gebhart/patrepeval huggingface dataset:
MOLECULAR EVIDENCE FOR NATURAL SELECTION (1995)

neutral theory, nearly neutral theory, population genetics ABSTRACT Our understandi ng of the causes of molec ular evolution is not as certain as it was a decade ago when Kimura's neutral theory appeared to explain major features of DNA conservation and change. The last ten years have seen the development of empirical approaches and statistical tests for detecting selec­ tion in DNA and a proliferation of data that challenge our current understanding of the molecular evolutionary process. We begin this review with a discussion of protein polymorphism and divergence: two major areas of research where the strictly neutral model cannot explain general patterns in the data. We then present a survey of statistical methods for detecting positive selection, which includes tests for balancing selection, for sequence convergence, and for un­ usually high rates of evolution that cannot be accounted for by neutral models. Finally, we present findings of a number of groups working on within- and between-species variation in Drosophila: These highlight the importance of adaptive evolution, purifying selection, and recombination in understanding levels and patterns of nucleotide variation.
Signal processing techniques in network-aided positioning: a survey of state-of-the-art positioning designs (2005)

Wireless positioning has attracted much research attention and has become increasingly important in recent years. Wireless positioning has been found very useful for other applications besides E911 service, ranging from vehicle navigation and network optimization to resource management and automated billing. Although many positioning devices and services are currently available, it is necessary to develop an integrated and seamless positioning platform to provide a uniform solution for different network configurations. This article surveys the state-of-the-art positioning designs, focusing specifically on signal processing techniques in network-aided positioning. It serves as a tutorial for researchers and engineers interested in this rapidly growing field. It also provides new directions for future research for those who have been working in this field for many years.
Schwann cells induce sprouting in motor and sensory axons in the adult rat spinal cord (1994)

Circumscribed lesions were made within either the corticospinal tract or the ascending dorsal column tracts at the upper cervical level in adult rats. The responses of the tract axons were studied by orthograde transport from injections of horseradish peroxidase or biocytin. At 2 d, the ends of the cut axons were swollen, and the lesions induced en passant varicosities in the adjacent uncut axons. Although there have been reports of retraction, we found that even after several weeks, large numbers of cut axons still persisted in the central lesion area (where there was complete tissue destruction and intense macrophage infiltration), and also in the adjacent regions of the tract. The cut ends were expanded into a variety of shapes--large, complex, bulbous, and recurved--and many had profuse local branches with or without small, terminal-type varicosities. A suspension of Schwann cells cultured from neonatal sciatic nerve was injected by a minimally traumatic air pressure microinjection technique so as to form a bolus, comparable in size to the lesions, in either the corticospinal or the ascending dorsal column tracts at the upper cervical level. Despite previous findings that corticospinal axons do not elongate into peripheral nerve grafts, we found that both corticospinal and ascending dorsal column axons sprouted in response to contact with the transplanted Schwann cells. The response to the Schwann cells was much more rapid than to the lesions. By 2 d, in both descending and ascending tracts, both the axons that had been severed at the time of injection and also the adjacent uncut axons had already given rise to the branches that (unlike the localized sprouting seen after the long-term lesions) extended for considerable distances parallel to and fasciculating with each other and with the uncut tract axons. In addition, a mass of fine, tortuous, varicose branches invaded the superficial parts of the Schwann cell grafts, where they formed aborizations with small bead-like expansions resembling presynaptic boutons; as in their normal terminal fields, the aborizations formed by the corticospinal axons were smaller and finer than those formed by the ascending axons.
Prediction of the stability of protein mutants based on structural environment-dependent amino acid substitution and propensity tables (1997)

An approach to the prediction of mutant stability is described using knowledge of amino acid replacements that are tolerated within the families of homologous proteins of known 3-D structure. Amino acid variations in families of homologous proteins are converted to propensity and substitution tables; these provide quantitative information about the existence of an amino acid in a structural environment and the probability of replacement by any other amino acid. The tables are used to calculate a 'stability difference score', analogous to the difference in free energy between a mutant and the wild type. The method has been developed and tested using the high-resolution structures for T4 lysozyme and 159 site-specific mutants. We show that differences in stability scores are correlated with experimentally observed free energy differences and differences in melting temperature. Blind tests, using only structural information derived from the parent wild-type crystal structures, on a combined set of 83 staphylococcal nuclease and 68 barnase mutants showed a correlation of 0.80 in the predicted stability changes with experimental thermodynamic data. Approximately 86% of the predictions were correctly classified as destabilizing or stabilizing.
A Survey of General-Purpose Computation on Graphics Hardware (2005)

The rapid increase in the performance of graphics hardware, coupled with recent improvements in its programmability, have made graphics hardware a compelling platform for computationally demanding tasks in a wide variety of application domains. In this report, we describe, summarize, and analyze the latest research in mapping general-purpose computation to graphics hardware. We begin with the technical motivations that underlie general-purpose computation on graphics processors (GPGPU) and describe the hardware and software developments that have led to the recent interest in this field. We then aim the main body of this report at two separate audiences. First, we describe the techniques used in mapping general-purpose computation to graphics hardware. We believe these techniques will be generally useful for researchers who plan to develop the next generation of GPGPU algorithms and techniques. Second, we survey and categorize the latest developments in general-purpose application development on graphics hardware. This survey should be of particular interest to researchers who are interested in using the latest GPGPU applications in their systems of interest.
YM-231146, a Novel Orally Bioavailable Inhibitor of Vascular Endothelial Growth Factor Receptor-2, Is Effective against Paclitaxel Resistant Tumors (2005)

Chemotherapy using anticancer drugs induces serious the problem of multidrug resistance (MDR) in the cancer cells. In contrast, endothelial cells so rarely acquire MDR that antiangiogenesis therapy has recently been considered as an effective means for cancer chemotherapy. We screened compounds in the chemical library to find a novel and orally active antitumor agent with vascular endothelial growth factor receptor-2 tyrosine kinase (VEGF-R2 TK) inhibition. The result was YM-231146 (IC50=0.080 microM). YM-231146 inhibited VEGF-stimulated proliferation, VEGF-R2 autophosphorylation, and vessel sprout formation of human vascular endothelial cells at concentrations between 0.15-0.30 microM. However, YM-231146 did not inhibit cancer cell proliferation at these concentrations (IC50>5 microM). In the in vivo studies, once-daily oral dosing of YM-231146 to human cancer xenografts elicited antitumor activity at doses of 3-100 mg/kg. Moreover, YM-231146 completely inhibited tumor growth of paclitaxel-resistant cancer cells without decreasing body weight at a dose of 100 mg/kg. These results suggest that YM-231146 is a novel orally bioavailable inhibitor of VEGF-R2 that would be useful for the treatment of multidrug resistant tumors.
Diagnosis of Hemorrhage in a Prehospital Trauma Population Using Linear and Nonlinear Multiparameter Analysis of Vital Signs (2007)

In this study, we analyzed a dataset of time-series vital-signs data collected by standard Propaq travel monitor during helicopter transport of 898 civilian trauma casualties from the scene of injury to a receiving trauma center. The goals of the analysis are two fold. First, to determine which combination of the automatically-collected and -qualified vital signs provides the best discrimination between casualties with and without major hemorrhage. Second, to determine whether nonlinear classifiers provide improved discrimination over simpler, linear classifiers. Major hemorrhage is defined by the presence of injuries consistent with hemorrhage in casualties who received one or more units of blood. We randomly selected a subset of the casualties to train and test the classifiers with multiple combinations of the vital-signs variables, and used the area under the receiver operating characteristic curve (ROC AUC) as a decision metric. Based on the results of 100 simulations, we observe that: (i) the best two features obtained are systolic blood pressure and heart rate (mean AUC = 0.75 from a linear classifier), and (ii) the use of nonlinear classifiers does not improve discrimination. These results support earlier findings that the interaction of systolic blood pressure and heart rate is useful for the identification of trauma hemorrhage and that linear classifiers are adequate for many real-world applications.
Long-term conditions (2010)

www.bdsounddoctor.nhs.uk The Sound doctor is a website developed by NHS Barking and Dagenham that features medical specialists speaking about various long-term health conditions. At the click of a mouse people can access expert information and advice on a range of illnesses, including: cardiovascular disease, coronary obstructive pulmonary disease (chronic emphysema or bronchitis), weight management, cholesterol and hypertension, quitting smoking and recovering from a fall. For those without internet access the information is available on CD on request.
Control of glucose metabolism by enzyme IIGlc of the phosphoenolpyruvate-dependent phosphotransferase system in Escherichia coli (1991)

The quantitative effects of variations in the amount of enzyme IIGlc of the phosphoenolpyruvate:glucose phosphotransferase system (PTS) on glucose metabolism in Escherichia coli were studied. The level of enzyme IIGlc could be adjusted in vivo to between 20 and 600% of the wild-type chromosomal level by using the expression vector pTSG11. On this plasmid, expression of the structural gene for enzyme IIGlc, ptsG, is controlled by the tac promoter. As expected, the control coefficient (i.e., the relative increase in pathway flux, divided by the relative increase in amount of enzyme) of enzyme IIGlc decreased in magnitude if a more extensive pathway was considered. Thus, at the wild-type level of enzyme IIGlc activity, the control coefficient of this enzyme on the growth rate on glucose and on the rate of glucose oxidation was low, while the control coefficient on uptake and phosphorylation of methyl alpha-glucopyranoside (an enzyme IIGlc-specific, nonmetabolizable glucose analog) was relatively high (0.55 to 0.65). The implications of our findings for PTS-mediated regulation, i.e., inhibition of growth on non-PTS compounds by glucose, are discussed.
The Extracellular Toll-like Receptor 2 Domain Directly Binds Peptidoglycan Derived from Staphylococcus aureus (2002)

Toll-like receptor 2 (TLR2) has been recognized to mediate cell signaling in response to peptidoglycan (PGN), a major cell wall component of Gram-positive bacteria. The mechanism by which TLR2 recognizes PGN is unknown. It is not even clear whether TLR2 directly binds to PGN. In this study, we generated a soluble form of recombinant TLR2 (sTLR2) possessing only its putative extracellular domain by using the baculovirus expression system to examine the direct interaction between sTLR2 and PGN. sTLR2 bound avidly to insoluble PGN (iPGN) from Staphylococcus aureus coated onto microtiter wells in a concentration-dependent manner. In contrast, sTLR2 exhibited a very weak binding to lipopolysaccharide. iPGN cosedimented sTLR2 after the mixture of iPGN and sTLR2 had been incubated and centrifuged. sTLR2 partially attenuated the iPGN-induced NF-kappaB activation in TLR2-transfected HEK 293 cells and the iPGN-induced IL-8 secretion in U937 cells. One of anti-human TLR2 monoclonal antibodies, which blocked iPGN-induced NF-kappaB activation in TLR2-transfected cells, inhibited the binding of sTLR2 to iPGN. In addition, we found that sCD14 interacted with sTLR2 and increased the binding of sTLR2 to iPGN. From these results, we conclude that the extracellular TLR2 domain directly binds to PGN.
Chronic Rapid Atrial Pacing (1995)

Sustained AF was readily inducible in most dogs (82%) after rapid atrial pacing. This model was consistently associated with biatrial myopathy and marked changes in atrial vulnerability. An area in the posterior left atrium was uniformly shown to have the shortest AFCL. The results of restoration of sinus rhythm and prevention of inducibility of AF after cryoablation of this area of the left atrium suggest that this area may be critical in the maintenance of AF in this model.
Reductively Responsive siRNA-Conjugated Hydrogel Nanoparticles for Gene Silencing (2012)

A critical need still remains for effective delivery of RNA interference (RNAi) therapeutics to target tissues and cells. Self-assembled lipid- and polymer-based systems have been most extensively explored for transfection with small interfering RNA (siRNA) in liver and cancer therapies. Safety and compatibility of materials implemented in delivery systems must be ensured to maximize therapeutic indices. Hydrogel nanoparticles of defined dimensions and compositions, prepared via a particle molding process that is a unique off-shoot of soft lithography known as particle replication in nonwetting templates (PRINT), were explored in these studies as delivery vectors. Initially, siRNA was encapsulated in particles through electrostatic association and physical entrapment. Dose-dependent gene silencing was elicited by PEGylated hydrogels at low siRNA doses without cytotoxicity. To prevent disassociation of cargo from particles after systemic administration or during postfabrication processing for surface functionalization, a polymerizable siRNA pro-drug conjugate with a degradable, disulfide linkage was prepared. Triggered release of siRNA from the pro-drug hydrogels was observed under a reducing environment while cargo retention and integrity were maintained under physiological conditions. Gene silencing efficiency and cytocompatibility were optimized by screening the amine content of the particles. When appropriate control siRNA cargos were loaded into hydrogels, gene knockdown was only encountered for hydrogels containing releasable, target-specific siRNAs, accompanied by minimal cell death. Further investigation into shape, size, and surface decoration of siRNA-conjugated hydrogels should enable efficacious targeted in vivo RNAi therapies.
Managing and querying transaction-time databases under schema evolution (2008)

The old problem of managing the history of database information is now made more urgent and complex by fast spreading web information systems, such as Wikipedia. Our PRIMA system addresses this difficult problem by introducing two key pieces of new technology. The first is a method for publishing the history of a relational database in XML, whereby the evolution of the schema and its underlying database are given a unified representation. This temporally grouped representation makes it easy to formulate sophisticated historical queries on any given schema version using standard XQuery. The second key piece of technology is that schema evolution is transparent to the user: she writes queries against the current schema while retrieving the data from one or more schema versions. The system then performs the labor-intensive and error-prone task of rewriting such queries into equivalent ones for the appropriate versions of the schema. This feature is particularly important for historical queries spanning over potentially hundreds of different schema versions and it is realized in PRIMA by (i) introducing Schema Modification Operators (SMOs) to represent the mappings between successive schema versions and (ii) an XML integrity constraint language (XIC) to efficiently rewrite the queries using the constraints established by the SMOs. The scalability of the approach has been tested against both synthetic data and real-world data from the Wikipedia DB schema evolution history.
A Symbolic Execution Framework for JavaScript (2010)

As AJAX applications gain popularity, client-side JavaScript code is becoming increasingly complex. However, few automated vulnerability analysis tools for JavaScript exist. In this paper, we describe the first system for exploring the execution space of JavaScript code using symbolic execution. To handle JavaScript code's complex use of string operations, we design a new language of string constraints and implement a solver for it. We build an automatic end-to-end tool, Kudzu, and apply it to the problem of finding client-side code injection vulnerabilities. In experiments on 18 live web applications, Kudzu automatically discovers 2 previously unknown vulnerabilities and 9 more that were previously found only with a manually-constructed test suite.
The FUS3 gene of Arabidopsis thaliana is a regulator of gene expression during late embryogenesis (1994)

The fus3 mutation of Arabidopsis thaliana affects several aspects of seed development. Mutant seeds are desiccation intolerant, viviparous and accumulate anthocyanins. Two major classes of storage proteins, the 12S cruciferins and the 2S albumins, are nearly absent, storage lipids are reduced and their composition is changed. The transcription of heterologous storage protein gene promoters in a fus3 genetic background is similarly affected. Our data suggest that the FUS3 gene is together with other genes like ABI3 and LEC1 central to the regulation of developmental processes during late embryogenesis.
Photophysics, aggregation and amplified quenching of a water-soluble poly(phenylene ethynylene)Electronic supplementary information (ESI) available: details regarding the synthesis and structural characterization of PPE-SO3â€“ and PE-SO3â€“. See http://www.rsc.org/suppdata/cc/b1/b109630c/ (2002)

The fluorescence, absorption and fluorescence quenching properties of an anionic poly(phenylene ethynylene) are investigated in H2O and MeOH solutions.
Biosynthesis, maturation, and acid activation of the Semliki Forest virus fusion protein (1990)

The Semliki Forest virus spike protein has a potent membrane fusion activity which is activated in vivo by the low pH of endocytic vacuoles. The spike protein is composed of two transmembrane subunits, E1 and E2, plus E3, a peripheral polypeptide. Acid-induced conformational changes in the E1 or E2 subunits were analyzed by using monoclonal antibodies specific for the acid-treated spike protein. E1 and E2 reacted with the antibodies after treatment of wild-type or mutant virus at the pH of fusion. The E1 conformational change resembled fusion in its requirement for both low pH and cholesterol. Pulse-chase analysis and intracellular pH treatment were then used to determine the ability of the newly synthesized spike to undergo acid-induced conformational changes. p62, the precursor to E2 and E3, was shown to undergo a pH-dependent conformational change similar to that of E2 and was sensitive to acid very soon after biosynthesis. In contrast, a posttranslational maturation event was required for the conversion of E1 to the pH-sensitive form. E1 maturation occurred fairly late in the exocytic pathway, after the virus spike had passed the medial Golgi but before incorporation of the spike into a new virus particle.
Vasopressin Injected into the Hypothalamus Triggers a Stereotypic Behavior in Golden Hamsters (1984)

Microinjection of arginine vasopressin into the medial preoptic area of the hypothalamus of male and female golden hamsters triggered a complex, stereotypic behavior--flank marking--a type of scent marking used in olfactory communication. The flank marking was not elicited by saline, oxytocin, neurotensin, or angiotensin II. Vasopressin was ineffective when injected into other areas of the hypothalamus or into the lateral cerebroventricle.
Microheaters fabricated from a conducting composite (2006)

The authors report the fabrication of microheaters based on a conducting composite of silver microparticles embedded in polydimethylsioxane (PDMS). Experimental results show that the microheaters exhibit good performance in temperature rise and decay characteristics, with localized heating at targeted spatial domains. A unique feature of the microheater here is its excellent integration capability with biocompatible PDMS and other polymer materials, with potential microchip applications for bioprocessing and chemical reactions.
Pediatric Obstructive Sleep Apnea: Complications, Management, and Long-term Outcomes (2008)

Obstructive sleep apnea (OSA) in children has emerged not only as a relatively prevalent condition but also as a disease that imposes a large array of morbidities, some of which may have long-term implications, well into adulthood. The major consequences of pediatric OSA involve neurobehavioral, cardiovascular, and endocrine and metabolic systems. The underlying pathophysiological mechanisms of OSA-induced end-organ injury are now being unraveled, and clearly involve oxidative and inflammatory pathways. However, the roles of individual susceptibility (as dictated by single-nucleotide polymorphisms), and of environmental and lifestyle conditions (such as diet, physical, and intellectual activity), may account for a substantial component of the variance in phenotype. Moreover, the clinical prototypic pediatric patient of the early 1990s has been insidiously replaced by a different phenotypic presentation that strikingly resembles that of adults afflicted by the disease. As such, analogous to diabetes, the terms type I and type II pediatric OSA have been proposed. The different manifestations of these two entities and their clinical course and approaches to management are reviewed.
Prolonged Survival of Dendritic Cell–Vaccinated Melanoma Patients Correlates With Tumor-Specific Delayed Type IV Hypersensitivity Response and Reduction of Tumor Growth Factor β-Expressing T Cells (2009)

Our findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFbeta+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.