gebhart/patrepeval huggingface dataset:
Solution Structure, Mechanism of Replication, and Optimization of an Unnatural Base Pair (2010)

As part of an ongoing effort to expand the genetic alphabet for in vitro and eventual in vivo applications, we have synthesized a wide variety of predominantly hydrophobic unnatural base pairs and evaluated their replication in DNA. Collectively, the results have led us to propose that these base pairs, which lack stabilizing edge-on interactions, are replicated by means of a unique intercalative mechanism. Here, we report the synthesis and characterization of three novel derivatives of the nucleotide analogue dMMO2, which forms an unnatural base pair with the nucleotide analogue d5SICS. Replacing the para-methyl substituent of dMMO2 with an annulated furan ring (yielding dFMO) has a dramatically negative effect on replication, while replacing it with a methoxy (dDMO) or with a thiomethyl group (dTMO) improves replication in both steady-state assays and during PCR amplification. Thus, dTMO-d5SICS, and especially dDMO-d5SICS, represent significant progress toward the expansion of the genetic alphabet. To elucidate the structure-activity relationships governing unnatural base pair replication, we determined the solution structure of duplex DNA containing the parental dMMO2-d5SICS pair, and also used this structure to generate models of the derivative base pairs. The results strongly support the intercalative mechanism of replication, reveal a surprisingly high level of specificity that may be achieved by optimizing packing interactions, and should prove invaluable for the further optimization of the unnatural base pair.
Silencing Viral Infection (2006)

The authors describe recent progress and obstacles to harnessing RNA interference to prevent or treat viral infection.
The personal internet (2010)

PeCMan, the Personal Content Manager, is a content access gateway, aggregator, indexing, and sharing tool for all of a user's personally relevant content on the Internet, e.g., all the content a user has created, content that was explicitly shared by others, or publicly available Internet content of specific interest. PeCMan aggregates access to multiple network-based storage systems, services, or other “objects” by their reference. Examples of such objects are photographs, music, e-mail, text documents, or any addressable object on the Internet. The aggregated storage acts as a virtual read-write drive in which PeCMan addresses individual objects by reference, typically encoded in uniform resource locators (URLs). To address content in Web applications such as Google Docs, Flickr, and YouTube, the URL is based on the corresponding application programming interface (API), while content on a user's home machine's disk is addressed via a locally installed software driver supporting Web-based distributed authoring and versioning (WebDAV). This paper describes the motivation, design, and implementation prototype of PeCMan. é 2010 Alcatel-Lucent.
AUTOMATIC GENERATION OF BUILDING MODELS FROM LIDAR DATA AND THE INTEGRATION OF AERIAL IMAGES (2003)

ADC is a promising imaging biomarker that can help differentiate succinate dehydrogenase mutation-positive from mutation-negative paragangliomas in the head and neck.
Metabolite Profiling in Blood Plasma (2007)

Metabolite profiling has been established as a multiparallel strategy for relative quantification of a mixture of compounds or compound classes using chromatography and universal detection technologies (gas chromatography-mass spectrometry [GC-MS], liquid chromatography-MS). Despite its origins dating back to the late 1960s, it was only in the 1980s that its use was acknowledged to diagnose metabolic disorders in men, especially for rapid screening of inborn errors. Even faster electrospray ionization-MS/MS screening methods replaced longish chromatographic methods, and method development had stopped despite its potential use for other, less imminent diseases such as likelihood assessments of type II diabetes mellitus or cardiovascular risk factor evaluation. In addition to its diagnostic use, profiling blood samples can be employed to investigate specific biochemical responses. The broader scope of analysis outweighs the disadvantages by taking compromises in method development and the reduced accuracy for specific metabolites. This chapter exemplifies the strategies in metabolite profiling by GC-MS. It gives experimental details on basic steps like blood plasma withdrawal, storage, protein precipitation, extraction, concentration, derivatization, data acquisition, raw data processing, and result data tranformation. A major difference to profiling plant tissues is that no fractionation step is utilized, enabling the analysis of primary metabolites like sugars and amino acids concomitant with lipids such as sterols and free fatty acids.
Normal and Abnormal Heme Biosynthesis. 2.1 Synthesis and Metabolism of Type-III Pentacarboxylic Porphyrinogens:  Further Experimental Evidence for the Enzymic Clockwise Decarboxylation of Uroporphyrinogen-III (1998)

Uroporphyrinogen decarboxylase catalyses the sequential decarboxylation of uroporphyrinogen-III (1) to give coproporphyrinogen-III (2), a precursor to the hemes and chlorophylls. This involves the decarboxylation of four nonequivalent acetate side chains to produce methyl units and in principle could take place by 24 different pathways involving up to 14 intermediary porphyrinogens. In the past, seemingly contradictory data have been presented that either support an ordered “clockwise” decarboxylation pathway or a random decarboxylation process. Four pentacarboxylate porphyrinogens might be involved immediately before the formation of 2, and these compounds have been synthesized as the corresponding porphyrin pentamethyl esters via tripyrrene and a,c-biladiene intermediates. Hydrolysis of the methyl esters and reduction with 3% sodium amalgam gave the required porphyrinogens, and these were incubated with crude enzyme preparations derived from chicken red cell hemolysates. One of these pentacarboxylate porphyrinogens (5dab) consistently proved to be a much better substrate than the other three, providing new support for the “clockwise” pathway for coproporphyrinogen-III formation.
ePluribus: Ethnicity on Social Networks (2010)

We propose an approach to determine the ethnic breakdown of a population based solely on people's names and data provided by the U.S. Census Bureau. We demonstrate that our approach is able to predict the ethnicities of individuals as well as the ethnicity of an entire population better than natural alternatives. We apply our technique to the population of U.S. Facebook users and uncover the demographic characteristics of ethnicities and how they relate. We also discover that while Facebook has always been diverse, diversity has increased over time leading to a population that today looks very similar to the overall U.S. population. We also find that different ethnic groups relate to one another in an assortative manner, and that these groups have different profiles across demographics, beliefs, and usage of site features.
Streptococcus pneumoniae: virulence factors, pathogenesis, and vaccines. (1995)

Although pneumococcal conjugate vaccines are close to being licensed, a more profound knowledge of the virulence factors responsible for the morbidity and mortality caused by Streptococcus pneumoniae is necessary. This review deals with the major structures of pneumococci involved in the pathogenesis of pneumococcal disease and their interference with the defense mechanisms of the host. It is well known that protection against S. pneumoniae is the result of phagocytosis of invading pathogens. For this process, complement and anticapsular polysaccharide antibodies are required. Besides, relatively recent experimental data suggest that protection is also mediated by the removal of disintegrating pneumococci and their degradation products (cell wall, pneumolysin). These structures seem to be major contributors to illness and death caused by pneumococci. An effective conjugate vaccine should therefore preferably include the capsular polysaccharide and at least one of these inflammatory factors.
Self-Tolerance Checkpoints in B Lymphocyte Development (1995)

The chapter discusses humoral self-tolerance as the cumulative action of a series of separate checkpoints placed along the B cell lineage. The strategy of employing multiple and distinct checkpoints presumably minimizes the risk that one or two inherited or somatically acquired mutations leads to uncontrolled autoantibody production, analogous to the role of checkpoints in the cell cycle that minimize neoplasia. Each checkpoint may depend on distinct sets of genes and molecules. From a genetic perspective, the use of broad terms such as “deletion” or “anergy” can be used to describe several distinct checkpoint mechanisms that likely involve discrete molecular pathways. The chapter discusses self-tolerance checkpoints acting (1) during formation of the pre-immune B cell repertoire and (2) during subsequent formation of an immune repertoire. A series of cellular phenomena potentially censor and remove autoantibody-bearing B cells from the pathway to antibody secretion. Each of these checkpoints has triggering thresholds that depend on the local auto-antigen concentration, auto-antigen valency, and the B cell's binding affinity for elimination of auto-reactive B cells in the bone marrow. These thresholds impose limits on the extent of tolerance.
Structure and Mechanical Properties of an O70 (Fddd) Network-Forming Pentablock Terpolymer (2008)

Symmetric poly(ethylene oxide-b-styrene-b-isoprene-b-styrene-b-ethylene oxide) (OSISO) pentablock terpolymers with narrow molecular weight distributions in all blocks were synthesized by anionic polymerization. These OSISO pentablock terpolymers have a common poly(styrene-b-isoprene-b-styrene) (SIS) core containing equal volume fractions of polyisoprene and polystyrene but having different lengths of terminal poly(ethylene oxide) (PEO) chains. Small-angle X-ray scattering, transmission electron microscopy, dynamic mechanical spectroscopy, and differential scanning calorimetry were used to identify two-domain lamellae, O70 (the orthorhombic Fddd network), and three-domain lamellae (LAM3) in the OSISO materials; these morphologies were previously identified in poly(isoprene-b-styrene-b-ethylene oxide) (ISO) triblock terpolymers with comparable compositions. Mechanical tensile testing was employed to probe the consequences of adding different lengths of semicrystalline PEO to the ends of intrinsically tough SIS triblock. An OSISO sample with the LAM3 mesostructure fractured in a brittle fashion at a strain of 0.06 while an OSISO containing the O70 network, in contrast, had a strain at failure of 1.3, even though the crystallinity of the terminal PEO blocks was above the brittle threshold established in other multiblock materials. This improved toughness is attributed to the combined effects of a triply continuous morphology and an intrinsically tough SIS core.
Comprehensive Proteomic Analysis of Shigella flexneri 2a Membrane Proteins (2006)

Shigella flexneri is the causative agent of most shigellosis cases in developing countries. We used different proteolytic enzymes to selectively shave the protruding proteins on the surface of purified bacterial membrane sheets or vesicles, and recovered peptides were subsequently identified using 2-D LC-MS/MS. As a result, a total of 666 proteins were unambiguously assigned, including 159 integral membrane proteins, 35 outer membrane proteins and 114 proteins previously annotated as hypothetical. The former had an average grand average hydrophobicity score of 0.362 and were predicted to separate within a pH range of 4.1-10.6 with molecular mass 8-148 kDa, which represents the largest validated set of integral membrane proteins in this organism to date. A functional classification revealed that a large proportion of the identified proteins were involved in cell envelope biogenesis and energy production and conversion. For the first time, this work provides a global view of the S. flexneri 2a membrane subproteome.
Killing of Neisseria gonorrhoeae, Streptococcus agalactiae (Group B Streptococcus), Haemophilus ducreyi , and Vaginal Lactobacillus by 3- O -Octyl- sn -Glycerol (2008)

The microbicide candidate octylglycerol inactivates sexually transmitted bacterial pathogens at concentrations which spare normal vaginal flora (lactobacillus). Standard minimum microbicidal concentration assays and time-kill assays revealed the drug concentrations and times required for inactivation. Octylglycerol concentrations must exceed the binding capacity of any human serum albumin to be effective.
Replication and Repair of DNA in Cells of Escherichia coli Treated with Toluene (1970)

DNA synthesis has been studied in Escherichia coli cells made permeable to nucleotides by treatment with toluene. Replicative synthesis, as distinguished from repair synthesis, occurs at a rate comparable to that observed in vivo; it is dependent on the presence of all four deoxyribonucleoside triphosphates, but does not require exogenous DNA; and it is stimulated by ATP. Furthermore, replicative synthesis can be abolished at the restrictive temperature in DNA temperature-sensitive mutants. N-ethylmaleimide completely inhibits this type of synthesis, whereas it does not inhibit repair synthesis. Repair synthesis further differs from replicative synthesis in the following points: it does not require ATP; it persists at the restrictive temperature in DNA temperature-sensitive mutants; it can be induced by endogenous or exogenous nuclease activity; and its demonstration requires a Pol(+) strain.
Fabry Disease: Perspectives from 5 Years of FOS (2006)

Published to commemorate the first 5 years of the Fabry Outome Survey, this volume brings together contributions from leading experts in the field of lysosomal storage diseases (LSDs) in general and Fabry disease in particular in a single state-of-the-art publication. The first section covers general aspects of LSDs, with chapters on topics as diverse as the cellular pathophysiology of lysosomes, the development of enzyme replacement therapy (ERT), the central role played by patient groups, and the regulatory framework governing the treatment of orphan diseases. The second section describes the role of observational outcome surveys and the organization and development of FOS. The third and fourth sections draw largely, but not exclusively, from data in FOS. They describe the clinical features and natural course of Fabry disease and the multiple beneficial effects of ERT with agalsidase alfa on the function of affected organs and quality of life.By the end of 2005, FOS contained comprehensive information on over 750 patients from 13 countries. This outcome survey has therefore been able to greatly extend the information previously available from limited small-scale clinical trials, and reflects the clinical picture of Fabry disease and its response to ERT with agalsidase alfa within the context of normal clinical practice.
50인 이상 제조업 사업장의 비정규직 근로자 고용비율에 따른 재해율 (2008)

Objectives: The purpose of this study is to analyze the occupational safety and health(OSH) state of precarious employee. Methods: The questionnaire of this survey is composed of 9 categories that are the workplace general information and the state of occupational injury and disease, OSH organization, OSH education and training. The subjects of this survey were the Manufacturing. The hypothesis of this study is where the proportion of precarious employee is higher, the OSH state is worse. To verify this hypothesis, we grouped the subjects into three categories by the proportion of precarious employee like as 0%(all standard employee), less than 30% and 30% or more. Using the SPSS 12.0 program to analyze the data, logistic regression analysis were implemented to find affective factors for the rate of occupational injury and disease. Results: 2,633 manufacturing workplaces were included for subjects. The proportions of precarious employee were 9.6 %. In manufacturing industry, about 70 % companies had no precarious employee. 16.8 % companies were in less than 30 % group, 13.2% companies were in 30% or more group. For the rate of occupational injury and disease, the precarious group were 0.85(±1.8), 1.19(±2.9), 0.59(±1.1). There was a trend that the higher precarious proportion groups was the higher rate of occupational injury and disease by the logistic regression analysis. It is more strong relationship than company size and OSH committee. Conclusions: We could find a significant result there was a positive relationship between the hiring proportion of precarious employee and the rate of occupational injury and disease in manufacturing industry with 50 employees and more.
A "Silent" Polymorphism in the MDR 1 Gene Changes Substrate Specificity (2006)

Synonymous single-nucleotide polymorphisms (SNPs) do not produce altered coding sequences, and therefore they are not expected to change the function of the protein in which they occur. We report that a synonymous SNP in the Multidrug Resistance 1 (MDR1) gene, part of a haplotype previously linked to altered function of the MDR1 gene product P-glycoprotein (P-gp), nonetheless results in P-gp with altered drug and inhibitor interactions. Similar mRNA and protein levels, but altered conformations, were found for wild-type and polymorphic P-gp. We hypothesize that the presence of a rare codon, marked by the synonymous polymorphism, affects the timing of cotranslational folding and insertion of P-gp into the membrane, thereby altering the structure of substrate and inhibitor interaction sites.
On Environmental Thought at the Turn of the Century (2002)

Environmental issues are said to be "issues not just of science or economics but of governance." 1 If so, then these issues are at bottom philosophical.Since the time of Plato, the question of how we should govern ourselves cannot be asked without also asking, collectively, what kind of community we want to create and, individually, what kind of life each of us wants to live.Recent scholarship reveals a torrent of diverging approaches to the conceptual underpinnings of environmental law and policy.From historians chronicling the evolution of our understanding and attitudes toward nature, 2 political scientists analyzing the political ideology behind the modem green movement and philosophers exploring ways in which current ecological discourse can be enriched by a re-examination of the work of important thinkers in Western philosophy, such as Aristotle, Thomas Hobbes, and Immanuel Kant, 4 thinkers from a variety of fields are crossing disciplinary boundaries to address the environmental implications
Exercise Increases Neural Stem Cell Number in a Growth Hormone-Dependent Manner, Augmenting the Regenerative Response in Aged Mice (2009)

The exercise-induced enhancement of learning and memory, and its ability to slow age-related cognitive decline in humans led us to investigate whether running stimulates periventricular (PVR) neural stem cells (NSCs) in aging mice, thereby augmenting the regenerative capacity of the brain. To establish a benchmark of normal aging on endogenous NSCs, we harvested the PVR from serial vibratome sections through the lateral ventricles of juvenile (6-8 weeks), 6-, 12-, 18-, and 24-month-old mice, culturing the cells in the neural colony-forming cell assay. A significant decline in NSC frequency was apparent by 6 months ( approximately 40%), ultimately resulting in a approximately 90% reduction by 24 months. Concurrent with this decline was a progressive loss in regenerative capacity, as reflected by an incomplete repopulation of neurosphere-forming cells following gamma cell irradiation-induced depletion of the PVR. However, voluntary exercise (i.e., 21 days of running) significantly increased NSC frequency in mice > or = 18 months of age, augmenting the regeneration of irradiation-ablated periventricular cells and restoring NSC numbers to youthful levels. Importantly, and consistent with the demonstrated ability of growth hormone (GH) to increase NSC proliferation, and the elevated secretion of GH during exercise, exercise failed to stimulate NSCs in GH receptor-null mice. These findings now provide a novel basis for understanding the ability of exercise to delay the onset and rate of decline in neurodegenerative conditions not typically associated with the hippocampus and suggest that the GH-dependent activation of endogenous NSCs may be effective in reversing or preventing age-related neurodegeneration in humans.
Geometric Interpretation of Gene Coexpression Network Analysis (2008)

THE MERGING OF NETWORK THEORY AND MICROARRAY DATA ANALYSIS TECHNIQUES HAS SPAWNED A NEW FIELD: gene coexpression network analysis. While network methods are increasingly used in biology, the network vocabulary of computational biologists tends to be far more limited than that of, say, social network theorists. Here we review and propose several potentially useful network concepts. We take advantage of the relationship between network theory and the field of microarray data analysis to clarify the meaning of and the relationship among network concepts in gene coexpression networks. Network theory offers a wealth of intuitive concepts for describing the pairwise relationships among genes, which are depicted in cluster trees and heat maps. Conversely, microarray data analysis techniques (singular value decomposition, tests of differential expression) can also be used to address difficult problems in network theory. We describe conditions when a close relationship exists between network analysis and microarray data analysis techniques, and provide a rough dictionary for translating between the two fields. Using the angular interpretation of correlations, we provide a geometric interpretation of network theoretic concepts and derive unexpected relationships among them. We use the singular value decomposition of module expression data to characterize approximately factorizable gene coexpression networks, i.e., adjacency matrices that factor into node specific contributions. High and low level views of coexpression networks allow us to study the relationships among modules and among module genes, respectively. We characterize coexpression networks where hub genes are significant with respect to a microarray sample trait and show that the network concept of intramodular connectivity can be interpreted as a fuzzy measure of module membership. We illustrate our results using human, mouse, and yeast microarray gene expression data. The unification of coexpression network methods with traditional data mining methods can inform the application and development of systems biologic methods.