gebhart/patrepeval huggingface dataset:
Mouse Models of Cancer (2011)

Genetically engineered mouse models have significantly contributed to our understanding of cancer biology. They have proven to be useful in validating gene functions, identifying novel cancer genes and tumor biomarkers, gaining insight into the molecular and cellular mechanisms underlying tumor initiation and multistage processes of tumorigenesis, and providing better clinical models in which to test novel therapeutic strategies. However, mice still have significant limitations in modeling human cancer, including species-specific differences and inaccurate recapitulation of de novo human tumor development. Future challenges in mouse modeling include the generation of clinically relevant mouse models that recapitulate the molecular, cellular, and genomic events of human cancers and clinical response as well as the development of technologies that allow for efficient in vivo imaging and high-throughput screening in mice.
Phosphorylation. IV. Selective phosphorylation of the primary hydroxyl group in nucleosides (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhosphorylation. IV. Selective phosphorylation of the primary hydroxyl group in nucleosidesKinichi Imai, Shoichiro Fujii, Kunio Takanohashi, Yoshiyasu Furukawa, Toru Masuda, and Mikio HonjoCite this: J. Org. Chem. 1969, 34, 6, 1547–1550Publication Date (Print):June 1, 1969Publication History Published online1 May 2002Published inissue 1 June 1969https://pubs.acs.org/doi/10.1021/jo01258a004https://doi.org/10.1021/jo01258a004research-articleACS PublicationsRequest reuse permissionsArticle Views807Altmetric-Citations53LEARN 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
From IOPT Petri nets to C: An automatic code generator tool (2011)

This paper presents a tool for automatic generation of ANSI C code from models expressed in IOPT (Input-Output Place-Transition) Petri Nets. The inputs of the tool are PNML (Petri Nets Mark-up Language) files containing the IOPT Petri net models. The tool has two different interfaces: one relying on a simple graphical interface (amenable to be used by humans), and a second one with a command line interface (amenable to be used by humans as well as by other computational systems supporting tools interaction). The tool also allows the user to tune some parts of the automatically generated code considering some characteristics of the implementation platform improving the performance of the generated code. Generated code can be directly deployed into specific controllers; PIC low-cost microcontrollers as well as general purpose PCs have been used for validation.
In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers. (1992)

In the genetically restricted response that follows immunization with (4-hydroxy-3-nitrophenyl)acetyl coupled to protein carriers, two distinct populations of B cells are observed in the spleens of C57BL/6 mice. By 48 h postimmunization, foci of antigen-binding B cells appear along the periphery of the periarteriolar lymphoid sheaths. These foci expand to contain large numbers of antibody-forming cells that neither bind the lectin, peanut agglutinin, nor mutate the rearranged immunoglobulin variable region loci. Germinal centers containing peanut agglutinin-positive B cells can be observed by 96-120 h after immunization. Although specific for the immunizing hapten, these B cells do not produce substantial amounts of antibody, but are the population that undergoes somatic hypermutation and affinity-driven selection. Both focus and germinal center populations are pauciclonal, founded, on average, by three or fewer B lymphocytes. Despite the highly specialized roles of the focus (early antibody production) and germinal center (higher affinity memory cells) B cell populations, analysis of VH to D to JH joins in neighboring foci and germinal centers demonstrate that these B cell populations have a common clonal origin.
Estimation of probabilities from sparse data for the language model component of a speech recognizer (1987)

The description of a novel type of m-gram language model is given. The model offers, via a nonlinear recursive procedure, a computation and space efficient solution to the problem of estimating probabilities from sparse data. This solution compares favorably to other proposed methods. While the method has been developed for and successfully implemented in the IBM Real Time Speech Recognizers, its generality makes it applicable in other areas where the problem of estimating probabilities from sparse data arises.
A Training System of Orientation and Mobility for Blind People Using Acoustic Virtual Reality (2010)

A new auditory orientation training system was developed for blind people using acoustic virtual reality (VR) based on a head-related transfer function (HRTF) simulation. The present training system can reproduce a virtual training environment for orientation and mobility (O&M) instruction, and the trainee can walk through the virtual training environment safely by listening to sounds such as vehicles, stores, ambient noise, etc., three-dimensionally through headphones. The system can reproduce not only sound sources but also sound reflection and insulation, so that the trainee can learn both sound location and obstacle perception skills. The virtual training environment is described in extensible markup language (XML), and the O&M instructor can edit it easily according to the training curriculum. Evaluation experiments were conducted to test the efficiency of some features of the system. Thirty subjects who had not acquired O&M skills attended the experiments. The subjects were separated into three groups: a no-training group, a virtual-training group using the present system, and a real-training group in real environments. The results suggested that virtual-training can reduce "veering" more than real-training and also can reduce stress as much as real training. The subjective technical and anxiety scores also improved.
A Mutational Analysis of the Globotriaosylceramide-binding Sites of Verotoxin VT1 (2002)

Escherichia coli verotoxin, also known as Shiga-like toxin, binds to eukaryotic cell membranes via the glycolipid Gb(3) receptors which present the P(k) trisaccharide Galalpha(1-4)Galbeta(1-4)Glcbeta. Crystallographic studies have identified three P(k) trisaccharide (P(k)-glycoside) binding sites per verotoxin 1B subunit (VT1B) monomer while NMR studies have identified binding of P(k)-glycoside only at site 2. To understand the basis for this difference, we studied binding of wild type VT1B and VT1B mutants, defective at one or more of the three sites, to P(k)-glycoside and pentavalent P(k) trisaccharide (pentaSTARFISH) in solution and Gb(3) presented on liposomal membranes using surface plasmon resonance. Site 2 was the key site in terms of free trisaccharide binding since mutants altered at sites 1 and 3 bound this ligand with wild type affinity. However, effective binding of the pentaSTARFISH molecule also required a functional site 3, suggesting that site 3 promotes pentavalent binding of linked trisaccharides at site 1 and site 2. Optimal binding to membrane-associated Gb(3) involved all three sites. Binding of all single site mutants to liposomal Gb(3) was weaker than wild type VT1B binding. Site 3 mutants behaved as if they had reduced ability to enter into high avidity interactions with Gb(3) in the membrane context. Double mutants at site 1/site 3 and site 2/site 3 were completely inactive in terms of binding to liposomal Gb(3,) even though the site 1/site 3 mutant bound trisaccharide with almost wild type affinity. Thus site 2 alone is not sufficient to confer high avidity binding to membrane-localized Gb(3). Cytotoxic activity paralleled membrane glycolipid binding. Our data show that the interaction of verotoxin with the Gb(3) trisaccharide is highly context dependent and that a membrane environment is required for biologically relevant studies of the interaction.
Characteristics of silicon nano wire as piezoresistor for nano electro mechanical systems (2002)

In order to confirm ability of silicon nano wire piezoresistors as sensing element of mechanical sensors, current-voltage (I-V) characteristics and the piezoresistive effect were investigated. Electron beam (EB) direct writing and RIE were used for fabrication. Fabricated polycrystalline Si (poly-Si) nano wire piezoresistors have triangular or trapezoid cross sections. The minimum width is 53 nm and thickness is 32 nm. A remarkable phenomenon was observed. The longitudinal piezoresistive coefficient /spl pi//sub l/ of the nano wire piezoresistor increased with a decrease in the cross section area, while the transverse piezoresistive coefficient /spl pi//sub t/ was approximately zero and invariant despite variation of the cross section area. The maximum value of /spl pi//sub l/ was 22/spl times/10/sup -5/ (1/MPa) at impurity concentration N=5/spl times/10/sup 19/ (cm/sup -3/).
Invention (2007)

The analysis so far has hardly taken the passage of time into account. And yet it governs everything. Change is a universal process for humans, who have no equal in the animal kingdom when it comes to adaptability.1 This truism does not explain why small, simple societies tend to become larger, more complex ones. Adaptation to changing circumstances does not necessarily denote progress, but who can deny the cumulative growth of social complexity in every human group over the last 15,000 years? Humans have a longer period of dependency than any other primate, the most complex kin structures, and the widest generational overlapping, all of which help to transmit information and "social intelligence." This social intelligence becomes more accurate with usage, because humans everywhere display the same reflective rules of thumb that enable us to correct mistakes. Robert Wright invokes three important cognitive features that fuel invention: a genetic predisposition to want to understand how the world works; language, which enables us to strike bargains and share knowledge; and the universal desire to win the esteem of our peers, superiors, and subordinates, which works to reinforce the group to which we belong.
Going beyond the liver: Progress and challenges of targeted delivery of siRNA therapeutics (2015)

Therapeutic gene silencing promises significant progress in pharmacotherapy, including considerable expansion of the druggable target space and the possibility for treating orphan diseases. Technological hurdles have complicated the efficient use of therapeutic oligonucleotides, and siRNA agents suffer particularly from insufficient pharmacokinetic properties and poor cellular uptake. Intense development and evolution of delivery systems have resulted in efficient uptake predominantly in liver tissue, in which practically all nanoparticulate and liposomal delivery systems show the highest accumulation. The most efficacious strategies include liposomes and bioconjugations with N-acetylgalactosamine. Both are in early clinical evaluation stages for treatment of liver-associated diseases. Approaches for achieving knockdown in other tissues and tumors have been proven to be more complicated. Selective targeting to tumors may be enabled through careful modulation of physical properties, such as particle size, or by taking advantage of specific targeting ligands. Significant barriers stand between sufficient accumulation in other organs, including endothelial barriers, cellular membranes, and the endosome. The brain, which is shielded by the blood-brain barrier, is of particular interest to facilitate efficient oligonucleotide therapy of neurological diseases. Transcytosis of the blood-brain barrier through receptor-specific docking is investigated to increase accumulation in the central nervous system. In this review, the current clinical status of siRNA therapeutics is summarized, as well as innovative and promising preclinical concepts employing tissue- and tumor-targeted ligands. The requirements and the respective advantages and drawbacks of bioconjugates and ligand-decorated lipid or polymeric particles are discussed.
Transposons and genome evolution in plants (2000)

Although it is known today that transposons comprise a significant fraction of the genomes of many organisms, they eluded discovery through the first half century of genetic analysis and even once discovered, their ubiquity and abundance were not recognized for some time. This genetic invisibility of transposons focuses attention on the mechanisms that control not only transposition, but illegitimate recombination. The thesis is developed that the mechanisms that control transposition are a reflection of the more general capacity of eukaryotic organisms to detect, mark, and retain duplicated DNA through repressive chromatin structures.
Selection of Muscle-Binding Peptides from Context-Specific Peptide-Presenting Phage Libraries for Adenoviral Vector Targeting (2005)

Production of cell-targeting vectors in part involves the addition of new targeting ligands to the vector to mediate binding to the cells of interest. For viral vectors, the ideal approach is to genetically engineer new ligands into the capsid proteins of the virus to generate a single agent to mediate therapy. Although this is ideal, this insertion of an exogenous ligand from one structural context into the differing structural context of a capsid protein can ablate the function of the ligand or disrupt viral assembly and function. To address this context problem for adenoviral vectors, we have engineered a "context-specific" peptide-presenting phage library. We have displayed a 12-amino-acid (12-mer) random peptide library between the H and I sheets of the fiber protein of adenovirus type 5 on the pIII protein of fd bacteriophage. This library was used for peptide selection against C2C12 mouse skeletal muscle cells. Five rounds of selection combined with four rounds of clearing on nontarget cells selected one primary peptide designated 12.51, which bound target C2C12 cells approximately 100-fold better than the positive control RGD peptide. Translation of 12.51 back into the fiber protein produced a ligand-modified adenoviral vector that mediated 14-fold-better transduction of target C2C12 cells. These data suggest context-specific peptide-presenting libraries may allow selection of compatible peptide ligands for functional translation into viral vectors for retargeting.
Arginine Methylation Inhibits the Binding of Proline-rich Ligands to Src Homology 3, but Not WW, Domains (2000)

Src homology 3 (SH3) and WW domains are known to associate with proline-rich motifs within their respective ligands. Here we demonstrate that the proposed adapter protein for Src kinases, Sam68, is a ligand whose proline-rich motifs interact with the SH3 domains of p59(fyn) and phospholipase Cgamma-1 as well as with the WW domains of FBP30 and FBP21. These proline-rich motifs, in turn, are flanked by RG repeats that represent targets for the type I protein arginine N-methyltransferase. The asymmetrical dimethylation of arginine residues within these RG repeats dramatically reduces the binding of the SH3 domains of p59(fyn) and phospholipase Cgamma-1, but has no effect on their binding to the WW domain of FBP30. These results suggest that protein arginine methylation can selectively modulate certain protein-protein interactions and that mechanisms exist for the irreversible regulation of SH3 domain-mediated interactions.
Self interference digital holographic microscopy approach for inspection of technical and biological phase specimens (2011)

Quantitative holographic phase contrast imaging enables high-resolution inspection of reflective surfaces and technical phase specimen as well as the minimally invasive analysis of living cells. However, a drawback of many experimental arrangements is the requirement for a separate reference wave which results in a phase stability decrease and the demand for a precise adjustment of the intensity ratio between object and reference wave. Thus, a self interference digital holographic microscopy (DHM) approach was explored which only requires a single object illumination wave. Due to the Michelson interferometer design of the proposed setup two wave fronts with an almost identical curvature are superimposed. This results in a nearly ideal pattern of spatial off-axis carrier fringes and a constant interferogram contrast in the hologram plane. Moreover, the hologram evaluation with spatial phase shifting reconstruction algorithms and Fourier transformation-based spatial filtering methods as well as the integration of DHM in common research microscopes is simplified. Furthermore, the use of laser light sources with a short coherence length is enabled. The applicability of the proposed self interference principle is illustrated by data from the analysis of technical and biological phase specimens. The obtained results demonstrate that the method prospects to be a versatile tool for quantitative phase contrast imaging.
Generation of Gut-Homing IgA-Secreting B Cells by Intestinal Dendritic Cells (2006)

Normal intestinal mucosa contains abundant immunoglobulin A (IgA)-secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells (DC) from GALT induce T cell-independent expression of IgA and gut-homing receptors on B cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC-derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and effector activity through synergistically acting mediators.
Characterization of the Cell-penetrating Properties of the Epstein-Barr Virus ZEBRA trans-Activator (2010)

The Epstein-Barr virus basic leucine zipper transcriptional activator ZEBRA was shown recently to cross the outer membrane of live cells and to accumulate in the nucleus of lymphocytes. We investigated the potential application of the Epstein-Barr virus trans-activator ZEBRA as a transporter protein to facilitate transduction of cargo proteins. Analysis of different truncated forms of ZEBRA revealed that the minimal domain (MD) required for internalization spans residues 170-220. MD efficiently transported reporter proteins such as enhanced green fluorescent protein (EGFP) and beta-galactosidase in several normal and tumor cell lines. Functionality of internalized cargo proteins was confirmed by beta-galactosidase activity in transduced cells, and no MD-associated cell toxicity was detected. Translocation of MD through the cell membrane required binding to cell surface-associated heparan sulfate proteoglycans as shown by strong inhibition of protein uptake in the presence of heparin. We found that internalization was blocked at 4 degrees C, whereas no ATP was required as shown by an only 25% decreased uptake efficiency in energy-depleted cells. Common endocytotic inhibitors such as nystatin, chlorpromazine, and wortmannin had no significant impact on MD-EGFP uptake. Only methyl-beta-cyclodextrin inhibited MD-EGFP uptake by 40%, implicating the lipid raft-mediated endocytotic pathway. These data suggest that MD-reporter protein transduction occurs mostly via direct translocation through the lipid bilayer and not by endocytosis. This mechanism of MD-mediated internalization is suitable for the efficient delivery of biologically active proteins and renders ZEBRA-MD a promising candidate for therapeutic protein delivery applications.
Synergistic Lethality of a Binary Inhibitor of Mycobacterium tuberculosis KasA (2018)

We report GSK3011724A (DG167) as a binary inhibitor of β-ketoacyl-ACP synthase (KasA) in <i>Mycobacterium tuberculosis</i> Genetic and biochemical studies established KasA as the primary target. The X-ray crystal structure of the KasA-DG167 complex refined to 2.0-Å resolution revealed two interacting DG167 molecules occupying nonidentical sites in the substrate-binding channel of KasA. The binding affinities of KasA to DG167 and its analog, 5g, which binds only once in the substrate-binding channel, were determined, along with the KasA-5g X-ray crystal structure. DG167 strongly augmented the <i>in vitro</i> activity of isoniazid (INH), leading to synergistic lethality, and also synergized in an acute mouse model of <i>M. tuberculosis</i> infection. Synergistic lethality correlated with a unique transcriptional signature, including upregulation of oxidoreductases and downregulation of molecular chaperones. The lead structure-activity relationships (SAR), pharmacokinetic profile, and detailed interactions with the KasA protein that we describe may be applied to evolve a next-generation therapeutic strategy for tuberculosis (TB).<b>IMPORTANCE</b> Cell wall biosynthesis inhibitors have proven highly effective for treating tuberculosis (TB). We discovered and validated members of the indazole sulfonamide class of small molecules as inhibitors of <i>Mycobacterium tuberculosis</i> KasA-a key component for biosynthesis of the mycolic acid layer of the bacterium's cell wall and the same pathway as that inhibited by the first-line antitubercular drug isoniazid (INH). One lead compound, DG167, demonstrated synergistic lethality in combination with INH and a transcriptional pattern consistent with bactericidality and loss of persisters. Our results also detail a novel dual-binding mechanism for this compound as well as substantial structure-activity relationships (SAR) that may help in lead optimization activities. Together, these results suggest that KasA inhibition, specifically, that shown by the DG167 series, may be developed into a potent therapy that can synergize with existing antituberculars.
Building the Science for a Population Health Movement (2013)

A movement for population health starts with a basic understanding that health is determined by far more than health care and that the focus of health investments must go beyond health care alone. It follows that we need to invest in healthy environments, in efforts to ameliorate social and economic disparities and their impacts […]
<title>Photoresist metrology based on light scattering</title> (1996)

Angle resolved light scatterometry along with advanced data analysis is a promising new metrology technique to meet the challenges of today's and tomorrow's submicron technology. The measurement accuracy strongly depends on the performance capabilities of the algorithms utilized for data exploration and analysis. Presently, multivariate regression methods such as inverse least squares and principal component approaches are preferred. Substantial accuracy gains may be achieved by applying quasi-nonlinear methods, i.e. nonlinear data pretreatment followed by the usual linear regression. In this way, not only were the linewidth prediction errors in measuring developed resist lines pushed to below 20 nm, but likewise more complicated tasks such as silylation profile evaluation and latent image measurement could be addressed satisfactorily.