gebhart/patrepeval huggingface dataset:
A Kinetic Model Explains Why Shorter and Less Affine Enzyme-recruiting Oligonucleotides Can Be More Potent (2014)

Antisense oligonucleotides complementary to RNA targets promise generality and ease of drug design. The first systemically administered antisense drug was recently approved for treatment and others are in clinical development. Chemical modifications that increase the hybridization affinity of oligonucleotides are reasoned to confer higher potency, i.e., modified oligonucleotides can be dosed at lower concentrations to achieve the same effect. Surprisingly, shorter and less affine oligonucleotides sometimes display increased potency. To explain this apparent contradiction, increased uptake or decreased propensity to form structures have been suggested as possible mechanisms. Here, we provide an alternative explanation that invokes only the kinetics behind oligonucleotide-mediated cleavage of RNA targets. A model based on the law of mass action predicts, and experiments support, the existence of an optimal binding affinity. Exaggerated affinity, and not length per se, is detrimental to potency. This finding clarifies how to optimally apply high-affinity modifications in the discovery of potent antisense oligonucleotide drugs.
Concurrent Increases in the Storage and Release of Mucin-Like Molecules by Rat Airway Epithelial Cells in Response to Bacterial Endotoxin (1995)

Mucus hypersecretion is a prominent response of the airways to bacterial infections. Recent findings showed that bacterial endotoxin, a lipopolysaccharide complex released from the bacterial cell wall, was able to induce at least one component of the hypersecretory response, i.e., an increase in the amount of stored epithelial mucosubstances (1, 2). The goal of the present study was to determine whether endotoxin also was capable of increasing mucosubstance release from cells. Based on evidence that human mucin antibodies A10G5 and B6E8 cross-reacted with rat mucin-like molecules, we used the antibodies in enzyme-linked immunosorbent assays (ELISA) to compare mucin concentrations in bronchoalveolar lavage (BAL) fluid from endotoxin-treated and control rats. Results showed that endotoxin treatment increased the amount of released mucin over that in controls 1.5-fold at 96 h and 2.5-fold at 168 h after instillation. Thus, these studies have defined the previously detected mucosubstances as mucin-like molecules and showed that endotoxin increases their release from, as well as their storage in, rat airway epithelium. Concurrent increases in storage and release suggest that endotoxin also stimulates mucin synthesis and/or stability.
TectoRNA: modular assembly units for the construction of RNA nano-objects (2001)

Structural information on complex biological RNA molecules can be exploited to design tectoRNAs or artificial modular RNA units that can self-assemble through tertiary interactions thereby forming nanoscale RNA objects. The selective interactions of hairpin tetraloops with their receptors can be used to mediate tectoRNA assembly. Here we report on the modulation of the specificity and the strength of tectoRNA assembly (in the nanomolar to micromolar range) by variation of the length of the RNA subunits, the nature of their interacting motifs and the degree of flexibility of linker regions incorporated into the molecules. The association is also dependent on the concentration of magnesium. Monitoring of tectoRNA assembly by lead(II) cleavage protection indicates that some degree of structural flexibility is required for optimal binding. With tectoRNAs one can compare the binding affinities of different tertiary motifs and quantify the strength of individual interactions. Furthermore, in analogy to the synthons used in organic chemistry to synthesize more complex organic compounds, tectoRNAs form the basic assembly units for constructing complex RNA structures on the nanometer scale. Thus, tectoRNA provides a means for constructing molecular scaffoldings that organize functional modules in three-dimensional space for a wide range of applications.
A biomarker for the assessment of niacin nutriture as a potential preventive factor in carcinogenesis (1993)

The study of protective cellular responses to DNA damage has led to the working hypothesis that optimal niacin nutriture is a preventive factor in cancer. Described here is the development of a biomarker for determining niacin status termed Niacin Number. The combination of this biomarker with diet and cancer epidemiology will allow evaluation of the possible role of this nutrient in cancer risk.
Intratumoral Aromatase in Human Breast, Endometrial, and Ovarian Malignancies* (1998)

In human estrogen-dependent neoplasms such as breast, endometrioid endometrial, and surface epithelial-stromal ovarian carcinomas, intratumoral aromatase is considered to play important roles in converting circulating androgens derived from adrenal cortex and/or ovary to estrogens, possibly in association with 17 beta-HSD type 1 and estrogen sulfatase. Analysis of intratumoral aromatase in these estrogen-dependent neoplasms is important not only in understanding the development and biological behavior of these tumors, but also in the clinical management of these patients, because suppression of intratumoral aromatase by newly developed aromatase inhibitors may provide new potentials in endocrine therapy of these patients.
Pruritus—itching for a cause and relief? (1996)

The mechanisms of pruritus, an unpleasant irritation on the skin that provokes an urge to scratch, are reviewed. Whilst symptomatic treatment is only partially effective, antihistamines remain the first choice of treatment. However, recent novel treatment using opiate antagonists, propofol (subhypnotic doses) and serotonin antagonists offer attractive alternatives.
Comparison of the gut microbiota composition between obese and non-obese individuals in a Japanese population, as analyzed by terminal restriction fragment length polymorphism and next-generation sequencing (2015)

Gut microbial properties differ between obese and non-obese subjects in Japan, suggesting that gut microbiota composition is related to obesity.
Addition of dienophiles to the acridizinium ion. III. Evidence for a two-step reaction (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAddition of dienophiles to the acridizinium ion. III. Evidence for a two-step reactionCharles K. Bradsher and John Arthur StoneCite this: J. Org. Chem. 1969, 34, 6, 1700–1702Publication Date (Print):June 1, 1969Publication History Published online1 May 2002Published inissue 1 June 1969https://pubs.acs.org/doi/10.1021/jo01258a037https://doi.org/10.1021/jo01258a037research-articleACS PublicationsRequest reuse permissionsArticle Views48Altmetric-Citations13LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Proliferation and differentiation of mesenchymal stem cells in alginate beads solution in vitro (2006)

[Objective]To detect the effect on proliferation and differentiation of mesenchymal stem cells(MSCs)by alginate beads and to evaluate their possible use in bone tissue engineering.[Method]After MSCs were planted in alginate beads solution,proliferation and differentiation of MSCs were observed and detected.In growth medium,proliferation of MSCs was estimated by growth curve and cell cycle.In osteogenesis medium,differentiation of MSCs was evaluated by the value of intra-cellular alkaline phosphatase(ALP)and staining by alizarin Bordeaux.[Result]The different effects on proliferation of MSCs were made by different concentration alginate beads solution.With the increase of concentration,proliferation of MSCs was depressed.When concentration was 10 g/L,MSCs hardly proliferated in it.In osteogenesis medium,alginate beads solution could enhance produce of ALP in MSCs.Moreover,more high concentration alginate beads solution could promote differentiation of osteoblast from MSCs and produce of more extracecullar matrix including calcium.[Conclusion]The alginate beads solution under some concentration not only hardly affected proliferation of MSCs but also increased the produce of cues that lay in osteoblasts,and more extracellular matrix including calcium.
Planning a Coal Supply for Darwin (1987)

The paper describes the experience of the Northern Territory Electricity Commission in 1982-84 in attempting to procure a secure, cost effective supply of steaming coal for the then proposed, but now abandoned, Darwin coal-fired power station. It was found that the cost of interstate coal supplies was intolerably high because of the need for high quality coal, the high government charges which are imposed on the production and transport of such coal and the high cost of shipping in relatively small Australian coastal vessels.
Outlier detection in graph streams (2011)

A number of applications in social networks, telecommunications, and mobile computing create massive streams of graphs. In many such applications, it is useful to detect structural abnormalities which are different from the “typical” behavior of the underlying network. In this paper, we will provide first results on the problem of structural outlier detection in massive network streams. Such problems are inherently challenging, because the problem of outlier detection is specially challenging because of the high volume of the underlying network stream. The stream scenario also increases the computational challenges for the approach. We use a structural connectivity model in order to define outliers in graph streams. In order to handle the sparsity problem of massive networks, we dynamically partition the network in order to construct statistically robust models of the connectivity behavior. We design a reservoir sampling method in order to maintain structural summaries of the underlying network. These structural summaries are designed in order to create robust, dynamic and efficient models for outlier detection in graph streams. We present experimental results illustrating the effectiveness and efficiency of our approach.
Brain Dynamics and Hypnosis: Attentional and Disattentional Processes (1994)

This article reviews recent research findings, expanding an evolving neuropsychophysiological model of hypnosis (Crawford, 1989; Crawford & Gruzelier, 1992), that support the view that highly hypnotizable persons (highs) possess stronger attentional filtering abilities than do low hypnotizable persons, and that these differences are reflected in underlying brain dynamics. Behavioral, cognitive, and neurophysiological evidence is reviewed that suggests that highs can both better focus and sustain their attention as well as better ignore irrelevant stimuli in the environment. It is proposed that hypnosis is a state of enhanced attention that activates an interplay between cortical and subcortical brain dynamics during hypnotic phenomena, such as both attentional and disattentional processes, among others, are important in the experiencing of hypnosis and hypnotic phenomena. Findings from studies of electrocortical activity, event-related potentials, and regional cerebral blood flow during waking and hypnosis are presented to suggest that these attentional differences are reflected in underlying neurophysiological differences in the far fronto-limbic attentional system.
An in vivo study of turbidity suppression by optical phase conjugation (TSOPC) on rabbit ear (2009)

We present a holography-based in vivo optical phase conjugation experiment performed on a living rabbit ear. The motion of live tissues caused the phase conjugate signal to decay with a consistent decay time of less than two seconds. We monitor the signal decay time variation after the ear is excised to postulate different mechanisms that cause the signal decay. The experimental findings address the minimum speed limit of a broad range of optical time reversal experiments for in vivo applications on tissues.
Increased expression of inducible and endothelial constitutive nitric oxide synthases in rat colon tumors induced by azoxymethane. (1997)

Nitric oxide (NO) is an important bioregulatory mediator involved in a variety of biological processes under both physiological and pathological conditions. To assess whether NO production is altered in colon carcinogenesis, the expression levels and localization of two isoforms of NO synthase, inducible NO synthase (iNOS) and endothelial constitutive NO synthase (eNOS), were examined by immunoblot and immunohistochemical methods in normal colonic mucosa and colon carcinomas induced by azoxymethane in male F344 rats. All colon carcinoma tissues examined were found to have an increased expression of iNOS and eNOS proteins as compared to normal colonic mucosa. In particular, the pronounced staining of iNOS protein localized to the luminal surface of carcinoma epithelial cells was not detectable in normal colon epithelium. The neovasculature in tumor tissues also demonstrated intense eNOS immunoreactivity in endothelial cells. These findings indicate that NO production is markedly elevated in azoxymethane-induced rat colon carcinomas, suggesting that regulatory pathways involving this mediator have some biological relevance to colon carcinogenesis in this model.
Experiments with data-intensive NLP on a computational grid (2004)

Large databases of annotated text and speech are widely used for developing and testing language technologies. However, the size of these corpora and associated language models are outpacing the growth of processing power and network bandwidth available to most researchers. The solution, we believe, is to exploit four characteristics of language technology research: many large corpora are already held at most sites where the research is conducted; most dataintensive processing takes place in the development phase and not at run-time; most processing tasks can be construed as adding layers of annotation to immutable corpora; and many classes of language models can be approximated as the sum of smaller models. We report on a series of experiments with data-intensive language processing on a computational grid. Key features of the approach are its use of a scripting language for easy dissemination of control code to processing nodes, the use of a grid broker to manage the execution of tasks on remote nodes and collate their output, the use a data-decomposition approach by which parametric and parallel processing of individual language processing components occurs on segmented data, and the use of researchers ’ underutilized commodity machines. 1
DNA ligase I null mouse cells show normal DNA repair activity but altered DNA replication and reduced genome stability (2002)

DNA ligase I is the key ligase for DNA replication in mammalian cells and has also been reported to be involved in a number of recombination and repair processes. Our previous finding that Lig1 knockout mouse embryos developed normally to mid-term before succumbing to a specific haematopoietic defect was difficult to reconcile with a report that DNA ligase I is essential for the viability of cultured mammalian cells. To address this issue, we generated a second Lig1 targeted allele and found that the phenotypes of our two Lig1 mutant mouse lines are identical. Widely different levels of Lig1 fusion transcripts were detected from the two targeted alleles, but we could not detect any DNA ligase I protein, and we believe both are effective Lig1 null alleles. Using foetal liver cells to repopulate the haematopoietic system of lethally irradiated adult mice, we demonstrate that the haematopoietic defect in DNA-ligase-I-deficient embryos is a quantitative deficiency relating to reduced proliferation rather than a qualitative block in any haematopoietic lineage. DNA ligase I null fibroblasts from Lig1 mutant embryos showed an accumulation of DNA replication intermediates and increased genome instability. In the absence of a demonstrable deficiency in DNA repair we postulate that, unusually, genome instability may result directly from the DNA replication defect. Lig1 null mouse cells performed better in the survival and replication assays than a human LIG1 point mutant, and we suggest that the complete absence of DNA ligase I may make it easier for another ligase to compensate for DNA ligase I deficiency.
Abnormal intestinal permeability in children with autism (1996)

We determined the occurrence of gut mucosal damage using the intestinal permeability test in 21 autistic children who had no clinical and laboratory findings consistent with known intestinal disorders. An altered intestinal permeability was found in 9 of the 21 (43%) autistic patients, but in none of the 40 controls. Compared to the controls, these nine patients showed a similar mean mannitol recovery, but a significantly higher mean lactulose recovery (1.64% +/- 1.43 vs 0.38% +/- 0.14; P < 0.001). We speculate that an altered intestinal permeability could represent a possible mechanism for the increased passage through the gut mucosa of peptides derived from foods with subsequent behavioural abnormalities.
RECOGNITION OF RADICALS IN HANDWRITTEN CHINESE CHARACTERS BY MEANS OF PROBLEM REDUCTION AND KNOWLEDGE GUIDANCE (1996)

Recognizing handwritten Chinese characters is a complex problem. We break the problem down into a series of sub-problems and concentrate on the radical recognition problem. The sub-problems are linked in a hierarchy of three layers: radical, radical sub-unit, and salient stroke. This problem reduction technique enables us to solve complex recognition problems effectively. We describe how to analyze and choose radical sub-units and salient strokes in order to recognize a set of radicals. We also construct two knowledge bases in the form of decision trees to guide the hypothesis and test procedures used to solve the recognition sub-problems. The problem reduction is done in a top-down fashion, while the problem solving process proceeds in a bottom-up fashion. The advantages of our method are described. The representation and organization of the two knowledge bases are explicitly described. The method is tested on two sets of handprinted characters using an IBM PC (486-33). The recognition rate is over 95.7% and the computer time needed to recognize a radical averages about 0.07 s. The experimental results indicate that our method effectively copes with a wide range of ordinary variations encountered in handwritten Chinese characters.
Dihydroxyacetone Kinases in Saccharomyces cerevisiaeAre Involved in Detoxification of Dihydroxyacetone (2003)

The genes YML070W/DAK1 and YFL053W/DAK2 in the yeast Saccharomyces cerevisiae were characterized by a combined genetic and biochemical approach that firmly functionally classified their encoded proteins as dihydroxyacetone kinases (DAKs), an enzyme present in most organisms. The kinetic properties of the two isoforms were similar, exhibiting K(m)((DHA)) of 22 and 5 microm and K(m)((ATP)) of 0.5 and 0.1 mm for Dak1p and Dak2p, respectively. We furthermore show that their substrate, dihydroxyacetone (DHA), is toxic to yeast cells and that the detoxification is dependent on functional DAK. The importance of DAK was clearly apparent for cells where both isogenes were deleted (dak1 Delta dak2 Delta), since this strain was highly sensitive to DHA. In the opposite case, overexpression of either DAK1 or DAK2 made the dak1 Delta dak2 Delta highly resistant to DHA. In fact, overexpression of either DAK provided cells with the capacity to grow efficiently on DHA as the only carbon and energy source, with a generation time of about 5 h. The DHA toxicity was shown to be strongly dependent on the carbon and energy source utilized, since glucose efficiently suppresses the lethality, whereas galactose or ethanol did so to a much lesser extent. However, this suppression was found not to be explained by differences in DHA uptake, since uptake kinetics revealed a simple diffusion mechanism with similar capacity independent of carbon source. Salt addition strongly aggravated the DHA toxicity, independent of carbon source. Furthermore, the DHA toxicity was not linked to the presence of oxygen or to the known harmful agents methylglyoxal and formaldehyde. It is proposed that detoxification of DHA may be a vital part of the physiological response during diverse stress conditions in many species.
Molecular Mechanisms of Antibiotic Resistance in Gram-Positive Pathogens. (2001)

The widespread and uncontrolled use of antibiotics, both for human consumption and animal feed, has encouraged the development of drug resistance in a variety of pathogenic bacteria. Gram-positive species employ resistance mechanisms which include the modification of the antibiotic structure, mutagenesis of key amino acids in the macromolecular targets of specific chemotherapeutics, or drug efflux from the cell, among others. These three main mechanisms have been identified in resistance profiles for systems involved in protein biosynthesis, nucleic acid replication, and bacterial cell wall generation. This work will review how Gram-positive bacteria have manipulated all three classes of targets in the generation of resistance. Upcoming and recently approved antibacterials for human consumption will also be highlighted.
Algae biomass: production and use (1980)

Diagrs., illus., tables. Includes bibliographies. Summaries (En). Papers written or rev. and updated to 1980 of lectures presented at the Int. Symp. on the Prod. and Use of Micro-Algae Biomass, Akko Sep 1978
Event-based electric vehicle scheduling considering random user behaviors (2015)

Uncontrolled Electric Vehicle (EV) and Plug-in Hybrid Electric Vehicle (PHEV) charging within a local distribution grid may cause unexpected high load, which further results in power quality degradation. However, coordinating charging behaviors of a number of EVs is a challenging task, which involves not only the deterministic schedule computing but also nondeterministic EV driver behaviors with random arrival time and energy demands. Previous researches in this area rarely consider these random behaviors for real EV users. In this paper, an implementable event-based cost optimal scheduling algorithm (ECSA) is developed, which solves EV scheduling problem by dynamically estimating the stay duration and energy demand for each participating EV user. Datasets, including users' historical charging records and time series meter data collected from Electric Vehicle Supply Equipments (EVSEs) in UCLA campus, are utilized for feature extraction. Based on that, proper inference technique is employed to determine parameters within each charging session. In addition, solar generation integration into EVSEs is also considered in our problem formulation. The proposed approaches are tested and validated by real EV charging schedules of users in UCLA campus. The results from simulation experiment demonstrate that the proposed algorithm has a better performance in cost minimization and load shifting compared to existing equal-sharing scheduling algorithm (ESSA).