gebhart/patrepeval huggingface dataset:
Pyrrolo(1,4)benzodiazepine antitumor antibiotics. Comparative aspects of anthramycin, tomaymycin and sibiromycin. (1977)

Anthramycin, sibiromycin and tomaymycin are structurally related antibiotics produced by various actinomycetes. Anthramycin was originally isolated from the fermentation broth of a thermophilic actinomycete, Streptomyces refruineus var. thermotolerans found in a compost heap in the 1950's by M. D. TENDLER1). The active compound, originally called "refuin" (from the Hebrew "refuah" meaning a medicine), was isolated as a pure crystalline antibiotic by LEIMGRUBER2, 3) in 1965. This antibiotic was subsequently shown to have antibiotic, antitumor, antiprotozoal and chemosterilant activity against houseflies. Tomaymycin, a Japanese antibiotic, produced by Streptomyces achromogenes var. tomaymyceticus, was isolated from a soil sample collected in Musashikoganei-city. The isolation and properties of this antibiotic were first reported by ARIMA and coworkers4) in 1972. The structure of tomaymycin and the structurally related but biologically inactive compound, oxotomaymycin, were reported by KARIYONE5) in 1971. Tomaymycin has been shown to have antitumor, antiviral and antibiotic activities. Sibiromycin, the most recent of the three antibiotics to be fully characterized, is produced by the actinomycete, Streptosporangium sibiricum and was first reported by GAUSE and coworkers6) at the Moscow Institute for New Antibiotics. The isolation and partial characterization of this antibiotic was published in 1972.7) However, its full structure was not published until 1974 by MESENTEV and coworkers.8) Sibiromycin has been shown to have antitumor as well as antibiotic activity. In addition to anthramycin, sibiromycin and tomaymycin, three further structurally related antibiotics have appeared in the literature, although full structural information has not been published. The first of these compounds, dextrochrysin which is produced by Streptomyces calms var. dextrochrysus9), has been demonstrated to have antiviral as well as antibiotic activity. Most recently two isomeric anthramycin-related compounds, neothramycins A and B produced by Streptomyces No. MC916-C410) have been reported. These compounds have been shown to have weak antibiotic and antifungal activity as well as antitumor activity. Reviews on the mechanism of action of anthramycin11, 12) and sibiromycin have appeared.13-15)
Beta blockade, diuretics, and salt restriction for the management of mild hypertension: a randomised double blind trial. (1984)

Ninety four patients with mild hypertension (average supine diastolic blood pressure (phase V) 95-110 mm Hg) were allocated at random to receive restriction of dietary sodium (maximum allowed 70 mmol(mEq)/24 h) or a normal diet. In addition, they received in random order 25 mg chlorthalidone, 200 mg metoprolol (slow release), and a fixed combination of these two drugs. Each drug treatment was given for four weeks and alternated with four weeks of placebo. Forty four patients were allocated to sodium restriction (group 1) and 50 to normal diet (group 2). The mean 24 hour urinary sodium excretion in group 1 was 74 (SD 31) mmol(mEq)/24 h, and in group 2 132 (51) mmol/24 h. Compared with the screening blood pressure the average decrement of the supine blood pressure in group 1 was 16.0/8.6 mm Hg with placebo, 21.7/11.5 mm Hg with the diuretic, 28.5/17.8 mm Hg with the beta blocker, and 28.9/18.4 mm Hg with the combined agent; in group 2 these values were 13.3/6.1, 20.3/9.7, 21.3/12.9, and 29.4/16.8 mm Hg, respectively. There was a sharp decrease of the average potassium concentration during chlorthalidone and combination treatment periods (average value 3.3 mmol(mEq)/1). These results suggest that moderate salt restriction used as sole treatment has a limited though demonstrable blood pressure lowering effect but that when it is used as an adjuvant to beta blocker treatment its value is greatly enhanced.
Part I: Basic Considerations and Recommendations for Preparation, Measurement and Interpretation (1998)

A task force of invited experts in the field of diagnostic DNA image cytometry, especially consisting of participants from the PRESS (Prototype Reference Standard Slides) and EUROPATH (European Pathology Assisted by Telematics for Healthcare) projects, but open to any other scientist or physician revealing experience in that new diagnostic procedure (names are given in the Annex A) agreed upon the following updated consensus report during the 5th International Congress of the ESACP 1997 in Oslo. This report is based on the preceeding one [9] and on results of the above mentioned European research projects. It deals with the following items: Biological background and aims of DNA image cytometry, Principles of the method, Basic performance standards, Diagnostic interpretation of DNA measurements, Recommendations for practical use.
Advances in management of polycystic liver disease (2008)

The focus of this review is polycystic liver disease, a genetic disorder characterized by multiple macroscopic liver cysts that initially bud from biliary epithelium but subsequently lack communication with the biliary tree. There are two main clinical presentations: polycystic liver associated with autosomal dominant polycystic kidney disease and isolated polycystic liver disease. Both of these forms of polycystic liver disease exhibit an autosomal dominant pattern of inheritance. Clinical manifestations of polycystic liver disease are related to either mass effect of the volume of hepatic cysts or to complications arising within the cysts. Polycystic liver disease rarely progresses to hepatic failure or clinical complications of portal hypertension. Management is directed at counseling patients and families, treating complications and reducing cyst load by surgical techniques: cyst fenestration, hepatic resection or, rarely, hepatic transplantation. Recent research suggests that blockade of cyst secretion or inhibition of epithelial cells might be useful in halting progression of disease--these observations are discussed in this review.
Cardiovascular and Other Risk Factors for Alzheimer's Disease and Vascular Dementia (2000)

Factors accelerating cerebral degenerative changes represent potentially modifiable risks for cognitive decline. Putative risks accelerating subtle cognitive decline and dementia were correlated with repeated measures of cerebral atrophy, CT densitometry, perfusions, and cognitive testing among 224 neurologically and cognitively normative aging volunteers. After age 60, cerebral atrophy, ventricular enlargement, polioaraiosis, and leukoaraiosis geometrically increased as perfusions declined. Risks accelerating perfusional decline, cerebral atrophy, polioaraiosis, and leukoaraiosis were: transient ischemic attacks (TIAs), hypertension, smoking, hyperlipidemia, male gender. At age 71.5 +/- 11.9, subtle cognitive decline began, accelerated by TIAs, hypertension, and heart disease. Leukoaraiosis began before cognitive decline. TIAs, hypertension, and hyperlipidemia correlated with vascular dementias. Excessive cortical perfusional decreases and cerebral atrophy correlated with cognitive decline. Family history of neurodegenerative disease correlated with Alzheimer's disease. We concluded that TIAs, hypertension, hyperlipidemia, smoking, and male gender accelerate cerebral degenerative changes, cognitive decline, and dementia.
Electronic and Steric Effects on the Oxygenation of Organic Sulfides and Sulfoxides with Oxo(salen)chromium(V) Complexes (2003)

The kinetics of oxygenation of several para-substituted phenyl methyl sulfides and sulfoxides with a series of 5-substituted and sterically hindered oxo(salen)chromium(V) complexes have been studied by a spectrophotometric technique. Though the reaction of sulfides follows simple second-order kinetics, sulfoxides bind strongly with the metal center of the oxidant and the oxygen atom is transferred from the oxidant-sulfoxide adduct to the substrate. The reduction potentials, E(red), of eight Cr(V) complexes correlate well with the Hammett sigma constants, and the reactivity of the metal complexes is in accordance with the E(red) values. The metal complexes carrying bulky tert-butyl groups entail steric effects. Organic sulfides follow a simple electrophilic oxidation mechanism, and the nonligated sulfoxides undergo electrophilic oxidation to sulfones using the oxidant-sulfoxide adduct as the oxidant. Sulfoxides catalyze the Cr(V)-salen complexes' oxygenation of organic sulfides, and the catalytic activity of sulfoxides is comparable to pyridine N-oxide and triphenylphosphine oxide. The rate constants obtained for the oxidation of sulfides and sulfoxides clearly indicate the operation of a pronounced electronic and steric effect in the oxygenation reaction with oxo(salen)chromium(V) complexes.
Requirement for Neutralizing Antibodies to Control Bone Marrow Transplantation-Associated Persistent Viral Infection and to Reduce Immunopathology (2005)

Bone marrow transplantation (BMT) is commonly used in the treatment of leukemia, however its therapeutic application is partly limited by the high incidence of associated opportunistic infections. We modeled this clinical situation by infecting mice that underwent BMT with lymphocytic choriomeningitis virus (LCMV) and investigated the potential of immunotherapeutic strategies to counter such infections. All mice that received BMT survived LCMV infection and developed a virus carrier status. Immunotherapy by adoptive transfer of naive splenocytes protected against low (200 PFU), but not high (2 x 10(6) PFU), doses of LCMV. Attempts to control infection of high viral titers using strongly elevated frequencies of activated LCMV-specific T cells failed to control virus and resulted in immunopathology and death. In contrast, virus neutralizing Abs combined with naive splenocytes were able to efficiently control high-dose LCMV infection without associated side effects. Thus, cell transfer combined with neutralizing Abs represented the most effective means of controlling BMT-associated opportunistic viral infection in our in vivo model. These data underscore the in vivo efficacy and immunopathological "safety" of neutralizing antibodies.
PDZ binding motif of HTLV-1 Tax promotes virus-mediated T-cell proliferation in vitro and persistence in vivo (2005)

HTLV-1 cellular transformation and disease induction is dependent on expression of the viral Tax oncoprotein. PDZ is a modular protein interaction domain used in organizing signaling complexes in eukaryotic cells through recognition of a specific binding motif in partner proteins. Tax-1, but not Tax-2, contains a PDZ-binding domain motif (PBM) that promotes the interaction with several cellular PDZ proteins. Herein, we investigate the contribution of the Tax-1 PBM in HTLV-induced proliferation and immortalization of primary T cells in vitro and viral survival in an infectious rabbit animal model. We generated several HTLV-1 and HTLV-2 Tax viral mutants, including HTLV-1deltaPBM, HTLV-2+C22(+PBM), and HTLV-2+ C18(deltaPBM). All Tax mutants maintained the ability to significantly activate the CREB/ATF or NFkappaB signaling pathways. Microtiter proliferation assays revealed that the Tax-1 PBM significantly increases both HTLV-1- and HTLV-2-induced primary T-cell proliferation. In addition, Tax-1 PBM was responsible for the micronuclei induction activity of Tax-1 relative to that of Tax-2. Viral infection and persistence were severely attenuated in rabbits inoculated with HTLV-1deltaPBM. Our results provide the first direct evidence suggesting that PBM-mediated associations between Tax-1 and cellular proteins play a key role in HTLV-induced cell proliferation and genetic instability in vitro and facilitate viral persistence in vivo.
A preliminary list of the earthworms of northern New Jersey with notes (1954)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
Deep Brain Stimulation: Eye Movements Reveal Anomalous Effects of Electrode Placement and Stimulation (2012)

One of the major difficulties in evaluating the efficacy of deep brain stimulation (DBS), or understanding its mechanism, is the need to distinguish the effects of stimulation itself from those of the lesion inevitably created during surgery. Recent work has shown that DBS of the subthalamic nucleus in Parkinson's disease greatly reduces the time it takes the eyes to make a saccade in response to a visual stimulus. Since this saccadic latency can be rapidly and objectively measured, we used it to compare the effects of surgery and of stimulation. We used a saccadometer to measure the saccadic latencies of 9 DBS patients (1) preoperatively, (2) the day after insertion of subthalamic nucleus electrodes, (3) three weeks later, prior to turning on the stimulator, and (4) after commencement of stimulation. Patients were on their anti-Parkinsonian medication throughout the study. It revealed an entirely unexpected and puzzling finding. As in previous studies an amelioration of symptoms is seen immediately after surgery, and then a further improvement when finally the stimulator is turned on, but in the case of saccadic latency the pattern is different: surgery produces a transient increase in latency, returning to baseline within three weeks, while subsequent stimulation reduced latency. Thus the differential effects of electrode placement and stimulation are completely different for saccades and for more general motor symptoms. This important finding rules out some over-simple interpretations of the mechanism of DBS, and needs to be taken into account in future attempts at modelling the neurophysiology of DBS.
Speech coding scheme for personal communications under radio interference noises (2002)

This paper describes a new method of ADPCM which is robust against radio interference and capable of voiceband data transmission. The transmission errors are studied in with reference to bit errors in the data frame and frame erasures (packet loss). A new ADPCM method is proposed in this paper which is robust against bit errors. The adaptive quantizer has been improved to provide good quality under noise. The stability of the predictor is guaranteed. The frame compensation method for frame erasure is also described. The high speech quality and the predictor stability was confirmed by the proposed method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Development of F-18 labeled inflammation-reporting PET tracer using click chemistry (2013)

59 Objectives CXCR4/SDF-1 has been reported to play a critical role in the recruitment of inflammatory cells during early phase of inflammation. Blocking CXCR4 has been shown to significantly suppress inflammation in vivo (Zhu A. et al 2010, J Med Chem 53, 8556-68; Liang Z. et al 2012, PLoS ONE 7, e34038, 1-12). Therefore, in vivo imaging of CXCR4 receptor has significant potential to detect inflammation early. Methods We have identified a novel sulfonamide and cyclic sulfonamide derivatives as small molecule CXCR4 antagonists through rational design by molecular modeling and cell-based functional assays (Mooring S.R. 2010 American Chemical Society 241st Annual Meeting, Anaheim, CA). Their binding potency was evaluated by an affinity binding assay using the potent peptidic CXCR4 antagonist TN14003. For the secondary functional assays, Matrigel invasion assay and cAMP assay were used to rank-order their inhibitory efficacy against CXCR4/CXCL12 interaction. To generate 18F-labeled PET tracer candidates, [18F]fluoroethylazide was synthesized by reacting the corresponding azide derivative with K18F in the presence of K222 prior to conjugating alkyne derivatives of the selected sulfonamides with high potency through click reactions. Results The click chemistry approach for labeling yielded higher radiochemical conversion. To determine the specificity of labeled antagonists, we tested them in competition assays against corresponding 19F derivatives and CXCL12 at various concentrations. microPET images of labeled compounds in a carrageenan-induced paw edema model exhibited significant radioactivity in the inflamed area. Conclusions We designed and synthesized a novel series of CXCR4-PET tracers using molecular docking computer modeling and cell-based screening assays, which were labeled by high-yield click chemistry method. Our CXCR4-reporting 18F-PET tracer has a great potential to become a clinical diagnostic agent for inflammation. Research Support This research is supported by NCI R01 CA165306 and P50 CA128301.
Time‐correlated single‐photon counting fluorescence lifetime confocal imaging of decayed and sound dental structures with a white‐light supercontinuum source (2007)

We report the demonstration of time-correlated single-photon counting (TCSPC) fluorescence lifetime imaging (FLIM) to ex vivo decayed and healthy dentinal tooth structures, using a white-light supercontinuum excitation source. By using a 100 fs-pulsed Ti:Sapphire laser with a low-frequency chirp to pump a 30-cm long section of photonic crystal fibre, a ps-pulsed white-light supercontinuum was created. Optical bandpass interference filters were then applied to this broad-bandwidth source to select the 488-nm excitation wavelength required to perform TCSPC FLIM of dental structures. Decayed dentine showed significantly shorter lifetimes, discriminating it from healthy tissue and hard, stained and thus affected but non-infected material. The white-light generation source provides a flexible method of producing variable-bandwidth visible and ps-pulsed light for TCSPC FLIM. The results from the dental tissue indicate a potential method of discriminating diseased tissue from sound, but stained tissue, which could be of crucial importance in limiting tissue resection during preparation for clinical restorations.
Familial aggregation of colorectal cancer in the general population (1996)

To investigate the familial aggregation of colorectal cancer in Denmark, parents and siblings of colorectal cancer patients diagnosed below age 60 years in the years 1982-1984 were identified through population registries. For 1,470 probands with families eligible for tracing, 1,376 mothers, 1,303 fathers and 3,259 siblings were identified. They contributed 222,634 person-years, and 325 cases of colorectal cancer were observed during the follow-up period 1943-1992. All data were retrieved from population registries and consequently were free from any reporting bias. The overall standardized morbidity ratio (SMR) compared with the Danish population was 2.02 (95% confidence interval [CI] 1.81-2.25), significantly different between the parents (1.78, 95% CI 1.55-2.04) and the siblings (2.65, 95% CI 2.21-3.17). A strong dependence on the proband's age at diagnosis was seen for the sibling risk; siblings of probands less than 50 years old at diagnosis had a 5-fold risk compared with the general population. This dependence was not seen for parents, but the risk tended to be higher for parents of younger ages. No other factor was seen to influence the relative risk. The observation of an 80% increased risk among the parents and a 170% increased risk among the siblings indicates that the genetic component is one source, but probably not the only one, of familial aggregation of colorectal cancer. The cost benefit of screening siblings of colorectal cancer patients is substantially higher than that for the total population.
Stresses and Displacements on the Boundaries of Circular Rings Diametrically Loaded (1986)

The paper deals with stresses and displacements in circular rings of rectangular cross-section, loaded in the plane and perpendicular to the boundary. Values are given for all points at the inside and outside boundaries, are presented parametrically for rings for which the ratio of diameters ID/OD varies from 0 to very close to 1, and have been obtained from several sources, mainly Nelson’s equations. References to some previous contributions are included. The information presented in the paper was not available in a complete manner and will be useful in numerous structural applications. The analysis corresponding to loads applied tangentially to the boundary could be approached in a similar manner.
SHARPE at the age of twenty two (2009)

This paper discusses the modeling tool called SHARPE (Symbolic Hierarchical Automated Reliability and Performance Evaluator), a general hierarchical modeling tool that analyzes stochastic models of reliability, availability, performance, and performability. It allows the user to choose the number of levels of models, the type of model at each level, and which results from each model level are to act as which parameters in which higher-level models. SHARPE includes algorithms for analysis of fault trees, reliability block diagrams, acyclic series-parallel graphs, acyclic and cyclic Markov and semi-Markov models, generalized stochastic Petri nets, and closed single- and multi-chain product-form queueing networks. For many of these, the user can choose among alternative algorithms, and can decide whether to get a result in the form of a distribution function (symbolic in the time variable) or as a mean or probability. SHARPE has been useful to students, practicing engineers, and researchers. In this paper we discuss the history of SHARPE, give some examples of its use, and talk about some lessons learned.
The <i>Yersinia enterocolitica</i> Motility Master Regulatory Operon, <i>flhDC</i> , Is Required for Flagellin Production, Swimming Motility, and Swarming Motility (1999)

The ability to move over and colonize surface substrata has been linked to the formation of biofilms and to the virulence of some bacterial pathogens. Results from this study show that the gastrointestinal pathogen Yersinia enterocolitica can migrate over and colonize surfaces by swarming motility, a form of cooperative multicellular behavior. Immunoblot analysis and electron microscopy indicated that swarming motility is dependent on the same flagellum organelle that is required for swimming motility, which occurs in fluid environments. Furthermore, motility genes such as flgEF, flgMN, flhBA, and fliA, known to be required for the production of flagella, are essential for swarming motility. To begin to investigate how environmental signals are processed and integrated by Y. enterocolitica to stimulate the production of flagella and regulate these two forms of cell migration, the motility master regulatory operon, flhDC, was cloned. Mutations within flhDC completely abolished swimming motility, swarming motility, and flagellin production. DNA sequence analysis revealed that this locus is similar to motility master regulatory operons of other gram-negative bacteria. Genetic complementation and functional analysis of flhDC indicated that it is required for the production of flagella. When flhDC was expressed from an inducible ptac promoter, flagellin production was shown to be dependent on levels of flhDC expression. Phenotypically, induction of the ptac-flhDC fusion also corresponded to increased levels of both swimming and swarming motility.