gebhart/patrepeval huggingface dataset:
Molecular cloning of the glucoamylase I gene of Aspergillus awamori var. kawachi for localization of the raw-starch-affinity site. (1989)

The raw-starch-digesting glucoamylase I (GAI) of Aspergillus awamori var. kawachi contains a glycopeptide I (Gp-I) region as the raw-starch-affinity site essential for its raw-starch-adsorption and raw-starch-digestion. Molecular cloning of the GAI gene and analysis of its nucleotide sequence revealed some nucleotide replacements, in comparison with the Aspergillus niger and Aspergillus awamori glucoamylase genes. The deduced total ami no acid sequence of GAI contained 35 replacements and one deletion, of a mi no acid residues, and therefore a total of 615 residues, in comparison with the A. niger and A. awamori glucoamylases. The raw-starch-adsorbable Gp-I region in GAI was located between Ala470 and Val514 near the C-terminal, consisting of ATGG-TTTTATTTGSGGVTSTSKTTTTASKTSTTTSSTSCTTPTAV.
Pitch modification of speech using a low-sensitivity inverse filter approach (1998)

A simple and effective method for modifying the pitch of recorded speech units is described. This method was developed to overcome some limitations in the promising residual-excited linear prediction (RELP) technique. The key difference is that the choice of filter parameters in the new method is driven by a need for reducing sensitivity to pitch modification, rather than creating a residual with minimum energy as in RELP. Speech modifications using this method are superior in quality to those obtained with RELP, while at the same time being less sensitive than RELP to errors in pitch marking.
Development and in vitro Characterization of a Cationized Monoclonal Antibody against βA4 Protein: A Potential Probe for Alzheimer's Disease (1994)

The blood-brain barrier (BBB) is impermeable to IgG. Therefore, a delivery strategy has to be applied in order to use monoclonal antibodies (mAb) as diagnostic or therapeutic agents in the brain. It has been demonstrated that cationization of IgG allows for the BBB penetration following peripheral administration. A cationized mAb against beta A4-amyloid could be a sensitive and specific diagnostic tool for Alzheimer's disease (AD). The site-protected cationization and radiolabeling with 111In of the specific anti beta-amyloid mAb, AMY33, is described. The binding affinity of the antibody was retained after these procedures (Kd = 3.1 +/- 0.5 nM), as determined by solid-phase immunoradiometric assay and immunocytochemistry on AD brain sections. The in vitro binding by isolated brain capillaries indicated that the cationized antibody may be delivered to the brain in vivo. The ability of the modified antibody to detect cerebral beta-amyloid deposits in vivo can now be evaluated using single photon emission computed tomography (SPECT) and a suitable animal model for cerebral amyloidosis, such as non-human primates or aged canines.
When Defense Pathways Collide. The Response of Arabidopsis to a Combination of Drought and Heat Stress (2004)

Within their natural habitat, plants are subjected to a combination of abiotic conditions that include stresses such as drought and heat. Drought and heat stress have been extensively studied; however, little is known about how their combination impacts plants. The response of Arabidopsis plants to a combination of drought and heat stress was found to be distinct from that of plants subjected to drought or heat stress. Transcriptome analysis of Arabidopsis plants subjected to a combination of drought and heat stress revealed a new pattern of defense response in plants that includes a partial combination of two multigene defense pathways (i.e. drought and heat stress), as well as 454 transcripts that are specifically expressed in plants during a combination of drought and heat stress. Metabolic profiling of plants subjected to drought, heat stress, or a combination of drought and heat stress revealed that plants subject to a combination of drought and heat stress accumulated sucrose and other sugars such as maltose and glucose. In contrast, Pro that accumulated in plants subjected to drought did not accumulate in plants during a combination of drought and heat stress. Heat stress was found to ameliorate the toxicity of Pro to cells, suggesting that during a combination of drought and heat stress sucrose replaces Pro in plants as the major osmoprotectant. Our results highlight the plasticity of the plant genome and demonstrate its ability to respond to complex environmental conditions that occur in the field.
Sustained release tablets based on chitosan and carboxymethylcellulose sodium. (1987)

Chitosan and mixtures of chitosan with carboxymethylcellulose sodium (CMC-Na) were examined as vehicles for sustained release tablets of water-insoluble drugs. Prednisolone (PDS) was selected as a model of a water-insoluble drug for this study. Sustained release of PDS from tablets prepared by direct compression of chitosan and CMC-Na was demonstrated in model JP X fluids. Furthermore, the release rate of PDS could be controlled by changing the relative amounts of chitosan and CMC-Na, or the amount of PDS in the tablets, and by certain extra additives. Such chitosan/CMC-Na mixtures are a promising basis in the design of sustained release dosage forms of water-insoluble drugs.
Endonucleases: tools to correct the dystrophin gene (2011)

Endonucleases are able to: (i) restore the normal reading of a gene with a frame shift mutation; (ii) delete a nonsense codon; and (iii) knockout a gene. Endonucleases could thus be used to treat Duchenne muscular dystrophy and other hereditary diseases that are the result of a nonsense codon or a frame shift mutation.
Protein biomarkers associated with acute renal failure and chronic kidney disease (2006)

Acute renal failure (ARF) as well as chronic kidney disease (CKD) are currently categorized according to serum creatinine concentrations. Serum creatinine, however, has shortcomings because of its low predictive values. The need for novel markers for the early diagnosis and prognosis of renal diseases is imminent, particularly for markers reflecting intrinsic organ injury in stages when glomerular filtration is not impaired. This review summarizes protein markers discussed in the context of ARF as well as CKD, and provides an overview on currently available discovery results following 'omics' techniques. The identified set of candidate marker proteins is discussed in their cellular and functional context. The systematic review of proteomics and genomics studies revealed 56 genes to be associated with acute or chronic kidney disease. Context analysis, i.e. correlation of biological processes and molecular functions of reported kidney markers, revealed that 15 genes on the candidate list were assigned to the most significant ontology groups: immunity and defence. Other significantly enriched groups were cell communication (14 genes), signal transduction (22 genes) and apoptosis (seven genes). Among 24 candidate protein markers, nine proteins were also identified by gene expression studies. Next generation candidate marker proteins with improved diagnostic and prognostic values for kidney diseases will be derived from whole genome scans and protemics approaches. Prospective validation still remains elusive for all proposed candidates.
Stability mutants of staphylococcal nuclease: large compensating enthalpy-entropy changes for the reversible denaturation reaction (1988)

By use of intrinsic fluorescence to determine the apparent equilibrium constant Kapp as a function of temperature, the midpoint temperature Tm and apparent enthalpy change delta Happ on reversible thermal denaturation have been determined over a range of pH values for wild-type staphylococcal nuclease and six mutant forms. For wild-type nuclease at pH 7.0, a Tm of 53.3 +/- 0.2 degrees C and a delta Happ of 86.8 +/- 1.4 kcal/mol were obtained, in reasonable agreement with values determined calorimetrically, 52.8 degrees C and 96 +/- 2 kcal/mol. The heat capacity change on denaturation delta Cp was estimated at 1.8 kcal/(mol K) versus the calorimetric value of 2.2 kcal/(mol K). When values of delta Happ and delta Sapp for a series of mutant nucleases that exhibit markedly altered denaturation behavior with guanidine hydrochloride and urea were compared at the same temperature, compensating changes in enthalpy and entropy were observed that greatly reduce the overall effect of the mutations on the free energy of denaturation. In addition, a correlation was found between the estimated delta Cp for the mutant proteins and the d(delta Gapp)/dC for guanidine hydrochloride denaturation. It is proposed that both the enthalpy/entropy compensation and this correlation between two seemingly unrelated denaturation parameters are consequences of large changes in the solvation of the denatured state that result from the mutant amino acid substitutions.
Surface Functionalization of Graphene (2013)

The covalent interaction of atoms, molecules and functional groups such as a hydroxyl with the graphene sheet are reviewed, with particular emphasis on the advances from theoretical/computational perspectives in the understanding of graphene chemistry and the route to its functionalization for different applications.
Prognostic relevance of urokinase type plasminogen activator, its receptor and inhibitors in chondrosarcoma. (2000)

The plasminogen activation system plays an important role in enhancing pericellular proteolysis of tumor invasion/metastasis and in autocrine/paracrine tumor growth stimulation. To investigate the prognostic significance of the plasminogen activation system in human chondrosarcoma, the immunohistochemical expression of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), plasminogen activator inhibitor, 1 (PAI-1) and 2 (PAI-2) were analyzed in 28 patients with chondrosarcoma. In multivariate survival analysis, histological grade (p = 0.0008) and location (p = 0.02) were independent risk factors for local relapse. For metastasis-free survival, uPA index (p = 0.006) and PAI-2 index (p = 0.04) were independent prognostic factors. PAI-2 index (p = 0.02), uPAR index (p = 0.02) and histological grade (p = 0.03) predicted total survival. These results demonstrated the usefulness of uPA, uPAR and PAI-2 expression as biological prognostic indicator and the importance of the plasminogen activation system in tumor progression and metastasis in chondrosarcoma.
Correlation of Prostate Cancer Nuclear Deoxyribonucleic Acid, Size, Shape and Gleason Grade with Pathological Stage at Radical Prostatectomy (1992)

Using image cytometry and a video planimetry unit, various deoxyribonucleic acid (DNA) measurements, nuclear size and shape factors, and Gleason grade were correlated with capsular penetration, seminal vesicle invasion and lymph node involvement in 113 radical prostatectomy specimens. Percentage of nondiploid cells was the best DNA measurement and standard deviation of nuclear area was the best size measurement correlating with capsular penetration. However, stepwise regression analysis demonstrated that Gleason grade was the only independent predictor of capsular penetration. The only parameter that independently predicted seminal vesicle invasion in a stepwise regression analysis was percentage of tetraploid cells. The mode of optical density was the best DNA measurement for predicting lymph node involvement, although stepwise regression analysis found that Gleason grade was the only independent predictor. DNA ploidy was not as predictive of pathological stage. In summary, DNA measurements and nuclear morphometry performed on smears offered relatively little additional prediction of pathological stage over that of Gleason grade.
Application of Fluorescently Labeled Poly(dU) for Gene Expression Profiling on cDNA Microarrays (2001)

The membrane filter hybridization technique has been widely used for gene expression profiling. The preparation of sensitive and reliable probes is critical for quantitative analysis in this technique. We report a method in which fluorescently labeled poly(dU) is used to detect poly(A)-containing mRNA that hybridizes to specific gene targets. The probe can be used commonly for every sample, alleviating problems encountered in preparing cDNA probes by reverse transcription, particularly when many samples are to be analyzed. Moreover, the sensitivity is at least comparable to cDNA probes prepared by conventional protocols, and intensities of signals after hybridization are independent of mRNA sizes and solely dependent on copy numbers. This method was also shown to be applicable to DNA chip technology.
Discovery and Optimization of a Novel Series ofN-Arylamide Oxadiazoles as Potent, Highly Selective and Orally Bioavailable Cannabinoid Receptor 2 (CB2) Agonists (2008)

The CB2 receptor is an attractive therapeutic target for analgesic and anti-inflammatory agents. Herein we describe the discovery of a novel class of oxadiazole derivatives from which potent and selective CB2 agonist leads were developed. Initial hit 7 was identified from a cannabinoid target-biased library generated by virtual screening of sample collections using a pharmacophore model in combination with a series of physicochemical filters. 7 was demonstrated to be a selective CB2 agonist (CB2 EC50 = 93 nM, Emax = 98%, CB1 EC50 > 10 microM). However, this compound exhibited poor solubility and relatively high clearance in rat, resulting in low oral bioavailability. In this paper, we report detailed SAR studies on 7 en route toward improving potency, physicochemical properties, and solubility. This effort resulted in identification of 63 that is a potent and selective agonist at CB2 (EC50 = 2 nM, Emax = 110%) with excellent pharmacokinetic properties.
Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. (2004)

(18)F-FDHT localizes to tumor sites in patients with progressive clinically metastatic prostate cancer and may be a promising agent to analyze antigen receptors and their impact on the clinical management of prostate cancer.
Differential Effects of Anti-cytokine Treatment on Bronchoalveolar Hemostasis in Endotoxemic Chimpanzees (1998)

Activation and inhibition of coagulation and fibrinolysis was analyzed in bronchoalveolar lavage (BAL) fluids obtained from endotoxin-challenged chimpanzees. The mediatory role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) on endotoxin-induced changes in bronchoalveolar coagulation and fibrinolysis was investigated in experiments in which the infusion of endotoxin was combined with the administration of monoclonal anti-TNF-alpha or anti-IL-6 antibodies. Endotoxin infusion elicited a marked increase in bronchoalveolar thrombin generation as measured by levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes. Markers for intrinsic pathway activation were not detectable, suggesting that the thrombin generation was mediated by the tissue factor-dependent route. Levels of antithrombin were low before the injection of endotoxin and not detectable hereafter. The administration of anti-IL-6 antibody completely abolished the endotoxin-induced activation of bronchoalveolar coagulation, whereas treatment with anti-TNF-alpha antibody only partly inhibited this effect. Bronchoalveolar fibrinolytic activity, due to urokinase-type plasminogen activator (u-PA), was significantly depressed after endotoxin injection, mainly due to a striking increase in plasminogen activator inhibitor-2 levels in BAL fluid. The endotoxin-induced effects on bronchoalveolar fibrinolysis could be blocked by the simultaneous administration of anti- TNF-alpha antibodies. We conclude that endotoxemia results in the activation of bronchoalveolar coagulation, which is apparently mediated by the tissue factor route of coagulation activation and which may be amplified by consumption of antithrombin III. Bronchoalveolar fibrinolytic activity is significantly abolished by increased levels of mainly PAI-2 after the injection of endotoxin. The endotoxin-induced effects on bronchoalveolar coagulation appears to be mediated by IL-6, whereas TNF-alpha seems to be the pivotal mediator of the endotoxin-induced depression of bronchoalveolar fibrinolysis.
Claudin-2, a component of the tight junction, forms a paracellular water channel (2010)

Whether or not significant amounts of water pass the tight junction (TJ) of leaky epithelia is still unresolved, because it is difficult to separate transcellular water flux from TJ-controlled paracellular water flux. Using an approach without differentiating technically between the transcellular and paracellular route, we measured transepithelial water flux with and without selective molecular perturbation of the TJ to unequivocally attribute changes to the paracellular pathway. To this end, MDCK C7 cells were stably transfected with either claudin-2 or claudin-10b, two paracellular cation-channel-forming TJ proteins that are not endogenously expressed in this cell line. Claudin-2 is typical of leaky, water-transporting epithelia, such as the kidney proximal tubule, whereas claudin-10b is present in numerous epithelia, including water-impermeable segments of the loop of Henle. Neither transfection altered the expression of endogenous claudins or aquaporins. Water flux was induced by an osmotic gradient, a Na+ gradient or both. Under all conditions, water flux in claudin-2-transfected cells was elevated compared with vector controls, indicating claudin-2-mediated paracellular water permeability. Na+-driven water transport in the absence of an osmotic gradient indicates a single-file mechanism. By contrast, claudin-10b transfection did not alter water flux. We conclude that claudin-2, but not claudin-10b, forms a paracellular water channel and thus mediates paracellular water transport in leaky epithelia.
Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: twenty-four-hour versus 7-day infusion. (1997)

I.P. IL-2 is better tolerated as a weekly infusion as compared with a 7-day infusion and demonstrates evidence of possible long-term efficacy in a modest number of patients. A randomized trial is indicated to determine if the prolonged survival seen in this study is a due to I.P. IL-2 therapy or other factors that cannot be controlled for in a single-arm study.
Backbone Cyclic Peptidomimetic Melanocortin-4 Receptor Agonist as a Novel Orally Administrated Drug Lead for Treating Obesity (2008)

The tetrapeptide sequence His-Phe-Arg-Trp, derived from melanocyte-stimulating hormone (alphaMSH) and its analogs, causes a decrease in food intake and elevates energy utilization upon binding to the melanocortin-4 receptor (MC4R). To utilize this sequence as an effective agent for treating obesity, we improved its metabolic stability and intestinal permeability by synthesizing a library of backbone cyclic peptidomimetic derivatives. One analog, peptide 1 (BL3020-1), was selected according to its selectivity in activating the MC4R, its favorable transcellular penetration through enterocytes and its enhanced intestinal metabolic stability. This peptide was detected in the brain following oral administration to rats. A single oral dose of 0.5 mg/kg in mice led to reduced food consumption (up to 48% vs the control group) that lasted for 5 h. Repetitive once daily oral dosing (0.5 mg/kg/day) for 12 days reduced weight gain. Backbone cyclization was shown to produce a potential drug lead for treating obesity.
Fit-for-Purpose Development of the Enabling Route to Crizotinib (PF-02341066) (2011)

A robust six-step process for the synthesis of crizotinib, a novel c-Met/ALK inhibitor currently in phase III clinical trials, has been developed and used to deliver over 100 kg of API. The process includes a Mitsunobu reaction, a chemoselective reduction of an arylnitro group, and a Suzuki coupling, all of which required optimization to ensure successful scale-up. Conducting the Mitsunobu reaction in toluene and then crystallizing the product from ethanol efficiently purged the reaction byproduct. A chemoselective arylnitro reduction and subsequent bromination reaction afforded the key intermediate 6. A highly selective Suzuki reaction between 6 and pinacol boronate 8, followed by Boc deprotection, completed the synthesis of crizotinib 1.
Antioxidant Enzyme Induction: A New Protective Approach Against the Adverse Effects of Diesel Exhaust Particles (2007)

Exposure to airborne particulate pollutants such as diesel exhaust particles (DEPs) has been associated with allergic respiratory disorders, including asthma and allergic rhinitis. In this communication, we review recent advances in the mechanism by which DEPs elicit their harmful effects and the protective role of antioxidants. Reactive oxidative species (ROS) are believed to play a key role in cellular damage after exposure to DEPs. Numerous reports demonstrate that both proinflammatory and anti-inflammatory products are induced by DEPs via the activation of transcription factors. DEPs trigger multiple signaling pathways, which lead to DNA damage and cell apoptosis, inflammatory response, and antioxidant defense. Recent studies both in vitro and in mice show that antioxidants could alleviate the allergic inflammatory effects of DEPs. Human in vivo models suggest that the important phase II enzymes GSTM1 and GSTP1 modify the adjuvant effect of diesel exhaust particles on allergic inflammation. We have shown that the induction of phase II enzymes by the chemical sulforaphane can block DEP-induced enhanced immunoglobulin (Ig) E production in B cells and DEP-induced proinflammatory cytokine production in epithelial cells. These findings suggest that overexpression of antioxidant enzymes could constitute a powerful potential chemopreventive approach against adverse effects induced by oxidant pollutants such as DEPs.
[The inhibitory effect of apolipoproteins in HDL on experimental atherosclerosis in rabbits]. (1989)

The main apolipoproteins in HDL are known to be apo A1, A2, and A4. Apolipoprotein (mainly apo A1) were isolated and purified from about 100 liters of rabbit's serum for the purpose of studying their inhibitory effect on the development of atheromatous plaques in rabbits. Data indicated that lipid content in aortic intima: lipid deposition in intima morphologically; area of atheromatous lesion involved and the severity of atheromatous lesions obtained were much lower in animals of the experimental group after intravenous administration of apolipoproteins isolated from HDL for 8 to 12 weeks than those in animals of the cholesterol control groups in two successive experiments. In accordance with data obtained from epidemiological and experimental surveys. HDL level was known to be correlated reversely with the incidence of atherosclerosis. Data of these experiments confirmed that apolipoproteins (mainly apoA1) in HDL are the main factors of this inhibitory effect. This result provides a scientific basis for the measurement of preparation of certain apolipoproteins (apo A1 and possibly A1) by high bio-technology for prevention and treatment of atherosclerosis in the near future.