gebhart/patrepeval huggingface dataset:
Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation (2006)

Characteristics of the tumour that affect and predict the survival outcome of patients with cancer are prognostic markers for cancer. In non-small cell lung carcinoma (NSCLC), stage is the main determinant of prognosis and the basis for deciding options for treatment. Patients with early-stage tumour are treated by complete surgical resection, which is curative in 40-70% of patients. That there are other factors important in determining the biology of these tumours, especially genes that have a role in metastasis, is indicated. Such factors could potentially be used to further classify patients into groups according to substages that may be treated differently. During the past decade, a large number of proteins that are putatively important in carcinogenesis and cancer biology have been studied for their prognostic value in NSCLC, but none of them have been proved to be sufficiently useful in clinical diagnosis. Several markers (epidermal growth factor receptor, human epidermal growth factor receptor 2, Ki-67, p53 and Bcl-2) have been studied exhaustively. Ki-67, p53 and Bcl-2 are suggested to be important but weak prognostic markers, by meta-analyses of the results. Cyclin E, vascular endothelial growth factor A, p16(INK4A), p27(kip1) and beta-catenin are promising candidates, but require further study in large randomised clinical trial samples by using standardised assays and scoring systems. Some issues and inconsistencies in the reported studies to date are highlighted and discussed. A guideline for a multi-phase approach for conducting future studies on prognostic immunohistochemistry markers is proposed here.
Synthesis of Biologically Active Peptide Nucleic Acid−Peptide Conjugates by Sortase-Mediated Ligation (2007)

Sortase A is a transpeptidase that cleaves at a pentapeptide-motif and subsequently transfers the acyl component to a nucleophile containing N-terminal oligoglycines. We investigate the reaction conditions of the sortase-mediated ligation and demonstrate a useful application by the synthesis of a peptide nucleic acid-cell-penetrating peptide chimera, the reaction equilibrium of which can be shifted in favor of the product by dialyzing out the low molecular weight byproduct. The synthesized conjugate exhibits dose-dependent antisense activity.
Alexandrite-pumped alexandrite regenerative amplifier for femtosecond pulse amplification (1996)

We demonstrate a regenerative amplif ier incorporating alexandrite as the gain medium that is pumped by an alexandrite laser. Temperature-altered gain permitted the 728-nm alexandrite pump laser, operating at room temperature, to pump a 780-800-nm alexandrite laser that was maintained at elevated temperatures. 200-fs pulses from a Ti:sapphire oscillator were amplif ied to the millijoule level. This system also amplif ied femtosecond pulses from a frequency-doubled Er-doped fiber laser.
A NovelVal648IleSubstitution inRETProtooncogene Observed in aCys634ArgMultiple Endocrine Neoplasia Type 2A Kindred Presenting with an Adrenocorticotropin-Producing Pheochromocytoma (2002)

Multiple endocrine neoplasia type 2 (MEN 2) comprises a heterogeneous group of neoplasic disorders that most commonly have a single missense substitution of the RET protooncogene (RET) involving exons 10 and 11. It was previously reported a MEN 2A kindred in which the father presented with a rare phenotype consisting of bilateral ACTH-producing pheochromocytoma and medullary thyroid carcinoma. We recently performed mutational analysis of the father and his 4 children using a denaturing gradient gel electrophoresis approach and PCR-amplified genomic DNA, followed by direct sequencing or restriction fragment length polymorphism testing. All 4 children showed a RET sequence variation. The common exon 11 Cys(634)Arg RET mutation was present in 2 of the 4 children who had undergone thyroidectomy for C cell disease. The remaining 2 children, who did not harbor the Cys(634)Arg mutation and are negative for C cell and adrenal disease, carry a previously unreported Val(648)Ile missense change in RET exon 11. This novel substitution was not found in the unaffected mother or in 200 control alleles. Both RET variants were present in the father affected with MEN 2A and the unusual ACTH-producing pheochromocytoma. We speculate that the double RET mutation may have modified and contributed to the rare MEN 2A phenotype in the father.
Synthesis and antiviral activity of certain nucleoside 5'-phosphonoformate derivatives (1986)

(Ethoxycarbonyl)phosphonic dichloride (3) was synthesized by chlorination of bis(trimethylsilyl) (ethoxycarbonyl)phosphonate with thionyl chloride. Adenosine 5'-(ethoxycarbonyl)phosphonate (4), guanosine 5'-(ethoxycarbonyl)phosphonate (5), 2'-deoxyadenosine 5'-(ethoxycarbonyl)phosphonate (18) and 2'-deoxyguanosine 5'-(ethoxycarbonyl)phosphonate (19) were synthesized by coupling of compound 3 with adenosine, guanosine, 2'-deoxyadenosine, and 2'-deoxyguanosine, respectively. Alkaline treatment of 4, 5, 18, and 19 gave the corresponding adenosine 5'-(hydroxycarbonyl)phosphonate (14), guanosine 5'-(hydroxycarbonyl) phosphonate (15), 2'-deoxyadenosine 5'-(hydroxycarbonyl)phosphonate (20), and 2'-deoxyguanosine 5'-(hydroxycarbonyl) phosphonate (21). Treatment of 4 and 5 with methanolic ammonia resulted in the production of adenosine 5'-(aminocarbonyl)phosphonate (12) and guanosine 5'-(aminocarbonyl)phosphonate (13), respectively. The nucleotide analogue 20 exhibited the most potent antiviral activity of this group of nucleotide tested in vitro and was most active against herpes viruses especially HSV-2. The nucleotide analogue 21 had lower, but significant, activity against HSV-2. All of the compounds tested were nontoxic to confluent Vero cells at concentrations as high as 5000 microM.
The β-Oxidation Systems ofEscherichia coliandSalmonella entericaAre Not Functionally Equivalent (2005)

Based on its genome sequence, the pathway of beta-oxidative fatty acid degradation in Salmonella enterica serovar Typhimurium LT2 has been thought to be identical to the well-characterized Escherichia coli K-12 system. We report that wild-type strains of S. enterica grow on decanoic acid, whereas wild-type E. coli strains cannot. Mutant strains (carrying fadR) of both organisms in which the genes of fatty acid degradation (fad) are expressed constitutively are readily isolated. The S. enterica fadR strains grow more rapidly than the wild-type strains on decanoic acid and also grow well on octanoic and hexanoic acids (which do not support growth of wild-type strains). By contrast, E. coli fadR strains grow well on decanoic acid but grow only exceedingly slowly on octanoic acid and fail to grow at all on hexanoic acid. The two wild-type organisms also differed in the ability to grow on oleic acid when FadR was overexpressed. Under these superrepression conditions, E. coli failed to grow, whereas S. enterica grew well. Exchange of the wild-type fadR genes between the two organisms showed this to be a property of S. enterica rather than of the FadR proteins per se. This difference in growth was attributed to S. enterica having higher cytosolic levels of the inducing ligands, long-chain acyl coenzyme As (acyl-CoAs). The most striking results were the differences in the compositions of CoA metabolites of strains grown with octanoic acid or oleic acid. S. enterica cleanly converted all of the acid to acetyl-CoA, whereas E. coli accumulated high levels of intermediate-chain-length products. Exchange of homologous genes between the two organisms showed that the S. enterica FadE and FadBA enzymes were responsible for the greater efficiency of beta-oxidation relative to that of E. coli.
Combinatorial Genetic Technology for the Development of New Anti-infectives (2004)

Antimicrobials produced using CGT will provide new therapies for the treatment of infections caused by human pathogens that are resistant to current antibiotics. The new therapeutics will be less susceptible to de novo resistance because CGT identifies all mutations of the target that might lead to resistance during the earliest stages of the drug discovery process.
Transforming growth factor-beta 1 reduces infarct size after experimental cerebral ischemia in a rabbit model. (1993)

Transforming growth factor-beta 1 reduced brain infarct size in a rabbit model of thromboembolic stroke. This effect was not related to a direct effect on blood flow. Studies are ongoing to determine the mechanism by which transforming growth factor-beta 1 salvages ischemic brain.
UMTS Networks: Architecture, Mobility and Services (2001)

From the Publisher:
UMTS (Universal Mobile Telecommunication Services) systems are third-generation systems designed for multimedia communication. Traditionally mobile systems books have concentrated on the radio interface issues. Although the radio interface in any cellular system is extremely important it is only one part of a very large and sophisticated cellular system such as the third-generation system. UMTS Network provides a comprehensive introduction and reference to third-generation mobile systems, suitable for individuals at a variety of knowledge levels.
Evaluation of Microbial Products for Management of Powdery Mildew on Summer Squash and Cantaloupe in Florida (2010)

Powdery mildew, caused by Podosphaera xanthii (syn. Sphaerotheca fuliginea auct. p.p.), is a serious and frequently occurring disease of cucurbits worldwide. Efficacy of four microbial products (i.e., Actinovate AG, Companion, BU EXP 1216C, and BU EXP 1216S), which contain microbes as the active ingredient, were evaluated on summer squash and cantaloupe against powdery mildew when applied alone or in alternation with a half-rate of conventional fungicide under greenhouse and field conditions. In greenhouse experiments, the product BU EXP 1216S significantly (P < 0.05) reduced the disease severity by nearly 70% relative to the water control. The level of control achieved was not significantly different from that obtained with Procure 480SC (triflumizole), the half-rate of conventional fungicide treatment, in two of four greenhouse experiments. Compared with the untreated water control, BU EXP 1216C and BU EXP 1216S, when applied alternately with Procure 480SC, consistently promoted plant growth measured by plant height, stem caliper, total fresh weight, and chlorophyll content in the leaves. The degree of increase was 11.6 and 11.3% in plant height, 15.6 and 19.8% in stem caliper, 25 and 40.7% in chlorophyll content, and 164 and 250% in total fresh weight, respectively. Alternating applications of these products with Procure 480SC resulted in significantly less powdery mildew disease than in the water control. In the first field trial on summer squash, all products applied individually or in alternation with Procure 480SC significantly reduced the severity of powdery mildew at the early stage (60 days after planting [DAP]) of disease development. Moreover, these alternating treatments resulted in significantly better control than with Procure 480SC alone at the late assessment stage (88 DAP). The products in alternation with Procure 480SC had a level of disease reduction equivalent to Procure 480SC alone on cantaloupe and significantly reduced disease severity in comparison with the water control. Compared with applying the microbial products alone, alternating applications of these products with Procure 480SC significantly reduced disease severity on cantaloupe and improved the marketable fruit number and weight. The data from our studies suggest that these microbial products could be effectively incorporated into disease management programs. In particular, these microbial products could be integrated into the management of powdery mildew on summer squash and cantaloupe in Florida by alternating their application with low rates of conventional fungicides, potentially reducing the development of fungicide resistance in the pathogen population.
Printing meets lithography: Soft approaches to high-resolution patterning (2001)

We are developing a high-resolution printing technique based on transferring a pattern from an elastomeric stamp to a solid substrate by conformal contact. This is an attempt to enhance the accuracy of classical printing to a precision comparable with optical lithography, creating a low-cost, large-area, high-resolution patterning process. First, we introduce the components of this technique, called soft lithography, and review its evolution. Topics described in detail are the stamp material, stamp architecture, pattern design rules, and printing tools. The accuracy of the prints made by thin patterned elastomeric layers supported on a stiff and flexible backplane is then assessed, and defects are characterized using a new electrical metrology approach. This is followed by a discussion of various printing processes used in our laboratory: 1) thiol printing for high-resolution patterns of noble metals that may also be used as sacrificial masks; 2) confined contact processing with liquids in cavities or cha nnels to chemically convert a substrate or deposit layers of materials or biomolecules; 3) printing of catalysts to mediate patterned deposition of metals; and 4) structured, light-guiding stamps for transferring high-resolution patterns into photoresists. Finally, we compare classical and high-resolution printing approaches, and describe their potential for emerging micro- and nano-scale patterning technologies.
67Cu-2IT-BAT-Lym-1 pharmacokinetics, radiation dosimetry, toxicity and tumor regression in patients with lymphoma. (1999)

Because of the long residence time of 67Cu-21T-BAT-Lym-1 in tumors, high therapeutic ratios were achieved and, remarkably, numerous tumor regressions were observed after imaging doses. The results indicate considerable therapeutic potential for 67Cu-21T-BAT-Lym-1.
Influence of some operational variables on the radial keratotomy operation (2000)

All of the four variables have a positive effect on the operational outcome. The greater the four variables are the more correction effects of myopia can be obtained. Because the four variables are interinfluential, the operational variables can be optimised to get the best result in order to meet patients' differing requirements.
Plasma homocyst(e)ine and arterial occlusive diseases: a mini-review (1995)

Homocysteine (HCY), which is derived from the intracellular metabolism of methionine, is exported into plasma, where it circulates mostly in oxidized forms (i.e., homocystine and cysteine-HCY disulfide) and mainly bound to proteins. Concentrations of total HCY, or homocyst(e)ine [H(e)], are increased in 15-40% of patients with coronary, cerebral, or peripheral arterial diseases. Such association of H(e) with arterial occlusive diseases has been documented in retrospective, cross-sectional, and prospective studies. Concentrations of H(e) are also increased in subjects having thickened carotid arteries, as determined by ultrasonography, and who are asymptomatic for atherosclerosis. Statistical analyses of data from several series of patients demonstrate that H(e) concentrations are associated with coronary artery disease, independently from most other risk factors for atherosclerosis. The increased concentrations of H(e) are readily corrected by folic acid, occasionally supplemented with pyridoxine, vitamin B12, choline, or betaine. Whether these supplements affect the evolution of atherosclerotic disease needs to be established by prospective, placebo-controlled clinical trials.
Possible involvement of two proteins (phosphoprotein and CD9(p24)) in regulation of platelet calcium fluxes (1985)

The monoclonal antibody ALB6 directed against the leukocyte differentiation antigen CD9 (p24) increases the calcium incorporation into isolated platelet membrane vesicles enriched in internal membranes. The similarities of the effects of both the monoclonal antibody and the catalytic subunit of the cAMP-dependent protein kinase (C, subunit), which phosphorylates a protein of an apparent molecular mass of 23 kDa, led us to investigate the relationship between CD9 (p24) and the 23-kDa phosphoprotein (p23). ALB6IgG does not inhibit the C.subunit-induced phosphorylation of p23 and the immunoadsorption by ALB6IgG of p24 associated to membrane vesicles does not alter the phosphorylation pattern. Thus, proteins of similar molecular mass appear to be involved in calcium fluxes: one is recognized by the ALB6 antibody while the other can be phosphorylated by the C-subunit.
BindingDB Entry 5274: Characterization of the anxiolytic properties of a novel neuroactive steroid, Co 2-6749 (GMA-839; WAY-141839; 3alpha, 21-dihydroxy-3beta-trifluoromethyl-19-nor-5beta-pregnan-20-one), a selective modulator of gamma-aminobutyric acid(A) receptors. (2012)

The purpose of this study was to evaluate the effects of a novel neuroactive steroid, Co 2-6749 (GMA-839; WAY-141839; 3alpha, 21-dihydroxy-3beta-trifluoromethyl-19-nor-5beta-pregnan-20-one), on gamma-aminobutyric acid(A) receptors in vitro and to define its anxiolytic-like effects and side effect profile in vivo. Co 2-6749 fully inhibited [(35)S]t-butylbicyclophosphorothionate binding in rat brain cortical membranes with an IC(50) value of 230 nM and in human gamma-aminobutyric acid(A) receptor subunit combinations of alpha1beta2gamma2L, alpha2beta2gamma2L, alpha3beta2gamma2L, alpha4beta3gamma2L, alpha5beta2gamma2L, and alpha6beta3gamma2L receptors (IC(50) values of 200, 200, 96, 2300, 210, and 2000 nM). Rats were trained in a Geller-Seifter operant conflict paradigm. Co 2-6749 caused a dose-related increase in punished responding with a minimum effective dose of 1.6 mg/kg, p.o., a wide therapeutic index relative to a decrease in unpunished responding and relative to ataxia, and no tolerance. Additionally, ethanol caused less than a 2-fold shift to the left in the dose-response function of Co 2-6749 in the rotorod procedure in rats. In a pigeon conflict paradigm, punished responding was maximally increased to 784% of vehicle control by 30 mg/kg, p.o., with a 2-h duration and no effect on unpunished responding at this dose. Similarly, punished responding in squirrel monkeys was maximally increased to 1774% of control by 10 mg/kg, p.o., with no effect on unpunished responding at this dose. With robust anxiolytic-like activity across species, a large separation between anxiolytic-like effects and sedation/ataxia, a minimal interaction with ethanol, a lack of tolerance, and apparent oral bioavailability, Co 2-6749 makes an ideal candidate for development as a novel anxiolytic drug.
Active, a platform for building intelligent software (2006)

Computer systems keep growing in complexity, processing power and inter-connectivity. To leverage this rich environment and better assist users, a new type of intelligent assistant software is required. Building intelligent assistants is a difficult task that requires expertise in many AI related fields including natural language interpretation, dialog management, multimodal fusion and brokering of services. We believe that providing a unified tool and a set of associated methodologies to create intelligent software will bring many benefits to this area of research. Our solution, the Active framework, introduces the original concept of Active Ontologies to model and implement intelligent applications in a single and coherent software environment. As an example, this paper illustrates how Active has been used to implement an intelligent assistant to help surgeons in a computer equipped operating room.
A Small-Molecule Blocking Ribonucleotide Reductase Holoenzyme Formation Inhibits Cancer Cell Growth and Overcomes Drug Resistance (2013)

Ribonucleotide reductase (RNR) is an attractive target for anticancer agents given its central function in DNA synthesis, growth, metastasis, and drug resistance of cancer cells. The current clinically established RNR inhibitors have the shortcomings of short half-life, drug resistance, and iron chelation. Here, we report the development of a novel class of effective RNR inhibitors addressing these issues. A novel ligand-binding pocket on the RNR small subunit (RRM2) near the C-terminal tail was proposed by computer modeling and verified by site-directed mutagenesis and nuclear magnetic resonance (NMR) techniques. A compound targeting this pocket was identified by virtual screening of the National Cancer Institute (NCI) diverse small-molecule database. By lead optimization, we developed the novel RNR inhibitor COH29 that acted as a potent inhibitor of both recombinant and cellular human RNR enzymes. COH29 overcame hydroxyurea and gemcitabine resistance in cancer cells. It effectively inhibited proliferation of most cell lines in the NCI 60 human cancer panel, most notably ovarian cancer and leukemia, but exerted little effect on normal fibroblasts or endothelial cells. In mouse xenograft models of human cancer, COH29 treatment reduced tumor growth compared with vehicle. Site-directed mutagenesis, NMR, and surface plasmon resonance biosensor studies confirmed COH29 binding to the proposed ligand-binding pocket and offered evidence for assembly blockade of the RRM1-RRM2 quaternary structure. Our findings offer preclinical validation of COH29 as a promising new class of RNR inhibitors with a new mechanism of inhibition, with broad potential for improved treatment of human cancer.
ChemInform Abstract: SYNTHESIS OF PALLESCENSIN‐E: USE OF CROWN ETHER IN THE WADSWORTH PROCEDURE FOR OLEFIN FORMATION (1981)

Abstract Zß‐Dimethyl‐benzonitril (Ia) wird in die Carbonsäure (Ib) übergeführt, diese zum Carbinol (Ic) reduziert und weiter mit Pyridiniumchlorchromat zum Aldehyd (Id) oxidiert.
Novel Prolyl Tri/Tetra-Peptidyl Aminopeptidase from Streptomyces mobaraensis: Substrate Specificity and Enzyme Gene Cloning (2004)

The prolyl peptidase that removes the tetra-peptide of pro-transglutaminase was purified from Streptomyces mobaraensis mycelia. The substrate specificity of the enzyme using synthetic peptide substrates showed proline-specific activity with not only tripeptidyl peptidase activity, but also tetrapeptidyl peptidase activity. However, the enzyme had no other exo- and endo-activities. This substrate specificity is different from proline specific peptidases so far reported. The enzyme gene was cloned, based on the direct N-terminal amino acid sequence of the purified enzyme, and the entire nucleotide sequence of the coding region was determined. The deduced amino acid sequence revealed an N-terminal signal peptide sequence (33 amino acids) followed by the mature protein comprising 444 amino acid residues. This enzyme shows no remarkable homology with enzymes belonging to the prolyl oligopeptidase family, but has about 65% identity with three tripeptidyl peptidases from Streptomyces lividans, Streptomyces coelicolor, and Streptomyces avermitilis. Based on its substrate specificity, a new name, "prolyl tri/tetra-peptidyl aminopeptidase," is proposed for the enzyme.