gebhart/patrepeval huggingface dataset:
Apoptosis in the OC-k3 Immortalized Cell Line Treated with Different Agents: Apoptosis en linea celular OC k3 inmortalizada, tratada con diferentes agentes (2001)

The aim of this study is to outline the mechanisms leading cochlear cells to die. We utilized an immortalized cell line (OC-k3 cells) derived from the organ of Corti of transgenic mice in order to perform in-depth biochemical studies with no limitations on sample size and number. We probed these cells with cisplatin and gentamicin, two drugs which display in vivo undesired ototoxic side-effects. We investigated cell viability, reactive oxygen species (ROS) production and glutathione (GSH) levels and tested the effects of different concentrations of cisplatin and gentamicin from 0 to 48 h. Results show that cells undergo a dose- and treatment-time-dependent apoptosis characterized by nuclear fragmentation, integrity of the cell membrane and mitochondria, and absence of DNA endonuclease activity. During the early part of treatment, ROS production increases and intracellular GSH decreases, probably due to the activation of protein kinase C alpha. Use of antioxidants such as N-acetylcysteine, GSH and vitamin C rescues cells from apoptosis almost completely. Overall, these data indicate that ROS generation might play a central role in inducing inner ear cell apoptosis and may have an additive role in the ageing process.
Chemical Biology of Glycosylphosphatidylinositol Anchors (2012)

Glycosylphosphatidylinositols (GPIs) are complex glycolipids that are covalently linked to the C-terminus of proteins as a posttranslational modification. They anchor the attached protein to the cell membrane and are essential for normal functioning of eukaryotic cells. GPI-anchored proteins are structurally and functionally diverse. Many GPIs have been structurally characterized but comprehension of their biological functions, beyond the simple physical anchoring, remains largely speculative. Work on functional elucidation at a molecular level is still limited. This Review focuses on the roles of GPI unraveled by using synthetic molecules and summarizes the structural diversity of GPIs, as well as their biological and chemical syntheses.
Growth hormone-promoted tyrosyl phosphorylation of a 121-kDa growth hormone receptor-associated protein. (1993)

Previous work in multiple cell types has shown that endogenous GH receptors, as well as the cloned liver GH receptor, associate with a tyrosine kinase. However, in SDS-PAGE gels of highly purified, kinase-active GH receptor preparations from 35S-labeled 3T3-F442A cells, only one broad band was detected corresponding to the molecular weight of the GH receptor rather than two bands which might be expected to result from a kinase-receptor heterocomplex. In the present study, a transfected Chinese hamster ovary (CHO) cell line (CHO4) that expresses an 84-kDa GH receptor rather than a 121-kDa GH receptor was used to examine whether the GH receptor might form a complex with a protein (e.g. tyrosine kinase) that comigrates on SDS-polyacrylamide gel electrophoresis gels with the endogenous GH receptor (M(r) 121,000) in 3T3-F442A cells. GH-GH receptor complexes were immunoprecipitated with anti-GH antibody from GH-treated CHO4 cells and incubated with [gamma-32P]ATP. 32P was incorporated into a 121-kDa protein as well as the 84-kDa GH receptor. Phosphorylation of both the 84-kDa GH receptor and the 121-kDa protein was on tyrosyl residues as determined by Western blotting with anti-phosphotyrosine antibody. The 121-kDa protein does not appear to bind GH. It was also not detected in the immunoprecipitate when cells had not been incubated with GH or when untransfected CHO cells were used. These findings suggest that in CHO4 cells, the 121-kDa protein is precipitated by the GH antibody because of its ability to form a complex with the GH receptor (p84). Western blot analysis of whole cell lysates using anti-phosphotyrosine antibody revealed that GH promotes the tyrosyl phosphorylation of a 121-kDa protein and several other proteins (p97, p42, p39) in a dose- and time-dependent fashion. Taken together, these findings are consistent with either p121 being the tyrosine kinase that complexes with the GH receptor and is activated in response to GH binding or with p121 forming a ternary complex with both the GH receptor and a tyrosine kinase and serving as a substrate of the GH receptor-associated tyrosine kinase.
Superparamagnetic Nanocomposites of Poly(vinyl alcohol‐graft‐acrylonitrile) as Carrier for Magnetically Assisted Release of Ciprofloxacin (2012)

Abstract In the present study also a superparamagnetic nanocomposite of Poly (vinyl‐ alcohol‐g‐acrylonitrile) has been designed by homogeneous impregnation of iron oxide nanoparticles into the graft polymer matrix. The so prepared nanocomposite was characterized by FT‐IR, TEM and XRD techniques and studied for water sorption behavior and magnetization properties. The superparamagnetic nanocomposite was loaded with an antibiotic drug, ciprofloxacin (CFx), and its release behavior was investigated under varying experimental conditions such as chemical composition of the matrix, pH of the release media, applied magnetic field and percent loading of the drug. The drug transport mechanism was also analyzed using Ficks power law. The drug loaded magnetic nanocomposite was also studied for antibacterial and in‐vitro blood compatible properties.
Three dimensional multimodal image registration using implanted markers (1992)

Our goal is to register arbitrarily oriented, multimodal, volume images of the human head by aligning a configuration of three or more fiducial points. Each point is the geometric center of a marker implanted in the skull. To compute the centers we have extended an earlier thresholding algorithm based on image statistics. The extension, which relies on qualitative knowledge of the histogram in the region surrounding and including the marker, permits the segmentation of regions of interest with multiple objects. We have simulated markers of varying size and varying intensity in CT, MRI T1-weighted, MRI T2-weighted, and MRI proton density images, segmented the simulated markers, computed the geometric centers, and measured root mean square error between the computed and simulated geometric centers. We have developed a mechanism by which the accuracy of fiducial locations in a low resolution image can be improved by using the fiducial locations in a high resolution image. Because the markers are indistinguishable it is necessary to determine their correspondence across images. We have adopted and evaluated geometric algorithms for this purpose. The inherent discreteness and partial volume effect associated with digital images limit the accuracy of fiducial alignment, which in turn limits accuracy in the alignment of anatomical targets. We have conducted experiments to assess this limitation on simulated data, CT scans of a cadaver head with implanted markers, and CT and MRI scans of human volunteers with externally attached markers. Simulations involve generating arbitrarily oriented volume images of a hemispherical model of the head, randomly picking corresponding fiducial points and targets in the images, pertubing fiducial locations with uniformly distributed error, computing transformation needed to register the images using peturbed fiducials, and measuring error in target alignment in registered images. We have compared several transformation algorithms: rigid body with (3 point) Euler angle fit, non-rigid affine transformation with n point least squares fit, rigid body with n point centroid alignment followed by Euler angle fit, and rigid body with n point least squares fit using two different approaches, namely, iterative projections and singular value decomposition.
Targeting T cell costimulation in autoimmune disease (2002)

Many factors contribute to the pathogenesis of autoimmune diseases. Targets for treating such debilitating diseases will become more apparent by understanding the nature of immune activation. This review examines the possibility of targeting costimulation and discusses the molecules found on the T cell and the antigen-presenting cell (APC) that participate in T cell activation. Although new molecules continue to be discovered, the functions of B7-1 (CD80), B7-2 (CD86), CD28, cytotoxic T lymphocyte antigen 4 (CTLA-4), inducible costimulator (ICOS), programmed death 1 (PD-1), OX 40 (CD134) and CD40 ligand (CD40L, CD154) are now sufficiently understood that immunologists are targeting them to manipulate T cells to slow the progression of autoimmune diseases or treat tumours through the increase in T cell activation. CD28, ICOS, OX 40 and CD40L are considered the costimulatory molecules that increase T cell activation. However, ICOS and OX 40 appear to act on memory cells while CD28 is predominantly a naive T cell activator. Most therapies in the treatment of autoimmunity that target these molecules work through blockade of their function with receptor specific immunoglobulin (Ig). CTLA-4 and PD-1 are considered to be the inhibitory T cell costimulators. While stimulating CTLA-4 has not been a widely used therapy, using soluble CTLA-4Ig to block B7 and disrupt the B7/CD28 pathway is fairly common. The majority of therapeutic use for PD-1 stems from targeting PD-1 with its natural ligand. It is hoped that therapies targeting costimulation may provide a means of conserving the patient's normal T cell repertoire and immune function whilst eliminating or suppressing autoreactive T cells and thus provide a more efficient means to treat autoimmune disease.
Biological characterization of human monoclonal antibodies to rabies virus (1990)

Rabies virus antigen-specific human monoclonal antibodies (MAbs) that recognized either viral glycoprotein, ribonucleoprotein, or matrix proteins were generated. Only glycoprotein-specific MAb neutralized a variety of rabies viruses and protected laboratory rodents against lethal rabies virus infection. The determinant recognized by this MAb does not appear to reside in previously defined antigenic sites of the viral glycoprotein.
Pulmonary hypertension in TNF-α-overexpressing mice is associated with decreased VEGF gene expression (2002)

Tumor necrosis factor-alpha (TNF-alpha) transgenic mice have previously been found to have characteristics consistent with emphysema and severe pulmonary hypertension. Lungs demonstrated alveolar enlargement as well as interstitial thickening due to chronic inflammation and perivascular fibrosis. In the present report, we sought to determine potential mechanisms leading to development of pulmonary hypertension in TNF-alpha transgenic mice. To determine whether sustained vasoconstriction was an important component of this pulmonary hypertension, nitric oxide was administered and hemodynamics were measured. Nitric oxide (25 ppm) failed to normalize right ventricular pressure in transgene-positive mice, suggesting that the pulmonary hypertension was not due to sustained vasoconstriction. Structural analysis of the pulmonary arteries found adventitial thickening and a trend toward medial hypertrophy in pulmonary arteries of transgene-positive mice, suggesting that vascular remodeling had occurred. Echocardiographic measurement of the percent fractional shortening of the left ventricle as a measurement of ventricular function in vivo revealed that left ventricular dysfunction was not contributing to pulmonary hypertension. We examined expression of genes known to be important in regulation of vascular tone and structure. Messenger RNA expression of vascular endothelial growth factor and its receptor flk-1 was reduced compared with transgene-negative littermates at all ages. Endothelial and inducible nitric oxide synthase mRNA levels were similar in both groups. Endothelin-1 mRNA was also decreased in TNF-alpha transgenic mice. Interestingly, female transgenic mice had decreased survival rate compared with male transgenic mice. We conclude that chronic overexpression of TNF-alpha is associated with decreased vascular endothelial growth factor and flk-1 gene expression, pulmonary vascular remodeling, and severe pulmonary hypertension, although the precise mechanism is unknown.
NF-κB–inducing kinase plays an essential T cell–intrinsic role in graft-versus-host disease and lethal autoimmunity in mice (2011)

NF-κB–inducing kinase (NIK) is an essential upstream kinase in noncanonical NF-κB signaling. NIK-dependent NF-κB activation downstream of several TNF receptor family members mediates lymphoid organ development and B cell homeostasis. Peripheral T cell populations are normal in the absence of NIK, but the role of NIK during in vivo T cell responses to antigen has been obscured by other developmental defects in NIK-deficient mice. Here, we have identified a T cell–intrinsic requirement for NIK in graft-versus-host disease (GVHD), wherein NIK-deficient mouse T cells transferred into MHC class II mismatched recipients failed to cause GVHD. Although NIK was not necessary for antigen receptor signaling, it was absolutely required for costimulation through the TNF receptor family member OX40 (also known as CD134). When we conditionally overexpressed NIK in T cells, mice suffered rapid and fatal autoimmunity characterized by hyperactive effector T cells and poorly suppressive Foxp3(+) Tregs. Together, these data illuminate a critical T cell–intrinsic role for NIK during immune responses and suggest that its tight regulation is critical for avoiding autoimmunity.
Two-dimensional photonic crystal couplers for unidirectional light output (2000)

We investigate the use of two-dimensional photonic crystal slabs to improve the directionality of output coupling from planar waveguides and distributed-feedback lasers. We present the theory underlying the operation of such structures and design criteria for emission in desired directions. As an example, we demonstrate a vertical coupler that is integrated with an organic distributed-feedback laser, use computer simulations to find its coupling constant and efficiency, and then discuss its feasibility.
An Analysis of Arrhythmias Induced by Ouabain in Intact Dogs (1963)

The results of this study show that ouabain administration quite often causes idioventricular automaticity to undergo an initial depression and a subsequent enhancement. When the electrocardiogram shows normal sinus rhythm these changes in ventricular automaticity can be unmasked by vagal stimulation which causes either sinus arrest or atrioventricular block. On occasion, the depression of idioventricular automaticity is permanent; if ouabain produces complete atrioventricular block at this time, ventricular arrest ensues. When, on the contrary, the automaticity of Purkinje fibers is progressively enhanced, a stage is reached in which the idioventricular rhythm becomes faster than the sinus rhythm. Eventually the basic ventricular rhythm exhibits pauses during which electrocardio-graphic complexes of different form become apparent. The second class of arrhythmias comprises extrasystoles which may or may not show a constant coupling to sinus beats but which are characterized by a dependence on an initiating beat. It was demonstrated in this investigation that these extra beats appear during slow intravenous administration of ouabain and that they disappear not only on suppression but also on slowing of the sinus rhythm. Furthermore, it was shown that bigeminal rhythm may be transformed into extrasystoles occurring after every second sinus beat by means of vagal stimulation which slows the sinus rate. If, however, the heart was driven at faster rate, several extrasystoles followed one atrial beat. At a more advanced stage of ouabain intoxication these extrasystoles lose their fixed relationship with the sinus beat and runs of self-sustaining tachycardia appear. Such runs of ventricular tachycardia are unaffected by vagal stimulation but have a tendency to subside, spontaneously, and start anew after another initiating sinus beat. If vagal stimulation inhibits the initiating beat, the run of tachycardia also is suppressed. At an advanced stage of intoxication, however, when polymorphic ventricular complexes are present, vagal stimulation no longer produces any apparent effects. Finally, this investigation has shown that, during vagal stimulation which produces sinus arrest or A-V block, atrial fibrillation can be initiated by retrograde transmission of ventricular escape beats even though atrial escape beats are ineffective in eliciting the same phenomenon.
Clinical features of patients with antibodies directed against proliferating cell nuclear antigen (1983)

The clinical and serologic features of 7 patients whose sera contained antibodies directed against proliferating cell nuclear antigen (anti-PCNA) were studied. Five of the patients had systemic lupus erythematosus (SLE), 1 had idiopathic diffuse proliferative glomerulonephritis, and 1 had seronegative arthritis. In a study of various rheumatic diseases, anti-PCNA was found in 2% of SLE sera but was not found in the sera of 100 rheumatoid arthritis patients, 20 mixed connective tissue disease patients, or 50 diffuse scleroderma patients. Patients with anti-PCNA had no history of hemolytic anemia, leukopenia, thrombocytopenia, or pleuro-pericarditis. Evidence that the production of anti-PCNA antibodies is sensitive to corticosteroid therapy is also presented.
Cytogenetic profile of chronic myeloid leukemias. (2002)

Chronic Myeloid leukemia is a clonal disease of multipotent haematopoietic cells associated with specific cytogenetic changes involving a translocation t(9;22) (q34:q11), more commonly known as Philadelphia Chromosome (Ph1). A total of 525 patients with CML (480 adults and 45 children) diagnosed at the Nizam's Institute of Medical Sciences, Hyderabad, formed the subjects of this study. Hematological investigations were carried out using standard methods. Unstimulated peripheral blood samples and/or bone marrow aspirates were used for cytogenetic analysis. Hematological evaluation at presentation showed that 435 were in chronic phase, 36 in accelerated phase and 54 in blast crisis. Chromosomal analysis revealed that 86.3% were Ph1 positive and 13.7% Ph1 negative. Additional chromosome changes observed during blast crisis included an extra Ph1 chromosome, Trisomy 8 and Trisomy 19. The results were correlated with survival pattern and prognosis of patients following certain treatment protocols.
A Dominant Mutant of Inner Centromere Protein (INCENP), a Chromosomal Protein, Disrupts Prometaphase Congression and Cytokinesis (1998)

INCENP is a tightly bound chromosomal protein that transfers to the spindle midzone at the metaphase/anaphase transition. Here, we show that an INCENP truncation mutant (INCENP382-839) associates with microtubules but does not bind to chromosomes, and coats the entire spindle throughout mitosis. Furthermore, an INCENP truncation mutant (INCENP43-839) previously shown not to transfer to the spindle at anaphase (Mackay, A.M., D.M. Eckley, C. Chue, and W.C. Earnshaw. 1993. J. Cell Biol. 123:373-385), is shown here to bind chromosomes, but is unable to target to the centromere. Thus, association with the chromosomes, and specifically with centromeres, appears to be essential for INCENP targeting to the correct spindle subdomain at anaphase. An INCENP truncation mutant (INCENP1-405) that targets to centromeres but lacks the microtubule association region acquires strong dominant-negative characteristics. INCENP1-405 interferes with both prometaphase chromosome alignment and the completion of cytokinesis. INCENP1-405 apparently exerts its effect by displacing the endogenous protein from centromeres. These experiments provide evidence of an unexpected link between this chromosomal protein and cytokinesis, and suggest that one function of INCENP may be to integrate the chromosomal and cytoskeletal events of mitosis.
The Protein Information Resource (2003)

The Protein Information Resource (PIR) is an integrated public resource of protein informatics that supports genomic and proteomic research and scientific discovery. PIR maintains the Protein Sequence Database (PSD), an annotated protein database containing over 283 000 sequences covering the entire taxonomic range. Family classification is used for sensitive identification, consistent annotation, and detection of annotation errors. The superfamily curation defines signature domain architecture and categorizes memberships to improve automated classification. To increase the amount of experimental annotation, the PIR has developed a bibliography system for literature searching, mapping, and user submission, and has conducted retrospective attribution of citations for experimental features. PIR also maintains NREF, a non-redundant reference database, and iProClass, an integrated database of protein family, function, and structure information. PIR-NREF provides a timely and comprehensive collection of protein sequences, currently consisting of more than 1 000 000 entries from PIR-PSD, SWISS-PROT, TrEMBL, RefSeq, GenPept, and PDB. The PIR web site (http://pir.georgetown.edu) connects data analysis tools to underlying databases for information retrieval and knowledge discovery, with functionalities for interactive queries, combinations of sequence and text searches, and sorting and visual exploration of search results. The FTP site provides free download for PSD and NREF biweekly releases and auxiliary databases and files.
Peptide and Peptide Mimetic Inhibitors of Antigen Presentation by HLA-DR Class II MHC Molecules. Design, Structure−Activity Relationships, and X-ray Crystal Structures (2000)

Molecular features of ligand binding to MHC class II HLA-DR molecules have been elucidated through a combination of peptide structure-activity studies and structure-based drug design, resulting in analogues with nanomolar affinity in binding assays. Stabilization of lead compounds against cathepsin B cleavage by N-methylation of noncritical backbone NH groups or by dipeptide mimetic substitutions has generated analogues that compete effectively against protein antigens in cellular assays, resulting in inhibition of T-cell proliferation. Crystal structures of four ternary complexes of different peptide mimetics with the rheumatoid arthritis-linked MHC DRB10401 and the bacterial superantigen SEB have been obtained. Peptide-sugar hybrids have also been identified using a structure-based design approach in which the sugar residue replaces a dipeptide. These studies illustrate the complementary roles played by phage display library methods, peptide analogue SAR, peptide mimetics substitutions, and structure-based drug design in the discovery of inhibitors of antigen presentation by MHC class II HLA-DR molecules.