gebhart/patrepeval huggingface dataset:
Dual Mechanism of Toxicity for Extracellular Injection of Tau Oligomers versus Monomers in Human Tau Mice (2017)

The mechanism of tau toxicity is still unclear. Here we report that recombinant tau oligomers and monomers, intraventricularly injected in mice with a pure human tau background, foster tau pathology through different mechanisms. Oligomeric forms of tau alter the conformation of tau in a paired helical filament-like manner. This effect occurs without tau hyperphosphorylation as well as activation of specific kinases, suggesting that oligomers of tau induce tau assembly through a nucleation effect. Monomers, in turn, induce neurodegeneration through a calpain-mediated tau cleavage that leads to accumulation of a 17 kDa neurotoxic peptide and induction of apoptotic cell death.
The Critical Size Defect as an Experimental Model To Test Bone Repair Materials (1990)

Accuracy and reproducibility are the hallmarks of the scientific method. Too frequently, the scientific method is abandoned and short circuited. The development and eventual clinical application of dental and medical materials and devices requires strict adherence to scientific methodology. The development of new bone repair materials is no exception. A reliable, convenient, and scientifically sound evaluation system is available for testing new bone repair materials. Animal models that fulfill stringent testing criteria and analytical methodology for assessment are described in this review. Experimental design, surgical protocols, tissue preparation for quantitative histology and x-rays, and biochemical assessments are reviewed.
Medicinal Chemistry: Principles and Practice (2002)

This book introduces the principles and practices of modern medicinal chemistry and covers all aspects of drug discovery from the initial lead to final development. It teaches how to convert a lead compound into a potential drug and provides recent case histories as examples of successes. Medicinal Chemistry is unique in dealing with the subject in such a practical way and is the only book currently available to bring together all areas of the subject in one volume. This breadth of coverage is supplemented by references to specialist monographs and reviews, where the reader can find more detail on specific topics of interest if required. Medicinal Chemistry is essential reading for students studying medicinal chemistry, as it provides a grounding in all the required disciplines and subjects. It will also be of great interest to chemists, biochemists and pharmacologists either already working in or contemplating a career in the pharmaceutical and allied industries.
HIERARCHICAL REPRESENTATION OF OPTICALLY SCANNED DOCUMENTS (1984)

The objective of the research to be pursued is to develop a schema for representing raster-digitized (scanned) documents, The representation is to retain not only the spatial structure of a printed document, but should also facilitate automatic labeling of various components, such as text, figures, subtitles, and figure captions, and allow the extraction of important relationships (such as reading order) among them. Intended applications include (1) data compression for document transmission and archival, and (2) document entry, with out rekeying, into editing, formatting, and information retrieval systems.
Regulation by retinoids of P2Y2nucleotide receptor mRNA in human uterine cervical cells (1998)

Extracellular ATP stimulates acute changes in paracellular permeability across cultures of human uterine cervical epithelial cells [G. I. Gorodeski, D. E. Peterson, B. J. De Santis, and U. Hopfer. Am. J. Physiol. 270 (Cell Physiol. 39): C1715-C1725, 1996]. In this paper, we characterize mRNA for a P2Y2 nucleotide receptor in human cervical cells. Using oligonucleotide primers based on the sequence of human airway epithelium P2Y2 receptor, a single 632-bp cDNA band was identified in RT-PCR experiments in extracts of human endocervical and ectocervical tissues and in lysates of human cervical CaSki cells, but not in 3T3 fibroblasts. The nucleotide sequence was homologous to the corresponding human airway epithelium P2Y2 receptor. Northern blot analyses revealed hybridization of the P2Y2 receptor probe to a 2.0-kb mRNA fragment, as well as to 2.2-, 3. 0-, and 4.6-kb species, indicating that human cervical cells express P2Y2 receptor mRNA. Incubation of CaSki cells in retinoid-free medium abolished the ATP-induced changes in permeability and decreased the expression of the P2Y2 receptor mRNA; treatment with retinoids restored the responses to ATP and upregulated the P2Y2 receptor mRNA, suggesting that the receptor mediates ATP-related changes in permeability. Treatment with actinomycin D decreased the expression of the P2Y2 receptor RNA, but the ratio density of the receptor RNA relative to glyceraldehyde-3-phosphate dehydrogenase RNA remained unchanged, suggesting that retinoids upregulate transcription of the receptor mRNA. We conclude that retinoid-dependent modulation of the P2Y2 receptor expression, and hence of the responses to ATP, may be an important mechanism for the regulation of secretion of cervical mucus in vivo.
Dyslipidemias and HMG-CoA Reductase Inhibitor Prescription in Heart Transplant Recipients (2004)

Due to the potential for improved outcomes, a large proportion of patients are prescribed a statin. Our results support previous findings that statins are safe and effective in reducing LDL-C in the management of dyslipidemias in OHT recipients. Nonetheless, dyslipidemias are suboptimally managed in many post-OHT patients.
Interfollicular Epidermal Stem Cells Self-Renew via Autocrine Wnt Signaling (2013)

The skin is a classical example of a tissue maintained by stem cells. However, the identity of the stem cells that maintain the interfollicular epidermis and the source of the signals that control their activity remain unclear. Using mouse lineage tracing and quantitative clonal analyses, we showed that the Wnt target gene Axin2 marks interfollicular epidermal stem cells. These Axin2-expressing cells constitute the majority of the basal epidermal layer, compete neutrally, and require Wnt/β-catenin signaling to proliferate. The same cells contribute robustly to wound healing, with no requirement for a quiescent stem cell subpopulation. By means of double-labeling RNA in situ hybridization in mice, we showed that the Axin2-expressing cells themselves produce Wnt signals as well as long-range secreted Wnt inhibitors, suggesting an autocrine mechanism of stem cell self-renewal.
Content adaptive update for lifting-based motion-compensated temporal filtering (2005)

Content adaptive update steps based on the property of the human vision system are presented for lifting-based motion-compensated temporal filtering (MCTF). Simulations confirm that the proposed method improves both the rate-distortion performance for MCFT and the visual quality significantly.
Stereochemistry of polymerization by DNA-dependent RNA-polymerase from Escherichia coli: an investigation with a diastereomeric ATP-analogue. (1976)

The phosphodiester bond formation by DNA-dependent RNA-polymerase (RNA nucleotidyltransferase, nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) can in principle result in retention, inversion, or racemization of configuration at the alpha-phosphorus of the nucleoside 5'-triphosphate being polymerized. As a first step in elucidating the stereochemistry of this reaction, one diastereomer (A) of adenosine 5'-O-(1-thiotriphosphate) (ATPalphaS) was polymerized with UTP in the presence of poly(dA-dT)-poly(dA-dT). The resulting polymer was enzymatically cleaved to uridine 2',3'-cyclic phosphorothioate which was determined to be the endo-isomer by comparison with an authentic sample. This shows that no reacemization had occurred and that isomer A of ATPalphaS gives a phosphorothioate diester bond with the R-configuration. Whether this represents inversion of retention of configuration awaits elucidation of the absolute configuration of isomer A for ATPalphaS.
CYTOKINE INTER-RELATIONSHIPS AND THEIR ASSOCIATION WITH DISEASE ACTIVITY IN ARTHRITIS (1992)

In order to investigate the relationships between cytokine production and arthritic disease we have determined the concentrations of immunoreactive interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), IFN-gamma, and soluble IL-2-receptor (sIL-2R), as well as bioactive IL-1 and IL-6, in synovial fluids (SF) and plasma of patients with a variety of arthritides. Careful assay revealed only minimal concentrations of IL-1, particularly its biologically active form, in SF. No IL-1 was detectable in the plasma of patients that had IL-1 in their SF. Concentrations of both immunoreactive IL-1 beta and TNF-alpha in SF of rheumatoid arthritis (RA) patients were significantly higher than those in SF from patients with other inflammatory arthritides or osteoarthritis (OA). IL-6 and sIL-2R concentrations in both SF and plasma were higher in RA patients than in OA patients, and were significantly correlated. Approximately half of the SF from patients with all arthropathies contained detectable IFN-alpha, whilst IFN-Y was present in less than 10%. There were significant associations between IL-6, sIL-2R, IL-1 beta, TNF-alpha and IFN-alpha. The concentration of these cytokines, where detectable, was also related to leukocyte counts in the SF, as well as to parameters assessing local and systemic disease activity. Although IL-6 was the cytokine most clearly related to other cytokines, and to parameters assessing disease activity, the relationship between general articular disease activity and IL-6 was only evident in patients with arthropathies other than rheumatoid arthritis.
Vascular expression of clusterin in experimental cyclosporine nephrotoxicity. (1996)

Clusterin is a widely expressed glycoprotein, which appears to be induced during tissue damage. We have examined the expression of the clusterin gene in the kidney during the development of cyclosporine (CyA)-induced nephrotoxicity in the rat using in situ hybridization histochemistry. Female Sprague-Dawley rats (170 g) were divided into experimental or control groups and were given intraperitoneal injections of CyA (25 mg/kg) or vehicle respectively for 2, 4 and 6 weeks. Kidneys from animals sacrificed at these times were fixed in 4% paraformaldehyde and embedded in paraffin. Tissue sections were hybridized using either a sense or antisense riboprobe complementary to clusterin mRNA which was labelled with 32P-UTP. Clusterin gene expression was detected in scattered tubules in kidneys from control animals. Expression of clusterin in cortical collecting ducts of CyA-treated animals was evident at 2 weeks and increased substantially at 4 and 6 weeks. Clusterin expression was also seen in afferent arterioles, the glomerular capsule and transitional epithelium of the renal pelvis of kidney sections from rats treated with CyA for 6 weeks. No labelling above background was seen at any time with the sense probe. Renin immunostaining in afferent arterioles of kidney sections from animals treated with CyA showed a marked increase after 4 and 6 weeks of CyA treatment.
New Parenteral Lipid Emulsions for Clinical Use (2006)

Routine use of parenteral lipid emulsions (LE) in clinical practice began in 1961, with the development of soybean oil (SO) - based LE. Although clinically safe, experimental reports indicated that SO-based LE could exert a negative influence on immunological functions. Those findings were related to its absolute and relative excess of omega-6 polyunsaturated fatty acids (PUFA) and the low amount of omega-3 PUFA and also to its high PUFA content with an increased peroxidation risk. This motivated the development of new LE basically designed along the reduction of omega-6 PUFA and the omega-3 PUFA addition in order to obtain balanced levels of the omega-6/omega-3 ratio. The new LE for clinical use (available in Europe and South America) are differentiated by their content in polyunsaturated (omega-6 and omega-3), monounsaturated, and saturated fatty acids (FA), as well as FA source of their origin, including soy, coconut, olive, and fish oil. This article presents the new LE nutrition and energy functions but also its biochemical, metabolic, and immunomodulating aspects, according to their FA content. LE at 20% when infused from 1.0 to 2.0 g/kg body weight/day rates, either alone or in association with amino acids and glucose, are safe and well tolerated in routine clinical practice. LE combining SO with medium-chain triglycerides and/or olive oil have less omega-6 PUFA and are better metabolized, with less inflammatory and immunosuppressive effects than in relation to pure SO-based LE. The omega-3 PUFA used alone or as component of a new and complex LE (soy, MCT, olive and fish oil) has demonstrated anti-inflammatory and immunomodulatory effects.
Coupling of (amino)alkylchlorosilanes with lithium: new access to symmetrical di- and tetrafunctional alkyldisilanes (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCoupling of (amino)alkylchlorosilanes with lithium: new access to symmetrical di- and tetrafunctional alkyldisilanesKohei Tamao, Atsushi Kawachi, and Yoshihiko ItoCite this: Organometallics 1993, 12, 2, 580–582Publication Date (Print):February 1, 1993Publication History Published online1 May 2002Published inissue 1 February 1993https://pubs.acs.org/doi/10.1021/om00026a050https://doi.org/10.1021/om00026a050research-articleACS PublicationsRequest reuse permissionsArticle Views341Altmetric-Citations42LEARN 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
Identification of an aptamer targeting hnRNP A1 by tissue slide‐based SELEX (2009)

We report a new in situ tissue slide-based SELEX strategy targeting neoplastic tissues from breast cancer patients. The methodology, using the molecular differences between clinical specimens, can evolve aptamers to all fractions of tissue. The aptamers may be used as new molecular probes for pathological diagnosis and tumour imaging, and also to reveal the molecular differences that are responsible for the diseases. The specific aptamers were enriched by unequal length strand PCR employing a structured (-) strand primer. After 12 rounds of selection, using the paraffin tissue sections from infiltrating ductal carcinomas as targets, and using the adjacent normal tissue from the same case as controls, one of the enriched ssDNA aptamers, BC15, was selected from a nucleic acid library and characterized as recognizing breast cancer cells either within the tissue sections or from the culture medium, but only weakly binding to adjacent normal cells or immortalized breast cell line MCF10A. The calculated equilibrium dissociation constants (K(d)) of BC15 bound to MCF7 cells was 111.0 +/- 36.9 nM. Through streptavidin magnetic beads mediated affinity purification assay followed by mass spectrometry identification and western blot confirmation, the target of BC15 was characterized to be hnRNP A1, which was further verified to be specifically and highly expressed in cancerous tissues of breast by hnRNP A1 antibody immunostaining as well as western blot. BC15 aptamer was also used to probe cancer cells in tissues from other pathological types of breast cancers including lobular carcinoma, ductal carcinoma complicated with lobular carcinoma, comedo carcinoma, and lymph node metastasis of breast ductal carcinoma origin or breast lobular carcinoma origin. Therefore, tissue slide-based SELEX holds promise in identifying tumour markers and developing specific molecular probes for cancer diagnosis.
Effectiveness of PSD95 Inhibitors in Permanent and Transient Focal Ischemia in the Rat (2008)

Postsynaptic density-95 inhibitors administrated 3 hours after stroke onset reduced infarct volumes and improved long-term neurobehavioral functions in a wide therapeutic window. This raises the possibility that they may have future clinical usefulness.
Free-Standing Lipid Bilayers in Silicon Chips−Membrane Stabilization Based on Microfabricated Apertures with a Nanometer-Scale Smoothness (2009)

In the present study, we propose a method for preparing stable free-standing bilayer lipid membranes (BLMs). The BLMs were prepared in a microfabricated aperture with a smoothly tapered edge, which was prepared in a nanometer-thick Si(3)N(4) septum by the wet etching method. Owing to this structure, the stress on lipid bilayers at the contact with the septum was minimized, leading to remarkable membrane stability. The BLMs were not broken by applying a constant voltage of +/-1 V. The membrane lifetime was 15-45 h with and without an incorporated gramicidin channel. Gramicidin single-channel currents were recorded from the same BLM preparation when the aqueous solutions surrounding the BLM were repeatedly exchanged, demonstrating the tolerance of the present BLM to repetitive solution exchanges. Such stable membranes enable analysis of channel functions under various solution conditions from the same BLM, which will open up a variety of applications including a high throughput drug screening for ion channels.
Planning, construction, and statistical analysis of comparative experiments (2004)

Preface.Introduction.The Completely Randomized Design.Linear Models for Designed Experiments.Testing Hypotheses and Determining Sample Size.Methods of Reducing Unexplained Variation.Latin Squares.Split-Plot and Related Designs.Incomplete Block Designs.Repeated Teatments Designs.Factorial Experiments, the 2n System.Factorial Experiments, the 3n System.Analysis of Experiments Without Designed Error Terms.Confounding Effects with Blocks.Fractional Factorial Experiments.Response Surface Designs.Plackett-Burmann Hadamard Plans.The General Pn and Nonstandard Factorials.Factorial Experiments with Quantitative Factors.Plans for Which Run Order is Important.Supersaturated Plans.Sequences of Fractions of Factorials.Multi-Stage xperiments.Orthogonal Arrays and Related Structures.Factorial Plans Derived via Orthogonal Arrays.Experiments on the Computer.
Pollen tube guidance by the female gametophyte (1997)

In flowering plants, pollen grains germinate on the pistil and send pollen tubes down the transmitting tract toward ovules. Previous genetic studies suggested that the ovule is responsible for long-range pollen tube guidance during the last phase of a pollen tube's journey to the female gametes. It was not possible, however, to unambiguously identify the signaling cells within an ovule: the haploid female gametophyte or the diploid sporophytic cells. In an effort to distinguish genetically between these two possibilities, we have used a reciprocal chromosomal translocation to generate flowers wherein approximately half the ovules do not contain a functional female gametophyte but all ovules contain genotypically normal sporophytic cells. In these flowers, pollen tubes are guided to the normal but not to the abnormal female gametophytes. These results strongly suggest that the female gametophyte is responsible for pollen tube guidance, but leave open the possibility that the gametophyte may accomplish this indirectly through its influence on some sporophytic cells.
New Clues Found to Diabetes and Obesity (1999)

In work described on
 page 1544, researchers have identified a major new target for drugs aimed at treating type 2 diabetes--and possibly for anti-obesity drugs as well. The team made found that mice that have been genetically modified so that they can9t make an enzyme called phosphotyrosine phosphatase IB (PTP-IB) showed increased sensitivity to insulin, an intriguing finding since type 2 diabetes is thought to be due to decreased sensitivity to the hormone. In addition, the animals proved resistant to the obesity usually induced by a high fat diet. It9s currently unclear whether PTP-1B abnormalities play a causative role in diabetes or obesity, but even if they don9t, it might be possible to treat the conditions with drugs that inhibit the enzyme9s activity.
Co‐citation in the scientific literature: A new measure of the relationship between two documents (1973)

Abstract A new form of document coupling called co‐citation is defined as the frequency with which two documents are cited together. The co‐citation frequency of two scientific papers can be determined by comparing lists of citing documents in the Science Citation Index and counting identical entries. Networks of co‐cited papers can be generated for specific scientific specialties, and an example is drawn from the literature of particle physics. Co‐citation patterns are found to differ significantly from bibliographic coupling patterns, but to agree generally with patterns of direct citation. Clusters of co‐cited papers provide a new way to study the specialty structure of science. They may provide a new approach to indexing and to the creation of SDI profiles.
Ultra-low-power hydrogen sensing with palladium nanowires (2008)

Palladium nanowires (50 nm diameter, ~5 mum length) have been fabricated on silicon substrates using conventional techniques. The room temperature hydrogen sensing behavior of individual nanowires was investigated. The nanowires show a reversible response to hydrogen concentrations as low as 2.5 ppm with an ultra low power consumption of less than 10 nW. The electrical resistance increases nonlinearly with the hydrogen concentration. Response times (t90) vary from 5 seconds (H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> concentrations > 20%) to 30 seconds (H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> concentrations < 100 ppm). The response times can be decreased by increasing the applied bias at the cost of sensitivity.