gebhart/patrepeval huggingface dataset:
Cathepsin K Inhibitors for Osteoporosis: Biology, Potential Clinical Utility, and Lessons Learned (2017)

Cathepsin K is a cysteine protease member of the cathepsin lysosomal protease family. Although cathepsin K is highly expressed in osteoclasts, lower levels of cathepsin K are also found in a variety of other tissues. Secretion of cathepsin K from the osteoclast into the sealed osteoclast-bone cell interface results in efficient degradation of type I collagen. The absence of cathepsin K activity in humans results in pycnodysostosis, characterized by increased bone mineral density and fractures. Pharmacologic cathepsin K inhibition leads to continuous increases in bone mineral density for ≤5 years of treatment and improves bone strength at the spine and hip. Compared with other antiresorptive agents, cathepsin K inhibition is nearly equally efficacious for reducing biochemical markers of bone resorption but comparatively less active for reducing bone formation markers. Despite multiple efforts to develop cathepsin K inhibitors, potential concerns related to off-target effects of the inhibitors against other cathepsins and cathepsin K inhibition at nonbone sites, including skin and perhaps cardiovascular and cerebrovascular sites, prolonged the regulatory approval process. A large multinational randomized, double-blind phase III study of odanacatib in postmenopausal women with osteoporosis was recently completed. Although that study demonstrated clinically relevant reductions in fractures at multiple sites, odanacatib was ultimately withdrawn from the regulatory approval process after it was found to be associated with an increased risk of cerebrovascular accidents. Nonetheless, the underlying biology and clinical effects of cathepsin K inhibition remain of considerable interest and could guide future therapeutic approaches for osteoporosis.
Deer and antelope meat studies: Season of highest palatability and food value subject of investigation of California antelope and deer (1949)

Bucks of the California mule deer and the black-tailed deer usually are in prime condition—with the antlers hard—in August and early September. On the basis of palatability and vitamin content the meat of the mule deer from Santa Barbara and Ventura counties was found to be desirable from June through August and the meat of the black-tailed deer from Marin County was most palatable from the middle of March through July. The vitamin content of black-tailed deer meat seemed to be highest in the winter months.
Review Article : Genetics of Neurofibromatosis 1 and the NF1 Gene (2002)

Neurofibromatosis 1 serves as a paradigm for understanding the principles of human genetics. The concepts of gene mutation, penetrance of the condition, variable clinical expressivity, mosaicism, age-dependent expression of clinical manifestations, and pleiotropy are evident in this autosomal dominant condition. The lack of genotype-phenotype correlation, except the whole-gene deletion phenotype, leads to speculation on modifiers of the haploinsufficient state of the NF1 gene product neurofibromin. The variant form of neurofibromatosis, neurofibromatosis Noonan's syndrome, suggests potential interaction of independent biochemical pathways. Identification of the NF1 gene led to the discovery of its role in ras signal transduction. Neurofibromin is a negative regulator of intracellular ras signaling. This observation now provides the framework for the development of rational medical therapies. In addition, knowledge of the molecular basis of the variable expression of clinical manifestations could provide better anticipatory guidance and more effective management of the medical complications that are associated with this condition.
ChemInform Abstract: Parasite Glycoconjugates. Part 7. Synthesis of Further Substrate Analogues of Early Intermediates in the Biosynthetic Pathway of Glycosylphosphatidylinositol Membrane Anchors. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Effects of hyaluronan on the invasive properties of human breast cancer cells in vitro. (2001)

Hyaluronan (HA) is a high molecular weight glycosaminoglycan present mostly in the extracellular matrix (ECM). HA binds to specific receptors such as CD44. Its production is increased at the tumour-stroma interface, including those in breast cancer tumours. It has been suggested that it facilitates invasion of tumour cells into the ECM by a hydrodynamic effect, or by altering tumour cell behaviour. Using in vitro tests we studied the effect of immobilized (iHA) and soluble (sHA) HA on the invasive properties of four human breast cancer cell lines with different levels of CD44 expression. Our results show that iHA acts as an adhesive, haptotactic, and motility stimulating factor for the CD44 positive Hs578T cells and induces the expression of membrane CD44. sHA also changes the motility properties of the Hs578T and MDA-231 cells and increases their CD44 expression. sHA or iHA have no measurable effect on the adhesion, motility or CD44 expression of the ZR-75-1 and MCF-7 breast cancer cells. Our results establish that in high CD44 expressing breast cancer cells HA modulates tumour cell adhesion and motility and also increases the expression of its own receptor, CD44.
Influence of cyanogen-bromide-digested fibrinogen on the kinetics of plasminogen activation by urokinase (1984)

The catalytic efficiency (kcat/Km) of high-molecular-mass urokinase for the activation of Glu-plasminogen is increased about 10-fold in the presence of CNBr-digested fibrinogen. This stimulation is similar to that observed with 6-aminohexanoic acid, and yields kinetic parameters comparable to those for the activation of Lys-plasminogen by urokinase. The increase of the activation rate of Glu-plasminogen by urokinase in the presence of CNBr-Fg can thus be explained by a conformational change in the plasminogen molecule similar to that observed upon conversion of Glu-plasminogen to Lys-plasminogen and upon binding of 6-aminohexanoic acid to Glu-plasminogen. Stabilization of the Michaelis complex between urokinase and plasminogen by formation of a cyclic ternary complex with CNBr-Fg, which has been invoked to explain the dramatic stimulatory effect of CNBr-Fg on the activation of plasminogen by tissue-type plasminogen activator, does not appear to play a significant role in the increased activation rate.
Tables of critically evaluated oscillator strengths for the lithium isoelectronic sequence (1976)

Oscillator strengths for the lithium isoelectronic sequence have been critically evaluated and complied by means of a new generalized analysis which makes use of several types of systematic trends and fundamental spectroscopic constraints. Relativistic effects have also been considered. The data are presented in separate tables for each ion of the sequence from Li i through Ni xxvi, and are arranged within each table according to spectral series. Separate tables are presented for the 2s–2p and 2s–3p transitions, with both relativistic and nonrelativistic f-values listed for all ions of the sequence through Ni xxvi, as well as for a few selected ions of higher nuclear charge. The general tables contain transitions of the types ms−np, mp−ns, and mp−nd, with 2?m?4 (m is the lower principal quantum number) and 3?n?7. Since most recommended data were determined from a nonrelativistic analysis, hydrogenic relativistic considerations were applied to estimate when the data would be significantly altered by the inclusion of relativistic effects, and such f-values were excluded from the tabulation.
A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence (2006)

Our findings support the use of metadoxine in the management of alcohol dependence. However, randomized clinical trials are necessary to confirm and replicate them. This study raises the importance of identifying new pharmacological compounds effective on the outcome of alcoholism in order to help patients to best adhere to treatment programs and to prevent the development of mental and physical complications due to chronic and heavy use of alcohol.
The Competitive Formation of Different Olefins from Quaternary Amines (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Competitive Formation of Different Olefins from Quaternary AminesPeter A. S. Smith and Simon FrankCite this: J. Am. Chem. Soc. 1952, 74, 2, 509–513Publication Date (Print):January 1, 1952Publication History Published online1 May 2002Published inissue 1 January 1952https://pubs.acs.org/doi/10.1021/ja01122a067https://doi.org/10.1021/ja01122a067research-articleACS PublicationsRequest reuse permissionsArticle Views516Altmetric-Citations23LEARN 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
Inhibition of Type 1 Cytokine–mediated Inflammation by a Soluble CD30 Homologue Encoded by Ectromelia (Mousepox) Virus (2002)

CD30 is up-regulated in several human diseases and viral infections but its role in immune regulation is poorly understood. Here, we report the expression of a functional soluble CD30 homologue, viral CD30 (vCD30), encoded by ectromelia (mousepox) virus, a poxvirus that causes a severe disease related to human smallpox. We show that vCD30 is a 12-kD secreted protein that not only binds CD30L with high affinity and prevents its interaction with CD30, but it also induces reverse signaling in cells expressing CD30L. vCD30 blocked the generation of interferon gamma-producing cells in vitro and was a potent inhibitor of T helper cell (Th)1- but not Th2-mediated inflammation in vivo. The finding of a CD30 homologue encoded by ectromelia virus suggests a role for CD30 in antiviral defense. Characterization of the immunological properties of vCD30 has uncovered a role of CD30-CD30L interactions in the generation of inflammatory responses.
Dorsally derived netrin 1 provides an inhibitory cue and elaborates the`waiting period' for primary sensory axons in the developing spinal cord (2006)

Dorsal root ganglion (DRG) neurons extend axons to specific targets in the gray matter of the spinal cord. During development, DRG axons grow into the dorsolateral margin of the spinal cord and projection into the dorsal mantle layer occurs after a ;waiting period' of a few days. Netrin 1 is a long-range diffusible factor expressed in the ventral midline of the developing neural tube, and has chemoattractive and chemorepulsive effects on growing axons. Netrin 1 is also expressed in the dorsal spinal cord. However, the roles of dorsally derived netrin 1 remain totally unknown. Here, we show that dorsal netrin 1 controls the correct guidance of primary sensory axons. During the waiting period, netrin 1 is transiently expressed or upregulated in the dorsal spinal cord, and the absence of netrin 1 results in the aberrant projection of sensory axons, including both cutaneous and proprioceptive afferents, into the dorsal mantle layer. Netrin 1 derived from the dorsal spinal cord, but not the floor plate, is involved in the correct projection of DRG axons. Furthermore, netrin 1 suppresses axon outgrowth from DRG in vitro. Unc5c(rcm) mutant shows abnormal invasion of DRG axons as observed in netrin 1 mutants. These results are the first direct evidence that netrin 1 in the dorsal spinal cord acts as an inhibitory cue for primary sensory axons and is a crucial signal for the formation of sensory afferent neural networks.
Factors Controlling Anaerobic Ammonium Oxidation with Nitrite in Marine Sediments (2002)

Factors controlling the anaerobic oxidation of ammonium with nitrate and nitrite were explored in a marine sediment from the Skagerrak in the Baltic-North Sea transition. In anoxic incubations with the addition of nitrite, approximately 65% of the nitrogen gas formation was due to anaerobic ammonium oxidation with nitrite, with the remainder being produced by denitrification. Anaerobic ammonium oxidation with nitrite exhibited a biological temperature response, with a rate optimum at 15 degrees C and a maximum temperature of 37 degrees C. The biological nature of the process and a 1:1 stoichiometry for the reaction between nitrite and ammonium indicated that the transformations might be attributed to the anammox process. Attempts to find other anaerobic ammonium-oxidizing processes in this sediment failed. The apparent K(m) of nitrite consumption was less than 3 microM, and the relative importance of ammonium oxidation with nitrite and denitrification for the production of nitrogen gas was independent of nitrite concentration. Thus, the quantitative importance of ammonium oxidation with nitrite in the jar incubations at elevated nitrite concentrations probably represents the in situ situation. With the addition of nitrate, the production of nitrite from nitrate was four times faster than its consumption and therefore did not limit the rate of ammonium oxidation. Accordingly, the rate of this process was the same whether nitrate or nitrite was added as electron acceptor. The addition of organic matter did not stimulate denitrification, possibly because it was outcompeted by manganese reduction or because transport limitation was removed due to homogenization of the sediment.
A dielectric-defined process for the formation of T-gate field-effect transistors (1991)

A novel process for the fabrication of tee- or gamma-shaped gate structures is presented. This process was utilized to fabricate 0.25 mu m*60 mu m and 0.25 mu m*150 mu m T-gate MESFETs. From S-parameter data up to 40 GHz, extrapolated cutoff frequencies as high as 55-65 GHz were obtained. DC yields as high as 80% over 3-in wafers were obtained using this dielectric defined T-gate (DDTG) process. Step-stress measurements indicate device reliability comparable to the normal MESFET process. Relative to multilayer resist processing techniques usually used to form T-gates, it is believed that the DDTG process will substantially increase the yield, uniformity, and reliability of FET-like devices/circuits using T-gates with geometries at or below 0.25 mu m.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Oxidative Rearrangement of Imidazoles with Dimethyldioxirane (2004)

Tetrahydrobenzimidazoles, on treatment with dimethyldioxirane, rearrange to provide 5-imidazolones exclusively. These rearrangements proceed with a broad range of substrates and with good to excellent levels of diastereoselectivity. [reaction: see text]
GDNF and BDNF gene interplay in chronic tinnitus (2012)

The present findings serve as an incentive for further explorations of neurotrophic factors' role in predicting clinical features of tinnitus. Possible implications of sexually dimorphic at-risk genotypes are discussed with regard to hearing and neural plasticity.
Radiation Sterilization of Medical Devices and Supplies. I : Disposable Syringes and Needles. (1967)

Disposable polystyrene syringes and needles were irradiated with cobalt-60 gamma rays at various doses, and were subjected to sterility test, safety test, and function tests such as, breaking test, load test, fluid tightness test. A dose of 3 Mrad sterilized completely the samples inoculated heavily with Bacillus spores. Even at this dose level, neither the occurrence of the toxicity nor detrimental effect on the function of syringes were observed. From these results, it is presumed that 3 Mrad is suitable dose for the radiation sterilization of disposable syringes and needles.
Human Insulin-Receptor Gene: Partial Sequence and Amplification of Exons by Polymerase Chain Reaction (1990)

The partial sequence of the human insulin-receptor (hINSR) gene is presented. Using the gene sequence as a guide, we selected pairs of oligonucleotide primers from sites in the introns that flank each exon. These primers allowed each of the 22 exons of the hINSR gene to be amplified in vitro by the polymerase chain reaction. The sequences of the gene and oligonucleotide primers will facilitate studies of genetic variation in the hINSR gene and thereby increase our understanding of the role of this gene in the development of insulin-resistant states and glucose intolerance.
Age-associated deterioration in follicular fluid induces a decline in bovine oocyte quality (2016)

Maternal age affects the quality of oocytes. The present study examined whether follicular fluid (FF) is a casual factor for age-associated decline in oocyte quality. First, we measured the concentration of advanced glycation end-products (AGE) in FF derived from young (21-45 months; Young-FF) and aged (≥120 months; Aged-FF) cows and found significantly higher concentrations of AGE in Aged-FF than Young-FF. Second, oocytes were collected from ovaries of young or aged cows and cultured in maturation medium containing 10% FF derived from young or aged cows. Regardless of oocyte origin, Aged-FF accelerated nuclear maturation progression and gap junction closure between oocytes and cumulus cells, increased reactive oxygen species (ROS) content and the rate of abnormal fertilisation of oocytes and decreased blastulation rate compared with Young-FF. Furthermore, supplementation of maturation medium with AGE induced similar age-associated events in oocytes derived from young cows, in that AGE accelerated the progression of nuclear maturation, increased ROS content in oocytes, increased the rate of abnormal fertilisation and decreased blastulation rate. In conclusion, maternal aging increased the concentration of AGE in FF, and both AGE and Aged-FF accelerated nuclear maturation and reduced the developmental competence of oocytes.
Monitoring path nearest neighbor in road networks (2009)

This paper addresses the problem of monitoring the k nearest neighbors to a dynamically changing path in road networks. Given a destination where a user is going to, this new query returns the k-NN with respect to the shortest path connecting the destination and the user's current location, and thus provides a list of nearest candidates for reference by considering the whole coming journey. We name this query the k-Path Nearest Neighbor query (k-PNN). As the user is moving and may not always follow the shortest path, the query path keeps changing. The challenge of monitoring the k-PNN for an arbitrarily moving user is to dynamically determine the update locations and then refresh the k-PNN efficiently. We propose a three-phase Best-first Network Expansion (BNE) algorithm for monitoring the k-PNN and the corresponding shortest path. In the searching phase, the BNE finds the shortest path to the destination, during which a candidate set that guarantees to include the k-PNN is generated at the same time. Then in the verification phase, a heuristic algorithm runs for examining candidates' exact distances to the query path, and it achieves significant reduction in the number of visited nodes. The monitoring phase deals with computing update locations as well as refreshing the k-PNN in different user movements. Since determining the network distance is a costly process, an expansion tree and the candidate set are carefully maintained by the BNE algorithm, which can provide efficient update on the shortest path and the k-PNN results. Finally, we conduct extensive experiments on real road networks and show that our methods achieve satisfactory performance.
Activation of the aryl hydrocarbon receptor by a component of cigarette smoke reduces germ cell proliferation in the human fetal ovary (2015)

Peer reviewed
A Study of the Telephone Survey Method (2003)

Until now, social surveys (i.e., public opinion surveys) heve been conducted using the face-to-face interview method. This is due to the facts that: (a) resident registrations (or voting registries), which are regarded as a sampling frame which adequately represents total populations, are available in Japan and can relatively easily facilitate obtaining unbiased probability samples, and (b) the reliability of the face-to-face interview method in surveys is regarded as high. Conversely, from the perspective of the spread of household telephones, the telephone survey method has been regarded as one by which it is impossible to obtain probability samples which represent ordinary citizens. Since the 1980s, household telephone coverage has increased (to over 90%). Consequently, the telephone survey method, which is especially useful for its promptness, has been used for voter forecasting surveys, and in the 1990s this method also has been utilized in public opinion surveys. However, not enough research on the telephone survey method has yet been done with respect to the representativeness of its samples or the reliability of survey results. This paper discusses past and current research regarding telephone surveys (specifically the current RDD survey method), and actual survey results, including their errors (except sampling errors). Moreover, by comparing the responses using both the telephone survey method and face-to-face interviews, the differences between the two methods are discussed. The current RDD method is viable; however, we cannot predict this method's future due to developments in communication technology. Finally, because there are many problems to overcome with respect to actual survey methods, further research, e.g., accumulating actual survey results and re-analyzing existing survey data, is necessary.
Nickel‐Catalyzed Mizoroki–Heck Reaction of Aryl Sulfonates and Chlorides with Electronically Unbiased Terminal Olefins: High Selectivity for Branched Products (2014)

Achieving high selectivity in the Heck reaction of electronically unbiased alkenes has been a longstanding challenge. Using a nickel-catalyzed cationic Heck reaction, we were able to achieve excellent selectivity for branched products (≥19:1 in all cases) over a wide range of aryl electrophiles and aliphatic olefins. A bidentate ligand with a suitable bite angle and steric profile was key to obtaining high branched/linear selectivity, whereas the appropriate base suppressed alkene isomerization of the product. Although aryl triflates are traditionally used to access the cationic Heck pathway, we have shown that, by using triethylsilyl trifluoromethanesulfonate, we can effect a counterion exchange of the catalytic nickel complex, such that cheaper and more stable aryl chlorides, mesylates, tosylates, and sulfamates can be used to yield the same branched products with high selectivity.