gebhart/patrepeval huggingface dataset:
Blocking Respiratory Syncytial Virus Entry: A Story with Twists (2015)

Respiratory syncytial virus (RSV) is responsible for majority of infant hospitalizations due to viral infections. Despite its clinical importance, no vaccine against RSV or effective antiviral therapy is available. Several structural classes of small-molecule RSV entry inhibitor have been described and one compound has advanced to clinical testing. Mutations in either one of two resistance hot spots in the F protein mediate unusual pan-resistance to all of these inhibitor classes. Based on the biochemical characterization of resistant viruses and structural insight into the RSV F trimer, we propose a kinetic escape model as the origin of pan-resistance. Since a resistant RSV remained pathogenic in the mouse model, pan-resistance mutations could emerge rapidly in circulating RSV strains. We evaluate clinical implications and discuss consequences for the design of future RSV drug discovery campaigns.
Toward Two-Dimensional All-Carbon Heterostructures via Ion Beam Patterning of Single-Layer Graphene (2015)

Graphene has many claims to fame: it is the thinnest possible membrane, it has unique electronic and excellent mechanical properties, and it provides the perfect model structure for studying materials science at the atomic level. However, for many practical studies and applications the ordered hexagon arrangement of carbon atoms in graphene is not directly suitable. Here, we show that the atoms can be locally either removed or rearranged into a random pattern of polygons using a focused ion beam (FIB). The atomic structure of the disordered regions is confirmed with atomic-resolution scanning transmission electron microscopy images. These structural modifications can be made on macroscopic scales with a spatial resolution determined only by the size of the ion beam. With just one processing step, three types of structures can be defined within a graphene layer: chemically inert graphene, chemically active amorphous 2D carbon, and empty areas. This, along with the changes in properties, gives promise that FIB patterning of graphene will open the way for creating all-carbon heterostructures to be used in fields ranging from nanoelectronics and chemical sensing to composite materials.
Picosecond studies of ruthenium(II) and ruthenium(III) porphyrin photophysics (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPicosecond studies of ruthenium(II) and ruthenium(III) porphyrin photophysicsC. Drew Tait, Dewey Holten, Mark Barley, David Dolphin, and Brian R. JamesCite this: J. Am. Chem. Soc. 1985, 107, 7, 1930–1934Publication Date (Print):April 1, 1985Publication History Published online1 May 2002Published inissue 1 April 1985https://doi.org/10.1021/ja00293a022RIGHTS & PERMISSIONSArticle Views272Altmetric-Citations36LEARN 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 InReddit PDF (728 KB) Get e-Alerts Get e-Alerts
Cutting Edge: Induced Indoleamine 2,3 Dioxygenase Expression in Dendritic Cell Subsets Suppresses T Cell Clonal Expansion (2003)

In mice, immunoregulatory APCs express the dendritic cell (DC) marker CD11c, and one or more distinctive markers (CD8alpha, B220, DX5). In this study, we show that expression of the tryptophan-degrading enzyme indoleamine 2,3 dioxygenase (IDO) is selectively induced in specific splenic DC subsets when mice were exposed to the synthetic immunomodulatory reagent CTLA4-Ig. CTLA4-Ig did not induce IDO expression in macrophages or lymphoid cells. Induction of IDO completely blocked clonal expansion of T cells from TCR transgenic mice following adoptive transfer, whereas CTLA4-Ig treatment did not block T cell clonal expansion in IDO-deficient recipients. Thus, IDO expression is an inducible feature of specific subsets of DCs, and provides a potential mechanistic explanation for their T cell regulatory properties.
Human Papillomavirus Type 16 and Early Cervical Neoplasia (1984)

Flat warts (condylomata) of the uterine cervix are sometimes cytologically atypical and have abnormal mitotic figures; they are thought to be possible precursors of cancer of the cervix. Flat warts are caused by any of a number of types of human papillomaviruses (HPVs), one of which (HPV 16) has been previously associated with invasive cancer of the cervix. To determine whether HPV 16 is also associated with flat warts with abnormal mitoses, we analyzed 23 flat warts by DNA-hybridization techniques for the presence of HPV 16 and other HPV types, and correlated the results with the histology. Of 10 lesions with abnormal mitotic figures, 7 contained HPV 16, and 1 contained another type of HPV. Of 13 lesions without abnormal mitotic figures, only 1 contained HPV 16, and 7 contained other types of HPV. We conclude that the presence of HPV 16 correlates with the presence of abnormal mitotic figures in flat warts of the cervix, and that this type of flat wart is a precursor of invasive cancer of the cervix.
The Handbook of Plant Genome Mapping (2005)

Part I: Genetic Mapping.1 Mapping Populations and Principles of Genetic Mapping (Katharina Schneider).2 Molecular Marker Systems for Genetic Mapping (Henry T. Nguyen and Xiaolei Wu).3 Methods and Software for Genetic Mapping (James C. Nelson).4 Single nucleotide Polymorphisms: Detection Techniques and Their Potential for Genotyping and Genome Mapping (Gunter Kahl, Andrea Mast, Nigel Tooke, Richard Shen, and Dirk van den Boom).5 Breeding By Design: Exploiting Genetic Maps and Molecular Markers Through Marker-assisted Selection (Johan D. Peleman, Anker P. Sorensen, and Jeroen Rouppe van der Voort).Part II: Physical Mapping.6 Physical Mapping of Plant Chromosomes (Barbara Hass-Jacobus and Scott A. Jackson).7 Chromosome Flow Sorting and Physical Mapping (Jaroslav Dolezel, Marie Kubalakova, Jan Bartos, and Jiri Macas).8 Genomic DNA Libraries and Physical Mapping (Chengwei Ren, Zhanyou Xu, Shuku Sun, Mi-Kyung Lee, Chengcang Wu, Chantel Scheuring, and Hong-Bin Zhang).9 Integration of Physical and Genetic Maps (Khalid Meksem, Hirofumi Ishihara, and Tacco Jesse).10 Positional Cloning of Plant Developmental Genes (Peter M. Gresshoff).11 Whole-genome Physical Mapping: An Overview on Methods for DNA Fingerprinting (Chengcang Wu, Shuku Sun, Mi-Kyung Lee, Zhanyou Xu, Chengwei Ren, Teofila S. Santos, and Hong-Bin Zhang).12 Software for Restriction Fragment Physical Maps (William Nelson and Carol Soderlund).13 Reduced Representation Strategies and Their Application to Plant Genomes (Daniel G. Peterson).14 Large-scale DNA Sequencing (Christopher D. Town).Glossary.Subject Index.
Properties and Phosphorylation Sites of Baculovirus-expressed Nuclear Inhibitor of Protein Phosphatase-1 (NIPP-1) (1997)

NIPP-1 is the RNA-binding subunit of a major species of protein phosphatase-1 in the nucleus. We have expressed nuclear inhibitor of protein phosphatase-1 (NIPP-1) in Sf9 cells, using the baculovirus-expression system. The purified recombinant protein was a potent (Ki = 9.9 +/- 0.3 pM) and specific inhibitor of protein phosphatase-1 and was stoichiometrically phosphorylated by protein kinases A and CK2. At physiological ionic strength, phosphorylation by these protein kinases drastically decreased the inhibitory potency of free NIPP-1. Phosphorylation of NIPP-1 in a heterodimeric complex with the catalytic subunit of protein phosphatase-1 resulted in an activation of the holoenzyme without a release of NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A, whereas Thr161 and Ser204 were phosphorylated by protein kinase CK2. These residues all conform to consensus recognition sites for phosphorylation by protein kinases A or CK2 and are clustered near a RVXF sequence that has been identified as a motif that interacts with the catalytic subunit of protein phosphatase-1.
The Effects of Streptomycin, Desiccation, and UV Radiation on Ice Nucleation by Pseudomonas viridiflava (1986)

Streptomycin (100 micrograms per milliliter), desiccation (over CaSO(4)), and ultraviolet radiation (4500 microwatts per square centimeter at 254 nanometers for 15 minutes) reduced ice nucleation activity by Pseudomonas viridiflava strain W-1 as determined by freezing drops of the bacterial suspensions. Highest residual ice nucleation activity by dead cells was obtained by desiccation, although no freezing above -3.5 degrees C was detected. The rate and extent of loss of ice nucleation activity following streptomycin and ultraviolet treatment was affected by preconditioning temperature. At 21 degrees C and above, loss of activity by dead cells was rapid and irreversible.
Models for antigen receptor gene rearrangement: CDR3 length (2007)

Despite the various processing steps involved in V(D)J recombination, which could potentially introduce many biases in the length distribution of complementarity determining region 3 (CDR3) segments, the observed CDR3 length distributions for complete repertoires are very close to a normal-like distribution. This raises the question of whether this distribution is simply a result of the random steps included in the process of gene rearrangement, or has been optimized during evolution. We have addressed this issue by constructing a simulation of gene rearrangement, which takes into account the DNA modification steps included in the process, namely hairpin opening, nucleotide additions, and nucleotide deletions. We found that the near-Gaussian- shape of CDR3 length distribution can only be obtained under a relatively narrow set of parameter values, and thus our model suggests that specific biases govern the rearrangement process. In both B-cell receptor (BCR) heavy chain and T-cell receptor beta chain, we obtained a Gaussian distribution using identical parameters, despite the difference in the number and the lengths of the D segments. Hence our results suggest that these parameters most likely reflect the optimal conditions under which the rearrangement process occurs. We have subsequently used the insights gained in this study to estimate the probability of occurrence of two exactly identical BCRs over the course of a human lifetime. Whereas identical rearrangements of the heavy chain are highly unlikely to occur within one human lifetime, for the light chain we found that this probability is not negligible, and hence the light chain CDR3 alone cannot serve as an indicator of B-cell clonality.
Development of morphological and functional polarity in primary cultures of immature rat uterine epithelial cells. (1988)

The present study describes a culture environment in which luminal epithelial cells isolated from immature rat uteri and cultured on a matrix-coated permeable surface, with separate apical and basal secretory compartments, proliferate to confluence. Subsequently the cells undergo a process of differentiation accompanied by progressive development of functional polarity. Ultrastructural and immunocytochemical evidence verifies the ability of these primary cultures to regain polar organization, separate membrane domains, and form functional tight junctions as demonstrated by the development of transepithelial resistance. The appearance of uvomorulin is restricted to the lateral cell surface. Coordinated indices of functional polarity that develop progressively in post-confluent cultures include the preferential uptake of [35S]methionine from the basal surface and a rise in uterine epithelial cell secretory activity characterized by a progressive preference for apical secretion. The time dependent development of polarity was characterized by differences in the protein profiles of the apical and basolateral secretory compartments. The maintenance of hormone responsiveness by the cultured cells was validated by the secretion of two proteins identified as secretory markers of estrogen response in the intact uterus. The technique of culturing the cells on a matrix-coated permeable surface with separate secretory compartments produces a uterine epithelial cell that morphologically and functionally resembles its in situ equivalent. The culture method and analytical approach used in this present study may be applied to primary cultures of a variety of natural epithelia, which have hitherto proven resistant to more conventional culture methodologies.
Mechanisms of mucosal inflammation in the nose and lungs. (1998)

The early inflammatory response during allergic rhinitis and asthma is associated with IgE-mediated mast cell activation and resultant release of primary inflammatory mediators. The late phase reaction is characterized by recruitment, activation and tissue infiltration of leucocyte populations, including T lymphocytes, eosinophils, basophils and neutrophils. T helper type 2 CD4+ cells, a T lymphocyte subset with a distinctive cytokine profile, are thought to regulate the recruitment and activation of other effector cells. This review discusses the results of studies conducted under experimental and natural conditions of allergen exposure, which confirm the presence of eosinophilia, changes in lymphocyte populations, and increased expression of a TH2-cytokine profile in the nasal mucosa following allergen-induced rhinitis, and the alleviation of both clinical symptoms and inflammatory responses by prior treatment with topical fluticasone propionate. Similar effects are demonstrated to occur in the lower airway following allergen challenge in asthma patients, and to be ameliorated by oral corticosteroid therapy. These studies add weight to the argument that asthma and rhinitis share a common pathophysiology characterized by similar inflammatory events, and should both benefit from early preventative treatment with topical corticosteroids.
An anti-CD30 chimeric receptor that mediates CD3-zeta-independent T-cell activation against Hodgkin's lymphoma cells in the presence of soluble CD30. (1998)

Hodgkin's lymphoma patients fail to establish an efficient cellular response against CD30+ Hodgkin/Reed-Sternberg cells. An impaired T-cell receptor/CD3-zeta-mediated activation of T cells is thought to be involved in this situation. We here present a chimeric anti-CD30 receptor that mediates MHC and T-cell receptor/CD3-zeta-independent T-cell activation against CD30+ lymphoma cells even in the presence of soluble CD30. The receptor consists of the binding domain of the monoclonal antibody HRS3 and the signaling unit of the Fc epsilonRI-receptor gamma-chain. After expression in MD45 T cells, receptor cross-linking with immobilized anti-idiotypic monoclonal antibody and CD30+ cells, respectively, results in increased interleukin 2 secretion and specific cytolysis of CD30+ Hodgkin's lymphoma cells. Soluble CD30 in concentrations up to 6000 units/ml did not interfere with cellular activation induced by membrane-bound antigen. This demonstrates the feasibility of the chimeric anti-CD30-scFv-gamma receptor in CD30+ lymphoma cell targeting, even in the presence of as high concentrations of soluble CD30 as are found in patients during progression of the disease.
Single β-Actin mRNA Detection in Neurons Reveals a Mechanism for Regulating Its Translatability (2014)

The physical manifestation of learning and memory formation in the brain can be expressed by strengthening or weakening of synaptic connections through morphological changes. Local actin remodeling underlies some forms of plasticity and may be facilitated by local β-actin synthesis, but dynamic information is lacking. In this work, we use single-molecule in situ hybridization to demonstrate that dendritic β-actin messenger RNA (mRNA) and ribosomes are in a masked, neuron-specific form. Chemically induced long-term potentiation prompts transient mRNA unmasking, which depends on factors active during synaptic activity. Ribosomes and single β-actin mRNA motility increase after stimulation, indicative of release from complexes. Hence, the single-molecule assays we developed allow for the quantification of activity-induced unmasking and availability for active translation. Further, our work demonstrates that β-actin mRNA and ribosomes are in a masked state that is alleviated by stimulation.
Clinical effect of nerve growth factor on personality disorders after cerebral trauma (2009)

Objective To explore the effect of nerve growth factor (NGF) on personality disorders after cerebral trauma. Methods 39 inpatients (Glasgow coma scale, GCS10～12) with cerebral injury were dividedinto two groups. The patients in control group (n=19) was given conventional therapy such as vitamineB1, vitamineB12 and high pressure oxygen; the patients in study group (n=11) was given NGF 6000U/d intramuscularly for 28 days. During the treatment, liver and kidney function were monitored continually and GCS were measured. Personality disorders of patients were assessed with SCL-90 and EPQ analysis. Results There was no difference in GCS between two groups. Compared with the control group, there was a significant improvement in psychology and personality in study group. Conclusions Nerve growth factor (NGF) is effective in the treatment of brain injury.

Key words: 
Cerebral trauma;  Nerve growth factor; Personality
Investigating link service infrastructures (2000)

Variations on the Distributed Link Service have now been deployed across a spectrum of hypermedia and multimedia projects. Although some implementations have utilised standard database technologies and hypermedia tools behind the scenes, most of the network services have been proprietary implementations. In this paper we discuss the motivation and requirements for a large scale, dynamic and open distributed link service using third party components, and explore the use of off-the-shelf services to provide the distributed infrastructure for link services. In particular we investigate HTTP, LDAP and Whois++ as candidate technologies.
Solubility Prediction of Drugs in Water-Polyethylene Glycol 400 Mixtures Using Jouyban-Acree Model (2006)

A numerical method is proposed for predicting solubility of drugs in water-PEG 400 mixtures based on the Jouyban-Acree cosolvency model. The accuracy of the proposed method is evaluated by computing mean percentage deviation (MPD) and compared with that of log-linear model of Yalkowsky. The overall MPDs of the Jouyban-Acree model and the most accurate version of Yalkowsky's model are 39.8 (+/-46.7) % and 175.8 (+/-266.4) %, respectively, and the mean difference is statistically significant (p < 0.0005). The proposed method produces acceptable residual distribution and the probability of solubility prediction with residual log of solubility <0.5 unit is 0.86. The applicability of the proposed method could be extended for predicting the solubility of drugs in water-PEG 400 mixtures at various temperatures. The impact of various log P values computed using different software is also studied and the results of ANOVA revealed that there are no significant differences between the accuracy of the predicted solubilities employing various log P values.
Zinc Competition among the Intestinal Microbiota (2012)

Zinc is an essential trace element for the growth of most organisms. Quantities of zinc inside cells are highly regulated, as too little zinc does not support growth, while too much zinc is toxic. Numerous bacterial cells require zinc uptake systems for growth and virulence. The work presented here demonstrates that the microbiota in the gastrointestinal tract reduces the quantity of zinc. Without a high-affinity zinc transporter, Campylobacter jejuni, a commensal organism of chickens, is unable to replicate or colonize the gastrointestinal tract. This is the first demonstration of zinc competition between microbiota in the gastrointestinal tract of a host. These results could have profound implications in the field of microbial pathogenesis and in our understanding of host metabolism and the microbiota.
Nitric oxide: novel therapy for osteoporosis (2008)

Postmenopausal NO deficiency is rectified with hormone replacement therapy, which enhances local production of NO. Declining local NO production secondary to estrogen deficiency in postmenopausal women, and perhaps in older men, could be one of the key reasons for age-related increased incidences of cardiovascular events, sexual dysfunction as well as osteoporosis. Thus, in addition to supplementation of NO compounds in acute situations such as alleviating angina and erectile dysfunction, it could be a valuable addition to the armamentarium of therapies for chronic conditions such as osteoporosis.
A yeast cyclophilin gene essential for lactate metabolism at high temperature. (1992)

The cyclophilins are a family of ubiquitous eukaryotic proteins first identified by high affinity for cyclosporin A (CsA). The immunosuppressant and cytotoxic effects of CsA are thought to result from formation of a toxic complex between cyclophilin and CsA rather than from inhibition of cyclophilin function. The physiological role(s) of the cyclophilins is unknown. Cyclophilins have in vitro peptidylprolyl cistrans isomerase (PPIase) activity, and thus may be involved in protein folding in vivo. We have isolated a yeast cyclophilin gene, CPR3, which encodes a presumptive mitochondrial isoform. While CPR3 disruption mutants lack any phenotype at 30 degrees C, they are unable to grow on L-lactate at 37 degrees C. Disruptions of two other cyclophilin genes (CPR1, CPR2) and of FPR1, the gene encoding an FK506 binding protein with PPIase activity, do not affect growth on L-lactate at 37 degrees C. L-Lactate metabolism requires transcriptional induction of CYB2, the gene encoding flavocytochrome b2; cpr3 mutants induce transcription of this gene normally. This result demonstrates a conditional lethal phenotype for a cyclophilin mutation and presents a system for genetic and biochemical analysis of cyclophilin function.
Alzheimer's disease, β‐amyloid, glutamate, NMDA receptors and memantine – searching for the connections (2012)

β-amyloid (Aβ) is widely accepted to be one of the major pathomechanisms underlying Alzheimer's disease (AD), although there is presently lively debate regarding the relative roles of particular species/forms of this peptide. Most recent evidence indicates that soluble oligomers rather than plaques are the major cause of synaptic dysfunction and ultimately neurodegeneration. Soluble oligomeric Aβ has been shown to interact with several proteins, for example glutamatergic receptors of the NMDA type and proteins responsible for maintaining glutamate homeostasis such as uptake and release. As NMDA receptors are critically involved in neuronal plasticity including learning and memory, we felt that it would be valuable to provide an up to date review of the evidence connecting Aβ to these receptors and related neuronal plasticity. Strong support for the clinical relevance of such interactions is provided by the NMDA receptor antagonist memantine. This substance is the only NMDA receptor antagonist used clinically in the treatment of AD and therefore offers an excellent tool to facilitate translational extrapolations from in vitro studies through in vivo animal experiments to its ultimate clinical utility.