gebhart/patrepeval huggingface dataset:
Characterization of the Ca2+-binding Sites of Annexin II Tetramer (2000)

Annexin II heterotetramer (AIIt) is a multifunctional Ca(2+)-binding protein composed of two 11-kDa subunits and two annexin II subunits. The annexin II subunit contains three type II and two type III Ca(2+)-binding sites which are thought to regulate the interaction of AIIt with anionic phospholipid, F-actin, and heparin. In the present study we utilized site-directed mutagenesis to create AIIt mutants with inactive type III (TM AIIt), type II (CM AIIt), and both type II and III Ca(2+)-binding sites (TCM AIIt). Surprisingly, we found that in the presence of Ca(2+), the TM, CM, and TCM AIIt bound phospholipid and F-actin with similar affinity to the wild type AIIt (WT AIIt). Furthermore, the TCM mutant, and to a lesser extent the TM and CM AIIt displayed dose-dependent Ca(2+)-independent phospholipid aggregation and binding. While the TM and CM AIIt demonstrated Ca(2+)-dependent binding to F-actin, the binding of the TCM AIIt was Ca(2+)-independent. These results suggest that the type II or type III Ca(2+)-binding sites do not directly participate in anionic phospholipid or F-actin binding. We therefore propose that in the absence of Ca(2+), the type II and type III Ca(2+)-binding sites of AIIt stabilize a conformation of AIIt that is unfavorable for binding phospholipid and F-actin. Ca(2+) binding to these sites, or the inactivation of these Ca(2+)-binding sites by site-directed mutagenesis, results in a conformational change that promotes binding to anionic phospholipid and F-actin. Since the TM, CM, and TCM AIIt require Ca(2+) for binding to heparin, we also propose that novel Ca(2+)-binding sites regulate this binding event.
Generation and Therapeutic Efficacy of Highly Oligomer-Specific β-Amyloid Antibodies (2010)

Oligomers of the beta-amyloid (Abeta) peptide have been indicated in early neuropathologic changes in Alzheimer's disease. Here, we present a synthetic Abeta(20-42) oligomer (named globulomer) with a different conformation to monomeric and fibrillar Abeta peptide, enabling the generation of highly Abeta oligomer-specific monoclonal antibodies. The globulomer-derived antibodies specifically detect oligomeric but not monomeric or fibrillar Abeta in various Abeta preparations. The globulomer-specific antibody A-887755 was able to prevent Abeta oligomer binding and dynamin cleavage in primary hippocampal neurons and to reverse globulomer-induced reduced synaptic transmission. In amyloid precursor protein (APP) transgenic mice, vaccination with Abeta globulomer and treatment with A-887755 improved novel object recognition. The cognitive improvement is likely attributable to reversing a deficit in hippocampal synaptic spine density in APP transgenic mice as observed after treatment with A-887755. Our findings demonstrate that selective reduction of Abeta oligomers by immunotherapy is sufficient to normalize cognitive behavior and synaptic deficits in APP transgenic mice.
Intensity Calibration for Stereo Images Based on Segment Correspondence. (1998)

The comparative toxicity of polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) in thyroid glands was studied in male Holtzman rats. Four-week-old animals were fed at dietary levels of 0, 5, 50, and 500 ppm for 5 weeks and then sacrificed. PCB and PBB produced similar dose-dependent ultrastructural lesions in thyroid follicular cells of rats. The daily administration of 5 ppm of either PCB or PBB resulted in the accumulation of large membrane-limited colloid droplets and electron-dense lysosomal bodies within the cytoplasm of follicular cells. Microvilli were short and abnormally branched, and unique cytoplasmic processes extended from the apical surface of follicular cells into the luminal colloid. Similar but more severe ultrastructural changes were observed in thyroid glands of rats administered 50 and 500 ppm of either PCB or PBB. Many follicular cells were distended with large abnormal lysosomal bodies and colloid droplets. Mitochondria were often vacuolated with disrupted cristae. Microvilli were blunt with abnormal branching or absent from areas of the luminal surface of follicular cells. Processes of apical cytoplasm often extended into the follicular lumen in areas devoid of microvilli. Follicular cells remained responsive after the feeding of either PCB or PBB and underwent moderate compensatory hypertrophy and hyperplasia. Thyroid follicles were smaller than in controls and were lined by more columnar cells that occasionally formed papillary projections into the follicular lumens. PCB and PBB produced similar ultrastructural lesions in thyroid follicular cells which appeared to interfere with the synthesis and secretion of thyroxine.
Cancer genetics of epigenetic genes (2007)

The cancer epigenome is characterised by specific DNA methylation and chromatin modification patterns. The proteins that mediate these changes are encoded by the epigenetics genes here defined as: DNA methyltransferases (DNMT), methyl-CpG-binding domain (MBD) proteins, histone acetyltransferases (HAT), histone deacetylases (HDAC), histone methyltransferases (HMT) and histone demethylases. We review the evidence that these genes can be targeted by mutations and expression changes in human cancers.
Design and Manufacturing of Biologically Inspired Micro Aerial Vehicle Wings Using Rapid Prototyping (2013)

Micro Aerial Vehicles (MAVs) are an emerging class of uninhabited aerial vehicle (UAV). Their reduced scale (maximum dimension of approximately 150 mm) provides advantages in terms of advanced mission capabilities, such as wildlife monitoring and urban search and rescue. This introduces the design challenge of flying efficiently at very low Reynolds numbers (e.g. Re&lt;10000). To date, three basic MAV design concepts have been developed: fixed, rotary and flapping wings. Each approach has been met with limited success due to gust stability, flight control and propulsive efficiency. The design of both fixed and rotary wing aircraft is relatively mature, whereas flapping wing design is in its infancy and therefore its viability cannot yet be assessed. Nonetheless flapping wing MAVs have the potential to offer advantages such as stealth, manoeuvrability, and improved propulsive efficiencies. This paper focuses on the challenging problem of the manufacture and testing of flapping wings for MAVs. A review of the current state of flapping wing aerodynamics, manufacturing, and wing structures is provided. A detailed assessment of the aerodynamic performance of flexible MAV-scale wings was carried out. Aerodynamic force measurements were collected using a spin rig to assess the effect of design details on lift generation. It was found that a simple three-vein wing structure manufactured using a fused filament fabrication 3D printer could produce lift forces close to those of natural insect wings. The lift and stall performance was found to be sensitive to chordwise stiffness by testing wings without veins. These results demonstrate that it is possible to produce low cost biologically inspired wings with aerodynamic performance equal to or better than natural wings – a critical step on the path to a functional and practical flapping wing MAV.
Blockade of transforming growth factor-β signaling in tumor-reactive CD8+ T cells activates the antitumor immune response cycle (2006)

Transforming growth factor-beta (TGF-beta) is a potent immunosuppressant. Overproduction of TGF-beta by tumor cells leads to evasion of host immune surveillance and tumor progression. Results of our early studies showed that adoptive transfer of tumor-reactive, TGF-beta-insensitive CD8(+) T cells into immunocompetent mice was able to eradicate lung metastasis of mouse prostate cancer. The present study was conducted with three objectives. (a) We tested if this technology could be applied to the treatment of solid xenograft tumors in allogeneic immunodeficient hosts. (b) We determined relevant variables in the tumor microenvironment with the treatment. (c) We tested if immune cells other than CD8(+) T cells were required for the antitumor effect. Mouse prostate cancer cells, TRAMP-C2 of the C57BL/6 strain, grown in immunodeficient allogeneic hosts of BALB/c strain, were used as a xenograft model. Tumor-reactive CD8(+) T cells from C57BL/6 mice were isolated, expanded ex vivo, and rendered insensitive to TGF-beta by introducing a dominant-negative TGF-beta type II receptor vector. Seven days following s.c. injection of TRAMP-C2 cells (5 x 10(5)) into the flank of male BALB/c-Rag1(-/-) mice, tumor-reactive, TGF-beta-insensitive CD8(+) T cells (1.5 x 10(7)) were transferred with and without the cotransfer of an equal number of CD8-depleted splenocytes from C57BL/6 donors. Naive CD8(+) T cells or green fluorescent protein-empty vector-transfected tumor-reactive CD8(+) T cells were transferred as controls. Forty days following the transfer, the average tumor weight in animals that received cotransfer of tumor-reactive, TGF-beta-insensitive CD8(+) T cells and CD8-depleted splenocytes was at least 50% less than that in animals of all other groups (P < 0.05). Tumors in animals of the former group showed a massive infiltration of CD8(+) T cells. This was associated with secretion of relevant cytokines, decreased tumor proliferation, reduced angiogenesis, and increased tumor apoptosis. Based on these results, we postulated a concept of antitumor immune response cycle in tumor immunology.
Classic Preconditioning Decreases the Harmful Accumulation of Nitric Oxide During Ischemia and Reperfusion in Rat Hearts (1999)

Our results show that (1) although NO synthesis by the heart is necessary to trigger classic preconditioning, preconditioning in turn attenuates the accumulation of NO during ischemia/reperfusion, and (2) blockade of ischemia/reperfusion-induced accumulation of cardiac NO by preconditioning or by an appropriate concentration of NOS inhibitor alleviates ischemia/reperfusion injury as demonstrated by enhanced postischemic function.
A secure Scan Design Methodology (2006)

It has been proven that scan path is a potent hazard for secure chips. Scan based attacks have been recently demonstrated against DES or AES and several solutions have been presented in the literature in order to securize the scan chain. Nevertheless, the different proposed techniques are all ad hoc techniques, which are not always easy to integrate into a completely automated design flow or in an IP reuse environment. In this paper, we propose a scan chain integrity detection mechanism, which respects both automated design flow and IP reuse environment
Design, Synthesis, and Evolution of a Novel, Selective, and Orally Bioavailable Class of Thrombin Inhibitors:  P1-Argininal Derivatives Incorporating P3-P4 Lactam Sulfonamide Moieties (1996)

ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTDesign, Synthesis, and Evolution of a Novel, Selective, and Orally Bioavailable Class of Thrombin Inhibitors: P1-Argininal Derivatives Incorporating P3-P4 Lactam Sulfonamide Moieties 1J. Edward Semple, David C. Rowley, Terence K. Brunck, Theresa Ha-Uong, Nathaniel K. Minami, Timothy D. Owens, Susan Y. Tamura, Erick A. Goldman, Daniel V. Siev, Robert J. Ardecky, Stephen H. Carpenter, Yu Ge, Brigitte M. Richard, Thomas G. Nolan, Kjell Håkanson, Al Tulinsky, Ruth F. Nutt, and William C. RipkaView Author Information Corvas International, Inc., 3030 Science Park Road, San Diego, California 92121-1102, and Department of Chemistry, Michigan State University, East Lansing, Michigan 48824-1322 Cite this: J. Med. Chem. 1996, 39, 23, 4531–4536Publication Date (Web):November 8, 1996Publication History Received5 August 1996Published online8 November 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jm960572nhttps://doi.org/10.1021/jm960572nrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views1065Altmetric-Citations61LEARN 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 SUBJECTS:Amides,Inhibitors,Peptides and proteins,Selectivity,Sulfones Get e-Alerts
Exosome Secretion Ameliorates Lysosomal Storage of Cholesterol in Niemann-Pick Type C Disease (2010)

Niemann-Pick type C1 disease is an autosomal-recessive lysosomal storage disorder. Loss of function of the npc1 gene leads to abnormal accumulation of free cholesterol and sphingolipids within the late endosomal and lysosomal compartments resulting in progressive neurodegeneration and dysmyelination. Here, we show that oligodendroglial cells secrete cholesterol by exosomes when challenged with cholesterol or U18666A, which induces late endosomal cholesterol accumulation. Up-regulation of exosomal cholesterol release was also observed after siRNA-mediated knockdown of NPC1 and in fibroblasts derived from NPC1 patients and could be reversed by expression of wild-type NPC1. We provide evidence that exosomal cholesterol secretion depends on the presence of flotillin. Our findings indicate that exosomal release of cholesterol may serve as a cellular mechanism to partially bypass the traffic block that results in the toxic lysosomal cholesterol accumulation in Niemann-Pick type C1 disease. Furthermore, we suggest that secretion of cholesterol by exosomes contributes to maintain cellular cholesterol homeostasis.
Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. (1992)

Topotecan (TPT, 9-dimethylaminomethyl-10-hydroxycamptothecin) is the first topoisomerase I-directed cytotoxic agent to enter clinical trials in the United States in two decades. The effect of P-glycoprotein (Pgp) overexpression on TPT cytotoxicity was examined in CHRC5 (colchicine-resistant) and AuxB1 (parental) Chinese hamster ovary cells. Examination of the IC50 values observed in colony-forming assays revealed that the CHRC5 cells were 15-fold (SD, +/- 3; n = 3) resistant to TPT after a 1-h exposure and 3.2-fold (SD, +/- 1.4; n = 4) resistant in continuous exposure experiments. Band depletion immunoblotting revealed that 4-fold higher concentrations of extracellular TPT were required to induce the formation of topo I-DNA complexes in CHRC5 cells as compared to AuxB1 cells. To assess the role of Pgp in this resistance, drug accumulation and cytotoxicity assays were repeated in the absence and presence of quinidine. Addition of quinidine enhanced TPT accumulation (measured by high-performance liquid chromatography) and diminished the IC50 for TPT to a greater extent in CHRC5 cells than in AuxB1 cells. To examine whether similar effects could be detected in Pgp-expressing human cells, MCF-7/Adriar breast cancer cells and KG1a human acute myelogenous leukemia cells were examined. Quinidine or verapamil enhanced TPT accumulation in both of these cell lines but had no effect in parental MCF-7 cells or a variety of human leukemia cell lines that do not overexpress Pgp. Cytotoxicity measurements performed by counting the number of surviving cells (MCF-7/Adriar) or employing a modified, highly stable tetrazolium dye reduction assay (leukemia cell lines) revealed that quinidine diminished the IC50 for TPT in the Pgp-overexpressing cell lines but not in the control lines. These results suggest that Pgp overexpression diminishes TPT accumulation and TPT cytotoxicity in hamster and human cells. It should be stressed, however, that these effects were substantially smaller than the effects of Pgp overexpression on the accumulation and cytotoxicity of the anthracycline daunorubicin and the epipodophyllotoxin etoposide in the same cell lines.
Ferrozine---a new spectrophotometric reagent for iron (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFerrozine---a new spectrophotometric reagent for ironLawrence L. StookeyCite this: Anal. Chem. 1970, 42, 7, 779–781Publication Date (Print):June 1, 1970Publication History Published online1 May 2002Published inissue 1 June 1970https://pubs.acs.org/doi/10.1021/ac60289a016https://doi.org/10.1021/ac60289a016research-articleACS PublicationsRequest reuse permissionsArticle Views14284Altmetric-Citations3485LEARN 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
Invariant and Noninvariant Natural Killer T Cells Exert Opposite Regulatory Functions on the Immune Response during Murine Schistosomiasis (2007)

CD1d-restricted natural killer T (NKT) cells represent a heterogeneous population of innate memory immune cells expressing both NK and T-cell markers distributed into two major subsets, i.e., invariant NKT (iNKT) cells, which express exclusively an invariant T-cell receptor (TCR) alpha chain (Valpha14Jalpha18 in mice), and non-iNKT cells, which express more diverse TCRs. NKT cells quickly produce Th1- and/or Th2-type cytokines following stimulation with glycolipid antigen (Ag) and, through this property, play potent immunoregulatory roles in autoimmune diseases, cancer, and infection. No study has addressed the role of NKT cells in metazoan parasite infections so far. We show that during murine schistosomiasis, the apparent frequency of both iNKT cells and non-iNKT cells decreased in the spleen as early as 3 weeks postinfection (p.i.) and that both populations expressed a greater amount of the activation marker CD69 at 6 weeks p.i., suggesting an activated phenotype. Two different NKT-cell-deficient mouse models, namely, TCR Jalpha18-/- (exclusively deficient in iNKT cells) and CD1d-/- (deficient in both iNKT and non-iNKT cells) mice, were used to explore the implication of these subsets in infection. We show that whereas both iNKT and non-iNKT cells do not have a major impact on the immune response during the early phase (1 and 4 weeks) of infection, they exert important, although opposite, effects on the immune response during the acute phase of the disease (7 and 12 weeks), after schistosome egg production. Indeed, iNKT cells contribute to Th1 cell differentiation whereas non-iNKT cells might be mostly implicated in Th2 cell differentiation in response to parasite Ag. Our findings suggest, for the first time, that helminths activate both iNKT and non-iNKT cells in vivo, enabling them to differentially influence the Th1/Th2 balance of the immune response.
Fertility-Associated Proteins in Holstein Bull Seminal Plasma1 (1993)

This study was undertaken to determine whether bovine seminal plasma contained protein markers associated with bull fertility, and whether these markers were of value in predicting bull fertility. Seminal plasma was obtained from 35 Holstein bulls of known fertility. Two-dimensional PAGE of seminal plasma samples indicated that two proteins (26 kDa, pI 6.2; 55 kDa, pI 4.5) predominated in higher-fertility bulls, and two proteins (16 kDa, pI 4.1; 16 kDa, pI 6.7) predominated in lower-fertility bulls. Densitometry data for these proteins in individual samples were combined for bulls grouped by fertility level. Average density of the 26-kDa protein was significantly greater in seminal plasma of high-fertility bulls, and high-fertility seminal plasma also contained more of the 55-kDa protein than that of average- and below average-fertility bulls. Below average- and low-fertility bull seminal plasma had significantly more of both 16-kDa proteins than that of average- and high-fertility bulls. A regression model was developed to predict bull fertility using the four fertility-associated protein densities. A plot of actual bull fertility versus that calculated by this model was linear and positively correlated (r = 0.89). These findings indicate that bull seminal plasma contains fertility-associated proteins that are predictive of bull fertility.
Lumped-parameter model for in vivo cochlear stimulation (1993)

This paper presents a lumped-parameter model that stimulates the in vivo electrical properties of a guinea pig cochlea implanted with a multielectrode stimulating array. A basic model of the low-frequency electroanatomy in a normally functioning guinea pig cochlea is developed by adding critical membrane capacitances to Strelioff's resistive network model [1]. The basic model of normal cochlear tissues is modified to account for anatomical and physiological differences between a normal and implanted cochlea, which results in an impedance model of an implanted cochlea. Simulating the results of in vivo cochlear stimulation verifies the accuracy with which the modified cochlear model represents electrical properties within an electrically stimulated cochlea. Generalized simulations using this model suggest a straightforward phasing scheme capable of achieving sharply focused, channel-independent multielectrode cochlear stimulation.
Verocytotoxin‐ producing Escherichia coli 0157 on a farm open to the public: outbreak investigation and longitudinal bacteriological study (2000)

Verocytotoxin-producing Escherichia coli (VTEC) O157 phage type 2 (PT2) was isolated from three calves and two goats on a farm open to the public. Phenotypic and DNA-based typing showed that the strains were identical or very closely related to those obtained from an outbreak of VTEC O157 infection in two separate family groups who visited the farm. No VTEC O157 PT2 was isolated again from the farm during a 12-month longitudinal bacteriological study undertaken after the infected animals had been removed. However, phenotypically and genotypically indistinguishable VTEC O157 PT2/28 strains were detected in two of 474 faecal samples collected at monthly visits from 15 species of animals of various ages. The two isolates were obtained from calves from different sources sampled 146 days apart, suggesting that the infection had persisted on the farm although it was not detected in the other species. The same strain was subsequently isolated from another calf housed in the same pen as one of the infected calves. The longest period during which the organism was excreted was seven days. No VTEC O157 was isolated either from 204 replacement animals (including 138 orphan lambs and 10 calves) brought in from various sources, and sampled while they were kept in isolation for two weeks before being introduced to the farm, or from environmental samples. During the study a visitor became ill with VTEC O157 PT2. However, the isolate was distinct from those recovered from the farm and there was no evidence to suggest that the visit was the source of the infection.