallel analogy, paired parallel analogy and inferring based on the consistency between form and meaning, are used. More than 40,000 words of all the 54000 bi-syllabic words in Hownet are fully or half semantically tagged by these three automatic methods. In the process of manual tagging, the difficulties and corresponding solving schemes are also presented in this paper. After manual and automatic tagging, two methods are used for checking their results. First, several heuristic rules are used on manual tagging results to mine abnormal tagging. Second, the manual and automatic tagging results are comparing with each other and the inconsistent tagging results are also considered as abnormal tagging. All abnormal tagging results are reserved for further checking.
The heat method for distance computation

We introduce the heat method for solving the single- or multiple-source shortest path problem on both flat and curved domains. A key insight is that distance computation can be split into two stages: first find the direction along which distance is increasing, then compute the distance itself. The heat method is robust, efficient, and simple to implement since it is based on solving a pair of standard sparse linear systems. These systems can be factored once and subsequently solved in near-linear time, substantially reducing amortized cost. Real-world performance is an order of magnitude faster than state-of-the-art methods, while maintaining a comparable level of accuracy. The method can be applied in any dimension, and on any domain that admits a gradient and inner product---including regular grids, triangle meshes, and point clouds. Numerical evidence indicates that the method converges to the exact distance in the limit of refinement; we also explore smoothed approximations of distance suitable for applications where greater regularity is desired.
Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER

Ceramides are central intermediates of sphingolipid metabolism with critical functions in cell organization and survival. They are synthesized on the cytosolic surface of the endoplasmic reticulum (ER) and transported by ceramide transfer protein to the Golgi for conversion to sphingomyelin (SM) by SM synthase SMS1. In this study, we report the identification of an SMS1-related (SMSr) enzyme, which catalyses the synthesis of the SM analogue ceramide phosphoethanolamine (CPE) in the ER lumen. Strikingly, SMSr produces only trace amounts of CPE, i.e., 300-fold less than SMS1-derived SM. Nevertheless, blocking its catalytic activity causes a substantial rise in ER ceramide levels and a structural collapse of the early secretory pathway. We find that the latter phenotype is not caused by depletion of CPE but rather a consequence of ceramide accumulation in the ER. Our results establish SMSr as a key regulator of ceramide homeostasis that seems to operate as a sensor rather than a converter of ceramides in the ER.
Pharmacodynamics of metronidazole determined by a time-kill assay for Trichomonas vaginalis

The pharmacodynamic effects of metronidazole on Trichomonas vaginalis have been poorly characterized. The present in vitro study was performed to characterize the relationship between killing of trichomonads and metronidazole exposure (metronidazole concentration and time of exposure). Five laboratory strains and five recent clinical isolates of T. vaginalis were studied. The minimum lethal concentrations (MLCs) of metronidazole for the strains ranged from 0.8 to 25 micrograms/ml under anaerobic conditions. Metronidazole exhibited concentration-dependent killing against T. vaginalis at concentrations ranging from 0.1 to > 10 times the MLC. The endpoint measurement, the kill rate constant, which was derived from the reduction in the logarithm of the colony count divided by exposure time, compared with the kill rate constant for the growth control was not affected by the time of assessment between 2 and 24 h. The kill rate constant-versus-metronidazole exposure curves were similar when concentration was expressed as a multiple of the MLC. There were no apparent differences between the clinical isolates and laboratory strains. These data suggest that peak metronidazole concentration and/or area under the plasma concentration-versus-time curve are the important pharmacodynamic parameters to be optimized.
Classification of Intraocular Tuberculosis

Abstract Tuberculosis in the TB endemic countries commonly manifests in the eye as tuberculous uveitis. There is a wide spectrum of the clinical manifestations of intraocular tuberculosis (IOTB). For want of any gold standard diagnostic tests or diagnostic criteria, the estimates of IOTB prevalence have varied greatly. None of the previously suggested guidelines for diagnosis of IOTB have been validated. We give definitions of clinical signs and diagnostic tests that have been used in the literature. Based on these, we propose a classification of IOTB comprising “confirmed IOTB,” “probable IOTB,” and “possible IOTB. ” This of necessity needs consensus among experts before carrying out studies to validate this classification.
A wideband zero index metamaterial lens for directive emission based on Z-shaped meta-atom

In this paper, a zero index metamaterial lens (ZIML) based on Z-shaped meta-atom is proposed to achieve directive emission. Z-shaped meta-atom is implement as the unit cell of the ZIML to achieve near zero permittivity for wideband. Patch antennas work at, respectively, 7.27 GHz, 8.02 GHz and 9.14GHz are used to test the directivity enhancement of the ZIML. Simulation results demonstrate that the ZIML we designed is able to significantly improve the directivity of the patch antennas.
Childhood hardship, maternal smoking, and birth outcomes: a prospective cohort study.

OBJECTIVE To determine the association between type, chronicity, and severity of childhood hardships and smoking status during pregnancy, preterm birth (PTB), and low birth weight (LBW). DESIGN Prospective cohort study. SETTING The National Child Development Study, a nationally representative study of births in Great Britain in 1958. PARTICIPANTS Four thousand eight-hundred sixty-five women with at least 1 singleton live birth. MAIN EXPOSURES Hardship during childhood, indicated by several variables, including financial/structural hardship, lack of parental interest in education, family dysfunction, violence/mental health issues, and family structure. MAIN OUTCOME MEASURES Smoking in pregnancy, LBW, and PTB. RESULTS A consistent and graded association was seen between all types of childhood hardships and smoking status during pregnancy (odds ratio [OR] for 4 or more hardships, 2.02; 95% confidence interval [CI], 1.58-2.58; P < .001 for all comparisons). Most hardships were also associated with risk of LBW and PTB, with associations between number of hardships and both outcomes persisting after controlling for smoking status and adult social class (for LBW, OR, 1.51; 95% CI, 1.10-2.06; for PTB, OR, 1.44; 95% CI, 1.08-1.92). CONCLUSION Childhood hardships have an enduring impact on future pregnancy outcomes, in part through their association with smoking during pregnancy and adult socioeconomic position.
Mobile manipulation of humanoid robots-optimal posture for generating large force based on statics

The optimal posture of a humanoid robot for generating large desired force at its hands is discussed. The robot is required to stand stably and to support the force and its weight under the constraint of maximum joint torques. Furthermore, it is important to keep the robot controllable against sudden change in the force. From this point of view, an evaluation function for the task with large force based on statics is proposed; we focus on Jacobian matrices of two arms and legs to give the robot adaptability to force change. Then the method of obtaining the optimal posture, footholds and joint torques of the robot is described. Effectiveness of the method are verified through computer simulations.
Efficient self-embedding of butterfly networks with random faults

The author studies the embedding of the butterfly network in a faulty version of itself where each node is independently faulty with some constant probability. He shows that such a self-embedding of the N-node butterfly with O(1) load, O((log logN)/sup 2.6/) dilation, and 0((log log N)/sup 8.2/) congestion is possible with high probability, assuming sufficiently small node-failure probability. This embedding is level-preserving in the sense that each node is mapped to a node in the same level of the butterfly. He also derives a lower bound of log log log N-c on the dilation of a level-preserving embedding with O(log/sup alpha / N) load, for any alpha , 0< alpha <1, any node-failure probability p>0, and some constant c depending on alpha and p.<<ETX>>
Targeted Mutagenesis, Precise Gene Editing, and Site-Specific Gene Insertion in Maize Using Cas9 and Guide RNA[OPEN]

Genome editing and gene insertion in maize is advanced with Cas9-guide RNA technology. Targeted mutagenesis, editing of endogenous maize (Zea mays) genes, and site-specific insertion of a trait gene using clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)-guide RNA technology are reported in maize. DNA vectors expressing maize codon-optimized Streptococcus pyogenes Cas9 endonuclease and single guide RNAs were cointroduced with or without DNA repair templates into maize immature embryos by biolistic transformation targeting five different genomic regions: upstream of the liguleless1 (LIG1) gene, male fertility genes (Ms26 and Ms45), and acetolactate synthase (ALS) genes (ALS1 and ALS2). Mutations were subsequently identified at all sites targeted, and plants containing biallelic multiplex mutations at LIG1, Ms26, and Ms45 were recovered. Biolistic delivery of guide RNAs (as RNA molecules) directly into immature embryo cells containing preintegrated Cas9 also resulted in targeted mutations. Editing the ALS2 gene using either single-stranded oligonucleotides or double-stranded DNA vectors as repair templates yielded chlorsulfuron-resistant plants. Double-strand breaks generated by RNA-guided Cas9 endonuclease also stimulated insertion of a trait gene at a site near LIG1 by homology-directed repair. Progeny showed expected Mendelian segregation of mutations, edits, and targeted gene insertions. The examples reported in this study demonstrate the utility of Cas9-guide RNA technology as a plant genome editing tool to enhance plant breeding and crop research needed to meet growing agriculture demands of the future.
Learning bimanual end-effector poses from demonstrations using task-parameterized dynamical systems

Very often, when addressing the problem of human-robot skill transfer in task space, only the Cartesian position of the end-effector is encoded by the learning algorithms, instead of the full pose. However, orientation is just as important as position, if not more, when it comes to successfully performing a manipulation task. In this paper, we present a framework that allows robots to learn the full poses of their end-effectors in a task-parameterized manner. Our approach permits the encoding of complex skills, such as those found in bimanual manipulation scenarios, where the generalized coordination patterns between end-effectors (i.e. position and orientation patterns) need to be considered. The proposed framework combines a dynamical systems formulation of the demonstrated trajectories, both in ℝ3 and SO(3), and task-parameterized probabilistic models that build local task representations in both spaces, based on which it is possible to extract the relevant features of the demonstrated skill. We validate our approach with an experiment in which two 7-DoF WAM robots learn to perform a bimanual sweeping task.
Cytotoxic CD4+ T cells in viral hepatitis

Summary. CD4+ T cells are thought to contribute to antiviral immune responses by secretion of cytokines thereby providing help to CD8+ T and B cells. However, perforin‐positive cytotoxic CD4+ T cells have been described in human immunodeficiency virus‐positive patients suggesting a role not only of CD8+ but also of CD4+ T cells for killing virus‐infected cells. We investigated 76 patients with viral hepatitis [15 hepatitis B virus (HBV), 22 HBV/hepatitis D virus and 17 hepatitis C virus (HCV)] for cytotoxic CD4+ T cells. The frequency of perforin‐positive CD4+ T cells in viral hepatitis was highly variable ranging from <1% to more than 25%. Perforin‐positive CD4+ T cells displayed the phenotype of terminally differentiated effector cells (CD28−, CD27−). The highest frequencies of CD4+ cytotoxic T lymphocytes (CTLs) were found in patients with delta hepatitis (P = 0.04 vs HBV and HCV patients), and the presence of CD4+ CTLs was associated with elevated aspartate aminotransferase levels (P = 0.01) and decreased platelet counts (P = 0.03). Perforin‐positive CD4+ T cells decreased in two individuals during spontaneous clearance of acute hepatitis C. Significant associations were found between the frequency of perforin‐expressing CD4+ cells and age (P = 0.04), perforin‐positive CD8+ cells (P < 0.001) and perforin‐positive CD4−/CD8− lymphoid cells (P = 0.002). Differentiated CD27− effector CD4+ CTLs can be detected in patients with viral hepatitis. In particular in patients with more advanced liver disease, the accumulation of perforin‐positive T cells with age could be one correlate for the more severe course of viral hepatitis in elderly individuals.
CD8 Locus Nuclear Dynamics during Thymocyte Development

Nuclear architecture and chromatin reorganization have recently been shown to orchestrate gene expression and act as key players in developmental pathways. To investigate how regulatory elements in the mouse CD8 gene locus are arranged in space and in relation to each other, three-dimensional fluorescence in situ hybridization and chromosome conformation capture techniques were employed to monitor the repositioning of the locus in relation to its subchromosomal territory and to identify long-range interactions between the different elements during development. Our data demonstrate that CD8 gene expression in murine lymphocytes is accompanied by the relocation of the locus outside its subchromosomal territory. Similar observations in the CD4 locus point to a rather general phenomenon during T cell development. Furthermore, we show that this relocation of the CD8 gene locus is associated with a clustering of regulatory elements forming a tight active chromatin hub in CD8-expressing cells. In contrast, in nonexpressing cells, the gene remains close to the main body of its chromosomal domain and the regulatory elements appear not to interact with each other.
Tracheotomy: timing and techniques

Purpose of reviewUntil the past 40 years, the timing of tracheotomy was of little concern. It was an emergency procedure developed for the relief of airway obstruction. Following the development of positive pressure ventilation, tracheotomy became an elective procedure. Today, the optimal time for tracheotomy is a subject of dispute and continued investigation. As this operation has become one of the most commonly performed procedures in the intensive care unit, nonoperative dilational methods have gained acceptability. The purpose of this review is to analyze the recent literature and draw insight into the timing and technique of the current state of tracheotomy. Recent findingsIndividualized assessment of patients should guide the timing of tracheotomy, with a preference toward early tracheotomy. Percutaneous dilational tracheotomy (PDT) can be performed with equivalent safety to open tracheotomy. Bedside open tracheotomy negates the cost-saving benefits of PDT. Endoscopic guidance in PDT decreases complications with needle placement and posterior tracheal wall injury. Major complications of PDT usually are associated with displacement of the tracheotomy tube. SummaryTracheotomy indications have remained unchanged, but the timing of the procedure has advanced to individualized assessment with a predilection for earlier tracheotomy. The traditional operative technique is a much safer procedure today. Percutaneous dilational tracheotomy has become an acceptable alternative with proper patient selection. A multidisciplinary team with a surgeon provides the best care for the patient undergoing percutaneous tracheotomy.
Robust pan-tilt-zoom tracking via optimization combining motion features and appearance correlations

This paper proposes a new pan-tilt-zoom (PTZ) tracking method to improve the robustness against occlusions and appearance changes by using motion likelihood map and scale change estimation as well as appearance correlation filter. For this purpose, we introduce a motion likelihood map constructed from motion detection result in addition to the correlation filter. The motion likelihood map is generated by blurring the motion detection result, which shows high probability in the center of target. To combine the correlation filter and the motion likelihood map, we formulate an optimization problem. In addition, to handle the scale change of target, we repeat the combining process for various scale of bounding box. The experiments show that the proposed method outperforms the state-of-the-art methods.
Allergic airway diseases in childhood – marching from epidemiology to novel concepts of prevention

In the past years, a wide range of epidemiological, clinical, and experimental studies have produced remarkable advances in the field of respiratory allergies in childhood. By the recent investigations on epidemiological trends, risk factors, and prevention of asthma and allergic rhinitis, various exiting concepts have been challenged, and novel innovative approaches have been developed. Pediatric Allergy and Immunology (PAI), with a number of highly relevant contributions between 2010 and 2012, has become an important forum in this area. The prevalence of asthma in some developed countries may have reached a plateau, while in developing countries, where the prevalence was previously low, allergic diseases are still on the increase. A wide array of risk and protective factors, including hygiene, infections, outdoor and indoor air pollution, allergen exposure, breast‐feeding practices, nutrition, and obesity, play a multifaceted role in shaping the observed worldwide trends of respiratory allergies. Under the guidance of recent research, prediction and prevention strategies in the clinical practice are progressively changing, the focus moving away from avoidance of allergen exposure and toward tolerance induction.
Ultrastructural investigation of neurons identified and localized using the confocal scanning laser microscope.

Studies of labeled neurons at the light-microscopic level often pinpoint a substructure of particular interest, i.e., a synapse or a spine. An ultrastructural investigation would explain a lot about how these structures arose, how they function, and how they are regulated. Finding a small region in a large block can require constant checking during sectioning, until past the structure. In our pursuit of the synaptic structure of varicosities on the axons of neurons identified physiologically and morphologically at the light level, we have combined confocal scanning laser microscopy (CSLM) with conventional and high-voltage electron microscopy (EM). CSLM images were collected in the reflection mode to view neurons filled with horseradish peroxidase and stained with nickel-intensified diaminobenzidine, which is compatible with EM. The CSLM optical sections provided a record of what one should expect to see at regular intervals throughout the depth of the tissue block. We have shown that the CSLM greatly simplified the task of localizing small structures in brain tissue prepared for EM.