gebhart/patrepeval huggingface dataset:
Isoform Heterogeneity of the Human Gephyrin Gene (GPHN), Binding Domains to the Glycine Receptor, and Mutation Analysis in Hyperekplexia (2003)

Gephyrin (GPHN) is an organizational protein that clusters and localizes the inhibitory glycine (GlyR) and GABAA receptors to the microtubular matrix of the neuronal postsynaptic membrane. Mice deficient in gephyrin develop a hereditary molybdenum cofactor deficiency and a neurological phenotype that mimics startle disease (hyperekplexia). This neuromotor disorder is associated with mutations in the GlyR alpha1 and beta subunit genes (GLRA1 and GLRB). Further genetic heterogeneity is suspected, and we hypothesized that patients lacking mutations in GLRA1 and GLRB might have mutations in the gephyrin gene (GPHN). In addition, we adopted a yeast two-hybrid screen, using the GlyR beta subunit intracellular loop as bait, in an attempt to identify further GlyR-interacting proteins implicated in hyperekplexia. Gephyrin cDNAs were isolated, and subsequent RT-PCR analysis from human tissues demonstrated the presence of five alternatively spliced GPHN exons concentrated in the central linker region of the gene. This region generated 11 distinct GPHN transcript isoforms, with 10 being specific to neuronal tissue. Mutation analysis of GPHN exons in hyperekplexia patients revealed a missense mutation (A28T) in one patient causing an amino acid substitution (N10Y). Functional testing demonstrated that GPHNN10Y does not disrupt GlyR-gephyrin interactions or collybistininduced cell-surface clustering. We provide evidence that GlyR-gephyrin binding is dependent on the presence of an intact C-terminal MoeA homology domain. Therefore, the N10Y mutation and alternative splicing of GPHN transcripts do not affect interactions with GlyRs but may affect other interactions with the cytoskeleton or gephyrin accessory proteins.
TRU-016, a humanized anti-CD37 IgG fusion protein for the potential treatment of B-cell malignancies. (2009)

TRU-016, under development by Trubion Pharmaceuticals Inc and Facet Biotech Corp, is an intravenously administered anti-CD37 IgG fusion protein for the potential treatment of B-cell malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), as well as for autoimmune and inflammatory diseases. TRU-016 was created by humanizing SMIP-016, a mouse/human chimeric protein that demonstrated antitumor activity against lymphoid malignancies in preclinical studies, including in human B-cell tumor mouse xenograft models. In addition, TRU-016 demonstrated synergistic or additive activity in NHL cells in combination with rituximab, rapamycin, doxorubicin and bendamustine. In a phase I/II clinical trial in refractory or relapsed patients with CLL or small lymphocytic lymphoma, TRU-016 was well tolerated, with clinical benefit and a reduced absolute lymphocyte count observed in all cohorts dosed at > 0.1 mg/kg. TRU-016 is a promising therapeutic agent for patients with B-cell lymphoid malignancies, especially patients refractory to standard treatment.
How to Prepare Tunable Planar Molecular Chemical Gradients (2001)

Mechanically assembled monolayers (MAMs) can be employed to adjust the surface density of the initiators and consequently that of molecular gradients prepared on flexible supports. The steepness and the position of the gradient of molecules on a substrate are fine-tuned by a combination of grafting and mechanical manipulation of the films. Planar molecular gradients ranging from several millimeters to several centimeters can thus be fabricated. In addition, the wetting properties of the hydrophobic part of the substrate can be adjusted by altering the chemical nature of the films.
The Fontan circulation: who controls cardiac output? (2009)

In a Fontan circuit the mechanisms involved in control of cardiac output at rest and during exercise differ significantly from normal. The classical model presumes an unlimited preload which is not available in the Fontan circuit. This review critically analyses the role of contractility, heart rate, and afterload and highlights the importance of pulmonary vascular resistance (PVR) in determining adequate preload and, therefore, cardiac output in these patients. A conceptual model of the determinants of cardiac output in Fontan patients is presented.
Liposomes as ‘smart’ pharmaceutical nanocarriers (2010)

Since the discovery of liposomes, these phospholipid ‘bubbles’ have received enormous attention to be recognized as ‘smart’ pharmaceutical nanocarriers. Recently, much effort has been directed to the development of so-called ‘smart’ stimuli-sensitive liposomes that will respond to certain internal or external stimuli, such as, pH, temperature, redox potential or magnetic field. These programmable delivery systems can also be made ‘multifunctional’ so as to expose certain functions in an orchestrated manner which can be readily modulated by the stimulus. In this article, the evolution of liposomes with emphasis on the recent advances in stimuli-sensitive liposomes has been reviewed.
Relationship between sex hormones, body composition and metabolic risk parameters in premenopausal women (1995)

The metabolic complications associated with obesity are dependent upon the degree of obesity and the distribution of adipose tissue. In order to evaluate the associations between sex hormone status, metabolic risk parameters, obesity and distribution of adipose tissue, 25 premenopausal women with a wide range of body mass index (19.3-48.1 kg/m2 were studied. Body composition was determined by dual-energy x-ray absorptiometry scan and anthropometric measurements; in addition, lipid and sex hormone status were determined and an oral glucose tolerance test was performed. We found that sex hormone-binding globulin was correlated negatively with total fat mass (r = -0.77, p < 0.001) and especially with abdominal localization of adipose tissue (r = -0.85, p < 0.001). Free testosterone was correlated positively with total fat mass (r = 0.40, p < 0.05) and with abdominal fat accumulation (r = 0.64, p < 0.001). Free estrogen was correlated negatively with total amount of adipose tissue (r = -0.40, p < 0.05) but not with the distribution of adipose tissue. Finally, total fatness, abdominal localization of adipose tissue and free testosterone were all associated with elevated metabolic risk factors. However, multiple regression analysis revealed that only abdominal localization of adipose tissue was independently associated with a higher risk profile, whereas the effects of sex hormones or total fatness disappeared when abdominal localization of adipose tissue was included in the analysis. In conclusion, these findings in premenopausal women indicate that the connection between sex hormones and metabolic risk factors might be indirect, probably operating through alterations in the amount of adipose tissue in the abdominal region.
Exploiting image semantics for picture libraries (2001)

We consider the application of a system for learning the semantics of image collections to digital libraries. We discuss our approach to browsing and search, and investigate the integration both in more detail.
A Role for the RNase III Enzyme DCR-1 in RNA Interference and Germ Line Development in Caenorhabditis elegans (2001)

An early event in RNA interference (RNAi) is the cleavage of the initiating double-stranded RNA (dsRNA) to short pieces, 21 to 23 nucleotides in length. Here we describe a null mutation in dicer-1 (dcr-1), a gene proposed to encode the enzyme that generates these short RNAs. We find that dcr-1(-/-) animals have defects in RNAi under some, but not all, conditions. Mutant animals have germ line defects that lead to sterility, suggesting that cleavage of dsRNA to short pieces is a requisite event in normal development.
In vitro toxicological support to establish specification limit for anti-CD3 monospecific impurity in a bispecific T cell engager drug, ERY974 (2020)

An emerging structure for anti-tumor antibody drugs utilizes a bispecific antibody (BiAb) that recognizes a tumor surface antigen and CD3 on T cells. An impurity that commonly contaminates these BiAb products is an anti-CD3 monoclonal antibody (mAb). The most plausible cause of toxic activity by an anti-CD3 mAb is the induction of cytokines via T cell activation. In this in vitro study, we compared cytokine induction and T cell activation after treatment with an anti-glypican-3/CD3 BiAb (ERY974), anti-CD3 mAb impurity (aCD3), or ERY974 spiked with 5% aCD3. We found that contamination with up to 5% aCD3 did not affect cytokine release by ERY974. Cytokine levels induced by ERY974 in the presence of target cells were significantly higher than those induced by aCD3, but were very similar to those by the spiked treatment. The results supported the specification of a 5% limit for aCD3. OKT-3 had much higher activity to induce cytokines from peripheral blood mononuclear cells in an in vitro assay than aCD3. This suggests that specification limit should be decided for each type of anti-CD3 impurity that affects T cell-activating BiAb drug products. In vitro cytokine assays can provide useful information for determining these specification limits.
Plasma/serum levels of flt3 ligand are low in normal individuals and highly elevated in patients with Fanconi anemia and acquired aplastic anemia (1995)

The flt3 ligand is a growth factor that stimulates the proliferation of hematopoietic progenitor and stem cells. We established a sensitive enzyme-linked immunosorbent assay (ELISA) to measure the concentration of flt3 ligand in plasma or serum from normal individuals, as well as in patients with hematopoietic disorders. Concentrations of flt3 ligand in plasma or serum from normal individuals were quite low: only 12% (7 of 60) of normal individuals had flt3 ligand levels above 100 pg/mL (the limit of detection). In contrast, 86% (19 of 22) of samples from patients with Fanconi anemia and 100% (eight of eight) of samples from patients with acquired aplastic anemia had plasma or serum levels above 100 pg/mL. Mean plasma or serum concentrations (calculated by assigning a value of 0 pg/mL to any sample reading below the level of detection) were as follows: normal volunteers, 14 pg/mL; patients with Fanconi anemia, 1,331 pg/mL; and patients with acquired aplastic anemia, 460 pg/mL. Concentrations of flt3 ligand in blood are, therefore, specifically elevated to a level that may be physiologically relevant in hematopoietic disorders with a suspected stem cell component. The elevated flt3 ligand concentrations in these individuals may be part of a compensatory hematopoietic response to boost the level of progenitor cells.
Evaluation of a (1→3)-β- d -Glucan Assay for Diagnosis of Invasive Fungal Infections (2005)

The Fungitell assay (Associates of Cape Cod, Inc.) is a commercial test that detects (1-3)-beta-D-glucan (BG) and is intended for diagnosis of invasive fungal infections. To evaluate the Fungitell assay, we tested serum and plasma samples from healthy blood donors and from patients with blood cultures positive for yeast or bacteria. All 36 blood donors were BG negative, and 13 of 15 candidemic patients were BG positive. Of 25 bacteremic patients, 14 (10 with gram-positive bacteremia) were BG positive. One of the latter patients with Staphylococcus aureus bacteremia also had invasive candidiasis, based on histological findings in a tissue biopsy; therefore, the BG result was a true positive. The sensitivity, specificity, and positive and negative predictive values of the Fungitell assay, by patient, for these three groups were 93.3%, 77.2%, 51.9%, and 97.8%, respectively. We also performed the Fungitell assay on sera that had been tested for Aspergillus galactomannan or Histoplasma antigen. All six Histoplasma antigen-positive patients and 31 of 32 Aspergillus galactomannan-positive patients were also BG positive. BG results for the 10 Histoplasma antigen-negative and the 32 Aspergillus galactomannan-negative patients varied, but we were unable to confirm many of the results. Between-run coefficients of variance (CVs) for the assay ranged from 3.2% to 16.8%; within-run CVs were < or =4.8%. The correlation coefficient for an interlaboratory reproducibility study was 0.9892. Concentrations of hemoglobulin, bilirubin, and triglycerides that caused 20% interference were 588, 72, and 466 mg/dl, respectively. Our results suggest that the Fungitel assay may be most useful for excluding invasive fungal infection.
Viral Entry through CXCR4 Is a Pathogenic Factor and Therapeutic Target in Human Immunodeficiency Virus Type 1 Disease (2000)

The chemokine receptors CCR5 and CXCR4 function as the principal coreceptors for human immunodeficiency virus type 1 (HIV-1). Coreceptor function has also been demonstrated for a variety of related receptors in vitro. The relative contributions of CCR5, CXCR4, and other putative coreceptors to HIV-1 disease in vivo have yet to be defined. In this study, we used sequential primary isolates and recombinant strains of HIV-1 to demonstrate that CXCR4-using (X4) viruses emerging in association with disease progression are highly pathogenic in ex vivo lymphoid tissues compared to CXCR4-independent viruses. Furthermore, synthetic receptor antagonists that specifically block CXCR4-mediated entry dramatically suppressed the depletion of CD4(+) T cells by recombinant and clinically derived X4 HIV-1 isolates. Moreover, in vitro specificity for the additional coreceptors CCR3, CCR8, BOB, and Bonzo did not augment cytopathicity or diminish sensitivity toward CXCR4 antagonists in lymphoid tissues. These data provide strong evidence to support the concept that adaptation to CXCR4 specificity in vivo accelerates HIV-1 disease progression. Thus, therapeutic intervention targeting the interaction of HIV-1 gp120 with CXCR4 may be highly valuable for suppressing the pathogenic effects of late-stage viruses.
Macromolecular electronic device: Field-effect transistor with a polythiophene thin film (1986)

The first solid-state field-effect transistor has been fabricated utilizing a film of an organic macromolecule, polythiophene, as a semiconductor. The device characteristics have been optimized by controlling the doping levels of the polymer. The device is a normally off type and the source (drain) current can be modulated by a factor of 102–103 by varying the gate voltage. The carrier mobility and the transconductance have also been determined to be ∼10−5 cm2/V s and 3 nS, respectively, by means of electrical measurements.
Computer Networks: An Open Source Approach (2011)

Chapter 1: Fundamentals Chapter 2: Physical Layer Chapter 3: Link Layer Chapter 4: Internet Protocol Layer Chapter 5: Transport Layer Chapter 6: Application layer Chapter 7: Internet QoS Chapter 8: Network Security Appendix A: Who's Who Appendix B: Linux Kernel Overview Appendix C: Development Tools Appendix D: Network Utilities
Control of the Rhesus Monkey Menstrual Cycle: Permissive Role of Hypothalamic Gonadotropin-Releasing Hormone (1980)

In rhesus monkeys with hypothalamic lesions (which appear to abolish the endogenous production of gonadotropin-releasing hormone), normal ovulatory mestrual cycles were reestablished by an unvarying, long-term replacement regimen consisting of one intravenous pulse of synthetic gonadotropic-releasing hormone per hour. This finding is in accord with the hypothesis that the pattern of pituitary gonadotropin secretion throughout the menstrual cycle (basal secretion interrupted, once every 28 days on the average, by a preovulatory surge) is not directed by alterations in hypothalamic gonadotropin-releasing hormone secretion but by the ebb and flow of ovarian estrogens acting directly on the pituitary gland.
Dissociation kinetics of 125I-nerve growth factor from cell surface receptors. Acceleration by unlabeled ligand and its relationship to negative cooperativity. (1981)

The dissociation kinetics of 125I-labeled nerve growth factor (NGF) from dissociated cells of the 9-day chick embryo dorsal root ganglion were studied following preincubation for 2 h at 25 degrees C with 15 to 30 pM125I-NGF. Subsequent dilution in the presence of 4 nM NGF resulted in greater initial dissociation than occurred with dilution alone. This effect was largely limited to the first half-hour after addition of unlabeled NGF; thereafter, cell-associated radioactivity declined at the same rate for both dilution conditions. In addition, dissociation kinetics did not follow a single first order rate law in the presence or absence of excess unlabeled NGF. These data are not consistent with a model of a single class of high affinity NGF receptors, whether or not they are noninteracting or negatively cooperative. Alternative models based on multiple noninteracting or negatively cooperative receptors might explain these results, but the current data do not allow clear discrimination among them.
Abstracts of Sapporo Symposium on Anisotropic Effects in a Crystal Growth Problem and its Mathematical Analysis (SAM) (1999)

Double obstacle phase field models and interfacial
Automatic extraction of Irregular Network digital terrain models (1979)

For representation of terrain, an efficient alternative to dense grids is the Triangulated Irregular Network (TIN), which represents a surface as a set of non-overlapping contiguous triangular facets, of irregular size and shape. The source of digital terrain data is increasingly dense raster models produced by automated orthophoto machines or by direct sensors such as synthetic aperture radar. A method is described for automatically extracting a TIN model from dense raster data. An initial approximation is constructed by automatically triangulating a set of feature points derived from the raster model. The method works by local incremental refinement of this model by the addition of new points until a uniform approximation of specified tolerance is obtained. Empirical results show that substantial savings in storage can be obtained.
The Low-Affinity Receptor for Neurotrophins p75NTR Plays a Key Role for Satellite Cell Function in Muscle Repair Acting via RhoA (2009)

Regeneration of muscle fibers, lost during pathological muscle degeneration or after injuries, is mediated by the production of new myofibres. This process, sustained by the resident stem cells of the muscle, the satellite cells, is finely regulated by local cues, in particular by cytokines and growth factors. Evidence in the literature suggests that nerve growth factor (NGF) is involved in muscle fiber regeneration; however, its role and mechanism of action were unclear. We have investigated this issue in in vivo mouse models of muscle regeneration and in primary myogenic cells. Our results demonstrate that NGF acts through its low-affinity receptor p75(NTR) in a developmentally regulated signaling pathway necessary to myogenic differentiation and muscle repair in vivo. We also demonstrate that this action of NGF is mediated by the down-regulation of RhoA-GTP signaling in myogenic cells.
How to diagnose rheumatoid arthritis early: A prediction model for persistent (erosive) arthritis (2002)

A clinical prediction model was developed with an excellent ability to discriminate, at the first visit, between 3 forms of arthritis outcome. Validation in other early arthritis clinics is necessary.
Myc Function and Regulation (1992)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Describing the Mechanism of Antimicrobial Peptide Action with the Interfacial Activity Model (2010)

Antimicrobial peptides (AMPs) have been studied for three decades, and yet a molecular understanding of their mechanism of action is still lacking. Here we summarize current knowledge for both synthetic vesicle experiments and microbe experiments, with a focus on comparisons between the two. Microbial experiments are done at peptide to lipid ratios that are at least 4 orders of magnitude higher than vesicle-based experiments. To close the gap between the two concentration regimes, we propose an "interfacial activity model", which is based on an experimentally testable molecular image of AMP-membrane interactions. The interfacial activity model may be useful in driving engineering and design of novel AMPs.
Reduktion aromatischer Säuren zu Aldehyden und Alkoholen im zellfreien System (1969)

An enzyme catalyzing the reduction of the carboxyl group of aromatic acids to the respective aldehydes has been isolated from mycelia of the fungus Neurospora crassa grown in the presence of salicylic acid as an inducer. This protein has been purified about 300-fold by precipitation of nucleic acids with protamine sulfate, ammonium sulphate fractionation, adsorption on calcium-phosphate gel and chromatography on TEAE-cellulose (at pH 7.6 and 8.4) and on hydroxylapatite. The enzyme, the molecular weight of which was estimated to be about 120,000 by chromatography on a calibrated Sephadex G-200 column requires NADPH and ATP as cofactors. The Km-values for salicylic acid as a substrate are 1.67 × 10−4 M and for ATP 1.52 × 10−4 M. The presence of Mg-ions and of a reduced thiol in the incubation mixture is necessary to achieve full activity. The purified enzyme is most active around pH 8.0 and 35°. It shows a broad range of substrate specificity towards aromatic acids, especially to phenyl carboxylic and phenyl acrylic acids, but does not catalyze the reduction of aliphatic carboxyl groups. During the reaction ATP is split into ADP and inorganic phosphate, while stoichiometric amounts of aldehyde are produced from the corresponding acid. NADPH used as a reductant, the formation of the carbonyl group involves the oxidation of the hydrogen donor in a molar ratio of 1:1. Since no intermediate could be detected and there was no evidence for a reverse reaction we formulate the reaction as R–COOH + ATP + NADPH + H+ R-CHO + ADP + NADP++ PO43-+ H2O; the systematic name aryl aldehyde: NADP oxidoreductase (ADP) is proposed; the enzyme belongs to EC group 1.2.1. By supplying α-, or β-[3H]NADP the enzyme was shown to be of the “B-type”.
Adoptive Transfer of Cloned Melanoma-Reactive T Lymphocytes for the Treatment of Patients with Metastatic Melanoma (2001)

This report describes a phase I study of the adoptive transfer of cloned melanoma antigen-specific T lymphocytes for therapy of patients with advanced melanoma. Clones were derived from peripheral blood lymphocytes or tumor-infiltrating lymphocytes of patients who had received prior immunization with the melanoma-associated antigen, gpl00. In response to its cognate antigen, each clone used for treatment secreted large amounts of interferon-gamma and granulocyte-macrophage colony-stimulating factor, lesser amounts of interleukin (IL)-2 and tumor necrosis factor-alpha, and little or no IL-4 and IL-10. Clones also demonstrated recognition of human leukocyte antigen-matched melanomas using cytokine secretion and lysis assays. Twelve patients received 2 cycles of cells alone; 11 patients received additional cycles of cells and were randomized between two schedules of IL-2 (125,000 IU/kg subcutaneously daily for 12 days versus 720,000 IU/kg intravenously every 8 h for 4 days). A total of 51 cycles of cells were administered, with an average of 1 x 10(10) cells per cycle. Peripheral blood samples were analyzed for persistence of transferred cells by T-cell receptor-specific polymerase chain reaction. Transferred cells reached a maximum level at 1 h after transfer but rapidly declined to undetectable levels by 2 weeks. One minor response and one mixed response were observed (both in the high-dose IL-2 arm). This report demonstrates the safety and feasibility of cloned T-cell transfer as a therapy for patients with cancer. The lack of clinical effectiveness of this protocol suggests that transfer of different or additional cell types or that modulation of the recipient host environment is required for successful therapy.