gebhart/patrepeval huggingface dataset:
Sensitive in vitro Bioassay for the Measurement of Serum Follicle-Stimulating Hormone (1985)

A sensitive in vitro bioassay for measuring serum follicle-stimulating hormone (FSH) levels has been developed based on the stimulation of estrogen production by cultured rat granulosa cells. In the presence of androstenedione, FSH stimulated estrogen production in a dose-dependent manner. Cell sensitivity to FSH was further enhanced by the addition of diethylstilbestrol, a phosphodiesterase inhibitor, insulin, and human chorionic gonadotropin. Although the inclusion of 4% gonadotropin-free serum from hypophysectomized rats inhibited granulosa cell responsiveness, pretreatment of serum with polyethylene glycol (12%) substantially eliminated the serum interfering effect without loss of FSH activity. In normal male and female rats, serum bioactive FSH levels were low, while castration increased these levels 2.6-and 5.7-fold, respectively. These increases were suppressed by treatment with testosterone propionate or estradiol benzoate. This in vitro assay allows the measurement of circulating bioactive FSH and provides a convenient tool to advance studies on the role of FSH in the neuroendocrine control of gonadal maturation and reproductive cycles.
Two Novel Mutations Found in a Patient with 17α-Hydroxylase Enzyme Deficiency (2006)

Identification of novel mutations in the CYP17 gene is vital in understanding the molecular mechanisms of its deficiency and in providing additional information about the structure and enzymatic functions of P450c17.
Modeling Hard-Disk Power Consumption (2003)

Excessive power consumption is a major barrier to the market acceptance of hard disks in mobile electronic devices. Studying and reducing power consumption, however, often involves running timeintensive disk traces on real hardware with specialized power-monitoring equipment. This paper presents Dempsey, a disk simulation environment that includes accurate modeling of disk power consumption. It includes tools to automatically extract performance and power consumption parameters from a given disk drive, without needing detailed specifications from the manufacturer. The tools use stimulus-based measurements to extract these parameters. Dempsey is experimentally validated for two mobile hard disks, namely, the 1 GB IBM Microdrive and the 5 GB Toshiba Type II PC Card HDD. In the worst observed case, Dempsey&amp;apos;s estimate of power consumption di#ers from the measured consumption by 7.5%. This demonstrates that disk power consumption can be simulated both e#ciently and accurately.
High Throughput Mutation Screening by Automated Capillary Electrophoresis (2000)

Molecular diagnosis of complex inherited disorders, population screening of genetic diseases, studies of the genetic basis of variable drug response (pharmacogenetics) as well as discovery and investigation of new drug targets (pharmacogenomics) involve screening for mutations in multiple DNA samples. Furthermore, the development of a third generation of the human genome map, based on single nucleotide polymorphisms (SNPs), requires screening for allelic variants through all of the three billion basepairs in the human genome. Thus, the need for high throughput mutation screening methods is great and is rapidly increasing. Traditional methods for mutation screening often involve slab-gel electrophoresis analyses which are laborious and difficult to automate. However, recent developments in capillary electrophoresis systems for DNA fragment analysis have made fully automated mutation screening possible and have dramatically increased the possible sample throughput. This review describes the recent advances in capillary electrophoresis of DNA and summarize the various methods for mutation screening based on this technique.
A Common Mechanism Underlying Promiscuous Inhibitors from Virtual and High-Throughput Screening (2002)

High-throughput and virtual screening are widely used to discover novel leads for drug design. On examination, many screening hits appear non-drug-like: they act noncompetitively, show little relationship between structure and activity, and have poor selectivity. Attempts to develop these peculiar molecules into viable leads are often futile, and much time can be wasted on the characterization of these "phony" hits. Despite their common occurrence, the mechanism of action of these promiscuous molecules remains unknown. To investigate this problem, 45 diverse screening hits were studied. Fifteen of these were previously reported as inhibitors of various receptors, including beta-lactamase, malarial protease, dihydrofolate reductase, HIV Tar RNA, thymidylate synthase, kinesin, insulin receptor, tyrosine kinases, farnesyltransferase, gyrase, prions, triosephosphate isomerase, nitric oxide synthase, phosphoinositide 3-kinase, and integrase; 30 were from an in-house screening library of a major pharmaceutical company. In addition to their original targets, 35 of these 45 compounds were shown to inhibit several unrelated model enzymes. These 35 screening hits included compounds, such as fullerenes, dyes, and quercetin, that have repeatedly shown activity against diverse targets. When tested against the model enzymes, the compounds showed time-dependent but reversible inhibition that was dramatically attenuated by albumin, guanidinium, or urea. Surprisingly, increasing the concentration of the model enzymes 10-fold largely eliminated inhibition, despite a 1000-fold excess of inhibitor; a well-behaved competitive inhibitor did not show this behavior. One model to explain these observations was that the active form of the promiscuous inhibitors was an aggregate of many individual molecules. To test this hypothesis, light scattering and electron microscopy experiments were performed. The nonspecific inhibitors were observed to form particles of 30-400 nm diameter by both techniques. In control experiments, a well-behaved competitive inhibitor and an inactive dye-like molecule were not observed to form aggregates. Consistent with the hypothesis that the aggregates are the inhibitory species, the particle size and IC(50) values of the promiscuous inhibitors varied monotonically with ionic strength; a competitive inhibitor was unaffected by changes in ionic strength. Unexpectedly, aggregate formation appears to explain the activity of many nonspecific inhibitors and may account for the activity of many promiscuous screening hits. Molecules acting via this mechanism may be widespread in drug discovery screening databases. Recognition of these compounds may improve screening results in many areas of pharmaceutical interest.
Characterization of a cinnamoyl-CoA reductase that is associated with stem development in wheat (2007)

Cinnamoyl-CoA reductase (CCR) is responsible for the CoA ester to aldehyde conversion in monolignol biosynthesis, which diverts phenylpropanoid-derived metabolites into the biosynthesis of lignin. To gain a better understanding of lignin biosynthesis and its biological function, a cDNA encoding CCR was identified from wheat (Triticum aestivum L.), and designated as Ta-CCR1. Phylogenetic analysis indicated that Ta-CCR1 grouped together with other monocot CCR sequences while it diverged from Ta-CCR2. DNA gel-blot and mapping analyses demonstrated that Ta-CCR1 is present as a single copy gene in the wheat genome. Recombinant Ta-CCR1 protein converted feruloyl CoA, 5-OH-feruloyl CoA, sinapoyl CoA, and caffeoyl CoA, but feruloyl-CoA was the best substrate, suggesting the preferential biosynthesis of G-type lignin. RNA gel-blot analysis indicated that Ta-CCR1 was highly expressed in stem, with lower expression in leaves, and undetectable expression in roots. CCR enzyme activity was increased progressively along with the lignin biosynthesis and stem maturity. During stem development, Ta-CCR1 mRNA levels remained high at elongation, heading, and milky stages in the wheat H4564 cultivar, while they declined dramatically at the heading and milky stages in stems of the C6001 cultivar. Ta-CCR1 mRNA expression paralleled extractable CCR enzyme activity in these two cultivars. Furthermore, high Ta-CCR1 mRNA levels and high CCR enzyme activity in wheat stem were correlated with a higher Klason lignin content and greater stem mechanical strength in the H4564 cultivar. This suggests that Ta-CCR1 and its related CCR enzyme may be involved in the regulation of lignin biosynthesis during stem maturity and then contributes to stem strength support in wheat.
Architectures of dynamically reconfigurable wavelength routing/switching networks (1993)

The enormous bandwidth available in single-mode optical fiber far exceeds the speed that it can be accessed by electronics. To utilize more efficiently this huge bandwidth some means of concurrency is needed. The easiest way to access this bandwidth is directly through the wavelength domain, where many wavelengths are multiplexed together. This technique is called wavelength division multiplexing (WDM). This thesis examines new network architectures made possible by utilizing recent advances in WDM technology. We propose several new architectural concepts together with their realizations. The work focuses on design issues and performance analysis taking into account technological constraints.
The first contribution is the generalization of classical rearrangeable and non-blocking switching networks to the wavelength dimension, defining the interplay between the space and wavelength dimensions. This results in new network architectures called wavelength-space division switches featuring higher capacity, higher connectivity and less complexity than is possible when using either the space or wavelength dimensions alone.
The second contribution is the concept of multi-dimensional switching networks. We generalize the two most commonly used types of WDM networks to the multi-dimensional case resulting in multi-dimensional routing networks and multi-dimensional broadcast networks. Using several dimensions (e.g., wavelength, time, space) results in increased connectivity and reduced complexity, due to reuse of network resources.
The third contribution is a new WDM switch design based on wavelength grouping/dilation. Wavelength-dilated switches are high density, low crosstalk wavelength-selective switches. This technique is found to be very useful when implemented in acousto-optic tunable filter (AOTF) technology, suppressing a severe type of coherent crosstalk, making the AOTF practical for sub-nanometer wavelength spacings.
The final contribution is a static power control scheme for dynamically reconfigurable networks. We propose a static power distribution rule. This guarantees small fluctuations in power levels and can simplify power control when the network is dynamically reconfigured and the number of wavelengths per link varies in time.
Finally, analytical models of distributed networks are provided, and the performance limits due to optical amplifier noise accumulation, crosstalk and dispersion are calculated.
Compact non-invasive millimeter-wave glucose sensor (2015)

The authors describe a compact non-invasive CMOS-circuit-based glucose monitor using millimeter-wave transmission for use on animal and human subjects. Using an earlier device, in vivo measurements were performed through the ear in anesthetized animals and correlated with blood glucose concentration from test strips. In addition, millimeter wave absorption through glucose-containing solutions was measured in specialized liquid transmission cells and is shown to correlate with the animal and separate in vitro data. Design and performance information on the CMOS transceiver are given.
Graft-versus-host disease after liver transplantation: a comprehensive literature review. (2012)

This study showed that an age difference between the recipient and donor is an independent risk factor for mortality in patients who develop GvHD after LT.
Expression of different tenascin isoforms in normal, hyperplastic and neoplastic human breast tissues (1992)

Functionally different tenascin (TN) isoforms, containing varying numbers of a 91 amino-acid motif resembling the fibronectin type-III homology repeat, may be generated by alternative splicing of the TN primary transcript. In fact, only the TN isoform containing the alternatively spliced region can induce loss of focal adhesion in cultured cells and seems to be able to facilitate cell migration. We examined the patterns of alternative splicing of the TN primary transcript in normal, hyperplastic and neoplastic breast tissues, and found that, in all the invasive breast carcinomas analyzed, the relative amount of TN mRNA in which the alternatively spliced region was included was about 10 times higher than in RNA from normal breast tissues. A similar result was observed in phyllodes tumors and in those fibroadenomas which showed very high stromal cellularity. Western-blot analysis using different monoclonal antibodies showed the same pattern as that seen in Northern blotting. The data reported here suggest that, in the breast, expression of the high-molecular-mass TN isoform is a marker of stromal element proliferation and that, in invasive breast carcinomas, this TN isoform could play a role in generating a permissive environment for proliferation, invasion and metastasis of neoplastic epithelial cells.
TRK-T1 is a novel oncogene formed by the fusion of TPR and TRK genes in human papillary thyroid carcinomas. (1992)

We have recently reported the frequent activation of the TRK oncogene in human papillary thyroid carcinoma. In this paper we describe the isolation and characterization of one of the thyroid TRK oncogenes, designated TRK-T1. A 1746-bp-long cDNA was isolated from a library derived from a primary transformant. The cDNA was able to induce foci in NIH3T3 cells. Sequence analysis revealed that TRK-T1 is created by an intrachromosomal rearrangement that juxtaposes the 5' end of the TPR gene to the TRK tyrosine kinase domain. The resulting hybrid mRNA contains 598 nucleotides of the TPR gene and 1148 nucleotides of the TRK proto-oncogene. TRK-T1 mRNA encodes a protein of 55 kDa reacting with antibodies against the carboxy terminus of the proto-TRK protein. We show also the involvement of TPR in the generation of another TRK-T oncogene.
Structure- and Property-Based Design of Aminooxazoline Xanthenes as Selective, Orally Efficacious, and CNS Penetrable BACE Inhibitors for the Treatment of Alzheimer’s Disease (2012)

A structure- and property-based drug design approach was employed to identify aminooxazoline xanthenes as potent and selective human β-secretase inhibitors. These compounds exhibited good isolated enzyme, cell potency, and selectivity against the structurally related aspartyl protease cathepsin D. Our efforts resulted in the identification of a potent, orally bioavailable CNS penetrant compound that exhibited in vivo efficacy. A single oral dose of compound 11a resulted in a significant reduction of CNS Aβ40 in naive rats.
CRISPR-Cas9 targeted deletion of the C9orf72 repeat expansion mutation corrects cellular phenotypes in patient-derived iPS cells (2016)

Abstract The large hexanucleotide (GGGGCC) repeat expansion in the non-coding promoter region of C9orf72 is the leading cause of Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). Mechanisms underlying neurodegeneration are not clear, and both a C9orf72 loss of function and a gain of toxicity, in the form of RNA foci or dipeptide repeat deposition, are implicated. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9-mediated genome editing is an attractive strategy for disease modeling and therapeutic intervention. Here we show that this system can be utilized to completely remove the large repeat expansion mutation within C9orf72 in patient-derived induced pluripotent stem (iPS) cells. Removal of the mutation prevented RNA foci formation and promoter hypermethylation, two phenotypes of the C9orf72 mutation. Interestingly, these changes did not significantly alter C9orf72 expression at the mRNA or protein level. This work provides a proof-of-principle for the use of CRISPR-Cas9-mediated excision of the pathogenic C9orf72 repeat expansion as a therapeutic strategy in FTD/ALS. One Sentence Summary CRISPR-Cas9-mediated excision of the large C9orf72 repeat expansion mutation rescues RNA foci formation and promoter hypermethylation without altering C9orf72 transcript and protein expression.
Virions released from cells transfected with a molecular clone of human T-cell leukemia virus type I give rise to primary and secondary infections of T cells (1995)

The ability of molecular clones of human T-cell leukemia virus type I (HTLV-I) to direct the synthesis of infectious virions has not previously been demonstrated. An HTLV-I provirus originating from an adult T-cell leukemia patient was cloned into a plasmid vector and is designated pCS-HTLV. This molecular clone was shown to direct the synthesis of viral mRNA and proteins in transiently transfected cells; in addition, virus structural proteins were released into the culture medium. Viral proteins were assembled into virions that sedimented at a buoyant density characteristic of retrovirus particles and whose morphology was verified by electron microscopy. Virions concentrated from transiently transfected cell supernatants were incubated with primary cord blood lymphocytes or with transformed T-cell lines to establish that these particles were infectious. Expression of spliced, viral mRNAs in the T-cell cultures after both primary and secondary infections with cell-free virus revealed that pCS-HTLV encodes an infectious provirus.
Recent insights into the structure and functions of heparan sulfate proteoglycans in the human glomerular basement membrane (1999)

As the first barrier to be crossed on the way to urinary space, the glomerular basement membrane (GBM) plays a key role in renal function. The permeability of the GBM for a given molecule is highly dependent on its size, shape and charge. As early as 1980, the charge-selective permeability was demonstrated to relate to the electrostatic properties of covalently bound heparan sulfates (HS) within the GBM. Since the identification of perlecan as a heparan sulfate proteoglycan (HSPG) of basement membranes, the hypothesis that perlecan could be a crucial determinant of GBM permselectivity received considerable attention. In addition to perlecan, the GBM also contains other HSPG species, one of which was identified as agrin. The high local expression of agrin in the GBM, together with the presence of agrin receptors at the cell matrix interface, suggests that this HSPG contributes to glomerular function in multiple ways. Here, we review the current knowledge regarding the structure and functions of HSPGs in the GBM, and discuss how these molecules could be involved in various glomerular diseases. Possible directions for future investigation are suggested.
The study of metals by neutron diffraction (1984)

Discussion des avantages de la diffusion de neutrons dans l'etude des materiaux magnetiques et de la facon dont la diffraction de neutrons peut completer et etendre les etudes de diffraction de rayons X
Rearrangement of β-amino alcohols via aziridiniums: a review (2009)

This tutorial review focuses on the rearrangement of beta-amino alcohols via aziridinium intermediates. It covers the literature from 1947 to January 2009 (55 references). The rearrangement of beta-amino alcohols can be performed by activation of the hydroxy group followed by the addition of nucleophiles (Nu). In most examples, an aziridinium intermediate is involved in the rearrangement. The ratio of amines resulting from the attack of nucleophiles at either the C-1 or C-2 position of the aziridinium intermediate, depends on the nature of the nucleophiles and the R(2) substituent. In some cases, solvent as well as temperature can influence the ratio of amines.
Hydrogels based on water-soluble poly(ether urethanes) derived from L-lysine and poly(ethylene glycol) (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrogels based on water-soluble poly(ether urethanes) derived from L-lysine and poly(ethylene glycol)Aruna Nathan, Durgadas Bolikal, Narendra Vyavahare, Samuel Zalipsky, and Joachim KohnCite this: Macromolecules 1992, 25, 18, 4476–4484Publication Date (Print):August 1, 1992Publication History Published online1 May 2002Published inissue 1 August 1992https://pubs.acs.org/doi/10.1021/ma00044a004https://doi.org/10.1021/ma00044a004research-articleACS PublicationsRequest reuse permissionsArticle Views562Altmetric-Citations41LEARN 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
Minocycline attenuates HIV‐1 infection and suppresses chronic immune activation in humanized NOD/LtsZ‐scidIL‐2Rγnull mice (2014)

More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T-cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB-HPCs) -transplanted humanized NOD/LtsZ-scidIL-2Rγ(null) mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up-regulation of several T-cell immune activation markers such as CD38, HLA-DR, CD69 and co-receptor CCR5. T-cell exhaustion markers PD-1 and CTLA-4 were found to be significantly up-regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin-10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T-cell counts in HIV-infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low-cost adjunctive treatment to regulate chronic immune activation and replication of HIV.
Role of host phosphotyrosine phosphatase SHP-1 in the development of murine leishmaniasis (2001)

Activation of host phosphotyrosine phosphatase SHP-1 by Leishmania and its subsequent impact on tyrosine phosphorylation-based signaling cascades were shown to represent an important mechanism whereby this pathogen may alter host cell functions. Herein, we report that Leishmania-induced macrophage SHP-1 activity is necessary for its survival within phagocytes through the attenuation of nitric oxide-dependent and -independent microbicidal mechanisms. In vivo, Leishmania major infection, which footpad inflammation is mostly undetectable in SHP-1-deficient viable motheaten mice, was accompanied by increased inducible nitric oxide synthase and activation of neutrophils. These enhanced cellular activities were paralleled by a marked activation of signaling events usually negatively regulated by SHP-1. Overall, this study firmly establishes that modulation of the signaling terminator SHP-1 by Leishmania is essential for its installment and propagation.