gebhart/patrepeval huggingface dataset:
Clinical review: severe asthma. (2002)

Severe asthma, although difficult to define, includes all cases of difficult/therapy-resistant disease of all age groups and bears the largest part of morbidity and mortality from asthma. Acute, severe asthma, status asthmaticus, is the more or less rapid but severe asthmatic exacerbation that may not respond to the usual medical treatment. The narrowing of airways causes ventilation perfusion imbalance, lung hyperinflation, and increased work of breathing that may lead to ventilatory muscle fatigue and life-threatening respiratory failure. Treatment for acute, severe asthma includes the administration of oxygen, beta2-agonists (by continuous or repetitive nebulisation), and systemic corticosteroids. Subcutaneous administration of epinephrine or terbutaline should be considered in patients not responding adequately to continuous nebulisation, in those unable to cooperate, and in intubated patients not responding to inhaled therapy. The exact time to intubate a patient in status asthmaticus is based mainly on clinical judgment, but intubation should not be delayed once it is deemed necessary. Mechanical ventilation in status asthmaticus supports gas-exchange and unloads ventilatory muscles until aggressive medical treatment improves the functional status of the patient. Patients intubated and mechanically ventilated should be appropriately sedated, but paralytic agents should be avoided. Permissive hypercapnia, increase in expiratory time, and promotion of patient-ventilator synchronism are the mainstay in mechanical ventilation of status asthmaticus. Close monitoring of the patient's condition is necessary to obviate complications and to identify the appropriate time for weaning. Finally, after successful treatment and prior to discharge, a careful strategy for prevention of subsequent asthma attacks is imperative.
GaN enhancement/depletion-mode FET logic for mixed signal applications (2005)

The first demonstration of enhancement/depletion (E/D)-mode integrated digital circuits in GaN technology is reported. Specifically, the performance of static divide by 2 circuit implemented in direct coupled FET logic and of a 23-stage ring oscillator, implemented in super-buffered FET logic are presented. The reported E/D technology is potentially suitable for fabrication of mixed signal GaN circuits.
The EBV IL-10 homologue is a selective agonist with impaired binding to the IL-10 receptor (1997)

BCRF1 is an EBV homologue of human IL-10 (hIL-10) and is known as viral IL-10 (vIL-10). As found earlier for the effects of vIL-10 on mouse mast cells and CD4+ T cells, the efficiency of inhibition by vIL-10 of IL-2 production by human CD4+ T cell clones is approximately 1000-fold diminished compared with hIL-10. We studied the interaction of vIL-10 and an epitope-tagged homologue, vIL-10His6, with recombinant mouse and human IL-10 receptors (mIL-10R, hIL-10R). vIL-10His6 has approximately 1000-fold lower affinity for recombinant IL-10R than does hIL-10, yet stimulates proliferation of mouse Ba/F3 (BaF)-mIL-10R- and human TF1-hIL-10R-transfected cells with a sp. act. comparable to or greater than that of the cellular cytokine. In contrast, BaF-hIL-10R cells are approximately 1000-fold less sensitive to vIL-10His6 than are BaF-mIL-10R cells. An anti-hIL-10R mAb (3F9) blocks responses to both hIL-10 and vIL-10His6, while a soluble form of hIL-10R effectively neutralizes biologic responses only to hIL-10 by both BaF-IL-10R transfectants and normal human peripheral blood cells. The results indicate that biologic responses to both hIL-10 and vIL-10 require the known IL-10R, and suggest the existence of at least one additional IL-10R subunit. We suggest that vIL-10 is a selective agonist that is impaired in its ability to bind the defined IL-10R, which we now designate as IL-10R alpha.
The outer membrane permeability-increasing action of linear analogues of polymyxin B nonapeptide. (1991)

Polymyxin nonapeptides such as polymyxin B nonapeptide (PMBN) are polymyxin-derived deacylated nonapeptides which contain a heptapeptide ring and are known as effective permeabilizers of the outer membrane (OM) of Gram-negative bacteria. In order to assess the role of the cyclic moiety of PMBN in the permeabilization of the OM, the author compared the OM permeabilizing activity of two synthetic linear PMBN analogues with the well-characterized activity of PMBN. While a low concentration (1-3 micrograms/ml) of PMBN was sufficient to sensitize both Escherichia coli and Pseudomonas aeruginosa to hydrophobic probe antibiotics (rifampin, fusidic acid) by a factor of 100, even a high concentration (100 micrograms/ml) of linear arginyl polymyxin B decapeptide sensitized E. coli only by a factor of 3 and did not sensitize P. aeruginosa at all. In identical assays, linear lysyl polymyxin B nonapeptide completely lacked any sensitizing activity. These findings indicate that the cyclic peptide ring is crucial for the OM-permeabilizing activity of polymyxin nonapeptides.
Mutation detection using fluorescent enzyme mismatch cleavage with T4 endonuclease VII (1999)

Mutation detection techniques are often limited by sensitivity, ease of use and short fragment lengths. Enzyme mismatch cleavage (EMC) is a technique capable of rapidly scanning 1 kbp fragments of DNA for mutations. It relies on the ability of a bacteriophage resolvase enzyme, T4 endonuclease VII, to cleave DNA at single base pair mismatches and small heteroduplex loops. Originally the process was performed using radioactively labeled DNA and the results analysed after denaturing polyacrylamide gel electrophoresis and autoradiography. However, access to systems capable of detecting fluorescent species migrating through a gel and the widespread availability of fluorescently tagged primers have greatly improved upon the original technique. A number of mutations were detected using fluorescent EMC and the results compared to performing the technique using radiolabeled DNA. Fluorescent EMC detected the presence, position and number of mutations in DNA fragments as large as 1 kbp. The fluorescent method was found to have advantages over the original method in its ease of use, increase in signal-to-noise ratio and the ability to multiplex samples by labeling DNA fragments with different fluorophores. This improvement on an already established method provides a sensitive, robust technique for mutation detection.
Dual origin of the floor plate in the avian embryo (2002)

Molecular analysis carried out on quail-chick chimeras, in which quail Hensen's node was substituted for its chick counterpart at the five- to six-somite stage (ss), showed that the floor plate of the avian neural tube is composed of distinct areas: (1) a median one (medial floor plate or MFP) derived from Hensen's node and characterised by the same gene expression pattern as the node cells (i.e. expression of HNF3beta and Shh to the exclusion of genes early expressed in the neural ectoderm such as CSox1); and (2) lateral regions that are differentiated from the neuralised ectoderm (CSox1 positive) and form the lateral floor plate (LFP). LFP cells are induced by the MFP to express HNF3beta transiently, Shh continuously and other floor-plate characteristic genes such as NETRIN: In contrast to MFP cells, LFP cells also express neural markers such as Nkx2.2 and Sim1. This pattern of avian floor-plate development presents some similarities to floor-plate formation in zebrafish embryos. We also demonstrate that, although MFP and LFP have different embryonic origins in normal development, one can experimentally obtain a complete floor plate in the neural epithelium by the inductive action of either a notochord or a MFP. The competence of the neuroepithelium to respond to notochord or MFP signals is restricted to a short time window, as only the posterior-most region of the neural plate of embryos younger than 15 ss is able to differentiate a complete floor plate comprising MFP and LFP. Moreover, MFP differentiation requires between 4 and 5 days of exposure to the inducing tissues. Under the same conditions LFP and SHH-producing cells only induce LFP-type cells. These results show that the capacity to induce a complete floor plate is restricted to node-derived tissues and probably involves a still unknown factor that is not SHH, the latter being able to induce only LFP characteristics in neuralised epithelium.
Prolonged signaling at the parathyroid hormone receptor by peptide ligands targeted to a specific receptor conformation (2008)

The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both the amino-terminal extracellular (N) domain, and transmembrane/extracellular loop, or juxtamembrane (J) regions of the receptor. Recently, we found that PTH(1-34), but not PTH-related protein, PTHrP(1-36), or M-PTH(1-14) (M = Ala/Aib(1),Aib(3),Gln(10),Har(11),Ala(12),Trp(14),Arg(19)), binds to the PTHR in a largely GTPgammaS-resistant fashion, suggesting selective binding to a novel, high-affinity conformation (R(0)), distinct from the GTPgammaS-sensitive conformation (RG). We examined the effects in vitro and in vivo of introducing the M substitutions, which enhance interaction to the J domain, into PTH analogs extended C-terminally to incorporate residues involved in the N domain interaction. As compared with PTH(1-34), M-PTH(1-28) and M-PTH(1-34) bound to R(0) with higher affinity, produced more sustained cAMP responses in cells, formed more stable complexes with the PTHR in FRET and subcellular localization assays, and induced more prolonged calcemic and phosphate responses in mice. Moreover, after 2 weeks of daily injection in mice, M-PTH(1-34) induced larger increases in trabecular bone volume and greater increases in cortical bone turnover, than did PTH(1-34). Thus, the putative R(0) PTHR conformation can form highly stable complexes with certain PTH ligand analogs and thereby mediate surprisingly prolonged signaling responses in bone and/or kidney PTH target cells. Controlling, via ligand analog design, the selectivity with which a PTH ligand binds to R(0), versus RG, may be a strategy for optimizing signaling duration time, and hence therapeutic efficacy, of PTHR agonist ligands.
Brief introduction of the primary aluminium industry of China (2013)

This paper analyses the main problems faced in the development of China primary aluminium industry recently, based on the present situation of Chinese bauxite, alumina and primary aluminium production chain. These are related to two key elements of bauxite and electricity supply which effects its development. The author puts forward some constructive opinions on the developing trends and direction.
Enzymic polymerisation of an unactivated diol/diacid system (1993)

The polyesterification of adipic acid and butane-1,4-diol by a commercial lipase (Lipozyme IM-20) has been studied using a two-chamber reactor and molecular sieve as a dehydrating agent. The lower oligomeric products were identified and a low-dispersity polyester averaging 20 repeat units was produced.
Calcium-dependent proteolysis of actin during storage of platelet concentrates (1989)

In an ongoing study of the changes that occur in platelet concentrates during storage, we investigated two 28–26-Kd proteins designated SP–1 and SP–2, respectively, which increase markedly during blood-bank storage of platelet concentrates at room temperature. Formation of SP–1 and SP–2 was inhibited by storage at 4 degrees C as well as by treatment of the concentrates with leupeptin, N–ethylmaleimide, and EDTA; DFP and PPACK had no effect. The calcium ionophore A23187 markedly stimulated production of SP–1 and SP–2. After partial purification, the two proteins were found to be associated with platelet cytoskeletal protein. Two-dimensional peptide mapping and amino acid sequencing identified SP-1 and SP-2 as fragments of actin formed by cleavage on the N-terminal side of residues Thr–106 and Ala- 114, respectively. Generation of SP–1 and SP–2 during storage of platelet concentrate is likely attributable to calcium-dependent neutral protease degradation of actin and may have implications for development of the platelet storage lesion.
Interaction of lipoprotein lipase with native and modified heparin-like polysaccharides (1980)

1. Lipoprotein lipase (EC 3.1.1.34), which was previously shown to bind to immobilized heparin, was now found to bind also to heparan sulphate and dermatan sulphate and to some extent to chondroitin sulphate. 2. The relative binding affinities were compared by determining (a) the concentration of NaCl required to release the enzyme from polysaccharide-substituted Sepharose; (b) the concentration of free polysaccharides required to displace the enzyme from immobilized polysaccharides; and (c) the total amounts of enzyme bound after saturation of immobilized polysaccharides. By each of these criteria heparin bound the enzyme most efficiently, followed by heparan sulphate and dermatan sulphate, which were more efficient than chondroitin sulphate. 3. Heparin fractions with high and low affinity for antithrombin, respectively, did not differ with regard to affinity for lipoprotein lipase. 4. Partially N-desulphated heparin (40–50% of N-unsubstituted glucosamine residues) was unable to displace lipoprotein lipase from immobilized heparin. This ability was restored by re-N-sulphation or by N-acetylation; the N-acetylated product was essentially devoid of anticoagulant activity. 5. Partial depolymerization of heparin led to a decrease in ability to displace lipoprotein lipase from heparin–Sepharose; however, even fragments of less than decasaccharide size showed definite enzyme-releasing activity. 6. Studies with hepatic lipase (purified from rat post-heparin plasma) gave results similar to those obtained with milk lipoprotein lipase. However, the interaction between the hepatic lipase and the glycosaminoglycans was weaker and was abolished at lower concentrations of NaCl. 7. The ability of the polysaccharides to release lipoprotein lipase to the circulating blood after intravenous injection into rats essentially conformed to their affinity for the enzyme as evaluated by the experiments in vitro.
Biologic and molecular characterization of non-Hodgkinʼs lymphoma (1993)

The wide clinicopathologic heterogeneity of non-Hodgkin's lymphoma is reflected by the various molecular pathways underlying non-Hodgkin's lymphoma pathogenesis, including activation of dominantly acting oncogenes, deletion and inactivation of tumor-suppressor genes, viral infection, deregulation of cytokine networks, and chronic antigenic stimulation. Molecular lesions involving protooncogenes include activation of bcl-2 and bcl-1 in specific subsets of low-grade non-Hodgkin's lymphomas and c-myc in a proportion of intermediate- and high-grade non-Hodgkin's lymphomas. The deregulation of these genes promotes cell growth or protects the tumor population from programmed cell death, or both. Additional genetic abnormalities representing putative sites of novel oncogenes contributing to lymphomagenesis include chromosomal breaks at 3q27 in intermediate-grade non-Hodgkin's lymphoma and at 9p13 in small lymphocytic lymphoma. The role of inactivation of tumor-suppressor loci is best exemplified by the frequent inactivation of p53 in Burkitt's lymphoma and by the recurrent deletion of 6q25-q27 and 6q21-q23 in intermediate- and high-grade non-Hodgkin's lymphoma, respectively. Infection by Epstein-Barr virus occurs in a variable fraction of high-grade non-Hodgkin's lymphomas, whereas it is usually absent in other types of non-Hodgkin's lymphoma. Other mechanisms supporting non-Hodgkin's lymphoma growth and development include autocrine or paracrine cytokine loops, or both, and clonal expansion through antigen receptor stimulation. The heterogeneity of non-Hodgkin's lymphoma pathogenesis provides a framework for the development of novel classification methods of potential clinical relevance.
Shooting over the seismic spread (2017)

Conventional marine seismic surveys typically mobilize a single vessel towing two airgun source arrays in front of a spread of ten or more streamers. The data acquired in this way are narrow-azimuth and lack near offsets owing to the distance between the sources and the streamers which can be in the range of 100 to 200 m for the inner cables and up to 500 m for the outer cables. Several solutions, such as coil shooting (French, 1984; Ross, 2008) or advanced multi-vessel operations (Mandroux et al., 2013), have been proposed and deployed to improve azimuth coverage and fold. Although these are excellent solutions for achieving wide-azimuth data, they are generally expensive and/ or time-consuming, and none of them record zero-offset data. Near- and zero-offset data are, however, especially critical for imaging shallow geological targets and of great benefit for multiple attenuation. In this paper, we present a tailored solution to this challenge that allows the recording of both zero-offset data and dual azimuths in an effective and safe way. We call this acquisition solution TopSeis. This solution was created in close co-operation between Lundin Norway and CGG and is designed to deliver excellent broadband (2.5-200 Hz) imaging of shallow to intermediate targets at depths of up to 3000 m or more.
Antifungal antibodies: a new approach to the treatment of systemic candidiasis. (2001)

Antibody-based therapeutics have come of age, with advances in the genetic engineering of recombinant antibodies allowing application of a growing knowledge of the immunopathology of diseases to the development of novel drugs. For infections such as systemic candidiasis, which still have a mortality of 40 to 50%, antifungal antibodies could provide long-awaited novel therapies for use in combination with antifungal agents. They may also evolve into safe, broad-spectrum agents for prophylaxis in high-risk immunocompromised patients. Mycograb, a human genetically recombinant antibody against heat shock protein 90 (hsp90), has just started trials in patients with systemic candidiasis.
Options for Radionuclide Therapy: From Fixed Activity to Patient-Specific Treatment Planning (2002)

The therapeutic use of radioisotopes in medicine as unsealed sources has a long history dating back to the 1930s. The established and continuing objectives are to provide radiation dose to the target tissue at the desired cytotoxic level while avoiding or minimizing toxic effects. Selected radionuclide therapy protocols including 32P for polycythemia vera, 131I for Graves' disease, and 131I for postsurgical ablation of thyroid remnants in the management of differentiated thyroid cancer are presented for historical review with the focus on protocols for administering the radiopharmaceuticals and the role played by dosimetry. The discussion also includes consideration of complications and the assessment of outcome for these diseases. The vista for radionuclide therapy today is reviewed along with the options for determining the administered activity. Patient specific dosimetry encompasses a number of levels ranging from basic measurement of relevant biokinetic parameters and use of standard models to calculate (and extrapolate) radiation dose to sophisticated three-dimensional techniques employing fusion of physiologic and high-resolution anatomic images coupled with advanced 3-D voxel patient representation and Monte Carlo techniques for use in radiation dose calculation. The role of patient specific dosimetry in clinical trials (Phase I, II, III trials) along with its utility in treatment planning, follow-up evaluation, and elucidation of dose-response relationships is discussed. The challenge ahead for those who advocate patient specific dosimetry is to assemble the outcome data and perform the analysis to support this contention.
Bioabsorbable Polymers for Implantable Therapeutic Systems (1998)

For a long time, subcutaneous implantable drug pellets using nondegradable polymers have been used for long-term, continuous drug administration. The procedure requires surgical implantation and removal of the drug-containing devices or polymeric matrices, which has a significant negative impact on the acceptability of the product candidate. In addition, the release profile from such devices is neither constant nor readily controlled in terms of precision of rate of release and duration of action. These facts have led to the research and development of novel, controllable, nonirritating, noncarcinogenic, biocompatible, and bioabsorbable drug delivery systems for overcoming the drawbacks of nondegradable implantable pellets for prolonged continuous release. Biodegradable implantable systems release the drug over a long period of time with simultaneous or subsequent degradation in the tissue of the polymer to harmless constituents, thus avoiding removal once the therapy is complete. This approach has considerably improved patient acceptability and patient compliance. Various bioabsorbable polymers have been evaluated for controlled implantable drug delivery, including hydrogels, copolymers of polylactic and polyglycolic acids, polylactic acid, poly(orthoesters), polyanhydrides, poly(E-caprolactone), and polyurethanes. Their characteristics have been studied using a variety of drugs, like anticancer agents, hormone agonists and antagonists, nonsteroidal anti-inflammatory agents, neuroleptics, contraceptives, and others. The present paper describes the current research on implantable therapeutic systems, the bioabsorbable polymers, and the biologically active agents being used in this approach.
The Cleavage of Esters of Inorganic Acids (2003)

This chapter contains sections titled: Introduction De-esterification of Organic Nitrates and Nitrites Introduction In vivo Metabolism Mechanisms of Cleavage Chemical Hydrolysis of Organic Nitrates Chemical Hydrolysis of Organic Nitrites Thiol-Dependent Cleavage of Organic Nitrates and Nitrites Hemoprotein-Dependent Reductive Cleavage of Organic Nitrates and Nitrites Hydrolysis and Oxidative Cleavage of Organophosphates Introduction Hydrolysis of Medicinal Phosphoric Acid Alkyl and Aryl Monoesters Hydrolysis of Medicinal Phosphoric Acid Diesters and Triesters Cleavage of Industrial Phosphoric Acid Triesters Cleavage of Phosphonates Cleavage of Phosphorothioates and Phosphonothioates Hydrolysis of Phosphoramidates and P-Halide Compounds Hydrolysis of Sulfuric Acid Esters and Related Compounds Introduction Sulfuric Acid Esters Related Compounds
Evaluation of Protection Afforded by Brucella abortus and Brucella melitensis Unmarked Deletion Mutants Exhibiting Different Rates of Clearance in BALB/c Mice (2006)

Research for novel Brucella vaccines has focused upon the development of live vaccine strains, which have proven more efficacious than killed or subunit vaccines. In an effort to develop improved vaccines, signature-tagged mutant banks were screened to identify mutants attenuated for survival. Mutants selected from these screens exhibited various degrees of attenuation characterized by the rate of clearance, ranging from a failure to grow in macrophages after 24 h of infection to a failure to persist in the mouse model beyond 8 weeks. Ideal vaccine candidates should be safe to the host, while evoking protective immunity. In the present work, we constructed unmarked deletion mutants of three gene candidates, manBA, virB2, and asp24, in both Brucella abortus and Brucella melitensis. The Deltaasp24 mutants, which persist for extended periods in vivo, are superior to current vaccine strains and to other deletion strains tested in the mouse model against homologous challenge infection after 12, 16, and 20 weeks postvaccination. The Deltaasp24 mutants also display superior protection compared to DeltamanBA and DeltavirB2 mutants against heterologous challenge in mice. From this study, a direct association between protection against infection and cytokine response was not apparent between all vaccine groups and, therefore, correlates of protective immunity will need to be considered further. A distinct correlation between persistence of the vaccine strain and protection against infection was corroborated.