gebhart/patrepeval huggingface dataset:
Treatments in Chronic Cholestasis in Children (2008)

Few specific treatments for children with chronic cholestasis are available. Most therapy strategies relieve bile component retention or palliate some of the consequences of chronic cholestasis. Ursodeoxycholic acid is the most frequently used pharmacological agent in children with chronic cholestasis. This bile acid is administered at dosages between 10 and 30 mg/kg/day to patients with cystic fibrosis, inborn errors of bile acid metabolism, progressive familial intrahepatic cholestasis, sclerosing cholangitis, biliary atresia, Alagille syndrome, or those receiving total parenteral nutrition. Ursodeoxycholic acid mainly increases bile flow and has a membrane-stabilizing effect, reducing the toxicity of more hydrophobic bile acids. Rifampicin, an antibiotic, at dosages between 10 and 20 mg/kg/day is very efficient in relieving pruritus. Similar effects are obtained using nonabsorbable ion exchange resins. In addition, these molecules decrease the serum cholesterol levels contributing to reduce xanthomas. Replacement of some deficiencies created by total parenteral nutrition by administration of essential fatty acids or cysteine can prevent or contribute to improve the associated liver disorders. In some cholestatic diseases, surgical procedures can help to relieve the obstacle to the bile flow, as it is the case for portoenterostomy in patients with biliary atresia. In cases of intrahepatic cholestasis, a clinical and biochemical improvement can be recorded after bile diversion or other procedure (ileum exclusion) limiting the absorption of bile acids by the intestine. In the future, the association of these different pharmacological agents, increasing the bile flow, protecting cell membranes, or restoring nutritional deficiencies, could contribute to an improvement in quality of life in children with chronic cholestasis and eventually delay the need of a more drastic therapy such as liver transplantation. Advances in gene therapy and hepatocyte transplantation could also be of great help; however, many years of intense research are still necessary before even a pilot study using one of these therapies can be considered on liver diseases resulting in chronic cholestasis.
The diverse CB1and CB2receptor pharmacology of three plant cannabinoids: Δ9‐tetrahydrocannabinol, cannabidiol and Δ9‐tetrahydrocannabivarin (2007)

Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (-)-trans-delta9-tetrahydrocannabinol (delta9-THC), (-)-cannabidiol (CBD) and (-)-trans-delta9-tetrahydrocannabivarin (delta9-THCV), interact with cannabinoid CB1 and CB2 receptors. Delta9-THC, the main psychotropic constituent of cannabis, is a CB1 and CB2 receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB1/CB2 receptor agonists in CB1- and CB2-expressing cells or tissues, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. Delta9-THCV behaves as a potent CB2 receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB1-expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. Delta9-THCV also interacts with CB1 receptors when administered in vivo, behaving either as a CB1 antagonist or, at higher doses, as a CB1 receptor agonist. Brief mention is also made in this review, first of the production by delta9-THC of pharmacodynamic tolerance, second of current knowledge about the extent to which delta9-THC, CBD and delta9-THCV interact with pharmacological targets other than CB1 or CB2 receptors, and third of actual and potential therapeutic applications for each of these cannabinoids.
Docetaxel (Taxotere) in HER-2-positive patients and in combination with trastuzumab (Herceptin). (2000)

In addition to being an important indicator of poor prognosis, human epidermal growth factor receptor-2 (HER-2) status may help identify those patients in whom chemotherapy is the most appropriate choice of therapy. In several studies, including a trial of sequential neoadjuvant therapy in which certain patients received docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) following four courses of cyclophophamide 1000 mg/m2, doxorubicin 50 mg/m2, vincristine 1.5 mg/m2 on day one, and prednisone 40 mg by mouth for 5 days, HER-2 positivity predicted response (including pathologic response) to chemotherapy. In vitro and in vivo, docetaxel has demonstrated true synergy with the recombinant human anti-HER-2 monoclonal antibody trastuzumab (Herceptin; Genentech, San Francisco, CA). In a phase III study comparing trastuzumab alone with trastuzumab plus chemotherapy (either paclitaxel or doxorubicin plus cyclophosphamide), combining the antibody with cytotoxic drugs increased response duration, time to progression, and survival in first-line metastatic breast cancer patients. Preliminary clinical data suggest that the combination of trastuzumab with docetaxel is active and well tolerated, and pilot studies of adjuvant therapy using trastuzumab and docetaxel combinations are under way in high-risk patients.
Recombinant insulinlike growth factor-I as therapy in states of altered carbohydrate homeostasis (1997)

Insulinlike growth factor-I (IGF-I) displays considerable structural and functional homology to insulin, as does its cognate receptor, which appears to utilize signal transduction molecules similar if not identical to those of the insulin receptor. Over the past several years, major emphasis has been placed on defining the range of biologic effects of IGF-I in vivo and in determining the physiologic consequences of interaction of IGF-I with a range of specific serum carrier proteins, the IGF binding proteins. Although early studies enrolled mainly healthy volunteers, recent studies have addressed the potential role of recombinant human IGF-I (rhIGF-I) as a therapeutic agent in a variety of clinical syndromes of altered carbohydrate homeostasis, including severe insulin resistance and types I and II diabetes mellitus. Initial studies demonstrated considerable efficacy for all of these conditions but raised concerns over the potential short-term toxicity of rhIGF-I, particularly in older individuals. Recent studies have concentrated on defining the doses of rhIGF-I that are well tolerated and provide therapeutic efficacy. Work also has concentrated on defining rhIGF-I's mechanisms of action. These more recent studies raise the possibility that rhIGF-I will be a useful addition to the treatment of diabetes mellitus.
TOLERANCE INDUCTION BY "MEGADOSE" HEMATOPOIETIC TRANSPLANTS (1998)

It is possible, that CD34+ cells in the megadose transplants-perhaps by their inability to provide costimulatory molecules-are actively reducing the frequency of CTL-p directed against their antigens, and thereby help to overcome allogeneic rejection, and enhance their own engraftment.
Recombinant Human Erythropoietin Prevents the Death of Mice during Cerebral Malaria (2006)

Cerebral involvement during malaria is a complication that leads to seizure, coma, and death. The effect of new neuroprotective therapies has not yet been investigated, although cerebral malaria shares some features with neurological stroke. Erythropoietin (EPO) is one of the more promising drugs in this area. We measured the effect of EPO on the survival of mice infected with Plasmodium berghei ANKA and demonstrated that inoculations of recombinant human EPO at the beginning of the clinical manifestations of cerebral malaria protect >90% of mice from death. This drug has no effect on the course of parasitemia. The effect of EPO was not related to either the inhibition of apoptosis in the brain or the regulation of the increase and decrease of nitric oxide production in the brain and blood, respectively. Tumor necrosis factor-alpha and interferon-gamma mRNA overexpression was inhibited by EPO, and treated mice had fewer brain hemorrhages. EPO has been used in patients with chronic diseases for years, and more recently it has been used to treat acute ischemic stroke. The data presented here provide the first evidence indicating that this cytokine could be useful for the symptomatic prevention of mortality during the acute stage of cerebral malaria.
Object oriented techniques for lifecycle modelling of complex control systems (1994)

The central concept of the work described is that a database can be created which contains all the information about a complex engineering system, specifically a building management system (BMS). This database will be updated and modified throughout the system lifecycle. Due to the large amount of information required to be entered into these databases, all data entry is done through graphical interfaces according to the maxim 'a picture is worth ten thousand words'. The user draws a picture of what is required, and this is then compiled into the desired database form. BMSs are used to control intelligent buildings. A BMS usually consists of a number of universal network controllers (outstations) which are connected together in a local area network (LAN), or wide area network (WAN). A number of PCs (terminals) can be connected to allow user access to the system for supervisory purposes. An outstation is connected to the hardware components which it controls and from where it gets its operating information. These components are called points; examples being sensors such as temperature, humidity, wind and solar effect, and actuators such as pumps, fans, valves, heating and cooling coils and humidifiers.
Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor (1997)

Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived, multifunctional paracrine regulator possessing mitogenic, motogenic, and morphogenetic activities in cultured epithelial cells containing its tyrosine kinase receptor, Met. c-met has been implicated in oncogenesis through correlation of expression with malignant phenotype in specific cell lines and tumors. Paradoxically, however, HGF/SF can also inhibit the growth of some tumor cells. To elucidate the oncogenic role of HGF/SF in vivo, transgenic mice were created such that HGF/SF was inappropriately targeted to a variety of tissues. HGF/SF transgenic mice developed a remarkably broad array of histologically distinct tumors of both mesenchymal and epithelial origin. Many neoplasms arose from tissues exhibiting abnormal development, including the mammary gland, skeletal muscle, and melanocytes, suggesting a functional link between mechanisms regulating morphogenesis and those promoting tumorigenesis. Most neoplasms, especially melanomas, demonstrated overexpression of both the HGF/SF transgene and endogenous c-met, and had enhanced Met kinase activity, strongly suggesting that autocrine signaling broadly promotes tumorigenesis. Thus, subversion of normal mesenchymal-epithelial paracrine regulation through the forced misdirection of HGF/SF expression induces aberrant morphogenesis and subsequent malignant transformation of cells of diverse origin.
A unified framework for optimizing communication in data-parallel programs (1996)

This paper presents a framework, based on global array data-flow analysis, to reduce communication costs in a program being compiled for a distributed memory machine. We introduce available section descriptor, a novel representation of communication involving array sections. This representation allows us to apply techniques for partial redundancy elimination to obtain powerful communication optimizations. With a single framework, we are able to capture optimizations like (1) vectorizing communication, (2) eliminating communication that is redundant on any control flow path, (3) reducing the amount of data being communicated, (4) reducing the number of processors to which data must be communicated, and (5) moving communication earlier to hide latency, and to subsume previous communication. We show that the bidirectional problem of eliminating partial redundancies can be decomposed into simpler unidirectional problems even in the context of an array section representation, which makes the analysis procedure more efficient. We present results from a preliminary implementation of this framework, which are extremely encouraging, and demonstrate the effectiveness of this analysis in improving the performance of programs.
Epitope Mapping of Bovine Leukemia Virus Transactivator Protein Tax. (1998)

The immunogenicity of the bovine leukemia virus (BLV) transactivator protein (tax) was studied by mapping its B-cell and T-cell epitopes. Peptides (18 to 20-mer) overlapping by 10 amino acids, spanning whole amino acid sequence of BLVtax were synthesized. Recombinant BLVtax protein was used to immunize two different strains of mice, C57BL/6 and BALB/c. B-cell and T-cell epitopes of recombinant BLVtax protein was determined by screening all the 30 synthetic peptides, against immune serum in ELISA for antibody reactivity, and against immune spleen cells in lymphocyte proliferation assay for T-cell stimulation. Peptides with amino acids at position 111-130 and 131-150 were T-cell epitopes for C57BL/6 and BALB/c mice immune cells, respectively. B-cell epitope was mapped to amino acid sequence at 261-280 in both strains of mice. These results imply that BLVtax protein contains some of BLV- immunodominant epitopes and this information may be applied for designing an effective peptide vaccine capable of inducing neutralizing antibodies as well as cellular immunity.
Comment on “Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics” (2016)

Li et al (Research Articles, 28 August 2015, aab3500) purport to present solutions to long-standing challenges in live-cell microscopy, reporting relatively fast acquisition times in conjunction with improved image resolution. We question the methods' reliability to visualize specimen features at sub-100-nanometer scales, because the mandatory mathematical processing of the recorded data leads to artifacts that are either difficult or impossible to disentangle from real features. We are also concerned about the chosen approach of subjectively comparing images from different super-resolution methods, as opposed to using quantitative measures.
A Conformation-Dependent Epitope in Addison’s Disease and Other Endocrinological Autoimmune Diseases Maps to a Carboxyl-Terminal Functional Domain of Human Steroid 21-Hydroxylase (1999)

Idiopathic Addison's disease develops as a consequence of autoimmune destruction of steroid-producing cells in the adrenal gland. A major autoantigen is 21-hydroxylase (21OH; P450c21), which is involved in the biosynthesis of cortisol and aldosterone in the adrenal cortex. We selected a number of functionally important 21OH amino acid substitutions, found in patients with congenital adrenal hyperplasia, to study their effects on the binding of 21OH autoantibodies (21OHAb) to 21OH. The ability of 21OHAb to bind in vitro transcribed and translated wild-type 21OH and five different 21OH mutant proteins was quantified by liquid-phase assays. Sera from 21OHAb-positive patients with idiopathic Addison's disease (n = 24), Graves' disease (n = 3), and insulin-dependent diabetes mellitus (n = 1) were used. While the P105L, delE196, and G291S mutations had no effect on autoantibody binding, the P453S mutation had a considerable effect, and the R483P mutation almost completely abolished binding. Synthetic peptides corresponding to linear epitopes defined by amino acids 447-461 and 477-491 were unable to compete with wild-type 21OH for binding to autoantibodies. Direct 21OH DNA sequencing could not reveal any specific genetic variation in alleles found in 21OHAb-positive patients. We conclude that the region involving R483 plays a key role in the formation of a three-dimensional epitope in a functionally important C-terminal domain of the enzyme.
John Terrane: A Study of a First World War Revisionist (1997)

Of all the British military historians who started writing about the First World War during the "boom" of the sixties, perhaps no one has had greater influence or generated more controversy than John Alfred Terraine. As G.F. Elliot wrote in a 1965 review, "John Terraine is one of the younger generation of British military analysts who are now proving, with brilliance and vigour, the value of the long view in putting World War I in proper perspective." It is this idea of perspective, trying to bring balance to the historical arguments concerning the British contribution to the First World War, that drove John Terraine in all his work. Terraine's nine books on the British Expeditionary Force challenged the comfortable mainstream theories and assumptions, defended the generals, and debunked the myths. His opinions gave him both notoreity and influence.
An Interactive Graphic Simulator for the Teaching of Fibrendoscopic Techniques (1987)

A simulator has been designed and implemented for teaching the skills required for fibrendoscopic investigation of the colon. The student using the simulator manipulates a dummy endoscope control head in which the rotary and linear movements are converted to voltages and interfaced to the computer via analogue to digital converters. The simulator is based on a three dimensional computer model of the colon and endoscope. The program reads the endoscope controls, determines the position of the tip of the endoscope, and using this as viewpoint draws the appropriate view. In the worst case, the whole cycle takes 0.185 seconds on an ordinary IBM PC, giving a frame rate of just under 6/sec.
ChemInform Abstract: POTENTIAL ANTICANCER AGENTS. XIII. SYNTHESIS OF NEW ALIPHATIC AND CYCLOALIPHATIC N‐NITROSOUREAS (1977)

Abstract Durch Nitrosierung der zugrundeliegenden Hanrstoffe werden die Verbindungen (I), (II) und (III) erhalten.
Characterization of adenylate cyclase toxin from a mutant of Bordetella pertussis defective in the activator gene, cyaC. (1993)

Bordetella pertussis adenylate cyclase (AC) toxin has the abilities to 1) enter target cells where it catalyzes cyclic AMP production and 2) lyse sheep erythrocytes, and these abilities require post-translational modification by the product of an accessory gene cyaC (Barry, E. M., Weiss, A. A., Ehrmann, E. E., Gray, M. C., Hewlett, E. L., and Goodwin, M. St. M. (1991) J. Bacteriol. 173, 720-726). In the present study, AC toxin has been purified from an organism with a mutation in cyaC, BPDE386, and evaluated for its physical and functional properties in order to determine the basis for its lack of toxin and hemolytic activities. AC toxin from BPDE386 is indistinguishable from wild-type toxin in enzymatic activity, migration on SDS-polyacrylamide gel electrophoresis, ability to bind calcium, and calcium-dependent conformational change. Although unable to elicit cAMP accumulation, AC toxin from BPDE386 exhibits binding to the surface of Jurkat cells which is comparable to that of wild-type toxin. This target cell interaction is qualitatively different, however, in that 99% of the mutant toxin remains sensitive to trypsin, whereas approximately 20% of cell-associated wild-type toxin enters a trypsin-resistant compartment. To evaluate the ability of this mutant AC toxin to function at its intracellular site of action, the cAMP-stimulated L-type calcium current in frog atrial myocytes was used. Extracellular addition of wild-type toxin results in cAMP-dependent events that include activation of calcium channels and enhancement of calcium current. In contrast, there is no response to externally applied toxin from BPDE386. When injected into the cell interior, however, the AC toxin from BPDE386 is able to produce increases in the calcium current comparable to those observed with wild-type toxin. Although AC toxin from BPDE386 is unaffected in its enzymatic activity, calcium binding, and calcium-dependent conformational change, the mutation in cyaC does result in a toxin which is able to bind to target cells but unable to elicit cAMP accumulation. In that AC toxin from BPDE386 is able to function normally when injected artificially to an intracellular site, we conclude that the disruption of cyaC produces a defect in insertion and transmembrane delivery of the catalytic domain.
Pseudomonas aeruginosa flagellin as an adjuvant: superiority of a conjugated form of flagellin versus a mixture with a human immunodeficiency virus type 1 vaccine candidate in the induction of immune responses (2015)

In the present study, the adjuvant activity of flagellin was compared, in the conjugated and mixed forms, against a peptide vaccine from human immunodeficiency virus type 1 (HIV-1) p24-Nef vaccine candidate. Mice were immunized with the HIV-1 p24-Nef peptide with flagellin in both conjugated and mixed forms. Lymphocyte proliferation, CTL activity, and IL-4 and IFN-γ cytokines were evaluated by bromodeoxyuridine, carboxyfluorescein succinimidyl ester and ELISA methods, respectively. At the same time, the frequency of IFN-γ-producing T-lymphocytes, as well as total and isotype-specific antibodies, were assessed by ELISPOT and indirect ELISA, respectively. Our experimental results showed that the immunized mice with the HIV-1 p24-Nef conjugated or mixed forms of flagellin led to increases in the proliferative responses and Th1 cytokine pattern. The conjugated form of vaccine led to increased CTL activity and a Th1 cytokine pattern of immune responses, as well as an IgM isotype of humoral responses in comparison with the mixed form. The flagellin-conjugated vaccine seems to be more potent in increasing vaccine immunogenicity.
A technique for combining microwave hyperthermia with intraluminal brachytherapy of the oesophagus (1989)

A technique for combining microwave hyperthermia with 192Ir brachytherapy for the treatment of oesophageal carcinoma is described. This approach uses an intraluminal afterloading applicator and up to six microwave antennae to deliver both hyperthermia and brachytherapy, with minimal modification of the existing procedure for brachytherapy alone. Each microwave antenna includes a built-in thermistor to control temperature and balance power. Longitudinal temperature distributions were measured in situ from within the applicator, and at the applicator-tissue interface in vivo. Two-dimensional SAR and steady-state temperature distributions measured in muscle-equivalent phantom are presented and discussed. The technique appears to be capable of elevating tissue temperature to greater than 42 degrees C in a radially symmetric volume of length greater than 5 cm, with radial penetration of 0.5 cm. The clinical technique is relatively simple and well tolerated.