gebhart/patrepeval huggingface dataset:
The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations (2000)

We have used spectral karyotyping to assess potential roles of three different components of the nonhomologous DNA end-joining pathway in the maintenance of genomic stability in mouse embryonic fibroblasts (MEFs). MEFs homozygous for mutations that inactivate either DNA ligase IV (Lig4) or Ku70 display dramatic genomic instability, even in the absence of exogenous DNA damaging agents. These aberrant events range from chromosomal fragmentation to nonreciprocal translocations that can involve several chromosomes. DNA-dependent protein kinase catalytic subunit deficiency also promotes genome instability. Deficiency for the p53 cell cycle checkpoint protein has little effect on spontaneous levels of chromosomal instability in Lig4-deficient fibroblasts. However, in the context of ionizing radiation treatment, p53 deficiency allowed visualization of massive acute chromosomal destruction in Lig4-deficient MEFs, which in surviving cells manifested as frequent nonreciprocal translocations. We conclude that nonhomologous DNA end-joining plays a crucial role as a caretaker of the mammalian genome, and that an alternative repair pathway exists that often leads to nonreciprocal translocations.
Quantification of the volume of articular cartilage in the metacarpophalangeal joints of the hand: accuracy and precision of three-dimensional MR imaging. (1995)

Fat-suppressed T1-weighted 3D MR imaging provides sufficient contrast and spatial resolution to allow accurate and reproducible quantification of articular cartilage volume in the metacarpophalangeal joints of the hand. This technique may be useful for monitoring cartilage loss in patients with arthritis.
Does “Clock” Matter in Prostate Cancer? (2006)

The ancient adaptation of a 24-hour circadian clock has profound effect on our daily biochemical, physiologic, and behavioral processes, including the monitoring of sex hormone levels. Although the disruption of the circadian cycle has been implicated in the etiology of hormone-related female breast cancer, few studies have been undertaken to determine if a link exists in the development of the most common cancer type among men whose etiology remains largely unknown: hormone-related prostate cancer. Here, we hypothesize that both altered-lighted environments and genetic variations in genes responsible for maintaining circadian rhythms may result in deregulation of clock-associated biological processes, such as androgen expression, and consequently influence an individual's risk of prostate cancer. There is also a potential for the interaction of genetic variants and exposures, such as evening shift work. Confirmation of this hypothesis will add to our understanding of the role of the circadian clock in prostate tumorigenesis and further facilitate the development of novel risk and prognostic biomarkers for prostate cancer.
Milk Composition of Insulin-Dependent Diabetic Women (1987)

The macronutrient, trace mineral, and immunological contents of milk of five moderately controlled, insulin-dependent diabetic women were studied at 3 months postpartum. Concentrations of total nitrogen, lactose, fat, and energy were not distinguishable from those in milk of nondiabetic women. Glucose concentrations in milk from diabetic women were significantly higher (p less than 0.001) and more variable. The macro- and trace minerals (Ca, P, Mg, K, Zn, Cu, and Fe) were within normal ranges with the exception of Na which was higher in milk from the diabetic women (p less than 0.05). The concentrations of lactoferrin and secretory IgA were not statistically different from reference norms. Milk composition of five insulin-dependent diabetic women was not distinguishable from that of the reference population, with the exceptions of Na and glucose concentrations, which were slightly elevated.
Simultaneous Evaluation of the Magnitude and Breadth of a Left- and Right-Censored Multivariate Response, With Application to HIV Vaccine Development (2009)

Both the magnitude and breadth of neutralization against multiple strains of virus are main endpoints for comparing antibody-based HIV-1 vaccine candidates in Phase I and II trials, and are key markers to be evaluated in vaccine efficacy trials as immune correlates of protection against HIV-1 infection. More generally, consideration of both magnitude and breadth is encountered when there is interest in comparing quantitative multivariate response data between groups. In this paper, we discuss two approaches to simultaneously evaluating the magnitude and breadth of a multivariate response. We suggest methods for the summarization and group comparison of multivariate response data that are subject to left and/or right censoring. Applications to data from a phase III clinical trial (Vax004) are discussed. Simulation-based sample size calculations and power analyses of the described methods also are presented.
Menorrhagia from a haematologist's point of view. Part II: management (2002)

The management of menorrhagia has until recently been the domain of the gynaecologist. As haematologists, we are now addressing the issue of optimal management of menorrhagia in our patients with bleeding disorders. Addressing three life periods, the menarche, reproductive years, and postchildbearing years, this review will discuss the use of oral contraceptive agents, antifibrinolytics, non-steroidal anti-inflammatory drugs, intranasal DDAVP and the new levonorgestrel-impregnated IUD. Management of specific bleeding disorders will also be reviewed for von Willebrand disease, haemophilia A and B carriers, women with factor XI deficiency and PAI-1 deficiency.
Fanconi Anemia Gene Editing by the CRISPR/Cas9 System (2014)

Genome engineering with designer nucleases is a rapidly progressing field, and the ability to correct human gene mutations in situ is highly desirable. We employed fibroblasts derived from a patient with Fanconi anemia as a model to test the ability of the clustered regularly interspaced short palindromic repeats/Cas9 nuclease system to mediate gene correction. We show that the Cas9 nuclease and nickase each resulted in gene correction, but the nickase, because of its ability to preferentially mediate homology-directed repair, resulted in a higher frequency of corrected clonal isolates. To assess the off-target effects, we used both a predictive software platform to identify intragenic sequences of homology as well as a genome-wide screen utilizing linear amplification-mediated PCR. We observed no off-target activity and show RNA-guided endonuclease candidate sites that do not possess low sequence complexity function in a highly specific manner. Collectively, we provide proof of principle for precision genome editing in Fanconi anemia, a DNA repair-deficient human disorder.
Advances in Determination of a High-Resolution Three-Dimensional Structure of Rhodopsin, a Model of G-Protein-Coupled Receptors (GPCRs), (2001)

ADVERTISEMENT RETURN TO ISSUECurrent Topics/Persp...Current Topics/PerspectivesNEXTAdvances in Determination of a High-Resolution Three-Dimensional Structure of Rhodopsin, a Model of G-Protein-Coupled Receptors (GPCRs)†,‡David C. Teller, Tetsuji Okada, Craig A. Behnke, Krzysztof Palczewski, and Ronald E. StenkampView Author Information Departments of Ophthalmology, Pharmacology, Chemistry, Biochemistry, and Biological Structure and Biomolecular Structure Center, University of Washington, Seattle, Washington 98195 Cite this: Biochemistry 2001, 40, 26, 7761–7772Publication Date (Web):April 14, 2001Publication History Received5 February 2001Revised7 March 2001Published online14 April 2001Published inissue 1 July 2001https://doi.org/10.1021/bi0155091Copyright © 2001 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1607Altmetric-Citations508LEARN 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 InReddit Read OnlinePDF (866 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Chromophores,Molecules,Monomers,Peptides and proteins,Receptors Get e-Alerts
On the importance of synthetic organic chemistry in drug discovery: reflections on the discovery of antidiabetic agent ertugliflozin (2012)

The discovery of antidiabetic agent ertugliflozin is described. In this article, emphasis is placed on the critical role that organic synthesis played in influencing our medicinal chemistry strategy.
Physical crosslinking of collagen fibers: Comparison of ultraviolet irradiation and dehydrothermal treatment (1995)

The strength, resorption rate, and biocompatibility of collagenous biomaterials are profoundly influenced by the method and extent of crosslinking. We compared the effects of two physical crosslinking methods, ultraviolet irradiation (UV) (254 nm) and dehydrothermal (DHT) treatment, on the mechanical properties and molecular integrity of collagen fibers extruded from an acidic dispersion of type I bovine dermal collagen. Collagen fibers exposed to UV irradiation for 15 min had ultimate tensile strength (54 MPa) and modulus (184 MPa) values greater than or equivalent to values for fibers crosslinked with DHT treatment for 3 or 5 days. UV irradiation is a rapid and easily controlled means of increasing the mechanical strength of collagen fibers. Characterization of collagen extracted from the crosslinked samples by dilute acetic acid and limited pepsin digestion indicate that both UV and DHT treatments cause fragmentation of at least a portion of the collagen molecules. Partial loss of the native collagen structure may influence attachment migration, and proliferation of cells on collagen fiberbased ligament analogs. These issues are currently being addressed in our laboratory.
Rabbit Monoclonal Antibodies: A Comparative Study Between a Novel Category of Immunoreagents and the Corresponding Mouse Monoclonal Antibodies (2005)

Rabbit monoclonal antibodies (RabMAbs) represent a novel category of immunoreagents that may combine the best properties of both mouse monoclonal antibodies (MMAs) and of rabbit antisera. In the attempt to verify the performance of this new class of antibodies on paraffin-embedded tissue, RabMAbs against estrogen receptor, progesterone receptor, Ki-67, cyclin D1, CD3, CD5, CD23, and synaptophysin were tested on several tumor types as well as normal tissues. The results were compared with those obtained with classic MMAs against the same antigens. RabMAbs appear to offer increased sensitivity with no apparent loss of specificity. On routine use they permit higher working dilutions (5 to 10 times on average), allowing significant improvement in terms of laboratory efficiency. The robustness of RabMAbs is further proved by the fact that in some instances optimal staining can be obtained even without antigen retrieval. In consideration of the high performance observed, routine use of RabMAbs may contribute significantly to standardize diagnostic immunohistochemical procedures.
Functional Analysis of Human P5, a Protein Disulfide Isomerase Homologue (2002)

Human P5 (hP5) was expressed in the Escherichia coli pET system and purified by sequential Ni(2+)-chelating resin column chromatography. Characterization of purified hP5 indicated that it has both isomerase and chaperone activities, but both activities are lower than those of human protein disulfide isomerase (PDI). Moreover, hP5 was observed to have peptide-binding ability, and its chaperone activity was confirmed with rhodanese and citrate synthase as substrates, but not with D-glyceraldehyde-3-phosphate dehydrogenase, showing that hP5 has substrate specificity with respect to chaperone activity. Mutation of two thioredoxin-related motifs in hP5 revealed that the first motif is more important than the second for isomerase activity and that the first cysteine in each motif is necessary for isomerase activity. Since thioredoxin motif mutants lacking isomerase activity retain chaperone activity with the substrate citrate synthase, the isomerase and chaperone activities of hP5 are probably independent, as was shown for PDI.
Resistance to meningococcemia apparently conferred by anti-H.8 monoclonal antibody is due to contaminating endotoxin and not to specific immunoprotection (1987)

We evaluated the ability of a monoclonal antibody directed against the common H.8 antigen of pathogenic Neisseria sp. to confer passive protection against meningococcal disease in mice. The apparent protection conferred by antibody purified from tissue culture supernatant was actually the result of endotoxin contamination of buffers and tissue culture media. Endotoxin-free anti-H.8 antibody was not protective. The possibility of endotoxin contamination should be considered when evaluating immunity conferred by passively administered antibody in animal models.
Intraventricular rifampicin in severe tuberculous meningo-encephalitis (1992)

We present a patient acutely ill from severe tuberculous meningo-encephalitis, in whom acute hepatic and renal failure, due to intercurrent septic shock, precluded the administration of full systemic dosage of antituberculous drugs. Daily direct intraventricular administration of 5 mg rifampicin, via a subcutaneous Ommaya reservoir connected to a catheter placed in the right lateral cerebral ventricle, resulted in rapid improvement without neurological sequelae. Intraventricular rifampicin administration for 50 consecutive days was well-tolerated without local or systemic side-effects. In well-selected patients with severe tuberculous meningo-encephalitis, intraventricular rifampicin may safely and highly effectively be added to systemic antituberculous therapy.
Dystrophin quantification (2014)

Considering the biological function of dystrophin at the sarcolemma, our data indicate that the combined use of quantitative immunohistochemistry and Western blotting are reliable biochemical outcome measures for Duchenne muscular dystrophy clinical trials, and that standardized protocols can be comparable between competent laboratories. The methodology validated in our study will facilitate the development of experimental therapies focused on dystrophin production and their regulatory approval.
Expression cloning of a novel Gal beta (1-3/1-4) GlcNAc alpha 2,3-sialyltransferase using lectin resistance selection. (1993)

This report describes the isolation of a cDNA encoding a novel human Gal beta (1-3/1-4)GlcNac alpha 2,3-sialyl-transferase involved in the biosynthesis of the sialyl Lewis x determinant (NeuAc alpha 2-3 Gal beta 1-4(Fuc alpha 1-3)GlcNAc). A cDNA library of the human melanoma cell line WM266-4 was constructed in an Epstein-Barr virus-based cloning vector. Selection of the B-cell line Namalwa expressing transfected cDNAs in the presence of the cytotoxic lectin Ricinus communis agglutinin 120 gave a cDNA encoding a protein with type II transmembrane topology, as found for mammalian glycosyltransferases. The use of this lectin, which is specific to galactose residues (especially the Gal beta 1-4GlcNAc structure), originates from our prediction that the modification of the Gal beta 1-4GlcNAc structure (a backbone of the sialyl Lewis x structure) by glycosyltransferases may increase the levels of resistance to this lectin. Comparison of this cDNA sequence with those of three other cloned sialyltransferases revealed two conserved regions shared by all four enzymes. Expression of the COOH-terminal catalytic domain of this protein showed alpha 2,3-sialyltransferase activity with substrate specificity different from that of CMP-N-acetylneuraminate:N-acetyllactosaminide alpha-2,3-sialyltransferase (Gal-beta 1-3(4)GlcNAc alpha 2,3-sialyltransferase, EC 2.4.99.6). Furthermore, expression of this cDNA in Namalwa cells increased the level of sialyl Lewis x antigens. The cloning approach based on lectin resistance may be useful for the isolation of cDNAs encoding other mammalian glycosyltransferases.
OBSERVATIONS ON FORTY TWIN INDEX CASES WITH CHRONIC EPILEPSY AND THEIR CO-TWINS (1960)

2 Institute of Brain Research, University of Tokyo School of Medicine, Tokyo, Japan. The author acknowledges with thanks the collaborations of Drs. H. Kamide, T. Suzuki and T. Fukada.
Shadow-based vehicle model refinement and tracking in advanced automotive driver assistance systems (2011)

Vision-based automotive driver assistance systems have to cope with complex outdoor illumination conditions. Many applications for vehicle detection and tracking consider shadows caused by the sunlight as distracting effects and try to computationally compensate or disregard them. In this paper we suggest a shape-from-shadow approach which uses cast shadows as additional supporting information for vehicle model refinement and tracking. To take the position of the sun into account we only use sensor systems that mid-range vehicles are normally equipped with. Analysing shadows is a suitable method to support rear-view based vehicle tracking. A vehicle's shadow turned out to be a strong feature since it is possible to track a vehicle solely based on its shadow. Another benefit is that we are able to set up and refine three-dimensional shape models of vehicles driving ahead in the same lane. In selected situations it is possible to visually track two vehicles driving on the same lane one after another.
Depletion of B Cells by a Humanized Anti-CD20 Antibody PRO70769 in Macaca Fascicularis (2005)

PRO70769 is a humanized IgG1 monoclonal antibody against the CD20 molecule that is present on normal and malignant B cells. PRO70769 is being evaluated for treatment of B-cell-mediated diseases and is in a phase 1 trial for rheumatoid arthritis. As part of the preclinical toxicology evaluation, B-cell depletion profiles and safety of PRO70769 were assessed in cynomolgus monkeys. Animals were administered drug (IV) on days 1 and 15 with 10, 50, or 100 mg/kg PRO70769 and killed 2 weeks after the second dose and after a 3-month recovery period. In a parallel study, animals were not necropsied but instead were retreated with a second cycle of PRO70769 administered under an identical regimen. PRO70769 suppressed B cells in the blood to undetectable levels and significantly reduced B cells in lymphoid tissues. Splenic B cells were depleted to a greater extent compared with lymph node B cells. A second cycle of treatment resulted in a greater extent of depletion in lymphoid tissues compared with the depletion observed after one cycle of treatment; however, residual B cells in lymphoid tissues were still detectable, even at the highest dose. The rate of B-cell recovery in peripheral blood appeared similar between one and two cycles of treatment. Upon depletion there was a change in the profile of lymph node B-cell subsets. After recovery, B-cell subsets were reconstituted to normal levels. Depletion of CD20-expressing cells and lymphoid follicular atrophy were the only treatment-related effects.
Genetic variability analysis in five populations of the sea cucumber Stichopus (Apostichopus) japonicus from China, Russia, South Korea and Japan as revealed by microsatellite markers (2009)

Abstract The genetic structure of populations of the sea cucumber Stichopus ( Apostichopus ) japonicus was investigated using 10 microsatellite markers. In all, 152 individuals from five natural populations were collected from Aomori, Japan (JA and JR), Yosu, South Korea (KY), Dalian, China (CD) and Vladivostock, Russia (RV). A total of 145 alleles were found at 10 loci. The number of alleles per locus ranged from 9 at PSC03 to 20 at SCZ06, with an average of 14.5. Average H o and H e ranged from 0.260 (JR) to 0.434 (JA) and from 0.654 (RV) to 0.778 (KY), respectively. No significant differences at A , H o and H e were found, indicating similar genetic diversity in the five populations. A single allele was found at the PSC05 locus in the RV population. Of the 50 loci, 42 significantly deviated from Hardy–Weinberg equilibrium, all showing heterozygote deficiency. The genetic distances were all relatively great, ranging from 0.497 (between JA and KY) to 1.029 (between KY and JR). This suggests the five populations are genetically distinct. Cluster analysis indicated that JA, KY and CD form one branch and RV and JR another in the UPGMA tree. A hypothesis is proposed for the evolution of the Japanese red sea cucumbers and the genetic relationship among the populations.
Mice lacking the ski proto-oncogene have defects in neurulation, craniofacial patterning, and skeletal muscle development (1997)

The c-ski proto-oncogene has been implicated in the control of cell growth and skeletal muscle differentiation. To determine its normal functions in vivo, we have disrupted the mouse c-ski gene. Our results show a novel role for ski in the morphogenesis of craniofacial structures and the central nervous system, and confirm its proposed function as a player in skeletal muscle development. Homozygous mutant mice show perinatal lethality resulting from exencephaly, a defect caused by failed closure of the cranial neural tube during neurulation. The timing of the neural tube defect in ski -/- embryos coincides with excessive apoptosis in the cranial neuroepithelium, as well as in the cranial mesenchyme. Homozygous ski mutants also exhibit a dramatic reduction in skeletal muscle mass, consistent with a defect in expansion of a myogenic precursor population. Nestin is an intermediate filament expressed in highly proliferative neuroepithelial stem cells and in myogenic precursors. Interestingly, we find decreased nestin expression in both the cranial neural tube and the somites of ski -/- embryos, compared with their normal littermates, but no reduction of nestin in the caudal neural tube. These results are consistent with a model in which ski activities are required for the successful expansion of a subset of precursors in the neuroepithelial or skeletal muscle lineages.
Human CD4+ T Cells Express TLR5 and Its Ligand Flagellin Enhances the Suppressive Capacity and Expression of FOXP3 in CD4+CD25+ T Regulatory Cells (2005)

Germline encoded pattern recognition receptors, such as TLRs, provide a critical link between the innate and adaptive immune systems. There is also evidence to suggest that pathogen-associated molecular patterns may have the capacity to modulate immune responses via direct effects on CD4+ T cells. Given the key role of both CD4+CD25+ T regulatory (Treg) cells and the TLR5 ligand flagellin in regulating mucosal immune responses, we investigated whether TLR5 may directly influence T cell function. We found that both human CD4+CD25+ Treg and CD4+CD25- T cells express TLR5 at levels comparable to those on monocytes and dendritic cells. Costimulation of effector T cells with anti-CD3 and flagellin resulted in enhanced proliferation and production of IL-2, at levels equivalent to those achieved by costimulation with CD28. In contrast, costimulation with flagellin did not break the hyporesponsiveness of CD4+CD25+ Treg cells, but rather, potently increased their suppressive capacity and enhanced expression of FOXP3. These observations suggest that, in addition to their APC-mediated indirect effects, TLR ligands have the capacity to directly regulate T cell responses and modulate the suppressive activity of Treg cells.