gebhart/patrepeval huggingface dataset:
Genetic Clues to Alzheimer's Disease (1996)

All cases of familial Alzheimer's disease are caused by mutations in either the gene for beta-amyloid precursor protein or the protein S182/STM. The normal functions of these transmembrane proteins are unknown, and it is unclear how they relate to one another. N. N. Dewji and S. J. Singer propose that these two proteins interact in a way analogous to the Sevenless and Bride of Sevenless proteins in the developing Drosophila eye and the lin-12 and sel-12 proteins in the developing vulva of Caenorhabditis elegans . He suggests that excess deposition of amyloid, a hallmark and likely cause of Alzheimer's disease, would be a result of the abnormal processing of the protein-protein complex. This proposal is likely to provoke responses from the community. If you have a question or would like to comment on the ideas presented by Drs. Dewji and Singer in this Perspective or if you would like to read the comments posted by others, please go to our interactive Forum (click on the Forum button below). You can also read the full text of this Perspective by clicking on the Full Text button below.
Characterization of Endonucleolytic Activity of HIV-1 Integrase Using a Fluorogenic Substrate (1995)

Retroviruses require viral DNA to be synthesized by reverse transcription in the cytoplasm followed by integration of the resulting viral DNA into the host chromosome in the nucleus. Reverse transcription and integration, essential steps in the life cycle of retroviruses, are possible targets in the development of antiviral reagents. One attractive target is the integrase protein, a product of the retroviral pol gene which is solely responsible for the retroviral integration process through cutting and joining reactions. When screening for massive numbers of antiviral agents, a rapid and precise assay is ideal. We report the application of fluorescence resonance energy transfer (FRET) with fluorescein and eosin as the energy transfer pair to characterize HIV-IN-mediated DNA cleavage reactions. Past concerns with applications of FRET to DNA were due to interactions of the fluorophore with the DNA, resulting in quenched fluorescence. However, in this study these concerns have been resolved with the use of a nucleotide analog with a 12-carbon linker arm, 5-amino (12)-2'-deoxyuridine beta-cyanoethyl phosphoramidite. Steady-state fluorescence studies show that cleavage of the fluorogenic substrate by integrase results in enhancement of quenched donor fluorescence intensity. The fluorescence assay was confirmed by autoradiographic analysis of the cleavage reaction with radiolabeled fluorogenic substrate. This fluorescence assay will facilitate both detailed kinetic studies and the rapid screening of novel integrase inhibitors.
Peptide microarrays for carbohydrate recognition (2009)

An application of high density random sequence peptide microarrays for rapid and reliable identification of artificial carbohydrate receptors is reported.
A Graph-Oriented Model for Articulation of Ontology Interdependencies (1999)

Abstract: Ontologies are knowledge structures to explicate the contents, essential properties, and relationships between terms in a knowledge source. Many sources are now accessible with associated ontologies. Most prior work on use of ontologies relies on the construction of a single global ontology covering all sources. Such an approach is not scalable and maintainable especially when the sources change frequently. Wepropose a scalable and easily maintainable approach based on the interoperation of ontologies. To handle user queries crossing the boundaries of the underlying information systems, the interoperation between the ontologies should be precisely de ned. Our approach is to use rules that cross the semantic gap by creating an articulation or linkage between the systems. The rules are generated using a semi-automatic articulation tool with the help of a domain expert. To make the ontologies amenable for automatic composition based on the accumulated knowledge rules, we represent them using a graph-oriented model extended with a small algebraic operator set. ONION, a user-friendly toolkit, aids the experts in bridging the semantic gap in real-life settings. Our framework provides a sound foundation to simplify the work of do-This work was partially supported by a grant from the Air Force O ce of Scienti c Research (AFOSR).main experts, enables integration with public semantic dictionaries, like Wordnet, and will derive ODMG-compliant mediators automatically.
Antispasmodic Effects of Rooibos Tea (Aspalathus linearis) is Mediated Predominantly through K+‐Channel Activation (2006)

Rooibos tea has been widely used for abdominal spasm and diarrhoea. The aim of the present study was to explore the possible mechanism for its use in such ailments. Its aqueous extract (RT) at 0.3-10 mg/ml produced relaxation of spontaneous and low K(+) (25 mM)-induced contractions of rabbit jejunum, with weak effect on high K(+) (80 mM)-induced contractions. In the presence of glibenclamide, relaxation of low K(+)-induced contractions was prevented. Cromakalim inhibited contractions induced by low K(+), but not high K(+), while verapamil did not differentiate in its inhibitory effect on contractions produced by the two concentrations of K(+). RT also exhibited antidiarrhoeal and antisecretory activities in mice. The spasmolytic effect was concentrated in organic fractions. Its constituents, chrysoeriol, orientin and vitexin showed a similar pattern of spasmolytic effects to the extract, while rutin was more like verapamil. So Rooibos tea possesses a combination of dominant K(ATP) channel activation and weak Ca(++) antagonist mechanisms and hence justifies its use in hyperactive gastrointestinal disorders.
Organization Of Babbling: A Case Study (1994)

Speech is probably the most complex serially ordered behavior in living forms. However, no systematic investigation of the organization of speech-related output when it is presumably simplest, namely during the babbling stage, has been attempted. Transcriptions of 423 babbled utterances (1145 syllables) were obtained from one subject 7-12 months of age. Most results could be interpreted in terms of a basic mouth opening-closing alternation, responsible not only for the typical vowel-consonant alternation of babbling, but also for many prominent details including within-utterance variation in vowel height (often stress-related) and in degree of closure for consonants. The results suggest that a "frame" for babbling is provided by mandibular oscillation, perhaps reflected, when operating alone, in the common alternation between labial consonants and central vowels. Variation in the amplitude of this oscillation may be responsible for the within-utterance vowel height and consonant manner variation and much of the perceived stress variation. Further variation is attributed to fronting movements of the tongue, the effects of which often spread beyond single vowels and consonants.
Analyzing and Visualizing Log Files: A Computational Science of Usability (1994)

. There is a good deal of work studying how we might display log file data in various abstract two-dimensional representations. These range from a simple table of the frequency of command pairings (how often command X follows command Y, for all X and Y) to Markov network charts (Figure 6) showing the observed probability of one command following another, action code charts (Figure 7) showing the ordering of events indexed by position in a hypertext database, and process pattern charts (Figure 8) showing the interleave of events on an absolute time scale. . 2-D Color and Dynamic. Color might be used to add additional dimensionality to an abstract two-dimensional visualization. One might also imagine using the geometry of the screen as part of a dynamic visualization of user events. . 3-D. Modern visualization techniques allow for complex, photorealistic three-dimensional images. While these techniques have not yet been used in log file visualizations, we suggest an application in the fo...
Organic syntheses under high pressure. 3. General approach to the synthesis of naturally occurring .delta.-lactones (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrganic syntheses under high pressure. 3. General approach to the synthesis of naturally occurring .delta.-lactonesMarek Chmielewski and Janusz JurczakCite this: J. Org. Chem. 1981, 46, 11, 2230–2233Publication Date (Print):May 1, 1981Publication History Published online1 May 2002Published inissue 1 May 1981https://pubs.acs.org/doi/10.1021/jo00324a008https://doi.org/10.1021/jo00324a008research-articleACS PublicationsRequest reuse permissionsArticle Views306Altmetric-Citations48LEARN 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
P-glycoprotein (Mdr1a/1b) and breast cancer resistance protein (Bcrp) decrease the uptake of hydrophobic alkyl triphenylphosphonium cations by the brain (2013)

These findings suggest that strategies to bypass ABC transporters in the BBB will enhance delivery of mitochondria-targeted antioxidants, probes and pharmacophores to the brain.
Factors influencing the immunogenicity of therapeutic proteins (2005)

Several diseases and disorders are treatable with therapeutic proteins, but some of these products may induce an immune response, especially when administered as multiple doses over prolonged periods. Antibodies are created by classical immune reactions or by the breakdown of immune tolerance; the latter is characteristic of human homologue products. Many factors influence the immunogenicity of proteins, including structural features (sequence variation and glycosylation), storage conditions (denaturation, or aggregation caused by oxidation), contaminants or impurities in the preparation, dose and length of treatment, as well as the route of administration, appropriate formulation and the genetic characteristics of patients. The clinical manifestations of antibodies directed against a given protein may include loss of efficacy, neutralization of the natural counterpart and general immune system effects (including allergy, anaphylaxis or serum sickness). An upsurge in the incidence of antibody-mediated pure red cell aplasia (PRCA) among patients taking one particular formulation of recombinant human erythropoietin (epoetin-alpha, marketed as Eprex(R)/Erypo(R); Johnson & Johnson) in Europe caused widespread concern. The PRCA upsurge coincided with removal of human serum albumin from epoetin-alpha in 1998 and its replacement with glycine and polysorbate 80. Although the immunogenic potential of this particular product may have been enhanced by the way the product was stored, handled and administered, it should be noted that the subcutaneous route of administration does not confer immunogenicity per se. The possible role of micelle (polysorbate 80 plus epoetin-alpha) formation in the PRCA upsurge with Eprex is currently being investigated.
Degradation of a CuxS/CdS solar cell in hot, moist air and recovery in hydrogen and air (1983)

A polycrystalline, thin-film CuxS/CdS solar cell was exposed to air saturated with water vapor at temperatures between 27 and 67 °C for up to 6 1/2 h. The short-circuit current decreased progressively from 11.7 to 1.02 mA/cm2. Subsequent heating in hydrogen at 150 °C for 680 h and in 170 °C air for 5 h restored the short-circuit current to 14.4 mA/cm2. Modeling of the measured quantum yield indicates that the degradation could be quantitatively explained by two effects: (1) the CuxS minority carrier electron diffusion length decreasing from 0.23 to 0.02 μm (±20%) and (2) the CuxS optical band gap increasing from 1.16 to 1.46 eV (±3%). The recovery was quantitatively modeled by the CuxS diffusion length increasing back to 0.24 μm and the CuxS band gap returning to 1.16 eV. A Burstein–Moss analysis shows the band-gap shift is due to the Fermi level penetration of the valence band as the measured hole concentration increased from 1.03(1020) cm−3 to 4.62(1021) cm−3 during degradation. A new band structure is proposed with six equivalent, indirect, valence band maxima located at 1.16 eV (±3%) below the conduction band edge followed by two direct maxima located at 1.28 and 1.8 eV (±3%) below the conduction band edge. A density-of-states effective mass ratio for holes of 2.0 (±30%) is found. The sharp decrease and recovery in diffusion length is explained by a transition between phonon-assisted and direct minority carrier recombination with changes in CuxS hole concentration.
Prediction of Functional Sites Based on the Fuzzy Oil Drop Model (2007)

A description of many biological processes requires knowledge of the 3-D structure of proteins and, in particular, the defined active site responsible for biological function. Many proteins, the genes of which have been identified as the result of human genome sequencing, and which were synthesized experimentally, await identification of their biological activity. Currently used methods do not always yield satisfactory results, and new algorithms need to be developed to recognize the localization of active sites in proteins. This paper describes a computational model that can be used to identify potential areas that are able to interact with other molecules (ligands, substrates, inhibitors, etc.). The model for active site recognition is based on the analysis of hydrophobicity distribution in protein molecules. It is shown, based on the analyses of proteins with known biological activity and of proteins of unknown function, that the region of significantly irregular hydrophobicity distribution in proteins appears to be function related.
Molecular Mechanism and Classification of von Willebrand Disease (1995)

The characterization of mutations in von Willebrand disease provides useful insight into the synthesis, structure, and function of von Willebrand factor. This growing body of information has prompted a reclassification of vWD types that is intended to reflect distinct pathophysiologic mechanisms. Despite this apparent progress, many aspects of vWF biology and pathophysiology remain poorly understood. These include the mechanism by which binding of vWF to platelets is induced at sites of vascular injury, and the factors that influence the likelihood of bleeding symptoms in patients with vWD type 1.
Efficient state estimators for load control policies in scalable Web server clusters (2002)

Replication of information across a server cluster provides a promising way to support popular Web sites. However a Web server cluster requires some mechanism for directing requests to the best server. One common approach is to use the Domain Name Server (DNS) as a centralized schedule. However address caching mechanisms and the non-uniformity of the load from different client domains complicate the load balancing issue and make existing scheduling algorithms for traditional distributed systems not applicable to Web server clusters. We consider the theoretical DNS policies that require some system state information. We extend them to realistic situations where state information needs to be estimated with low computation and communication overhead. We show that by incorporating these estimators into the DNS policies, load balancing improves substantially, even if the DNS control is limited to a small portion of client requests.
Genomics Analysis of Genes Expressed in Maize Endosperm Identifies Novel Seed Proteins and Clarifies Patterns of Zein Gene Expression (2001)

We analyzed cDNA libraries from developing endosperm of the B73 maize inbred line to evaluate the expression of storage protein genes. This study showed that zeins are by far the most highly expressed genes in the endosperm, but we found an inverse relationship between the number of zein genes and the relative amount of specific mRNAs. Although alpha-zeins are encoded by large multigene families, only a few of these genes are transcribed at high or detectable levels. In contrast, relatively small gene families encode the gamma- and delta-zeins, and members of these gene families, especially the gamma-zeins, are highly expressed. Knowledge of expressed storage protein genes allowed the development of DNA and antibody probes that distinguish between closely related gene family members. Using in situ hybridization, we found differences in the temporal and spatial expression of the alpha-, gamma-, and delta-zein gene families, which provides evidence that gamma-zeins are synthesized throughout the endosperm before alpha- and delta-zeins. This observation is consistent with earlier studies that suggested that gamma-zeins play an important role in prolamin protein body assembly. Analysis of endosperm cDNAs also revealed several previously unidentified proteins, including a 50-kD gamma-zein, an 18-kD alpha-globulin, and a legumin-related protein. Immunolocalization of the 50-kD gamma-zein showed this protein to be located at the surface of prolamin-containing protein bodies, similar to other gamma-zeins. The 18-kD alpha-globulin, however, is deposited in novel, vacuole-like organelles that were not described previously in maize endosperm.
Molecular typing and epidemiological survey of prevalence of Clostridium perfringens types by multiplex PCR (1997)

Clostridium perfringens has been classified into five toxigenic types (A through E) on the basis of its capability to produce major lethal toxins (alpha, beta, epsilon, and iota toxins). Seroneutralization with mice or guinea pigs has been used to type each toxin, but this conventional method has some disadvantages. Therefore, we used a molecular biological technique to type the bacterium in the present study. A multiplex PCR was developed for this purpose. This method has several advantages in comparison with seroneutralization with mice or guinea pigs. By this method, we also investigated the most prevalent type(s) of the organism in Korean calves, piglets, and chickens showing clinical symptoms such as diarrhea, enterotoxemia, and necrotic enteritis. Only type A was isolated from calves and chickens, while type C (2 of 14 isolates), in addition to type A, was isolated from piglets. These results suggested that seroneutralization could be replaced by our new method and that type A of C. perfringens is the most prevalent type in livestock in Korea.
Translating Stem and Progenitor Cell Biology to the Clinic: Barriers and Opportunities (2000)

Stem cells are the natural units of embryonic generation, and also adult regeneration, of a variety of tissues. Recently, the list of tissues that use the model of differentiation from stem to progenitor to mature cell has increased from blood to include a variety of tissues, including both central and peripheral nervous systems and skeletal muscle; it is also possible that all organs and tissues are derived from, and still contain, stem cells. Because the number and activities of stem cells and their progeny are homeostatically regulated, clinical stem cell transplantation could greatly add to the physician's armamentarium against degenerative diseases.
MK-0677, a potent, novel, orally active growth hormone (GH) secretagogue: GH, insulin-like growth factor I, and other hormonal responses in beagles. (1996)

MK-0677, a spiroindoline sulfonamide, is a novel, orally active GH secretagogue. The effects of MK-0677 on serum GH and other hormones after oral and iv single dose administrations in beagles were evaluated. After oral administration in a balanced eight-dog crossover study, treatment with MK-0677 significantly increased peak GH concentrations, with a 5.3-fold increase (mean +/- SEM, 10.5 +/- 1.9 ng/ml) at the 0.25 mg/kg dose, a 9.0-fold increase (18.0 +/- 3.3 ng/ml) at the 0.50 mg/kg dose, and a 15.8-fold increase (31.6 +/- 5.8 ng/ml) at the 1.0 mg/kg dose. Total GH release, expressed as the area under the curve, showed similar significant increases over the effect of the water placebo. A single oral 1 mg/kg dose in three dogs induced a mean GH peak of 27.6 +/- 1.5 ng/ml at 120 min, and GH levels remained elevated up to 360 min after treatment. Insulin-like growth factor I (IGF-I) levels were significantly increased by 30% at 480 min after treatment. Cortisol levels were increased 2.4-fold over pretreatment levels. After i.v. administration, compared to the saline control group which had a mean (+/- SEM) serum GH peak of 3.8 +/- 0.7 ng/ml, MK-0677 at 0.25 mg/kg significantly increased (P < 0.05) peak GH concentrations 20.4-fold (77.4 +/- 13.7 ng/ml). Total GH release, expressed as the area under the curve, showed a similar increase. The mean peak GH level was recorded 10 min after treatment, with GH levels elevated up to 180 min after treatment. IGF-I levels were significantly elevated by 25% 360 min after the administration of MK-0677. Cortisol levels were increased 2.3-fold over pretreatment levels. Insulin and glucose levels were higher, LH and PRL levels were unaltered, and T4 levels were marginally lower; the levels of each of these hormones remained within the normal ranges for dogs throughout the experiment. In summary, MK-0677 is a potent GH secretagogue that induces an immediate, large, long lasting increase in GH levels when administered orally or i.v. In contrast to GH-releasing peptide-6 and benzolactam secretagogues, GH levels were elevated up to 360 min after treatment, and this was associated with a significant increase in IGF-I levels. Cortisol levels were increased; however, the increases were modest compared to those in GH.
Optical properties of hexagonal boron nitride (1976)

Optical absorption, reflectivity, and photoconductivity in the near-uv range (1950-3200 \AA{}) of a thin film of hexagonal boron nitride were measured. The main absorption peak was observed at 6.2 eV. A sharp fall at about 5.8 eV was attributed to the direct band gap. The temperature dependence of the band gap was found to be less than 4 \ifmmode\times\else\texttimes\fi{} ${10}^{\ensuremath{-}5}$ eV/\ifmmode^\circ\else\textdegree\fi{}K. Self-consistent tight-binding band-structure calculations were performed on a two-dimensional hexagonal crystal model, using Hamiltonian matrix elements calculated by semiempirical LCAO (linear combination of atomic orbitals) methods. The calculated value for the band gap of hexagonal BN was in reasonably good agreement with the experimental value obtained in the present work, as well as with values reported earlier from electron-energy-loss and photoelectron-emission measurements. The calculations also predicted a very small change in the band gap with temperature, in agreement with the experimental observations.