gebhart/patrepeval huggingface dataset:
Human adenovirus serotypes 3 and 5 bind to two different cellular receptors via the fiber head domain (1995)

The adenovirus fiber protein is responsible for attachment of the virion to cell surface receptors. The identity of the cellular receptor which mediates binding is unknown, although there is evidence suggesting that two distinct adenovirus receptors interact with the group C (adenovirus type 5 [Ad5]) and the group B (Ad3) adenoviruses. In order to define the determinants of adenovirus receptor specificity, we have carried out a series of competition binding experiments using recombinant native fiber polypeptides from Ad5 and Ad3 and chimeric fiber proteins in which the head domains of Ad5 and Ad3 were exchanged. Specific binding of fiber to HeLa cell receptors was assessed with radiolabeled protein synthesized in vitro, and by competition analysis with baculovirus-expressed fiber protein. Fiber produced in vitro was found as both monomer and trimer, but only the assembled trimers had receptor binding activity. Competition data support the conclusion that Ad5 and Ad3 interact with different cellular receptors. The Ad5 receptor distribution on several cell lines was assessed with a fiber binding flow cytometric assay. HeLa cells were found to express high levels of receptor, while CHO and human diploid fibroblasts did not. A chimeric fiber containing the Ad5 fiber head domain blocked the binding of Ad5 fiber but not Ad3 fiber. Similarly, a chimeric fiber containing the Ad3 fiber head blocked the binding of labeled Ad3 fiber but not Ad5 fiber. In addition, the isolated Ad3 fiber head domain competed effectively with labeled Ad3 fiber for binding to HeLa cell receptors. These results demonstrate that the determinants of receptor binding are located in the head domain of the fiber and that the isolated head domain is capable of trimerization and binding to cellular receptors. Our results also show that it is possible to change the receptor specificity of the fiber protein by manipulation of sequences contained in the head domain. Modification or replacement of the fiber head domain with novel ligands may permit adenovirus vectors with new receptor specificities which could be useful for targeted gene delivery in vivo to be engineered.
Sequence specificity of triplex DNA formation: Analysis by a combinatorial approach, restriction endonuclease protection selection and amplification. (1996)

We have devised a combinatorial method, restriction endonuclease protection selection and amplification (REPSA), to identify consensus ligand binding sequences in DNA. In this technique, cleavage by a type IIS restriction endonuclease (an enzyme that cleaves DNA at a site distal from its recognition sequence) is prevented by a bound ligand while unbound DNA is cleaved. Since the selection step of REPSA is performed in solution under mild conditions, this approach is amenable to the investigation of ligand-DNA complexes that are either insufficiently stable or not readily separable by other methods. Here we report the use of REPSA to identify the consensus duplex DNA sequence recognized by a G/T-rich oligodeoxyribonucleotide under conditions favoring purine-motif triple-helix formation. Analysis of 47 sequences indicated that recognition between 13 bases on the oligonucleotide 3' end and the duplex DNA was sufficient for triplex formation and indicated the possible existence of a new base triplet, G.AT. This information should help identify appropriate target sequences for purine-motif triplex formation and demonstrates the power of REPSA for investigating ligand-DNA interactions.
In Search of Human Variation (1998)

There is widespread interest in documenting the amount and geographic distribution of genetic variation in the human species. This information is desired by the biomedical community, who want a densely packed map of SNP (single nucleotide polymorphism) sites to be used to identify genes associated with disease by linkage disequilibrium between sets of adjacent markers and the occurence of disease in populations, and to characterize disease-related variation among populations. Anthropologists use genetic variation to reconstruct our species' history, and to understand the role of culture and geography in the global distribution of human variation. The requirements for these two perspectives seem to be converging on a need for an accessible, representative DNA bank and statistical database of human variation. However, both fields have been using conceptual models that are oversimplified, and this may lead to unrealistic expectations of the questions that can be answered from genetic data.
Near-infrared fluorescent imaging of tumor apoptosis. (2003)

Noninvasive imaging using radioactive annexin V is an emerging strategy for the assessment of cell death in vivo (F. G. Blankenberg, and H. W. Strauss. Apoptosis, 6: 117-123, 2001.). Therefore, we investigated whether annexin V labeled with the fluorophore Cy5.5 (Cy) could serve as a probe for imaging of tumor apoptosis using near infrared fluorescence (NIRF). We prepared active Cy-annexin (an equimolar dye:protein ratio) that bound to apoptotic Jurkat T cells and an inactive Cy-annexin probe (>2 dyes/mol protein) that did not. Active Cy annexin was used to image a 9L gliosarcoma, constitutively expressing green fluorescent protein marker, and the CR8 variant of Lewis lung carcinoma, stably transfected to express DsRed2. The expression of transfected fluorescent protein provided an indication of tumor margins and a means of defining tumor-associated NIRF signal intensity with both tumor models. Tumors were imaged with and without cyclophosphamide treatment. In both tumor models active Cy-annexin V tumor NIRF signal increased two to three times after the treatment. Tumor NIRF signal developed by 75 min after active Cy-annexin injection and remained for a 20-h observation period. Inactive annexin V was used as a control in the CR8 carcinoma experiments and resulted in a low nonspecific signal. With the 9L gliomosacrcoma model, active Cy-annexin V bound to both tumor cells (Cy-annexin V staining only) and endothelial cells (costained with Cy-annexin V and antibody to the endothelial marker CD31). Our results demonstrate that active Cy-annexin can be used as a NIRF probe to image apoptosis from outside an intact living animal and may provide nonradioactive method of measuring the antiproliferative effects of cancer chemotherapeutic regimens.
Morphology of conducting organic polymers: Polythiophene and poly(3‐methyl thiophene) (1984)

Abstract Polythiophene and substituted polythiophene can be electrochemically generated as very adhesive thin films or as thick powdery deposits. The homogeneity of the thin films is very high, but it decreases when the film thickness is increased. Scanning electron microscopy shows that the nature of the dopant strongly influences the film morphology. Transmission electron microscopy reveals mainly a fibrillar structure, with a fibril diameter of 200 Å in the undoped state, and 800 Å in the doped conducting state.
Structural Studies of the Klentaq1 DNA Polymerase (2001)

DNA polymerase I enzymes have served as model systems to study the mechanism of template-directed DNA polymerization. This process requires that the enzyme cycles through a series of conformational changes, each cycle leading to the incorporation of a nucleotide to the primer strand of the DNA. The kinetics of nucleotide incorporation has been extensively studied leading to the definition of specific steps along the cycle. Efforts to visualize these steps using X-ray crystallography have recently come to fruition, notably for one particular DNA polymerase I system, that of Klentaq1. This review focuses on the structural characterization of the various steps along the nucleotide incorporation pathway.
Cloning and Analysis of the Genes for Polycyclic Aromatic Hydrocarbon Degradationa (1994)

Bacterial degradation of polycyclic aromatic hydrocarbons initially proceeds through monooxygenase or dioxygenase attack on the aromatic ring. The dihydroxylated compounds formed are substrates for ring cleavage and further catabolism to tricarboxylic acid cycle intermediates. A number of microbial strains, both gram positive and gram negative, have been isolated that have the metabolic capability to degrade polycyclic aromatic hydrocarbons to carbon dioxide and water. In addition, many of these strains have the ability to cometabolize structurally similar aromatic compounds that may not normally serve as metabolic inducers or as carbon sources. The genes from several of these strains have been cloned for the purpose of analyzing in more detail their structure and function. The cloned genes were used to determine the range of substrates that can be metabolized by the genetically encoded pathway. For instance, the cloned genes from Pseudomonas sp. XPW-2 placed in E. coli encoded for the oxidation of such polycyclic aromatic hydrocarbons as naphthalene, biphenyl, anthracene, phenanthrene, acenaphthylene, fluorene, fluoranthene, chrysene, and pyrene. The cloned genes were also used as genetic probes to determine the degree of homology, if any, there is between different microbial strains capable of degrading polycyclic aromatic hydrocarbons. These experiments indicated significant homology among the class of terrestrial naphthalene and phenanthrene-degrading strains. Nevertheless, little homology was seen across species lines or among strains capable of degrading higher molecular weight polycyclic aromatic hydrocarbons. This indicates that there is a diversity of genetically distinct pathways for polycyclic aromatic hydrocarbon degradation.
Direct perfluoroalkylation including trifluoromethylation of aromatics with perfluoro carboxylic acids mediated by xenon difluoride (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect perfluoroalkylation including trifluoromethylation of aromatics with perfluoro carboxylic acids mediated by xenon difluorideYoo Tanabe, Noritada Matsuo, and Nobuo OhnoCite this: J. Org. Chem. 1988, 53, 19, 4582–4585Publication Date (Print):September 1, 1988Publication History Published online1 May 2002Published inissue 1 September 1988https://pubs.acs.org/doi/10.1021/jo00254a033https://doi.org/10.1021/jo00254a033research-articleACS PublicationsRequest reuse permissionsArticle Views1433Altmetric-Citations93LEARN 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
Why Most Published Research Findings Are False (2005)

There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.
TheYersiniahigh-pathogenicity island is present in different members of the familyEnterobacteriaceae (2000)

A pathogenicity island termed high-pathogenicity island (HPI) is present in pathogenic Yersinia. This 35 to 45 kb island carries genes involved in synthesis, regulation and transport of the siderophore yersiniabactin. Recently, the HPI was also detected in various strains of Escherichia coli. In this study, the distribution of the HPI in the family Enterobacteriaceae was investigated. Among the 67 isolates pertaining to 18 genera and 52 species tested, nine (13.4%) harbored the island. These isolates were three E. coli, one Citrobacter diversus and five Klebsiella of various species (Klebsiella pneumoniae, Klebsiella rhinoscleromatis, Klebsiella ozaenae, Klebsiella planticola, and Klebsiella oxytoca). As in Yersinia sp., all nine isolates synthesized the HPI-encoded iron-repressible proteins HMWP1 and HMWP2. In the K. oxytoca strain, the right-end portion of the HPI was deleted, whereas the entire core region of the island was present in the eight other enterobacteria strains analyzed. In most of these isolates, the HPI was bordered by an asn tRNA locus, as in Yersinia sp. This report thus demonstrates the spread of the HPI among various members of the family Enterobacteriaceae.
Metalloproteinase-Dependent PredegenerationIn VitroEnhances Axonal Regeneration within Acellular Peripheral Nerve Grafts (2002)

Injury to peripheral nerve initiates a degenerative process that converts the denervated nerve from a suppressive environment to one that promotes axonal regeneration. We investigated the role of matrix metalloproteinases (MMPs) in this degenerative process and whether effective predegenerated nerve grafts could be produced in vitro. Rat peripheral nerve explants were cultured for 1-7 d in various media, and their neurite-promoting activity was assessed by cryoculture assay, in which neurons are grown directly on nerve sections. The neurite-promoting activity of cultured nerves increased rapidly and, compared with uncultured nerve, a maximum increase of 72% resulted by 2 d of culture in the presence of serum. Remarkably, the neurite-promoting activity of short-term cultured nerves was also significantly better than nerves degenerated in vivo. We examined whether in vitro degeneration is MMP dependent and found that the MMP inhibitor N-[(2R)-2(hydroxamidocarbonylmethyl)-4-methylpantanoyl]-l-tryptophan methylamide primarily blocked the degenerative increase in neurite-promoting activity. In the absence of hematogenic macrophages, MMP-9 was trivial, whereas elevated MMP-2 expression and activation paralleled the increase in neurite-promoting activity. MMP-2 immunoreactivity localized to Schwann cells and the endoneurium and colocalized with gelatinolytic activity as demonstrated by in situ zymography. Finally, in vitro predegenerated nerves were tested as acellular grafts and, compared with normal acellular nerve grafts, axonal ingress in vivo was approximately doubled. We conclude that Schwann cell expression of MMP-2 plays a principal role in the degenerative process that enhances the regeneration-promoting properties of denervated nerve. Combined with their low immunogenicity, acellular nerve grafts activated by in vitro predegeneration may be a significant advancement for clinical nerve allografting.
Antioxidant micronutrients and breast cancer. (1993)

We reviewed epidemiologic evidence on the relationship between four antioxidant micronutrients (vitamin A, vitamin C, vitamin E, and selenium) and breast cancer risk. Available data support a modest protective effect of vitamin A, although more studies are needed to examine further this association and to assess the relative contributions of preformed vitamin A (retinol) and carotenoids. In addition, the possibility that some other component of vitamin A-rich foods may account for this observed association should be explored. Data on the relationship between vitamins C and E and breast cancer risk are limited and inconsistent, and further information is necessary. A substantial body of evidence indicates a lack of any appreciable effect of selenium intake on breast cancer risk, at least within the range of human diets. Future observational studies should ideally be prospective in design, as prospective studies are less prone to selection and recall bias than are case-control studies, and should address methodologic issues such as confounding by other micronutrients and appropriate storage conditions of blood specimens. Although hypotheses relating micronutrient intake to risk of breast cancer should be tested in randomized trials, ethical and logistical constraints make these studies difficult to perform.
Visualizing tropoelastin in a long-term human elastic fibre cell culture model (2016)

Elastin is an essential protein found in a variety of tissues where resilience and flexibility are needed, such as the skin and the heart. When aiming to engineer suitable implants, elastic fibres are needed to allow adequate tissue renewal. However, the visualization of human elastogenesis remains in the dark. To date, the visualization of human tropoelastin (TE) production in a human cell context and its fibre assembly under live cell conditions has not been achieved. Here, we present a long-term cell culture model of human dermal fibroblasts expressing fluorescence-labelled human TE. We employed a lentiviral system to stably overexpress Citrine-labelled TE to build a fluorescent fibre network. Using immunofluorescence, we confirmed the functionality of the Citrine-tagged TE. Furthermore, we visualized the fibre assembly over the course of several days using confocal microscopy. Applying super resolution microscopy, we were able to investigate the inner structure of the elastin-fibrillin-1 fibre network. Future investigations will allow the tracking of TE produced under various conditions. In tissue engineering applications the fluorescent fibre network can be visualized under various conditions or it serves as a tool for investigating fibre degradation processes in disease-in-a-dish-models.
Three days that shook the world. (1996)

The Food and Drug Administration's (FDA) Drug Advisory Committee made significant changes to the way HIV infections are treated at its February 28 to March 1, 1996 meetings. As a result, AZT is no longer considered to be the centerpiece of first-line anti-HIV therapy, and CD4 cell counts are no longer the primary laboratory standards used to judge the effectiveness of a drug. The FDA recommended the approval of two older nucleoside analogs (ddI and ddC) and two new protease inhibitors (ritonavir and indinavir). Serono Laboratories' application for approval of its human growth hormone was rejected, largely because of the poor way the company presented its findings. Ritonavir demonstrated an ability to extend survival and delay the onset of new opportunistic infections in people with advanced HIV disease. Although ritonavir is more effective than AZT, the combination of the two drugs was no better than ritonavir monotherapy. There is no long-term data available on the safety of ritonavir. The committee recommended indinavir after the manufacturer, Merck, provided impressive safety and surrogate marker data for the drug alone and in combination with AZT. Charts are included to summarize the drugs' regimen. There is a growing conviction within the FDA that four-drug combination therapy will be the most effective means of treating HIV. However, treatment success will vary on an individual basis.
Influence of spiking activity on cortical local field potentials (2013)

The intra-cortical local field potential (LFP) reflects a variety of electrophysiological processes including synaptic inputs to neurons and their spiking activity. It is still a common assumption that removing high frequencies, often above 300 Hz, is sufficient to exclude spiking activity from LFP activity prior to analysis. Conclusions based on such supposedly spike-free LFPs can result in false interpretations of neurophysiological processes and erroneous correlations between LFPs and behaviour or spiking activity. Such findings might simply arise from spike contamination rather than from genuine changes in synaptic input activity. Although the subject of recent studies, the extent of LFP contamination by spikes is unclear, and the fundamental problem remains. Using spikes recorded in the motor cortex of the awake monkey, we investigated how different factors, including spike amplitude, duration and firing rate, together with the noise statistic, can determine the extent to which spikes contaminate intra-cortical LFPs. We demonstrate that such contamination is realistic for LFPs with a frequency down to ∼10 Hz. For LFP activity below ∼10 Hz, such as movement-related potential, contamination is theoretically possible but unlikely in real situations. Importantly, LFP frequencies up to the (high-) gamma band can remain unaffected. This study shows that spike-LFP crosstalk in intra-cortical recordings should be assessed for each individual dataset to ensure that conclusions based on LFP analysis are valid. To this end, we introduce a method to detect and to visualise spike contamination, and provide a systematic guide to assess spike contamination of intra-cortical LFPs.
Head-Worn Displays: A Review (2006)

Head-worn display design is inherently an interdisciplinary subject fusing optical engineering, optical materials, optical coatings, electronics, manufacturing techniques, user interface design, computer science, human perception, and physiology for assessing these displays. This paper summarizes the state-of-the-art in head-worn display design (HWD) and development. This review is focused on the optical engineering aspects, divided into different sections to explore principles and applications. Building on the guiding fundamentals of optical design and engineering, the principles section includes a summary of microdisplay or laser sources, the Lagrange invariant for understanding the trade-offs in optical design of HWDs, modes of image presentation (i.e., monocular, biocular, and stereo) and operational modes such as optical and video see-through. A brief summary of the human visual system pertinent to the design of HWDs is provided. Two optical design forms, namely, pupil forming and non-pupil forming are discussed. We summarize the results from previous design work using aspheric, diffractive, or holographic elements to achieve compact and lightweight systems. The applications section is organized in terms of field of view requirements and presents a reasonable collection of past designs
Guanylin regulates chloride secretion in the human gallbladder via the bile fluid (2004)

Based on the present findings and on the functional role of guanylin in other epithelia, it is likely that gallbladder epithelial cells synthesize and release guanylin into the bile to regulate electrolyte secretion by a paracrine/luminocrine signaling pathway.