gebhart/patrepeval huggingface dataset:
Neurons in the Rat Arcuate Nucleus Are Hyperpolarized by GABA<sub>B</sub> and μ-Opioid Receptor Agonists: Evidence for Convergence at a Ligand-Gated Potassium Conductance (1991)

Both gamma-aminobutyric acid (GABA) and the endogenous opioid peptides have pervasive effects on neuroendocrine function. This study examined the effects of selective activation of GABAB and/or mu-opioid receptors on neurons of the arcuate nucelus (ARC) of the rat hypothalamus using intracellular recording of cells in a hypothalamic slice. Some recorded neurons were filled with biocytin allowing subsequent identification and immunocytochemical evaluation for the presence of beta-endorphin. ARC neurons exhibited a broad array of active and passive conductances. Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGOL), a mu-opioid receptor agonist, inhibited spontaneous firing, hyperpolarized 68% of ARC cells in a dose-dependent manner and increased cell conductance. Baclofen, a GABAB receptor agonist, hyperpolarized all cells tested. The reversal potentials for both the DAGOL- and baclofen-induced currents were near that of a potassium conductance. Maximal activation by either of the agonists blocked the effects of the other agonist. Identified beta-endorphin cells were inhibited by both DAGOL and baclofen. The results of these in vitro studies suggest that GABAB and mu-opioid receptors are coupled to the same set of potassium channels and that these channels directly and powerfully inhibit most ARC cells, including beta-endorphin neurons. We propose that convergence of inhibitory influences at the ligand-gated potassium conductance described here may be an important site of interaction for opioidergic, GABAergic and other putative neurotransmitter systems in the control of neuroendocrine circuits by the ARC.
Health and disease (1994)

Journal Article Health and disease Get access Cardiovascular Research, Volume 28, Issue 12, December 1994, Page 1747, https://doi.org/10.1093/cvr/28.12.1747 Published: 01 December 1994
Colony-Stimulating Factor-1 Antibody Reverses Chemoresistance in Human MCF-7 Breast Cancer Xenografts (2006)

Overexpression of colony-stimulating factor-1 (CSF-1) and its receptor in breast cancer is correlated with poor prognosis. Based on the hypothesis that blockade of CSF-1 would be beneficial in breast cancer treatment, we developed a murinized, polyethylene glycol-linked antigen-binding fragment (Fab) against mouse (host) CSF-1 (anti-CSF-1 Fab). Mice bearing human, chemoresistant MCF-7 breast cancer xenografts were treated with combination chemotherapy (CMF: cyclophosphamide, methotrexate, 5-fluorouracil; cycled twice i.p.), anti-CSF-1 Fab (i.p., cycled every 3 days for 14 days), combined CMF and anti-CSF-1 Fab, or with Ringer's solution as a control. Anti-CSF-1 Fab alone suppressed tissue CSF-1 and retarded tumor growth by 40%. Importantly, in combination with CMF, anti-CSF-1 Fab reversed chemoresistance of MCF-7 xenografts, suppressing tumor development by 56%, down-regulating expression of the chemoresistance genes breast cancer-related protein, multidrug resistance gene 1, and glucosylceramide synthase, and prolonging survival significantly. Combined treatment also reduced angiogenesis and macrophage recruitment and down-regulated tumor matrix metalloproteinase-2 (MMP-2) and MMP-12 expression. These studies support the paradigm of CSF-1 blockade in the treatment of solid tumors and show that anti-CSF-1 antibodies are potential therapeutic agents for the treatment of mammary cancer.
GlcNAcstatin:  a Picomolar, Selective O-GlcNAcase Inhibitor That Modulates Intracellular O-GlcNAcylation Levels (2006)

Many phosphorylation signal transduction pathways in the eukaryotic cell are modulated by posttranslational modification of specific serines/threonines with N-acetylglucosamine (O-GlcNAc). Levels of O-GlcNAc on key proteins regulate biological processes as diverse as the cell cycle, insulin signaling, and protein degradation. The two enzymes involved in this dynamic and abundant modification are the O-GlcNAc transferase and O-GlcNAcase. Structural data have recently revealed that the O-GlcNAcase possesses an active site with significant structural similarity to that of the human lysosomal hexosaminidases HexA/HexB. PUGNAc, an O-GlcNAcase inhibitor widely used to raise levels of O-GlcNAc in human cell lines, also inhibits these hexosaminidases. Here, we have exploited recent structural information of an O-GlcNAcase-PUGNAc complex to design and synthesize a glucoimidazole-based inhibitor, GlcNAcstatin, which is a 5 pM competitive inhibitor of enzymes of the O-GlcNAcase family, shows 100000-fold selectivity over HexA/B, and binds to the O-GlcNAcase active site by mimicking the transition state as revealed by X-ray crystallography. This compound is able to raise O-GlcNAc levels in human HEK 293 and SH-SY5Y neuroblastoma cell lines and thus provides a novel, potent tool for the study of the role of O-GlcNAc in intracellular signal transduction pathways.
ESGE–ESGENA guideline: Cleaning and disinfection in gastrointestinal endoscopy (2008)

FIGURE 15. Scolelepis magnicornuta sp. n. A–H, paratypes (USNM 1096810) SEM micrographs. A, anterior end, lateral view; B, anterior end, lateral view (palps missing); C, anterior end, dorsal view; D, occipital tentacle (arrowhead shows cilia on side of tentacle); E, middle region of palp, frontal view (arrowhead indicates faint division in transverse rows of cilia; short rows top, long rows bottom); F, setigers 10–15 (right to left), lateral view; G, setigers 30–33 (right to left), lateral view (arrowhead indicates lateral organ); H, pygidium, dorsal view. Scale bars: A–C = 500 µm; D = 100 µm; E = 50 µm; F–H = 250 µm.
Reduced responsiveness of bone marrow megakaryocyte progenitors to platelet‐derived transforming growth factor β1, produced in normal amount, in patients with essential thrombocythaemia (1993)

In this study we evaluated the amount of transforming growth factor-beta 1 (TGF-beta 1) in platelet lysates obtained from 12 patients affected by essential thrombocythaemia (ET) in comparison with five patients affected by myelofibrosis with myeloid metaplasia (MMM) and 15 healthy donors. The levels of both bioactive and latent TGF-beta 1, evaluated in a bioassay on CCL64 cells, before and after transient acidification, were similar in platelet lysates from ET patients and normal donors and significantly (P < 0.01) elevated in platelet lysates from MMM patients. Moreover, platelet lysates from ET patients and normal controls, showed a similar degree of colony suppression when tested on haematopoietic progenitor (CD34+) cells, purified from normal bone marrows, whereas platelet lysates from MMM patients showed a higher (P < 0.01) inhibitory activity on normal CFU-meg and BFU-E growth. In parallel, platelet lysates form ET patients and normal controls were tested on CD34+ cells, purified from ET bone marrows. ET bone marrow BFU-E, similarly to normal bone marrow BFU-E, were markedly inhibited by platelet lysates, whereas ET bone marrow CFU-meg were significantly (P < 0.05) less responsive to the inhibitory activity of platelet lysates than normal bone marrow CFU-meg. The main factor responsible for the inhibitory activity contained in platelet lysates was transforming growth factor-beta 1 (TGF-beta 1), as demonstrated by the ability of a polyclonal neutralizing anti-TGF-beta 1 antibody to almost completely reverse the suppressive effect of platelet lysates on CFU-meg and BFU-E growth. Our data demonstrate that the amount of intraplatelet TGF-beta 1 is similar in ET patients and normal controls, whereas it is increased in platelets from MMM patients. Moreover, megakaryocyte progenitors in ET show a reduced sensitivity to platelet-derived inhibitors and, in particular, to TGF-beta 1.
Perfluorochemical Emulsions Can Increase Tumor Radiosensitivity (1984)

An oxygen-carrying perfluorochemical emulsion enhanced the effectiveness of radiation therapy in two transplantable solid tumors in mice. The perfluorochemical emulsion had no effect on tumor growth after x-irradiation, but delayed tumor growth significantly when administered to oxygen-breathing mice before or during irradiation.
Use of carbohydrate derivatives for studies of phosphorus stereochemistry. Part II. Synthesis and configurational assignments of 1,-3,2-oxathiaphosphorinan-2-ones and 1,3,2-dioxaphosphorinan-2-thiones (1974)

Methyl 2,3-di-O-methyl-4(or 6)-thio-α-D-glucopyranoside (R)- and (S)-4,6-methylphosphonothioates and methyl 2,3-di-O-methyl-α-D-glucopyranoside (R)- and (S)-4,6-methyl-(and phenyl)-phosphonothioates have been prepared by conventional procedures. The corresponding ethyl phosphorothioates are also described. The configuration at phosphorus in the thiolates has been assigned on the basis of n.m.r. and i.r. data. The thioxo-compounds have been correlated chemically with the corresponding phosphates of previously determined configuration. The preparation of methyl 2,3-di-O-methyl-4(and 6)-thio-α-D-glucopyranosides is described.
Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer (2005)

Real-time in vivo CT scanning of CED of iopamidol appears to be safe, feasible, and suitable for monitoring convective delivery of drugs with certain features and low infusion volumes.
IL-2 Receptor-Targeted Cytolytic IL-2/Fc Fusion Protein Treatment Blocks Diabetogenic Autoimmunity in Nonobese Diabetic Mice (1999)

High affinity IL-2R5 is present on recently activated but not on resting or memory T cells. Selective targeting of T cells bearing high affinity IL-2R is an attractive therapy for many T cell-dependent cytopathic disease processes. A variety of rodent mAbs directed against the alpha-chain of the IL-2R, as well as IL-2 fusion toxins, have been used in animals and humans to achieve selective immunosuppression. Here we report on the development of a novel IL-2R targeting agent, a cytolytic chimeric IL-2/Fc fusion protein. This immunoligand binds specifically and with high affinity to IL-2R and is structurally capable of recruiting host Ab-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity activities. The Ig component ensures an extended circulating t1/2 of 25 h following systemic administration. To subsequently explore the mechanisms of the antidiabetogenic effects of IL-2/Fc, we have mutated the FcR binding and complement C1q binding (Fc-/-) domains of the Fc fragment to render the Fc unable to direct Ab-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity activities. In a model of passive transfer of diabetes in nonobese diabetic mice, lytic IL-2/Fc, but not nonlytic IL-2/Fc-/-, exhibited striking antidiabetogenic effects. Together with the negligible potential of IL-2/Fc for immunogenicity, this finding forecasts that cytolytic IL-2/Fc may offer a new therapeutic approach for selective targeting of auto and alloimmune T cells.
The predictive value of anti-cyclic citrullinated peptide antibodies in early arthritis. (2003)

Anti-CCP positivity has a small additional value above the conventional prognostic variables for progressive erosive disease in a cohort of patients with early inflammatory oligo- and polyarthritis. The prognostic value of anti-CCP lies mainly in its ability to predict mild disease. This effect is accentuated in the subgroup of IgM-RF negative patients.
Derivation and Validation of a Simplified Predictive Index for Renal Replacement Therapy After Cardiac Surgery (2007)

RRT after cardiac surgery is predicted by readily available preoperative information. A simple predictive index based on this information discriminated well between low- and high-risk patients in derivation and validation cohorts. The index had improved generalizability when used to predict likelihood ratios for RRT.
Hepatocellular Transplantation for Metabolic Deficiencies: Decrease of Plasma Bilirubin in Gunn Rats (1976)

A sustained decrease of plasma bilirubin concentrations occurred in homozygous recessive Gunn rats lacking the enzyme uridine diphosphate glucuronyltransferase following infusion into the portal vein of hepatocytes from heterozygous nonjaundiced Gunn rats possessing the enzyme. Transplantation of cells capable of continuous enzyme production could be an effective mode of therapy for congenital enzyme deficiency diseases.
INDUCTION OF ANTI-TUMOR IMMUNITY BY MOUSE TUMOR CELLS TRANSFECTED WITH MOUSE INTERLEUKIN-12 GENE (1995)

Interleukin-12 (IL-12) is a heterodimeric cytokine. In order to transduce both cDNAs for p35 and p40 of IL-12 in the tumor cells, a polycistronic retroviral vector was constructed by inserting the internal ribosome entry site gene of encephalomyocarditis virus between two cDNAs. On the other hand, two cDNAs were sequentially transfected in the tumor cells. Both polycistronic gene transfectants and double transfectants produced biologically active mouse IL-12. IL-12-expressing tumor cells were all rejected in syngeneic mice, and induced cytotoxic T lymphocyte activity. The capacity to induce anti-tumor memory may depend on the amount of IL-12 produced by the transfectants, because the relatively higher IL-12 producer tumor cell line induced the anti-tumor memory in the rejected mice, but the lower producer did not.
<title>Micromachined acoustic matching layers</title> (1992)

Efficient coupling of acoustic energy between different media requires fabrication of materials with precisely controlled acoustic properties. Current materials are formed by suspending particles in an epoxy matrix. Last year, we proposed a technique for making such materials using silicon micromachining. This paper describes the fabrication procedure and acoustic measurements of these materials and their applications. The acoustic properties of the composite materials described in this paper depend on the volume fraction of silicon, and the material used for the other phase of the composite. We investigated two different fillers, epoxy resin and RTV. Silicon structures with graded volume fractions were fabricated to provide broader bandwidth matching.
In vitro gamma‐secretase cleavage of the Alzheimer's amyloid precursor protein correlates to a subset of presenilin complexes and is inhibited by zinc (2005)

The gamma-secretase complex mediates the final proteolytic event in Alzheimer's disease amyloid-beta biogenesis. This membrane complex of presenilin, anterior pharynx defective, nicastrin, and presenilin enhancer-2 cleaves the C-terminal 99-amino acid fragment of the amyloid precursor protein intramembranously at gamma-sites to form C-terminally heterogeneous amyloid-beta and cleaves at an epsilon-site to release the intracellular domain or epsilon-C-terminal fragment. In this work, two novel in vitro gamma-secretase assays are developed to further explore the biochemical characteristics of gamma-secretase activity. During development of a bacterial expression system for a substrate based on the amyloid precursor protein C-terminal 99-amino acid sequence, fragments similar to amyloid-beta and an epsilon-C-terminal fragment were observed. Upon purification this substrate was used in parallel with a transfected source of substrate to measure gamma-secretase activity from detergent extracted membranes. With these systems, it was determined that recovery of size-fractionated cellular and tissue-derived gamma-secretase activity is dependent upon detergent concentration and that activity correlates to a subset of high molecular mass presenilin complexes. We also show that by changing the solvent environment with dimethyl sulfoxide, detection of epsilon-C-terminal fragments can be elevated. Lastly, we show that zinc causes an increase in the apparent molecular mass of an amyloid precursor protein gamma-secretase substrate and inhibits its cleavage. These studies further refine our knowledge of the complexes and biochemical factors needed for gamma-secretase activity and suggest a mechanism by which zinc dysregulation may contribute to Alzheimer's disease pathogenesis.
Remote powered data transmission system (2003)

The authors consider remote powered data transmission system issues. In the systems under consideration, two stations, one at the beginning and one at the end, provide energy and regenerate the signal; several peripheral stations are serially powered along the line. Particular attention is given to energy problems, cable and operator safety, and noise generation. The objective is to ensure a low BER transmission. The systems examined are well suited for use on roads and highways where they replace traditional devices that can be used to call for emergency assistance. In fact these systems not only send calls for help to the central host but also manage and transmit digital signals (vehicle identification contacts) and analog signals (coming from wind speed meters, ice sensors, or gas density sensors), improving the general control of a highway network.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Development of antibodies to protective antigen and lethal factor components of anthrax toxin in humans and guinea pigs and their relevance to protective immunity (1986)

A competitive inhibition enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies in serum to the protective antigen (PA) and lethal factor (LF) components of anthrax toxin. Current human vaccination schedules with an acellular vaccine induce predictable and lasting antibody titers to PA and, when present in the vaccine, to LF. Live spore vaccine administered to guinea pigs in a single dose conferred significantly better protection than the human vaccines (P less than 0.001), although they elicited significantly lower (P less than 0.0005) anti-PA and anti-LF titers at time of challenge with virulent Bacillus anthracis. Substantial anti-PA and anti-LF titers may not, therefore, indicate solid protective immunity against anthrax infection. The ELISA system was also shown to be capable of detecting anti-PA and anti-LF antibodies in the sera of individuals with histories of clinical anthrax. The advantage of ELISA over the Ouchterlony gel diffusion test and indirect microhemagglutination assay are demonstrated. There was a highly significant degree of correlation between ELISA and the indirect microhemagglutination assay (P less than 0.0005); but ELISA was markedly superior in terms of reproducibility, reliability, specificity, and simplicity in performance and stability of the bound antigen.
Investigation of annealing effects and film thickness dependence of polymer solar cells based on poly(3-hexylthiophene) (2005)

Regioregular poly(3-hexylthiophene) (RR-P3HT) is a promising candidate for polymer photovoltaic research due to its stability and absorption in the red region. In this manuscript, we report polymer photovoltaic devices based on RR-P3HT:methanofullerene [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) 1:1 weight-ratio blend. We studied the effects of annealing temperature and time on the device performance for devices annealed before and after cathode deposition. Thermal annealing shows significant improvement in the performance for both types of annealing conditions, with postproduction annealing being slightly better. For devices with a 43-nm-thick active layer, maximum power conversion efficiency (PCE) of 3.2% and fill factor up to 67% is achieved under Air Mass 1.5, 100-mW∕cm2 illumination. We performed atomic force microscopy and ultraviolet-visible absorption spectroscopy on the P3HT:PCBM films to explain the effect of thermal annealing. By keeping the optimized thermal annealing condition and by varying the active layer thickness, we fabricated devices with PCE up to 4.0%, which is the highest efficiency reported so far for this system.
A Vulnerability Life Cycle-Based Security Modeling and Evaluation Approach (2012)

This paper presents a probabilistic model-based approach aimed at evaluating quantitative measures to assess the security risks faced by an information system in operation. The proposed approach takes into account the impact of three environmental factors and their interdependencies: the vulnerability life cycle, the behavior of the attackers and the behavior of the system administrator. Several quantitative security measures are defined and evaluated. Two different scenarios are distinguished corresponding to the case where the system vulnerabilities are discovered by a malicious user or by a non malicious user. The proposed models are based on stochastic activity networks and describe the system states resulting from the combined modeling of the three external factors. Five states are distinguished (vulnerable, exposed, compromised, patched and secure) and probability measures are associated to these states to assess the level of risk faced by the system as a result of the vulnerability exploitation process. The parameters of the models, e.g. those characterizing the occurrence of vulnerability life cycle events, are derived from the analysis of public information recorded in vulnerability databases. Several sensitivity analyses are carried out for the two scenarios, in order to quantify and illustrate the impact of various parameters, including the probability of security patch application, the attack rate, etc.
Oligonucleotide-directed peptide synthesis in a ribosome- and ribozyme-free system (2001)

Peptide bond formation by the ribosome requires 23S rRNA and its interaction with the 3'-CCA end of tRNA. To investigate the possible evolutionary development of the peptidyl transfer reaction, we tried to obtain peptide bond formation without the ribosome or rRNA simply by using a piece of tRNA--an aminoacyl-minihelix--mixed with sequence-specific oligonucleotides that contained puromycin. Peptide bond formation was detected by gel electrophoresis, TLC analysis, and mass spectrometry. Peptide synthesis depended on sequence complementarity between the 3'-CCA sequence of the minihelix and the puromycin-bearing oligonucleotide. However, proximity of the reacting species was not by itself sufficient for peptide bond formation. In addition, imidazole as a catalyst was required. Its role may be similar to the recently proposed mechanism, wherein A2451 of 23S rRNA works as a general base. Thus, peptide bond formation can be achieved with a simple, minimized system that captures the essence of an interaction seen in the ribosome.
Free volume and intrinsic microporosity in polymers (2005)

The concept of free volume is useful for explaining aspects of the chain mobility and permeability of polymers, even though its precise definition is subject to debate. Polymers that trap a large amount of interconnected free volume in the glassy state behave in many respects like microporous materials and potentially find application in membrane separations and heterogeneous catalysis. The development is outlined of a new type of polymer, for which the molecular structure contains sites of contortion (e.g. spiro-centres) within a rigid backbone (e.g. ladder polymer). These polymers of intrinsic microporosity (PIMs) include both insoluble network polymers and soluble non-network polymers that may be processed into membranes or other useful forms. Experimental methods are discussed for elucidating the free volume or micropore distribution, and the behaviour of PIMs is compared with that of the ultrapermeable polymer poly(1-trimethylsilyl-1-propyne).
Density functional theory of molecular structure for thin diblock copolymer films on chemically heterogeneous surfaces (1999)

A density functional theoretical formalism is applied to study the ordering of block copolymers near patterned surfaces. This formalism is capable of resolving with molecular-level detail the structure of the system in the directions parallel and perpendicular to an interface. The results of theoretical predictions are in good agreement with those of molecular simulations. This formalism permits a systematic study of the effects of temperature, chain architecture, surface–polymer interaction energy, and pattern shape and size on the surface-induced ordering that occurs in systems consisting of block copolymers deposited on chemically heterogeneous surfaces.