gebhart/patrepeval huggingface dataset:
Stabilization of microtubule dynamics by estramustine by binding to a novel site in tubulin: A possible mechanistic basis for its antitumor action (1997)

The cellular targets for estramustine, an antitumor drug used in the treatment of hormone-refractory prostate cancer, are believed to be the spindle microtubules responsible for chromosome separation at mitosis. Estramustine only weakly inhibits polymerization of purified tubulin into microtubules by binding to tubulin (Kd, approximately 30 microM) at a site distinct from the colchicine or the vinblastine binding sites. However, by video microscopy, we find that estramustine strongly stabilizes growing and shortening dynamics at plus ends of bovine brain microtubules devoid of microtubule-associated proteins at concentrations substantially below those required to inhibit polymerization of the microtubules. Estramustine strongly reduced the rate and extent both of shortening and growing, increased the percentage of time the microtubules spent in an attenuated state, neither growing nor shortening detectably, and reduced the overall dynamicity of the microtubules. Significantly, the combined suppressive effects of vinblastine and estramustine on the rate and extent of shortening and dynamicity were additive. Thus, like the antimitotic mechanisms of action of the antitumor drugs vinblastine and taxol, the antimitotic mechanism of action of estramustine may be due to kinetic stabilization of spindle microtubule dynamics. The results may explain the mechanistic basis for the benefit derived from combined use of estramustine with vinblastine or taxol, two other drugs that target microtubules, in the treatment of hormone-refractory prostate cancer.
A hypervariable segment in the human dopamine receptor D4 (DRD4) gene (1993)

The human dopamine D4 receptor contains a novel polymorphism within the putative third cytoplasmic loop of the protein. The polymorphism is characterized by a varying number of direct imperfect 48-bp repeats in the gene. Pharmacological characterization has suggested that this receptor is the site through which the atypical neuroleptic clozapine exerts its antipsychotic action and that some polymorphic variants display different pharmacological properties. Further analysis of the repeat region using innovative technologies indicates that the alleles vary not only in the number of repeats (2-8 or 10 repeat units) but also in the sequence of the repeats and the order in which they appear. In 178 unrelated chromosomes we have identified 19 different repeats in 25 different haplotypes coding for 18 different predicted amino acid sequences, making this one of the most variable functional proteins currently described.
Detection of bacterial interaction with lactoferrin by an enzyme-linked ligand binding assay (ELBA) (1992)

An enzyme-linked ligand binding assay (ELBA) was devised to measure the interaction between bacteria and human (H) or bovine (B) lactoferrin (Lf) linked to horseradish peroxidase. Reagents were calibrated for optimum colour development with o-phenylenediamine as chromophore and organisms that were either positive or negative in a radioisotope-labelled ligand binding assay (RLBA) with 125I-Lf. Good correlation of Lf binding (r = 0.89) was found between ELBA and RLBA with 169 randomly selected strains of Escherichia coli. A semi-quantitative scoring system for ELBA, corresponding to a similar system for RLBA, was established and shown to be valid for 517 strains from seven species of bacterial pathogens. ELBA was used to measure bacterial Lf binding-saturation and displacement kinetics and shown to be comparable with RLBA. ELBA may be a suitable method for examining the binding of Lf to bacteria without the need for radioactive isotopes.
Hericium erinaceus (Lion’s Mane) Mushroom Extracts Inhibit Metastasis of Cancer Cells to the Lung in CT-26 Colon Cancer-Tansplanted Mice (2013)

This study investigated the antimetastatic activity of four Hericium erinaceus edible mushroom extracts using CT-26 murine colon carcinoma cells as an indicator of inhibition of cell migration to the lung. Hot water (HWE) and microwaved 50% ethanol (MWE) extracts of H. erinaceus strongly elicited cancer cell death through apoptosis and inhibited metastasis of cancer cells to the lungs by 66% and 69%, respectively. HWE and MWE reduced the expression of matrix metalloproteinases MMP-2 and MMP-9 in cells and their activities in culture media. Urokinase-type plasminogen activator (u-PA), another extracellular matrix (ECM)-degrading proteinase, also showed decreased protein expression. In CT-26 cells, HWE and MWE down-regulated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) phosphorylations. The reduced phosphorylations seem to cause reduction of activity of the MMPs, thereby blocking migration and invasion of cells. Dietary administration of HWE and MWE reduced the formation of tumor nodules in the lung by about 50% and 55%, respectively, and prevented increases in lung weight caused by cancer cell metastasis. These results demonstrate the effectiveness of HWE and MWE as beneficial antimetastatic agents, targeting their upstream signaling molecules for mediating the expression of the ECM-degrading proteinases. Acidic and alkaline extracts were not bioactive. Bioactivity seems to be related to composition. H. erinaceus edible mushrooms have the potential to serve as a health-promoting functional food.
Molecular Engineering of Glucose-Regulated Insulin Secretion (1994)

Rapid advances in the technology of gene transfer into mammalian cells have been made in recent years. These improvements in methodology have allowed investigators to begin to use molecular strategies for testing hypotheses about the role of certain genes in the process of fuel-mediated insulin release (1). To this point, most of the work has focused on genes that regulate the acute insulin secretory response to glucose. Interest in the glucose response is naturally motivated by the fact that its loss is an early event in the etiology of both major forms of diabetes (2,3). In this chapter, recent studies employing molecular approaches for dissecting the relative contributions of glucose transport and glucose phosphorylation in the control of glucose-stimulated insulin release will be reviewed.
Diamond stabilization of ice multilayers at human body temperature (2007)

Diamond is a promising material for wear-resistant medical coatings. Here we report a remarkable increase in the melting point of ice resting on a diamond (111) surface modified with a submonolayer of Na+. Our molecular dynamics simulations show that the interfacial ice bilayer melts at a temperature 130 K higher than in free ice, and relatively thick ice films (2.6 nm at 298 K and 2.2 nm at 310 K ) are stabilized by dipole interactions with the substrate. This unique physical effect may enable biocompatibility-enhancing ice overcoatings for diamond at human body temperature.
Highly Enantioselective α-Alkenylation of Aldehydes and Ketones (1996)

The enantioselective synthesis of α-substituted β,γ-unsaturated aldehydes and ketones 6 via aldol reaction of SAMP-hydrazones (S)-2 with racemic α-phenylselenyl aldehydes 3 in good overall yields and high enantiomeric excesses (ee = 89-94%) is described.
Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies (2009)

We have analyzed host cell genes linked to HIV replication that were identified in nine genome-wide studies, including three independent siRNA screens. Overlaps among the siRNA screens were very modest (<7% for any pairwise combination), and similarly, only modest overlaps were seen in pairwise comparisons with other types of genome-wide studies. Combining all genes from the genome-wide studies together with genes reported in the literature to affect HIV yields 2,410 protein-coding genes, or fully 9.5% of all human genes (though of course some of these are false positive calls). Here we report an "encyclopedia" of all overlaps between studies (available at http://www.hostpathogen.org), which yielded a more extensively corroborated set of host factors assisting HIV replication. We used these genes to calculate refined networks that specify cellular subsystems recruited by HIV to assist in replication, and present additional analysis specifying host cell genes that are attractive as potential therapeutic targets.
Microcrystalline cellulose, a direct compression binder in a quality by design environment—A review (2014)

The ICH quality vision introduced the concept of quality by design (QbD), which requires a greater understanding of the raw material attributes, of process parameters, of their variability and their interactions. Microcrystalline cellulose (MCC) is one of the most important tableting excipients thanks to its outstanding dry binding properties, enabling the manufacture of tablets by direct compression (DC). DC remains the most economical technique to produce large batches of tablets, however its efficacy is directly impacted by the raw material attributes. Therefore excipients' variability and their impact on drug product performance need to be thoroughly understood. To help with this process, this review article gathers prior knowledge on MCC, focuses on its use in DC and lists some of its potential critical material attributes (CMAs).
Aminoglycoside Prescribing and Surveillance in Cystic Fibrosis (2003)

lean mass, of which 70% is body water and the remainder muscle. After intravenous administration, aminoglycosides distribute rapThe potential of aminoglycoside antibiotics to cause ototoxic idly throughout the extracellular fluid compartment, with peak seand nephrotoxic damage was first discovered in 1945, during rum levels achieved within 30 minutes of the end of a 30-minute early clinical trials of streptomycin (1). Despite the introduction infusion. of newer classes of antibiotics, aminoglycosides continue to be Patients with CF are typically prescribed high dose prolonged widely prescribed in cystic fibrosis (CF) clinics and are likely to courses of intravenous antibiotics based upon reports of altered retain an important role in the management of CF lung disease pharmacokinetics (7) and due to the nature and severity of CF for the foreseeable future. They are highly active against Pseu- disease. The volume of distribution and the rate of clearance of domonas aeruginosa, display synergism with -lactam antibiotics aminoglycosides are increased, with the half-life of tobramycin (2), and effectively penetrate the sputum of patients with CF (3). between 2 and 3 hours. Aminoglycosides undergo minimal proPatients with CF can now expect to live into the fourth decade tein binding and are eliminated almost entirely by glomerular and beyond, with full-time education followed by employment filtration. and an active lifestyle being attainable goals. Therefore, the role of the CF clinician when prescribing repeated courses of Starting Dose potentially toxic drugs is to ensure optimal efficacy with minimal The starting dose of aminoglycosides is traditionally calculated cumulative toxicity. Guidance on how to prescribe aminoglyco- from body surface area (60–75 mg/m 2 /dose) (8), body weight sides effectively and minimize the risks of developing toxicity is (3.3–5 mg/kg/dose) (9), or from past records of doses that needed. achieved therapeutic levels. In our practice, the maximum total There remains controversy surrounding the prevalence, im- daily dose prescribed is 660 mg in three divided doses. Although portance, and the role of surveillance of aminoglycoside-induced these clinician-led techniques require only simple calculations,
Role of NFκB in antigen presentation and development of regulatory T cells elucidated by treatment of dendritic cells with the proteasome inhibitor PSI (2001)

Dendritic cells (DC) are the most potent antigen-presenting cells for naive T cells, due to their high expression of MHC and costimulatory molecules, but relatively little is known about the biochemical pathways that regulate this function. We used the proteasome inhibitor N-benzyloxycarbonyl-Ile-Glu(O-tert-butyl)-Ala-leucinal (PSI) to demonstrate that DC antigen presentation is NFkappaB dependent. As PSI is not a specific inhibitor of NFkappaB, we reproduced this finding using a very specific approach, namely adenoviral gene transfer of IkappaBalpha, the naturally occurring inhibitor of NFkappaB. The mechanism for this inhibition of DC antigen presentation involves at least three aspects of antigen presenting function: down-regulation of HLA class II, down-regulation of CD86, and inhibition of the immunostimulatory cytokines IL-12 and TNF-alpha. In the light of the marked down-regulation of antigen-presentation cell function, it was of interest to investigate what effects exposure to PSI-treated DC might have on T cell function. It was found that immunological tolerance was induced, as challenge of T cells previously exposed to PSI-treated DC, with normal DC from the same donor did not restore their response, despite the presence of viable T cells. There were also changes in T cell surface markers, with down-regulation of CD3 and CD25 expression, and inhibition of the production of Th1 cytokines like IL-2 and IFN-gamma. These results demonstrates that NFkappaB is an effective target for blocking DC antigen presentation and inhibiting T cell-dependent immune responses, and this has implications for the development of therapeutic agents for use in multiple conditions, including transplantation, allergy and autoimmune diseases.
Comparison of routing metrics for static multi-hop wireless networks (2004)

Routing protocols for wireless ad hoc networks have traditionally focused on finding paths with minimum hop count. However, such paths can include slow or lossy links, leading to poor throughput. A routing algorithm can select better paths by explicitly taking the quality of the wireless links into account. In this paper, we conduct a detailed, empirical evaluation of the performance of three link-quality metrics---ETX, per-hop RTT, and per-hop packet pair---and compare them against minimum hop count. We study these metrics using a DSR-based routing protocol running in a wireless testbed. We find that the ETX metric has the best performance when all nodes are stationary. We also find that the per-hop RTT and per-hop packet-pair metrics perform poorly due to self-interference. Interestingly, the hop-count metric outperforms all of the link-quality metrics in a scenario where the sender is mobile.
Role of Tyrosine Phosphorylation in Potassium Channel Activation (1995)

Chinese hamster ovary (CHO) cells, stably transfected with the long form of the prolactin (PRL) receptor (PRL-R) cDNA, were used for PRL-R signal transduction studies. Patch-clamp technique in whole cell and cell-free configurations were employed. Exposure of transfected CHO cells to 5 nM PRL led to the increase of Ca(2+)- and voltage-dependent K+ channel (KCa) activity. The effect was direct as it was observed also in excised patch experiments. A series of tyrosine kinase inhibitors was studied to investigate the possible involvement of protein tyrosine kinases in KCa functioning and its stimulation by PRL. Genistein, lavendustin A, and herbimycin A decreased in a concentration and time-dependent manner the amplitude of the KCa current in whole cell and the open probability of KCa channels in cell-free experiments. The subsequent application of PRL was ineffective. The protein tyrosine phosphatase inhibitor orthovanadate (1 mM) stimulated KCa channel activity in excised patches, indicating that channels can be modulated in opposite directions by protein tyrosine kinase and protein tyrosine phosphatase. Moreover, in whole cell experiments as well as in excised patch recordings, anti-JAK2 tyrosine kinase antibody decreased the KCa conductance and the open probability of the KCa channels. Subsequent application of PRL was no longer able to stimulate KCa conductance. Immunoblotting studies using the same anti-JAK2 antibody, revealed the constitutive association of JAK2 kinase with PRL-R. Preincubation of anti-JAK2 antibody with the JAK2 Immunizing Peptide abolished the effects observed using anti-JAK2 antibody alone in both electrophysiological and immunoblotting studies. We conclude from these findings that these KCa channels are regulated through tyrosine phosphorylation/dephosphorylation; JAK2 tyrosine kinase, constitutively associated with PRL-R, is implicated in PRL stimulation of KCa channels.
New whitefly-transmitted closterovirus identified in tomatoes (1997)

A new virus of tomato, tomato infectious chlorosis virus (TICV), has been identified in both field-and greenhouse-grown tomatoes in California, North Carolina and Italy. TICV is transmitted by the greenhouse whitefly (Trialeurodes vaporariorum) in a semipersistent manner. TICV infects a wide range of plant hosts, and has been found naturally infecting Petunia and Ranunculus in greenhouses, and tree tobacco, commercial artichoke and bristly oxtongue in the southern coastal region of California. Because of its wide host range, the prevalence of the greenhouse whitefly in fields and greenhouses, and the movement of susceptible plant hosts within and among countries around the world, TICV is a potential problem for the world's tomato industry. TICV caused an estimated $2 million loss in Orange County in 1993. Control measures include whitefly control, confirmation of TICV infection by a diagnostic test and roguing of infected plants.
Mutagenesis of the phosphate‐binding pocket of KDPG aldolase enhances selectivity for hydrophobic substrates (2007)

Narrow substrate specificities often limit the use of enzymes in biocatalysis. To further the development of Escherichia coli 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase as a biocatalyst, the molecular determinants of substrate specificity were probed by mutagenesis. Our data demonstrate that S184 is located in the substrate-binding pocket and interacts with the phosphate moiety of KDPG, providing biochemical support for the binding model proposed on the basis of crystallographic data. An analysis of the substrate selectivity of the mutant enzymes indicates that alterations to the phosphate-binding site of KDPG aldolase changes the substrate selectivity. We report mutations that enhance catalysis of aldol cleavage of substrates lacking a phosphate moiety and demonstrate that electrophile reactivity correlates with the hydrophobicity of the substituted side chain. These mutations improve the selectivity for unnatural substrates as compared to KDPG by up to 2000-fold. Furthermore, the S184L KDPG aldolase mutant improves the catalytic efficiency for the synthesis of a precursor for nikkomycin by 40-fold, making it a useful biocatalyst for the preparation of fine chemicals.
Advanced Openhole Multilaterals (2002)

This article, written by Assistant Technology Editor Karen Bybee, contains highlights of paper SPE 77199, "Advanced Openhole Multilaterals," by D.G. Hurst, SPE, S.P. Hart, SPE, and W.H. Brown, SPE, Weatherford Intl., originally presented at the 2002 IADC/SPE Asia Pacific Drilling Technology, Jakarta, 9-11 September.
Natural Killer Cell Activity of Prostatic Cancer Patients (1987)

Natural killer (NK) cell activity of prostatic cancer patients was compared with that of control groups by the radioactive indium (IIIIn) release assay using the K562 and H494 cells as targets. Patients suffering from advanced prostatic cancer (clinical stages C and D) exhibited significantly lower NK activity against K562 cells (28 ± 18%) than did the normal group (41 ± 19%). The lower NK activity of these patients is not related to their age, since patients in the same age range with localized cancer (stage B) or benign prostatic hyperplasia did not show low NK activity (37% ± 19%). This lower NK activity is not due to a depletion of the NK cell precursor population, since the NK activity of advanced cancer patients improves significantly after in vitro incubation with interferon. The NK activity of normal subjects or patient groups showed wide fluctuations during the 18-month observation period. Because of these interassay variations, it is necessary to use standard control subjects during long-term monitoring of the NK activity of the patients.
Kinetics of heterogeneous hybridization on indium tin oxide surfaces with and without an applied potential (2002)

The rate of hybridization of oligonucleotide target sequences to chemically immobilized oligonucleotide probes has been studied both with and without an electrical field. The probe size was 20-24 nucleotides (nt) while the target size ranged from 157 to 864 nt. In agreement with previous studies, complete hybridization under normal conditions required 10-30 hours, depending on target size. The kinetics were characterized by a characteristic lag time followed by an asymptotic rise to the final value. In contrast, with an applied electrical field, all but the largest target hybridized in about 10 min while the longest hybridized within 1 h. Deleterious electrode reactions were avoided by close spacing of the anode and cathode and application of very small voltages. Our results suggest that probes and targets orient flat on the surface. A model is suggested to explain the kinetics observed that involves a series of surface states between initial target arrival and final hybridized state. Our results show that the electric field accelerated hybrid capture of solution-phase targets by surface-bound probes. This approach may have implications for enhancing array-based hybrid capture for mutation detection, copy number determination and/or gene expression profiling.
Water-stable organic transistors and their application in chemical and biological sensors (2008)

The development of low-cost, reliable sensors will rely on devices capable of converting an analyte binding event to an easily read electrical signal. Organic thin-film transistors (OTFTs) are ideal for inexpensive, single-use chemical or biological sensors because of their compatibility with flexible, large-area substrates, simple processing, and highly tunable active layer materials. We have fabricated low-operating voltage OTFTs with a cross-linked polymer gate dielectric, which display stable operation under aqueous conditions over >10(4) electrical cycles using the p-channel semiconductor 5,5'-bis-(7-dodecyl-9H-fluoren-2-yl)-2,2'-bithiophene (DDFTTF). OTFT sensors were demonstrated in aqueous solutions with concentrations as low as parts per billion for trinitrobenzene, methylphosphonic acid, cysteine, and glucose. This work demonstrates of reliable OTFT operation in aqueous media, hence opening new possibilities of chemical and biological sensing with OTFTs.
Efficient compression method for integral images using multi-view video coding (2011)

Integral imaging is an attractive auto-stereoscopic three dimensional (3D) technique for next generation 3DTV. To improve its video quality, new techniques are required to effectively compress the huge volume of integral image (II) data. In this paper, a new compression method implemented by multi-view video coding (MVC) is provided and used for sub-images (SI). SI is an alternative form of 2D image transformed from original II. Each SI represents the 3D scene from parallel viewing directions and contains superior compression capabilities than original captured elemental images (EI). For this reason, we consider arranging the group of SIs as the format of multi-view video (MVV) and then encode the generated MVV by MVC standard. Experimental results show that our proposed compression approach improves the compression efficiency when compared to the traditional MPEG-4/AVC compression method for II.