gebhart/patrepeval huggingface dataset:
Sequential dependent enhancement of caspase activation and apoptosis by flavopiridol on paclitaxel-treated human gastric and breast cancer cells. (1999)

Although in the past 10 years paclitaxel has emerged as a successful drug in cancer therapy, the overall response rate to this drug in patients with advanced metastatic disease remains low. Therefore, an understanding of the mechanism of the effect of paclitaxel on inducing apoptosis and the discovery of new ways to enhance the effect of paclitaxel will be critical to improving the therapeutic efficiency of this drug. In the present studies, we have determined that the cyclin-dependent kinase inhibitor flavopiridol significantly enhances paclitaxel-induced apoptosis in the human gastric and breast cancer cell lines MKN-74 and MCF-7. Flavopiridol enhances paclitaxel-induced apoptosis only when administered after paclitaxel treatment. The activation of caspases, specifically caspase 3, is enhanced by flavopiridol on paclitaxel-treated cells. In accordance with this, poly(ADP-ribose) polymerase cleavage is enhanced in combination therapy relative to single-agent paclitaxel. The induction of apoptosis, activation of caspase 3, and poly(ADP-ribose) polymerase cleavage in treatment regimens with paclitaxel and paclitaxel followed by flavopiridol were reversed by treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, which supports the notion that caspases are the executioners of apoptosis in these processes. Paclitaxel alone causes transient mitotic arrest with activation of cdc-2 kinase. Cells exit mitosis in a specific time window without cytokinesis, with a decrease in cdc-2 kinase activity and MPM-2 labeling. Flavopiridol accelerates the mitotic exit when administered after paclitaxel treatment in association with a more rapid decrease in MPM-2 labeling. In contrast, pretreatment with flavopiridol prevents cells from entering mitosis by inhibiting cdc-2 kinase activity, thus antagonizing the paclitaxel effect. Therefore, in this study we show that potentiation of paclitaxel-induced apoptosis by flavopiridol is highly sequence dependent, such that mitotic entry and cdc-2 kinase activation by paclitaxel must precede flavopiridol therapy, and the synergistic effect of flavopiridol on paclitaxel-treated cells is due to enhancement in caspase activation.
Antibacterial Activity of REP8839, a New Antibiotic for Topical Use (2005)

REP8839 is a novel methionyl-tRNA synthetase (MetS) inhibitor with potent antibacterial activity against clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, and other clinically important gram-positive bacteria but little activity against gram-negative bacteria. All isolates of S. aureus, including strains resistant to methicillin, mupirocin, vancomycin, and linezolid were susceptible to REP8839 at concentrations of < or =0.5 microg/ml. REP8839 was also active against Staphylococcus epidermidis, including multiply resistant strains (MIC, < or =0.25 microg/ml). All S. pyogenes isolates were susceptible to REP8839 at concentrations of < or =0.25 microg/ml, suggesting that MetS2, a second enzyme previously identified in Streptococcus pneumoniae, was not present in this organism. REP8839 was highly bound to the protein of human serum, and activity was not greatly influenced by inoculum size but was affected by pH, exhibiting optimal antibacterial activity in a neutral medium rather than a weak acidic medium. Like mupirocin, REP8839 exhibited bacteriostatic activity against key pathogens. The emergence of mupirocin resistance in S. aureus highlights the need for a new topical antibiotic with the ability to inhibit high-level mupirocin-resistant strains and other emerging phenotypes, such as vancomycin-resistant and community-acquired methicillin-resistant isolates.
Face recognition: features versus templates (1993)

Two new algorithms for computer recognition of human faces, one based on the computation of a set of geometrical features, such as nose width and length, mouth position, and chin shape, and the second based on almost-gray-level template matching, are presented. The results obtained for the testing sets show about 90% correct recognition using geometrical features and perfect recognition using template matching.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Conformational properties of α‐ and β‐azabicyclane opiates. The effect of conformation on pharmacological activity (1984)

Abstract Conformational energy calculations using the MM 2 (molecular mechanics II) program are reported for diastereoisomeric α‐ and β‐azabicyclanes (3‐methyl‐9‐methoxy‐9‐phenyl‐3‐azabicyclo [3.3.1] nonanes) which are prototypical phenyl‐axial and phenyl‐equatorial opiates. After energy minimization, both compounds are found to prefer a chair–chair conformation of the piperidine and cyclohexane rings with two mirror image orientations of the phenyl and methoxyl groups. The calculations also indicate that the equilibrium conformations of the phenyl and methoxyl groups are very similar in the two diastereoisomers. A morphine‐like conformation of the phenyl group was found to be very unfavorable because of a high barrier to rotation of the phenyl group. This does not have an apparent effect on opiate agonist properties, but does result in a significant weakening of the antagonist activity of the N‐allyl derivative of α‐azabicyclane. This is discussed in terms of a model for phenyl‐axial and phenyl‐equatorial opiate substrates which accounts for both similarities and differences in their structure–activity relationships. A detailed comparison is also made between the computed structures and those observed by x‐ray crystallography with excellent agreement between the two.
Fate of organohalogens in US wastewater treatment plants and estimated chemical releases to soils nationwide from biosolids recycling (2009)

This study examined the occurrence in wastewater of 11 aromatic biocides, pesticides and degradates, and their fate during passage through US treatment plants, as well as the chemical mass contained in sewage sludge (biosolids) destined for land application. Analyte concentrations in wastewater influent, effluent and sludge from 25 facilities in 18 US states were determined by liquid chromatography electrospray (tandem) mass spectrometry. Dichlorocarbanilide, fipronil, triclocarban, and triclosan were found consistently in all sample types. Dichlorophene, hexachlorophene, and tetrachlorocarbanilide were detected infrequently only, and concentrations of the phenyl urea pesticides diflubenzuron, hexaflumuron, and linuron were below the limit of detection in all matrixes. Median concentrations (+/-95% confidence interval) of quantifiable compounds in influent ranged from 4.2 +/- 0.8 microg L(-1) for triclocarban to 0.03 +/- 0.01 microg L(-1) for fipronil. Median concentrations in effluent were highest for triclocarban and triclosan (0.23 +/- 0.08 and 0.07 +/- 0.04 microg L(-1), respectively). Median aqueous-phase removal efficiencies (+/-95% CI) of activated sludge treatment plants decreased in the order of: triclosan (96 +/- 2%) > triclocarban (87 +/- 7%) > dichlorocarbanilide (55 +/- 20%) > fipronil (18 +/- 22%). Median concentrations of organohalogens were typically higher in anaerobically than in aerobically digested sludges, and peaked at 27 600 +/- 9600 and 15 800 +/- 8200 microg kg(-1) for triclocarban and triclosan, respectively. Mass balances obtained for three primary pesticides in six activated sludge treatment plants employing anaerobic digestion suggested a decreasing overall persistence from fipronil (97 +/- 70%) to triclocarban (87 +/- 29%) to triclosan (28 +/- 30%). Nationwide release of the investigated organohalogens to agricultural land via municipal sludge recycling and into surface waters is estimated to total 258 000 +/- 110 00 kg year(-1) (mean +/- 95% confidence interval), with most of this mass derived from antimicrobial consumer products of daily use. This study addresses some of the data gaps identified by the National Research Council in its 2002 study on standards and practices of biosolids application on land.
Dengue and Chikungunya Virus Infection in Man in Thailand, 1962–1964 (1969)

An attempt at a comprehensive measurement of illness documented by physicians and infection in man caused by dengue and chikungunya viruses was made in Bangkok and Thonburi during all or portions of 1962–1964. Inpatient data were collected directly from all metropolitan hospitals. Outpatients were studied only at Children's Hospital. In 1962, a seroepidemiologic study of arbovirus infection was made in 7,093 Bangkok households in 19 separate areas, from five of which mosquitoes were collected for enumeration and attempts to isolate virus. During the study, 10,194 patients with hemorrhagic fever were admitted to Bangkok hospitals, and 559 died. At least 80% of these cases were caused by dengue virus. In 1962 alone, it was estimated that between 181,000 and 287,000 dengue illnesses and 44,000 to 70,000 chikungunya illnesses were seen by physicians in outpatient children. Agespecific hospitalization rates peaked at less than 1 year and again at 3 or 4 years, few cases occurring after the age of 15. Hospitalizations were rare in infants during the first 3 months of life; rates then rose abruptly, peaking at 8 months then declining markedly. Hospitalization rates for girls over the age of 1 were consistently higher than for boys. Dengue- and chikungunya-infection rates measured in 1,887 persons bled before and after the rainy season in 1962 were 41% and 31%, respectively. Hospitalization rates varied directly with dengue-virus infection rates but not with income or ethnic group. Hospitalizations occurred within families at almost four times the expected rate. Disease progressed throughout the city and within study areas in a "brush-fire" manner. In contrast to the observations of others, we isolated dengue and chikungunya virus almost exclusively from Aedes aegypti. Although Culex tritaeniorhynchus and Culex gelidus were numerous in light-trap collections, they were rarely attracted to man. These observations suggest a low level of anthropophilia in these species in Thailand and the possibility of a biological barrier to transmission of arboviruses by them to man.
Bacillus megaterium strain XTBG34 promotes plant growth by producing 2-pentylfuran (2010)

Several chemical changes in soil are associated with plant growth-promoting rhizobacteria. An endosporeforming bacterium, strain XTBG34, was isolated from a Xishuangbanna Tropical Botanical Garden soil sample and identified as Bacillus megaterium. The strain's volatiles had remarkable plant growth promotion activity in Arabidopsis thaliana plants; after 15 days treatment, the fresh weight of plants inoculated with XTBG34 was almost 2-fold compared with those inoculated with DH5alpha. Head space volatile compounds produced by XTBG34, trapped with headspace solid phase microextraction and identified by gas chromatography-mass spectrometry, included aldehydes, alkanes, ketones and aroma components. Of the 11 compounds assayed for plant growth promotion activity in divided Petri plates, only 2-pentylfuran increased plant growth. We have therefore identified a new plant growth promotion volatile of B. megaterium XTBG34, which deserves further study in the mechanisms of interaction between plant growth-promoting rhizobacteria and plants.
Drug Delivery in Oncology (2011)

Volume 1: PRINCIPLES OF TUMOR TARGETING Limits of Conventional Cancer Chemotherapy Pathophysiological and Vascular Characteristics of Tumors in Relation to Drug Delivery Enhanced Permeability and Retention Effect in Relation to Tumor Targeting Pharmacokinetics of Immunoglobulin G and Serum Albumin: Impact of the Neonatal Fc Receptor on Drug Design Development of Cancer-Targeting Ligands and Ligand-Drug Conjugates Antibody-Directed Enzyme Prodrug Therapy (ADEPT) - Basic Principles and its Practice So Far TUMOR IMAGING Imaging Techniques in Drug Development and Clinical Practice Magnetic Nanoparticles in Magnetic Resonance Imaging and Drug Delivery Preclinical and Clinical Tumor Imaging with SPECT/CT and PET/CT Volume 2: MACROMOLECULAR DRUG DELIVERY SYSTEMS Antibody-Based Systems Empowered Antibodies for Cancer Therapy Mapping Accessible Vascular Targeting to Penetrate Organs and Solid Tumors Considerations of Linker Technologies Antibody-Maytansinoid Conjugates: From the Bench to the Clinic Calicheamicin Antibody-Drug Conjugates and Beyond Antibodies for the Delivery of Radionuclides Bispecific Antibodies and Immune Therapy Targeting POLYMER-BASED SYSTEMS Design of Polymer-Drug Conjugates Dendritic Polymers in Oncology: Facts, Features, and Applications Site-Specific Prodrug Activation and the Concept of Self-Immolation Ligand-Assisted Vascular Targeting of Polymer Therapeutics Drug Conjugates with Poly(Ethylene)Glycole Thermo-Responsive Polymers Polysaccharide-Based Drug Conjugates for Tumor Targeting Serum Proteins as Drug Carriers of Anticancer Agents Future Trends, Challenges, and Opportunities with Polymer-Based Combination Therapy in Cancer Clinical Experience with Drug-Polymer Conjugates NANO- AND MICROPARTICULATE DRUG DELIVERY SYSTEMS - LIPID-BASED SYSTEMS Overview on Nanocarriers as Delivery Systems Development of PEGylated Liposomes Immunoliposomes Responsive Liposomes (for Solid Tumor Therapy) Nanoscale Delivery Systems for Combination Chemotherapy NANO- AND MICROPARTICULATE DRUG DELIVERY SYSTEMS - POLYMER-BASED SYSTEMS Micellar Strcutures as Drug Delivery Systems Tailor-Made Hydrogels for Tumor Delivery pH-Triggered Micelles for Tumor Delivery Albumin-Drug Nanoparticles Carbon Nanotubes Volume 3: LIGAND-BASED DRUG DELIVERY SYSTEMS Cell-Penetrating Peptides in Cancer Targeting Targeting to Peptide Receptors Aptamer Conjugates: Emerging Delivery Platforms for Targeted Cancer Therapy Design and Synthesis of Drug Conjugates of Vitamins and Growth Factors Drug Conjugates with Polyunsaturated Fatty Acids SPECIAL TOPICS RNA Drug Delivery Approaches Local Gene Delivery for Therapy of Solid Tumors Viral Vectors for RNA Interference Applications in Cancer Research and Therapy Design of Targeted Protein Toxins Drug Targeting to the Central Nervous System Liver Tumor Targeting Photodynamic Therapy: Photosensitizers Targeting and Delivery Tumor-Targeting Strategies with Anticancer Platinum Complexes
Engineering cytochrome P450cam into an alkane hydroxylase (2003)

The haem monooxygenase cytochrome P450cam from Pseudomonas putida has been engineered into an alkane hydroxylase. Active site amino acid residues were substituted with residues that have bulkier and more hydrophobic side-chains. The residues F87, Y96, V247 and V396, which are further away from the haem, were targeted first for substitution in order to constrain the small alkanes n-butane and propane to bind closer to the haem. We found that just two mutations could increase the alkane oxidation activity of P450cam by two orders of magnitude. The F87W/Y96F/V247L triple mutant was then used as a basis for introducing further substitutions, at the residues T101, L244, V395 and D297 which are closer to the haem, to improve the enzyme/alkane fit and hence the alkane hydroxylase activity. The F87W/Y96F/T101L/V247L mutant oxidised n-butane with a catalytic turnover rate of 755 nmol(nmol P450cam)−1(min)−1, which is comparable to the camphor oxidation activity of the wild-type (1000 min−1). The F87W/Y96F/T101L/L244M/V247L mutant had lower n-butane oxidation activity but the highest propane oxidation rate (176 min−1) of the P450cam enzymes studied. All P450cam enzymes gave 2-butanol and 2-propanol as the only products. Determination of the extent of uncoupling showed that hydrogen peroxide generation was the dominant uncoupling mechanism. The data indicate that further mutations at residues higher up in the active site are required to localise the substrates close to the haem and to reduce substrate mobility. These next-generation mutants will have higher activity, and may be able to catalyse the oxidation of ethane and methane.
Conformational Studies of RS-66271, an Analog of Parathyroid Hormone-Related Protein with Pronounced Bone Anabolic Activity (1997)

Both the parathyroid hormone (PTH) and the functionally similar parathyroid hormone-related protein (PTHrP) have served as templates for the development of novel bone anabolic agents for the treatment of osteoporosis. The PTHrP analog RS-66271 (Vickery, B. H.; Avnur, Z.; Cheng Y.; Chiou, S.-S.; Leaffer, D.; Caulfield, J. P.; Kimmel, D. B.; Ho, T.; Krstenansky, J. L. J. Bone Miner. Res. 1996, 11, 1943-1951), in which the amino acids 22-31 have been substituted by the sequence E22-L-L-E-K-L-L-E-K-L31 (a model amphiphilic peptide), is a potent bone anabolic agent in vivo. Therefore, RS-66271 is a good candidate for structural analysis with the aim of developing a structure-activity relationship. The structural characterization described here was carried out in aqueous solution employing circular dichroism and nuclear magnetic resonance spectroscopy. We find that the incorporated amphiphilic decapeptide is indeed helical. In addition, it induces the adjacent residues, up to residue 16, to adopt the helical conformation. The helical domain, including residues 16-32, incorporates most of the previously identified principal receptor binding domain PTHrP(25-34). We discuss the relevance of the distinct and extensive helicity in light of the reduced in vitro receptor affinity/ activity and the enhanced in vivo bone anabolic efficacy of RS-66271.
Spectral density of random UWB signals (2002)

We derive the power spectral density of time-hopping (TH) spread-spectrum signals in the presence of random timing jitter. Detailed descriptions of different TH schemes, employing a random TH sequence, are given and spectral analysis of such TH signals in the presence of uniform timing jitter is carried out using a systematic and tractable technique.
Anti-Mullerian hormone as a predictor of follicular reserve in ovarian insufficiency: special emphasis on FSH-resistant ovaries (2012)

A serum AMH assay could be used to identify patients with decreasing ovarian reserves and POI. Moreover, our results support the notion that AMH is secreted mainly by small non-selected follicles, since follicular granulosa cells were AMH-positive and serum AMH levels were normal/low normal in women with FSHRO, who lack follicle development beyond the small antral stage.
Idiographic representation of conserved domain of a class II tRNA synthetase of unknown structure (1993)

We report here an idiographic representation of the secondary structure predicted for an enzyme whose threedimensional structure has not yet been determined. In our example, we applied the recently described neural network-based prediction program PHD (Rost & Sander, 1992) to identify secondary structure elements of a major portion of the active site of Escherichia coli alanyl-tRNA synthetase (AlaRS). The active site domain of AlaRS encompasses approximately the N-terminal half of the primary structure (Putney et al., 1981b; These proteins established the rules of the genetic code through the aminoacylation of RNA substrates. The alanine enzyme is of particular interest because it is one of the clearest examples of a tRNA synthetase that makes no contact with the tRNA anticodon Instead, the enzyme aminoacylates RNA helical structures, including short hairpin duplexes with as few as four base pairs, provided that they contain a G:U wobble base pair at the third position in the helix
Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction. (1993)

The binding of interleukin 2 (IL-2) to the IL-2 receptor (IL-2R) induces a rapid increase in tyrosine phosphorylation of cellular proteins. In a previous study, we have shown that p56lck (lck), a src-family protein tyrosine kinase (src-PTK), physically and functionally associates with the IL-2R beta chain (IL-2R beta). To further investigate a role of src-PTKs in IL-2 signaling, we analyzed a mouse pro-B-cell line, in which lck is not expressed detectably. We observed that in this cell line, IL-2 induces activation of at least two src-PTKs, p59fyn (fyn) and p53/56lyn (lyn). Interestingly, stimulation of this cell line with IL-3 also induces activation of src-PTKs. The activation of fyn or lyn seems to be selective for stimulation with IL-2 or IL-3 since stimulation with IL-6 fails to activate them. Furthermore, we provide evidence for the physical association of fyn with IL-2R beta. Taken together with previous results, our current study suggests that different src-PTKs, each of which is expressed in a cell-type-specific manner, can participate in the IL-2 signal transduction.
Functional Effects of Mutations in KvLQT1 that Cause Long QT Syndrome (1999)

LQT1-associated mutations in KVLQT1 caused a spectrum of dysfunction in I(Ks) and KvLQT1 channels. The degree of I(Ks) dysfunction did not correlate with the QTc interval or the presence of symptoms in the respective gene carriers. In contrast to previous reports, we found that loss of function mutations are not exclusive to recessively inherited LQT.
Human Parathyroid Hormone: Synthesis and Chemical, Biological, and Immunological Evaluation of the Carboxyl-Terminal Region* (1978)

The carboxyl-terminal region of human parathyroid hormone (hPTH) was synthesized by the solid phase method. The 32-amino acid fragment, hPTH-(53–84), was prepared for two reasons: 1) to produce antisera directed exclusively against the carboxyl-terminal region of hPTH, which represents the predominant form of the hormone in blood; and 2) to determine whether a portion of the hormone other than the amino-terminal region has any of the biological activity of intact hormone or can bind to PTH receptors. The synthetic fragment was evaluated for heterogeneity by amino acid composition and by several high resolution analytical systems (thin layer electrophoresis, polyacrylamide gel isoelectric focusing, and Edman sequence analysis). Synthetic hPTH-(53–84) lacked PTH-like activity in both in vitro (renal) and in vivo (bone) assays and failed to inhibit the action of native PTH in vitro, indicating lack of receptor binding by the carboxyl-terminal region of the molecule. Because the fragment lacked biological activity, nonchemical evaluation was performed to confirm that the peptide represents the carboxyl terminus of hPTH. Immunological comparison of synthetic hPTH-(53–84) to native hPTH was undertaken using an RIA that employed an antibovine PTH antiserum whose antigenic recognition was limited to the carboxyl-terminal region of the hormone. Synthetic hPTH-(53-84) was more immunoreactive than native hPTH. The immunological findings provide further evidence that the synthetic peptide accurately represents the carboxyl-terminal region of native hPTH