gebhart/patrepeval huggingface dataset:
Reversal of Drug Resistance in a Human Colon Cancer Xenograft Expressing MDR1 Complementary DNA by In Vivo Administration of MRK-16 Monoclonal Antibody (1991)

One strategy to overcome multidrug resistance in neoplasia is to inhibit the gp170 glycoprotein (relative molecular mass, 170,000) that functions as a plasma membrane, energy-dependent, drug-efflux pump. The human colon cancer cell line HT-29, which grows as an ascitic tumor in athymic NCr-nu/nu nude mice, was made multidrug resistant by infection with an MDR1 (also known as PGY1) retrovirus. Referred to as HT-29mdr1, it was used to study reversal of drug resistance in vivo by the anti-P-glycoprotein monoclonal antibody MRK-16. Flow cytometry and radioimmunoassay demonstrated a marked increase in MRK-16 reactivity on HT-29mdr1 cells as compared with its reactivity on the parental, uninfected cell line (HT-29par). The 50% inhibitory concentrations (IC50) of vincristine on HT-29par and HT-29mdr1 cells were 2.5 and 15 ng/mL, respectively. The MRK-16 monoclonal antibody did not affect the vincristine sensitivity of the HT-29par cells. Pretreatment of HT-29mdr1 cells with 10 micrograms/mL MRK-16 in tissue culture partially restored the vincristine sensitivity (IC50 = 7 ng/mL). This modulation of vincristine sensitivity by MRK-16 was then tested in vivo. The median survival times of mice given intraperitoneal transplants of 5 x 10(6) HT-29par or HT-29mdr1 were 37 and 39 days, respectively. Treatment of mice with 1 mg/kg vincristine weekly for 3 weeks, beginning 10 days after tumor injection, resulted in a significant increase in the median survival time of the HT-29par tumor-bearing mice (68 days, P less than .0001), but it had no effect on the HT-29mdr1 tumor-bearing mice. However, treatment of mice bearing the HT-29mdr1 tumor with MRK-16 before vincristine therapy reversed the resistance to the drug (median survival time = 64 days, P less than .0001). The MRK-16 monoclonal antibody alone had no effect on the median survival time of mice given an injection of either HT-29par or HT-29mdr1 cells. These results suggest that strategies employing monoclonal antibody against gp170 may be clinically useful to reverse multidrug resistance.
Differential Effects of Overexpressed Glucokinase and Hexokinase I in Isolated Islets (1996)

Glucose-stimulated insulin secretion is believed to require metabolism of the sugar via a high Km pathway in which glucokinase (hexokinase IV) is rate-limiting. In this study, we have used recombinant adenoviruses to overexpress the liver and islet isoforms of glucokinase as well as low Km hexokinase I in isolated rat islets of Langerhans. Glucose phosphorylating activity increased by up to 20-fold in extracts from islets treated with adenoviruses containing the cDNAs encoding either tissue isoform of glucokinase, but such cells exhibited no increase in 2- or 5-[3H]glucose usage, lactate production, glycogen content, or glucose oxidation. Furthermore, glucokinase overexpression enhanced insulin secretion in response to stimulatory glucose or glucose plus arginine by only 36-53% relative to control islets. In contrast to the minimal effects of overexpressed glucokinases, overexpression of hexokinase I caused a 2.5-4-fold enhancement in all metabolic parameters except glycogen content when measured at a basal glucose concentration (3 mM). Based on measurement of glucose phosphorylation in intact cells, overexpressed glucokinase is clearly active in a non-islet cell line (CV-1) but not within islet cells. That this result cannot be ascribed to the levels of glucokinase regulatory protein in islets is shown by direct measurement of its activity and mRNA. These data provide evidence for functional partitioning of glucokinase and hexokinase and suggest that overexpressed glucokinase must interact with factors found in limiting concentration in the islet cell in order to become activated and engage in productive metabolic signaling.
Teleconsultation in psychology: the use of videolinks for interviewing and assessing elderly patients (2001)

Although elderly people are one of the major target groups for telemedicine applications, they remain under-represented in studies of teleconsultation. Videolinks appear to be easily used by many elderly people as a means of communicating with health-care staff, including psychologists and doctors. To date, studies of psychometric teleconsultation have been confined to screening tests, or have used very small numbers of patients. There is a need to examine the reliability of more complex psychometric batteries and to use larger samples of older people. Some recommendations for conducting clinical interviews and psychometric tests are presented, based on clinical experience and a review of the literature. The importance of ergonomic considerations, patient comfort and professional preparation are explained.
HOLOGRAPHIC POLARIZATION RECORDING WITH AN ENCODED REFERENCE BEAM (1969)

Complete wavefront reconstruction, including polarization, is accomplished with an encoded reference beam, generated by using a single depolarizing diffuser as the reference beam source. The orthogonal polarization components of the object wave are encoded by different random wavefronts because of the scattering properties of the depolarizing diffuser.
Length dependence of active force production in skeletal muscle (1999)

The sliding filament and cross-bridge theories of muscle contraction provide discrete predictions of the tetanic force-length relationship of skeletal muscle that have been tested experimentally. The active force generated by a maximally activated single fiber (with sarcomere length control) is maximal when the filament overlap is optimized and is proportionally decreased when overlap is diminished. The force-length relationship is a static property of skeletal muscle and, therefore, it does not predict the consequences of dynamic contractions. Changes in sarcomere length during muscle contraction result in modulation of the active force that is not necessarily predicted by the cross-bridge theory. The results of in vivo studies of the force-length relationship suggest that muscles that operate on the ascending limb of the force-length relationship typically function in stretch-shortening cycle contractions, and muscles that operate on the descending limb typically function in shorten-stretch cycle contractions. The joint moments produced by a muscle depend on the moment arm and the sarcomere length of the muscle. Moment arm magnitude also affects the excursion (length change) of a muscle for a given change in joint angle, and the number of sarcomeres arranged in series within a muscle fiber determines the sarcomere length change associated with a given excursion.
Host Range Restriction and Pathogenicity in the Context of Influenza Pandemic (2006)

Influenza A viruses cause pandemics at random intervals. Pandemics are caused by viruses that contain a hemagglutinin (HA) surface glycoprotein to which human populations are immunologically naive. Such an HA can be introduced into the human population through reassortment between human and avian virus strains or through the direct transfer of an avian influenza virus to humans. The factors that determine the interspecies transmission and pathogenicity of influenza viruses are still poorly understood; however, the HA protein plays an important role in overcoming the interspecies barrier and in virulence in avian influenza viruses. Recently, the RNA polymerase (PB2) protein has also been recognized as a critical factor in host range restriction, while the nonstructural (NS1) protein affects the initial host immune responses. We summarize current knowledge of viral factors that determine host range restriction and pathogenicity of influenza A viruses.
Evaluating the benefits of assisted target recognition (2002)

Image exploitation systems that employ automatic target recognition (ATR) technology generally require that a human-in-the-loop validates the ATR results, i.e. assisted target recognition. To evaluate the benefits of assisted target recognition, one must first understand the human's interaction with the ATR algorithms plus the many factors that influence the performance of both the imagery analyst and the ATR. Thus, any assessment of assisted target recognition must be designed so that performance differences due to ATR assistance are isolated from other factors that affect image exploitation. An aided target acquisition perception testing (ATAPT) demonstration created procedures for assessing assisted and unassisted image exploitation, validating the methodology, metrics and software architecture. This paper describes the ATAPT demonstration and discusses the insights gained from this exercise that will improve future evaluations of systems that use ATR-assisted image exploitation.
Fluorescence-detected wave packet interferometry. II. Role of rotations and determination of the susceptibility (1992)

The recently developed technique of time-resolved spectroscopy with phase-locked optical pulse pairs is further explored with additional experimental data and more detailed comparison to theory. This spectroscopic method is sensitive to the overall phase evolution of an optically prepared nuclear wave packet. The phase locking scheme, demonstrated for the B←X transition of gas phase molecular iodine, is extended through the use of in-quadrature locked pulses and by examination of the dispersed fluorescence signal. The excited state population following the interaction with both pulses is detected as the resultant two-field-dependent fluorescence emission from the B state. The observed signals have periodically recurring features that result from rovibrational wave packet dynamics of the molecule on the excited state electronic potential energy curve. Quantum interference effects cause the magnitude and sign of the periodic features to be strongly modulated. The two-pulse phase-locked interferograms are interpreted with first order time-dependent perturbation theory. Excellent agreement is found between the experimental interferograms and those calculated from literature values of the parameters governing the electronic, vibrational and rotational structure of I2. A relationship between the phase-locked interferograms and the time-dependent linear susceptibility is obtained. The in-phase and in-quadrature phase-locked interferograms together provide a complete record of the optical free induction decay. Thus by combining the in-phase and in-quadrature data, we obtain the contributions to both the absorptive and dispersive linear susceptibilities arising from transitions within the pulse spectrum.
THE 2003 CARL A. MOYER AWARD (2004)

Real-time metabolic monitoring of varied vascular beds provides the raw data necessary to conduct ultraprecise burn shock resuscitation based on second-by-second assessment of regional tissue perfusion. It also illustrates shortcomings of current clinical practices. Arterial base deficit was continuously monitored during 11 clinical resuscitations of patients suffering burn shock using a Paratrend monitor. Separately, in a 30% TBSA rat burn model (N = 70), three Paratrend monitors simultaneously recorded arterial blood gas and tissue pCO2 of the burn wound and colonic mucosa during resuscitation at 0, 2, 4, 6, and 8 ml/kg/%TBSA. Paratrend data were analyzed in conjunction with previously reported laser Doppler images of actual burn wound capillary perfusion. With current clinical therapy, continuous monitoring of arterial base deficit revealed repetitive cycles of resolution/worsening/resolution during burn shock resuscitation. In the rat model, tissue pCO2 in both burn wounds and splanchnic circulation differed depending on the rate of fluid resuscitation (P <.01 between sham and 0 ml/kg/%TBSA and between 2 ml/kg/%TBSA and 4 ml/kg/%TBSA). Burn wound pCO2 values correlated well with laser Doppler determination of actual capillary perfusion (rho = -.48, P <.01). The following conclusions were reached: 1). Gratuitous and repetitive ischemia-reperfusion-ischemia cycles plague current clinical therapy as demonstrated by numerous "false starts" in the resolution of arterial base deficit; 2). in a rat model, real-time monitoring of burn wound and splanchnic pCO2 demonstrate a dose-response relationship with rate of fluid administration; and 3). burn wound and splanchnic pCO2 are highly correlated with direct measurement of burn wound capillary perfusion by laser Doppler imager. Either technique can serve as a resuscitation endpoint for real-time feedback-controlled ultraprecise resuscitation.
The objective assessment of contrast sensitivity function by electrophysiological means. (1984)

In recent years it has been shown that it is of considerable clinical value to determine the visual contrast sensitivity function of the patient. This can reveal the wider effects of pathology on the visual system where visual acuity may or may not be affected. There is a comprehensive literature on subjective approaches of obtaining this function in the clinical environment but very little on alternative objective methods. This paper describes the latter approach, which exploits electrophysiological techniques using the visual evoked cortical potential (VECP) to checkerboard onset-offset stimulation. Its application in a variety of disorders of the visual system is described. The importance of selecting the most appropriate stimulus parameters is discussed, and the relative advantages and disadvantages as compared with psychophysical methods are appraised.
Fluorescence-Based Isolation of Bacterial Genes Expressed Within Host Cells (1997)

A selection strategy was devised to identify bacterial genes preferentially expressed when a bacterium associates with its host cell. Fourteen Salmonella typhimurium genes, which were under the control of at least four independent regulatory circuits, were identified to be selectively induced in host macrophages. Four genes encode virulence factors, including a component of a type III secretory apparatus. This selection methodology should be generally applicable to the identification of genes from pathogenic organisms that are induced upon association with host cells or tissues.
Fabrication and Characterization of a Solid State Reference Electrode for Electroanalysis of Natural Waters with Ultramicroelectrodes (1997)

As an alternative to standard commercial reference electrodes, a solid state reference electrode is fabricated for in situ voltammetric analysis in solutions containing little or no added supporting electrolyte. In the fabrication process, a Ag/AgCl wire is coated with an electrolyte immobilized and protected with Nafion or polyurethane. The electrode potential is measured as a function of time, ionic strength, and pH. A stable potential is obtained for Nafion and polyurethane within 30−35 min in water. Both the polyurethane and Nafion solid state reference electrodes are stable for at least 90 days, but the Nafion electrode fluctuates more than the polyurethane electrode. The electrode is demonstrated using square wave anodic stripping voltammetry at a large electrode (3 mm), an ultramicroelectrode (10 μm), and an array of ultramicroelectrodes.
A General Method of Preparation of Tetramethyl Alkyl-1-hydroxy-1,1-diphosphonates (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA General Method of Preparation of Tetramethyl Alkyl-1-hydroxy-1,1-diphosphonatesD. Allan Nicholson and Harold VaughnCite this: J. Org. Chem. 1971, 36, 24, 3843–3845Publication Date (Print):December 1, 1971Publication History Published online23 December 2002Published inissue 1 December 1971https://pubs.acs.org/doi/10.1021/jo00823a621https://doi.org/10.1021/jo00823a621research-articleACS PublicationsRequest reuse permissionsArticle Views373Altmetric-Citations44LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Sialylation of Lipooligosaccharide Cores Affects Immunogenicity and Serum Resistance of Campylobacter jejuni (2000)

Three genes involved in biosynthesis of the lipooligosaccharide (LOS) core of Campylobacter jejuni MSC57360, the type strain of the HS:1 serotype, whose structure mimics GM(2) ganglioside, have been cloned and characterized. Mutation of genes encoding proteins with homology to a sialyl transferase (cstII) and a putative N-acetylmannosamine synthetase (neuC1), part of the biosynthetic pathway of N-acetylneuraminic acid (NeuNAc), have identical phenotypes. The LOS cores of these mutants display identical changes in electrophoretic mobility, loss of reactivity with cholera toxin (CT), and enhanced immunoreactivity with a hyperimmune polyclonal antiserum generated against whole cells of C. jejuni MSC57360. Loss of sialic acid in the core of the neuC1 mutant was confirmed by fast atom bombardment mass spectrometry. Mutation of a gene encoding a putative beta-1,4-N-acetylgalactosaminyltransferase (Cgt) resulted in LOS cores intermediate in electrophoretic mobility between that of wild type and the mutants lacking NeuNAc, loss of reactivity with CT, and a reduced immunoreactivity with hyperimmune antiserum. Chemical analyses confirmed the loss of N-acetylgalactosamine (GalNAc) and the presence of NeuNAc in the cgt mutant. These data suggest that the Cgt enzyme is capable of transferring GalNAc to an acceptor with or without NeuNAc and that the Cst enzyme is capable of transferring NeuNAc to an acceptor with or without GalNAc. A mutant with a nonsialylated LOS core is more sensitive to the bactericidal effects of human sera than the wild type or the mutant lacking GalNAc.
miR-375 Inhibits Proliferation of Mouse Pancreatic Progenitor Cells by Targeting YAP1 (2013)

Our results indicate that YAP1 is necessary for the proliferation of pancreatic progenitor cells and miR-375 participates in regulating YAP1 expression during pancreatic progenitor cells differentiation.
Antibodies to myelin basic protein, myelin oligodendrocytes peptides, α‐β‐crystallin, lymphocyte activation and cytokine production in patients with multiple sclerosis (2003)

Detection of antibodies against MBP, MOG peptides, alpha-beta-crystallin, lymphocyte stimulation and production of proinflammatory cytokines in response to these antigens could be used as surrogate markers for the confirmation of MS diagnosis. A combination of antibodies, lymphocyte activation or cytokine production with abnormal MRI may significantly increase the sensitivity and specificity of MS diagnosis.
Diagnosis and treatment of familial hypercholesterolaemia (2013)

Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder, associated with elevated levels of low-density lipoprotein-cholesterol (LDL-C), which can lead to premature cardiovascular disease. Early diagnosis of FH is important to prevent morbidity and mortality. Familial hypercholesterolaemia is usually diagnosed using clinical characteristics, such as family history, and cholesterol levels; however, genetic testing may provide a definite diagnosis of FH by detecting a pathological mutation. Current guidelines highlight the importance of reducing LDL-C levels in patients with FH. Statins are the current standard treatment for the majority of these patients, and have been shown to be effective in reducing the incidence of cardiovascular heart disease in patients with FH. Nevertheless, many FH patients do not achieve their target LDL-C levels; as such, new treatment options are required to decrease LDL-C levels beyond those currently achieved. There are currently several new classes of pharmacotherapy under investigation to control LDL-C levels. These include agents which modify LDL-C production, such as inhibitors of apolipoprotein B, or those which affect LDL-C catabolism, such as inhibition of pro-protein convertase subtilisin/kexin 9, a protein which is responsible for the degradation of the LDL receptor. Therapies which raise high-density lipoprotein cholesterol are also being evaluated. In this article, we consider the diagnosis of FH and the goals of therapy and review the current and potential future treatment options for patients with FH.
Morphable crowds (2010)

Crowd simulation has been an important research field due to its diverse range of applications that include film production, military simulation, and urban planning. A challenging problem is to provide simple yet effective control over captured and simulated crowds to synthesize intended group motions. We present a new method that blends existing crowd data to generate a new crowd animation. The new animation can include an arbitrary number of agents, extends for an arbitrary duration, and yields a natural-looking mixture of the input crowd data. The main benefit of this approach is to create new spatio-temporal crowd behavior in an intuitive and predictable manner. It is accomplished by introducing a morphable crowd model that allows us to encode the formations and individual trajectories in crowd data. Then, its original spatio-temporal behavior can be reconstructed and interpolated at an arbitrary scale using our morphable model.
Selective PPARγ modulator INT131 normalizes insulin signaling defects and improves bone mass in diet-induced obese mice (2012)

INT131 is a potent non-thiazolidinedione (TZD)-selective peroxisome proliferator-activated receptor-γ modulator being developed for the treatment of type 2 diabetes. In preclinical studies and a phase II clinical trial, INT131 has been shown to lower glucose levels and ameliorate insulin resistance without typical TZD side effects. To determine whether the insulin-sensitizing action of INT131 is mediated by effects on insulin-mediated glucose homeostasis and insulin signaling, high-fat diet-induced obese (DIO) insulin-resistant mice treated with INT131 were studied. INT131's effects on bone density were also investigated. Treatment with INT131 enhanced systemic insulin sensitivity, as revealed by lower insulin levels in the fasted state and an increase in the area above the curve during an insulin tolerance test. These effects were independent of changes in adiposity. Insulin-stimulated PI3K activity in skeletal muscle and adipose tissue of DIO mice was significantly reduced ∼50-65%, but this was restored completely by INT131 therapy. The INT131 effects on PI3K activity are most likely due to increased IRS-1 tyrosine phosphorylation. Concurrently, insulin-mediated Akt phosphorylation also increased after INT131 treatment in DIO mice. Importantly, INT131 therapy caused a significant increase in bone mineral density without alteration in circulating osteocalcin in these mice. These data suggest that a newly developed insulin-sensitizing agent, INT131, normalizes obesity-related defects in insulin action on PI3K signaling in insulin target tissues by a mechanism involved in glycemic control. If these data are confirmed in humans, INT131 could be used for treating type 2 diabetes without loss in bone mass.