gebhart/patrepeval huggingface dataset:
Fluorescence Polarization: An Analytical Tool for Immunoassay and_ Drug Discovery (1999)

Fluorescence polarization (FP) is an intrinsically powerful technique for the rapid and homogeneous analysis of molecular interactions in biological/chemical systems. The technique has been successfully used to diagnose various viral and infectious diseases in humans and animals, to monitor therapeutic drug levels and substances of abuse in body fluids and to determine food born pathogens, grain mycotoxins and pesticides. It has also been used in monitoring enzyme catalyzed hydrolysis, protein-protein interactions, DNA diagnostics and high throughput screening during the course of drug discovery. Work by various groups, including our own, have demonstrated that the technique can replace a substantial number of solid phase assays. FP, defined by the equation P = [IV - IH] / [IV + IH] (where V and H are the vertical and horizontal components of the intensity I of emitted light respectively when exited by vertically plane polarized light), is independent of the intensity of the light and the concentration of the fluorophore. Hence it is functional in colored and cloudy solutions. The FP of a fluorophore is proportional to its rotational relaxation time, which in turn depends upon its molecular volume (or molecular weight) at constant temperature and solution viscosity. When a fluorophore-labeled ligand binds to a larger molecule, equilibrium is established rapidly and the FP increases. This property has been successfully exploited in many fields as described in this review.
Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans (2000)

Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.
Conductivity, morphology, interfacial chemistry, and stability of poly(3,4‐ethylene dioxythiophene)–poly(styrene sulfonate): A photoelectron spectroscopy study (2003)

Abstract X‐ray photoelectron spectroscopy (XPS) has been used to characterize poly(3,4‐ethylene dioxythiophene)–poly(styrene sulfonate) (PEDT/PSS), one of the most common electrically conducting organic polymers. A correlation has been established between the composition, morphology, and polymerization mechanism, on the one hand, and the electric conductivity of PEDT/PSS, on the other hand. XPS has been used to identify interfacial reactions occurring at the polymer‐on‐ITO and polymer‐on‐glass interfaces, as well as chemical changes within the polymer blend induced by electrical stress and exposure to ultraviolet light. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 2561–2583, 2003
Expression, inducer spectrum, domain structure, and function of MopR, the regulator of phenol degradation in Acinetobacter calcoaceticus NCIB8250 (1997)

Degradation of phenol by Acinetobacter calcoaceticus NCIB8250 involves (sigma54-dependent expression of a multicomponent phenol hydroxylase and catechol 1,2-dioxygenase encoded by the mop operon. Complementation of a new mutant deficient in phenol utilization yielded the regulatory locus mopR. It is located in divergent orientation next to the mop operon. MopR is constitutively expressed at a low level from a sigma70-type promoter and belongs to the NtrC family of regulators. The amino acid sequence is similar to that of XylR regulating xylene degradation and to that of DmpR regulating dimethylphenol degradation in Pseudomonas spp. However, it shows a different effector profile for substituted phenols than DmpR. MopR activates phenol hydroxylase expression in the presence of phenol in Escherichia coli, indicating that it binds the effector. The phenol binding A domains of MopR and DmpR have fewer identical residues than the A domains of DmpR and XylR, despite the fact that XylR recognizes different effectors. This suggests that sequence conservation in the A domain does not reflect the potential to bind the respective effectors. Overexpression of the MopR A domain in the presence of wild-type MopR causes loss of mop inducibility by phenol, establishing its negative transdominance over MopR. Deletion of 110 residues from the N terminus did not affect transdominance of the truncated domain, whereas deletion of 150 residues abolished it completely. This result establishes the distinction of two subdomains, A(N) and A(C), which together constitute the A domain. The C-terminal portion of the A domain, A(C), shows considerable affinity for the C domain, even in the presence of the trigger phenol.
Compact, low-crosstalk, and low-propagation-loss quantum-well Y-branch switches (1996)

We demonstrate a quantum-well Y-branch switch designed for low crosstalk, low propagation loss, and compact size. The active waveguide core is composed of InGaAsP-InP quantum wells for reverse-bias electrorefractive switching. We achieve -20-dB crosstalk and 2-dB/cm propagation loss with a 2-mm-long switch.
Effect of Δ-9-Tetrahydrocannabinol and Cannabidiol on Nocturnal Sleep and Early-Morning Behavior in Young Adults (2004)

The effects of cannabis extracts on nocturnal sleep, early-morning performance, memory, and sleepiness were studied in 8 healthy volunteers (4 males, 4 females; 21 to 34 years). The study was double-blind and placebo-controlled with a 4-way crossover design. The 4 treatments were placebo, 15 mg Delta-9-tetrahydrocannabinol (THC), 5 mg THC combined with 5 mg cannabidiol (CBD), and 15 mg THC combined with 15 mg CBD. These were formulated in 50:50 ethanol to propylene glycol and administered using an oromucosal spray during a 30-minute period from 10 pm. The electroencephalogram was recorded during the sleep period (11 pm to 7 am). Performance, sleep latency, and subjective assessments of sleepiness and mood were measured from 8:30 am (10 hours after drug administration). There were no effects of 15 mg THC on nocturnal sleep. With the concomitant administration of the drugs (5 mg THC and 5 mg CBD to 15 mg THC and 15 mg CBD), there was a decrease in stage 3 sleep, and with the higher dose combination, wakefulness was increased. The next day, with 15 mg THC, memory was impaired, sleep latency was reduced, and the subjects reported increased sleepiness and changes in mood. With the lower dose combination, reaction time was faster on the digit recall task, and with the higher dose combination, subjects reported increased sleepiness and changes in mood. Fifteen milligrams THC would appear to be sedative, while 15 mg CBD appears to have alerting properties as it increased awake activity during sleep and counteracted the residual sedative activity of 15 mg THC.
Non‐conventional Frizzled ligands and Wnt receptors (2008)

The Wnt family of secreted signaling factors plays numerous roles in embryonic development and in stem cell biology. In the adult, Wnt signaling is involved in tissue homeostasis and mutations that lead to the overexpression of Wnt can be linked to cancer. Wnt signaling is transduced intracellularly by the Frizzled (Fzd) family of receptors. In the canonical pathway, accumulation of beta-catenin and the subsequent formation of a complex with T cell factors (TCF) or lymphoid enhancing factors (Lef) lead to target gene activation. The identification of Ryk as an alternative Wnt receptor and the discovery of the novel Fzd ligands Norrie disease protein (NDP) and R-Spondin, changed the traditional view of Wnts binding to Fzd receptors. Mouse R-Spondin cooperates with Wnt signaling and Low density lipoprotein (LDL) receptor related protein (LRP) to activate beta-catenin dependent gene expression and is involved in processes such as limb and placental development in the mouse. NDP is the product of the Norrie disease gene and controls vascular development in the retina, inner ear and in the female reproductive system during pregnancy. In this review a functional overview of the interactions of the different Wnt and non-Wnt ligands with the Fzd receptors is given as well as a survey of Wnts binding to Ryk and we discuss the biological significance of these interactions.
Purine-Scaffold Hsp90 Inhibitors (2009)

Hsp90 is a molecular chaperone with important roles in regulating the function of several proteins with potential pathogenic activity. Because many of these proteins are involved in cancer and neurodegenerative promoting pathways, Hsp90 has emerged as an attractive therapeutic target in these diseases. Molecules that bind to the N-terminal nucleotide pocket of Hsp90 inhibit its activity, and consequently, disrupt client protein function. A number of these inhibitors from several chemical classes are now known, and some are already in clinical trials. This review focuses on the purine class of Hsp90 inhibitors, their discovery through rational design, and on efforts aimed towards their optimization and development into clinically viable drugs for the treatment of cancer. Their potential towards neurodegenerative diseases will also be touched upon.
3D prestack plane-wave, full-waveform inversion (2008)

Abstract Prestack depth migration has been used for decades to derive velocity distributions in depth. Numerous tools and methodologies have been developed to reach this goal. Exploration in geologically more complex areas exceeds the abilities of existing methods. New data-acquisition and data-processing methods are required to answer these new challenges effectively. The recently introduced wide-azimuth data acquisition method offers better illumination and noise attenuation as well as an opportunity to more accurately determine velocities for imaging. One of the most advanced tools for depth imaging is full-waveform inversion. Prestack seismic full-waveform inversion is very challenging because of the nonlinearity and nonuniqueness of the solution. Combined with multiple iterations of forward modeling and residual wavefield back propagation, the method is computer intensive, especially for 3D projects. We studied a time-domain, plane-wave implementation of 3D waveform inversion. We found that plane-wave gathers are an attractive input to waveform inversion with dramatically reduced computer run times compared to traditional shot-gather approaches. The study was conducted on two synthetic data sets — Marmousi2 and SMAART Pluto 1.5 — and a field data set. The results showed that a velocity field can be reconstructed well using a multiscale time-domain implementation of waveform inversion. Although the time-domain solution does not take advantage of wavenumber redundancy, the method is feasible on current computer architectures for 3D surveys. The inverted velocity volume produces a quality image for exploration geologists by using numerous iterations of waveform inversion.
Polyamine amide toxins as pharmacological tools and pharmaceutical agents (1992)

Synopsis: The polyamine amides comprise a newly-discovered class of compounds which exhibits considerable potential for the development of selective pharmacological tools and pharmaceutical agents. In mammals and other vertebrates, they are selective, non-competitive antagonists of ionotropic glutamate receptors, but they also interact with other ionotropic receptors (e.g. nicotinic acetylcholine receptors). Thus, they are channel blockers which are selective for cation channels. We report on synthetic studies undertaken to produce hybrid analogues of these toxins based upon the argiotoxins of spider venoms and the philanthotoxins of parasitic, predatory wasp venom. The synthesis and characterisation of a mono-acylated spermine is also described. In addition, an account of current views on the many possible sites and modes of actions of the polyamine amides is presented and their potential for therapeutic neurochemistry, e.g. for the possible treatment of ischaemic damage to the nervous system, is highlighted.
Halide ion catalyzed glycosidation reactions. Syntheses of .alpha.-linked disaccharides (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHalide ion catalyzed glycosidation reactions. Syntheses of .alpha.-linked disaccharidesR. U. Lemieux, K. B. Hendriks, R. V. Stick, and K. JamesCite this: J. Am. Chem. Soc. 1975, 97, 14, 4056–4062Publication Date (Print):July 1, 1975Publication History Published online1 May 2002Published inissue 1 July 1975https://pubs.acs.org/doi/10.1021/ja00847a032https://doi.org/10.1021/ja00847a032research-articleACS PublicationsRequest reuse permissionsArticle Views4108Altmetric-Citations641LEARN 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
Tumor escape from immune surveillance. (1999)

The bases for an efficient anti-tumor immune response begin to be better defined. Nonetheless, neoplastic cells develop various strategies to escape immune surveillance, which are discussed here in order to better design the therapeutic possibilities of immune manipulation. The absence of specific tumor antigen as well as the weak expression of major histocompatibility complex (MHC) molecules hinder the recognition of the neoplastic cells by T lymphocytes. The defect of expression by the tumor of the ligands for the T cell activation costimulatory molecules is particularly harmful for the immune response since it induces tolerance. Finally, tumor cells can inactivate effector T lymphocytes through the secretion of inhibitory cytokines, induction of apoptosis or functional inactivation. The multiplicity of the means to oppose an effective anti-tumor response challenges the adaptative mechanisms of the immune system. For example, the natural killer cells target tumor cells not expressing MHC class I molecules. Numerous possibilities of tumor immunogenicity restoration have been demonstrated at least in vitro, such as stimulation of the cancerous cells by CD40 or cytokine treatment, which could lead to several promising therapeutical approaches.
Suppression of Tumorigenicity of Human Prostate Carcinoma Cells by Replacing a Mutated RB Gene (1990)

Introduction of a normal retinoblastoma gene (RB) into retinoblastoma cells was previously shown to suppress several aspects of their neoplastic phenotype, including tumorigenicity in nude mice, thereby directly demonstrating a cancer suppression function of RB. To explore the possibility of a similar activity in a common adult tumor, RB expression was examined in three human prostate carcinoma cell lines. One of these, DU145, contained an abnormally small protein translated from an RB messenger RNA transcript that lacked 105 nucleotides encoded by exon 21. To assess the functional consequences of this mutation, normal RB expression was restored in DU145 cells by retrovirus-mediated gene transfer. Cells that maintained stable exogenous RB expression lost their ability to form tumors in nude mice, although their growth rate in culture was apparently unaltered. These results suggest that RB inactivation can play a significant role in the genesis of a common adult neoplasm and that restoration of normal RB-encoded protein in tumors could have clinical utility.
Wrapper generation for semi-structured Internet sources (1997)

With the current explosion of information on the World Wide Web (WWW) a wealth of information on many different subjects has become available on-line. Numerous sources contain information that can be classified as semi-structured. At present, however, the only way to access the information is by browsing individual pages. We cannot query web documents in a database-like fashion based on their underlying structure. However, we can provide database-like querying for semi-structured WWW sources by building wrappers around these sources. We present an approach for semi-automatically generating such wrappers. The key idea is to exploit the formatting information in pages from the source to hypothesize the underlying structure of a page. From this structure the system generates a wrapper that facilitates querying of a source and possibly integrating it with other sources. We demonstrate the ease with which we are able to build wrappers for a number of internet sources in different domains using our implemented wrapper generation toolkit.
Regulation of proplatelet formation and platelet release by integrin αIIbβ3 (2006)

Mature megakaryocytes form structures called proplatelets that serve as conduits for platelet packaging and release at vascular sinusoids. Since the megakaryocyte expresses abundant levels of integrin alpha IIb beta3, we have examined a role for fibrinogen in proplatelet development and platelet release alongside that of other matrices. Primary mature murine megakaryocytes from bone marrow aspirates readily formed proplatelets when plated on fibrinogen at a degree that was significantly higher than that seen on other matrices. In addition, alpha IIb beta3 was essential for proplatelet formation on fibrinogen, as megakaryocytes failed to develop proplatelets in the presence of alpha IIb beta3 antagonists. Interestingly, inhibition of Src kinases or Ca2+ release did not inhibit proplatelet formation, indicating that alpha IIb beta3-mediated outside-in signals are not required for this response. Immunohistochemical studies demonstrated that fibrinogen is localized to the bone marrow sinusoids, a location that would allow it to readily influence platelet release. Further, thrombopoietin-stimulated alpha IIb-/- mice had a reduced increase in platelet number relative to controls. A similar observation was not observed for platelet recovery in alpha IIb-/- mice in response to antibody-induced thrombocytopenia, indicating the existence of additional pathways of regulation of proplatelet formation. These results demonstrate that fibrinogen is able to regulate proplatelet formation via integrin alpha IIb beta3.
Rifampin, a cytochrome P450 3A inducer, decreases plasma concentrations of antipsychotic risperidone in healthy volunteers (2007)

Rifampin when used concurrently with risperidone significantly decreases the plasma concentration of risperidone. Our results provide in vivo evidence of the involvement of CYP3A in the metabolism of risperidone, in addition to CYP2D6. Thus, co-administration of risperidone with CYP3A inducer(s), including rifampin should be recognized or avoided in clinical practice.
Amphiregulin is an essential mediator of estrogen receptor α function in mammary gland development (2007)

Most mammary gland development occurs after birth under the control of systemic hormones. Estrogens induce mammary epithelial cell proliferation during puberty via epithelial estrogen receptor alpha (ERalpha) by a paracrine mechanism. Epidermal growth factor receptor (EGFR) signaling has long been implicated downstream of ERalpha signaling, and several EGFR ligands have been described as estrogen-target genes in tumor cell lines. Here, we show that amphiregulin is the unique EGF family member to be transcriptionally induced by estrogen in the mammary glands of puberal mice at a time of exponential expansion of the ductal system. In fact, we find that estrogens induce amphiregulin through the ERalpha and require amphiregulin to induce proliferation of the mammary epithelium. Like ERalpha, amphiregulin is required in the epithelium of puberal mice for epithelial proliferation, terminal end buds formation, and ductal elongation. Subsequent stages, such as side-branching and alveologenesis, are not affected. When amphiregulin(-/-) mammary epithelial cells are in close vicinity to wild-type cells, they proliferate and contribute to all cell compartments of the ductal outgrowth. Thus, amphiregulin is an important paracrine mediator of estrogen function specifically required for puberty-induced ductal elongation, but not for any earlier or later developmental stages.
It's time to regulate: Coping with product‐induced nongenetic clonal instability in CHO cell lines via regulated protein expression (2014)

Clonal instability and titer loss during Chinese hamster ovary (CHO) cell line development (CLD) has several underlying causes, the most prominent of which are DNA copy number loss and DNA silencing. However, in some cases, clonal instability is due to the toxicity of the therapeutic protein(s) that clones express. Unlike DNA copy number loss, which may occur in some clones or DNA silencing that is prevalent in certain regions of the genome, the hallmark of product induced clonal instability is its manifestation in all the selected clones. To circumvent such product induced clonal instability, we have developed a vector construct that utilizes a regulated protein expression system in which the constitutive expression of the target protein(s) is prevented unless doxycycline is added to the culture. We have then successfully used this system to express, at high titers, an antibody for which constitutive expression results in clonal instability perhaps due to intracellular accumulation of the antibody. Our data shows that unlike the constitutively expressed or continuously induced clones, uninduced clones do not display instability. Furthermore, maintaining the uninduced clones in culture for months or subjecting them to freeze-thaws did not have any effects on their titers. All together, our findings suggest that a regulated expression system could be suitable for production of difficult proteins that trigger instability.