gebhart/patrepeval huggingface dataset:
Influence of vesicle size, lipid composition, and drug-to-lipid ratio on the biological activity of liposomal doxorubicin in mice. (1989)

The effects of vesicle size, lipid composition, and drug-to-lipid ratio on the biological activity of liposomal doxorubicin in mice have been investigated using a versatile procedure for encapsulating doxorubicin inside liposomes. In this procedure, vesicles exhibiting transmembrane pH gradients (acidic inside) were employed to achieve drug trapping efficiencies in excess of 98%. Drug-to-lipid ratios as high as 0.3:1 (wt:wt) could be obtained in a manner that is relatively independent of lipid composition and vesicle size. Egg phosphatidylcholine (EPC)/cholesterol (55:45; mol/mol) vesicles sized through filters with a 200-nm pore size and loaded employing transmembrane pH gradients to achieve a doxorubicin-to-lipid ratio of 0.3:1 (wt/wt) increased the LD50 of free drug by approximately twofold. Removing cholesterol or decreasing the drug-to-lipid ratio in EPC/cholesterol preparations led to significant decreases in the LD50 of liposomal doxorubicin whereas, the LD50 increased 4- to 6-fold when distearoylphosphatidylcholine was substituted for EPC. The results suggest that the stability of liposomally entrapped doxorubicin in the circulation is an important factor in the toxicity of this drug in liposomal form. In contrast, the antitumor activity of liposomal doxorubicin is not influenced dramatically by alterations in lipid composition. Liposomal doxorubicin preparations of EPC, EPC/cholesterol (55:45; mol:mol), EPC/egg phosphatidylglycerol (EPG)/cholesterol (27.5:27.5:45; mol:mol), and distearoylphosphatidylcholine/cholesterol (55:45; mol:mol) all demonstrated similar efficacy to that of free drug when given at doses of 20 mg/kg and below. Higher dose levels of the less toxic formulations could be administered, leading to enhanced increases in life span (ILS) values. Variations in vesicle size, however, strongly influenced the antitumor activity of liposomal doxorubicin. At a dose of 20 mg/kg, large EPC/cholesterol systems are significantly less effective than free drug (with ILS values of 65% and 145%, respectively). In contrast, small systems sized through filters with a 100-nm pore size are more effective than free drug, resulting in an ILS of 375% and a 30% long term (greater than 60 days) survival rate when administered at a dose of 20 mg/kg. Similar size-dependent effects are observed for distearoylphosphatidylcholine/cholesterol systems.
Hunchback IS REQUIRED FOR ABDOMINAL IDENTITY SUPPRESSION AND GERMBAND GROWTH IN THE PARTHENOGENETIC EMBRYOGENESIS OF THE PEA APHID, Acyrthosiphon pisum (2013)

Aphid, a short germband insect, displays an embryogenesis different from that of long germband insect species. Furthermore, the development of its parthenogenetic and viviparous embryo is different from that of the embryo resulting from sexual reproduction. To better understand the genetic regulation of this type of embryogenesis, the functions of hunchback in asexual Acyrthosiphon pisum were investigated by parental RNAi. Microinjection of Aphb double-stranded RNA yielded several defective phenotypes. Quantitative real-time PCR analysis revealed that these defects resulted from reduction of Aphb mRNA level in injected aphids. All these results suggested that the hb gene in parthenogenetic and viviparous Acyrthosiphon pisum was involved in abdominal identity suppression and germband growth as its homologue does in sexual insects.
A model for topoisomerase I-mediated insertions and deletions with duplex DNA substrates containing branches, nicks, and gaps (1995)

The ability of DNA topoisomerase I to promote insertions and deletions in vitro has been studied at nucleotide resolution for structurally diverse DNA substrates that uncouple the cleavage and ligation reactions of the enzyme. Topoisomerase I-mediated ligations afforded DNA duplexes having deletions and insertions with "branched" substrates and deletions up to 18 nucleotides in length with substrates containing nicks or gaps. In addition, a number of the acceptor substrates altered the preferred site of DNA cleavage, thereby increasing the diversity of accessible ligation products. Also demonstrated by the production of two "recombinant" duplexes from a single set of reactants was the potential for amplification of such alterations. These findings illustrate plausible mechanisms by which topoisomerase I-mediated illegitimate recombination may obtain at a molecular level.
Hypopnea, a Floating Metric: Implications for Prevalence, Morbidity Estimates, and Case Finding (1997)

The respiratory disturbance index (RDI) is the most frequently used metric to characterize sleep-disordered breathing. Clinically, the RDI is used to classify disease status and guide treatment decisions. For research purposes, the RDI is used to describe population distributions of sleep-disordered breathing. Its popularity as a cardinal disease-defining measure, however, may not be justified given that standardized criteria do not exist for defining hypopnea, a key component of the RDI. This paper reviews sources of variability in identifying hypopneas, including: the magnitude of changes in breathing amplitude necessary to describe breathing as "reduced" (from "discernible" to >50%), variations in the utilization of sensors with different sensitivities to detect airflow/ventilation (i.e. thermocouples, thermistors, and pressure transducers), and differential use of data on oxygen saturation and arousals to discriminate normal breathing from hypopneas. The extent to which disparate approaches influence the overall RDI and population estimates of disease also is discussed.
Canine Adenovirus Type 2 Attachment and Internalization: Coxsackievirus-Adenovirus Receptor, Alternative Receptors, and an RGD-Independent Pathway (2000)

The best-characterized receptors for adenoviruses (Ads) are the coxsackievirus-Ad receptor (CAR) and integrins alpha(v)beta(5) and alpha(v)beta(3), which facilitate entry. The alpha(v) integrins recognize an Arg-Gly-Asp (RGD) motif found in some extracellular matrix proteins and in the penton base in most human Ads. Using a canine adenovirus type 2 (CAV-2) vector, we found that CHO cells that express CAR but not wild-type CHO cells are susceptible to CAV-2 transduction. Cells expressing alpha(M)beta(2) integrins or major histocompatibility complex class I (MHC-I) molecules but which do not express CAR were not transduced. Binding assays showed that CAV-2 attaches to a recombinant soluble form of CAR and that Ad type 5 (Ad5) fiber, penton base, and an anti-CAR antibody partially blocked attachment. Using fluorescently labeled CAV-2 particles, we found that in some cells nonpermissive for transduction, inhibition was at the point of internalization and not attachment. The transduction efficiency of CAV-2, which lacks an RGD motif, surprisingly mimicked that of Ad5 when tested in cells selectively expressing alpha(v)beta(5) and alpha(v)beta(3) integrins. Our results demonstrate that CAV-2 transduction is augmented by CAR and possibly by alpha(v)beta(5), though transduction can be CAR and alpha(v)beta(3/5) independent but is alpha(M)beta(2), MHC-I, and RGD independent, demonstrating a transduction mechanism which is distinct from that of Ad2/5.
Binding of synthetic oligosaccharides to the hepatic Gal/GalNAc lectin. Dependence on fine structural features. (1983)

A series of synthetic oligosaccharides, resembling natural N-acetyllactosamine type glycans, were tested for their ability to inhibit the binding of labeled ligand to the mammalian hepatic lectin on rabbit hepatocytes at 2 degrees C. A dramatic hierarchy of inhibitory potency (tetraantennary greater than triantennary much greater than biantennary much greater than monoantennary) could be demonstrated. The range of concentration required for 50% inhibition of labeled ligand binding extended from approximately 1 mM, for the monoantennary oligosaccharides, to approximately 1 nM for triantennary oligosaccharides, even though the absolute Gal concentration increased only 3-fold. It was found that the number of Gal residues/cluster and their branching mode are major determinants of binding affinity of ligands to the hepatic lectin on the surface of hepatocytes.
Calibration of a vector-MEG helmet system. (2004)

The MEG system Argos 500, recently installed at the University of Ulm, is designed for clinical application and routine use, to allow investigation of a large number of patients per day. To reach this goal, the system design meets the requirements of reliability, high field sensitivity, minimal set-up overhead before each measurement and an easy-to-handle user interface. The sensor system consists of a 163 vector-magnetometer array oriented and located in a suitable way to cover the whole head of the patient. Four additional triplets are available as references to build software gradiometers. To use this system at a high performance level, it must be properly calibrated, with these goals: to determine the actual geometry of the sensors array, which can deviate from the design specifications, and to determine the actual sensitivity of each sensor. The calibrating source consists of 31 coils placed at the corners of a head-size dodecahedron. Various details of the calibration system and process are presented here.
Efficacy of adenovirus-mediated CD/5-FC and HSV-1 thymidine kinase/ganciclovir suicide gene therapies concomitant with p53 gene therapy. (1999)

Recent evidence has suggested that tumor cells having a wild-type p53 status are more sensitive to chemotherapeutic agents and radiation than cells that lack functional p53. The heightened sensitivity of wild-type p53 cells is thought to be attributable to their propensity to undergo p53-mediated apoptosis after insult. Given that suicide gene therapy is essentially tumor-targeted chemotherapy, we examined the hypothesis that coexpression of wild-type p53 could enhance the efficacy of adenovirus-mediated suicide gene therapy. Human Hep3B and SK-OV-3 cells, which are null for p53, were infected with a pair of replication-deficient adenoviruses that expressed a cytosine deaminase/herpes simplex virus thymidine kinase (CD/HSV-1 TK) fusion gene without (fusion gene nonreplicative adenovirus, FGNR) or with (FGNRp53) the wild-type human p53 gene. The sensitivity of cells to the CD/5-fluorocytosine (CD/5-FC) and HSV-1 TK/ ganciclovir (GCV) enzyme/prodrug systems was determined in vitro and in vivo. Coexpression of p53 did not enhance the cytotoxicity of either the CD/5-FC or HSV-1 TK/GCV system in vitro. The failure to observe an effect of p53 could not be explained on the basis of insufficient or transient p53 expression, because FGNRp53-infected cells growth arrested in G1, induced Bax, and underwent apoptosis at an increased rate after prodrug treatment, particularly when the adenovirus E1A protein was present. Intratumoral injection of FGNRp53 concomitant with single or double pro-drug therapy resulted in a tumor growth delay that was equal to or less than that observed with the FGNR virus. Our results indicate that coexpression of p53 may not necessarily improve the efficacy of adenovirus-mediated CD/ 5-FC and HSV-1 TK/GCV suicide gene therapies in vivo.
Transcriptional enhancers in the HLA-DQ subregion. (1987)

Using transient expression assays, the HLA-DQ alpha and HLA-DQ beta genes of the human major histocompatibility complex were screened for cis-acting regulatory elements. Two regions in the HLA-DQ alpha gene and one in the HLA-DQ beta gene were identified which fulfilled the criteria for transcriptional enhancers.
An Object-oriented Database for IVHS (1998)

The objective of this proposal was to develop a database that integrates various elements-traffic simulation packages, data sets, and computational tools. The difficulty in integration was felt to be the incompatibility of data structures, formats, and software.It was proposed to design, build and test a software environment with an open architecture that would facilitate a synergistic use of these software elements. The core of this environment was to be an object-oriented commercial database system that would be sufficiently general to support many software elements, and which would guide new software development.The deliverables of this project were:-&amp;nbsp;A specification of an object hierarchy implemented in C++, and a graphical user interface to facilitate object specification;- An interface to SmartPath so that simulation configurations and simulation runs can be stored in the database;-&amp;nbsp;An interface to the 1-880 database, developed in the Freeway Service Patrol project;-&amp;nbsp;Additional facilities to be determined after consultation with other PATH researchers.Work done under this project resulted in the system called SmartDB, implemented on top of the commercial object-oriented database management system, Versant. SmartDB includes a graphical user interface. SmartDB is documented in the PhD thesis included as Appendix, and in several papers.
Inhibitory Effect of Methyl Caffeate on Fos-Jun-DNA Complex Formation and Suppression of Cancer Cell Growth (2001)

The fos and jun proteins form a heterodimeric complex that interacts with the DNA regulatory element known as the AP-1 binding site. To search for inhibitors of the fos-jun-DNA complex formation, several natural plants extracts were screened. One of them, the methanol extract of Perilla frutescens showed inhibitory effect against the complex formation between the fos-jun dimer and the AP-1 binding site (TGAG/CTCA). Methyl caffeate and dibutyl phthalate (DBP) were isolated as the active constituents from the extract of P. frutescens by repeated column chromatography and HPLC. And their IC50 values for fos-jun-DNA complex formation were estimated as 0.29 mM and 0.55 mM, respectively. The more potent inhibitor, methyl caffeate showed cytotoxic effect against human cancer cell line (A549 and K562).
Synthesis of 9-Anthryl Ethers from trans-9,10-Dihydro-9,10-dimethoxyanthracene by Acid-Catalyzed Transetherification (2009)

During a study of electrophilic aromatic addition reactions (Ad E Ar) to anthracene, anthryl ethers at the C9-position of anthracene were obtained as the major products when trans-9,10-dihydro-9,10-dimethoxyanthracene was reacted (10 minutes at 75 ˚C) with various alcohols. 9-Anthryl ethers with primary, secondary, cyclic alcohols, and polyethylene glycol (PEG) were isolated in 47-73% yields under optimized conditions. It is hoped that the devised method offers a new synthetic route for the preparation of anthryl ethers via the acid-catalyzed transetherification of trans-9,10-dihydro-9,10-dimethoxyanthracene with various alcohols.
Antitumour imidazotetrazines. 1. Synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one, a novel broad-spectrum antitumor agent (1984)

Interaction of 5-diazoimidazole-4-carboxamide and alkyl and aryl isocyanates in the dark affords 8-carbamoyl-3-substituted-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-on es. In cold methanol or ethanol, the 3-(2-chloroethyl) derivative 7a decomposes to afford 2-azahypoxanthine (14) and methyl and ethyl N-(2-chloroethyl)carbamates, respectively. Compound 7a has curative activity against L-1210 and P388 leukemia and may act as a prodrug modification of the acyclic triazene 5-[3-(2-chloroethyl)triazen-1-yl]imidazole-4-carboxamide (MCTIC), since it ring opens to form the triazene in aqueous sodium carbonate.
A Review of the Clinical Use of Disulfiram and Calcium Carbimide in Alcoholism Treatment (1981)

The role of disulfiram and calcium carbimide in alcoholism treatment is currently under critical review. Evidence supporting the efficacy of these drugs is unclear: although many alcoholism therapists are of the opinion that the alcohol deterrents are useful in the treatment of the chronic alcoholic, clinical studies with disulfiram that use proper evaluation methodologies report no or only low improvement rates, and there have been no controlled studies with calcium carbimide. Although disulfiram is thought to be safe when administered in therapeutic dosages, toxicity can occur in alcoholics treated with this drug. Information concerning the toxicity of calcium carbimide in alcoholics is incomplete. In this article, the efficacy and toxicity of disulfiram and calcium carbimide are reviewed, and guidelines for their safe and effective use in alcoholism treatment are presented.
Clinical trials and progress with paclitaxel in ovarian cancer (2010)

Paclitaxel is a front-line agent for ovarian cancer chemotherapy, along with the platinum agents. Derived from the Pacific yew tree, Taxus brevifolia, paclitaxel has covered significant ground from the initial discovery of its antineoplastic properties to clinical applications in many forms of human cancers, including ovarian cancer. Although much has been published about the unique mechanism of action of this agent, several issues remain to be resolved. Finding the appropriate dosage schedule for paclitaxel in chemo-naïve and recurrent ovarian cancer, defining the role of paclitaxel in maintenance chemotherapy, and elucidating the mechanisms of taxane resistance are areas of intense research. Newer forms of taxanes are being manufactured to avoid troublesome adverse effects and to improve clinical efficacy. These issues are reviewed in detail in this paper with an emphasis on clinically relevant evidence-based information.
Jupyter Notebooks &ndash; a publishing format for reproducible computational workflows (2016)

It is increasingly necessary for researchers in all fields to write computer code, and in order to reproduce research results, it is important that this code is published. We present Jupyter notebooks, a document format for publishing code, results and explanations in a form that is both readable and executable. We discuss various tools and use cases for notebook documents.
Clinical and Laboratory Features of theNocardiaspp. Based on Current Molecular Taxonomy (2006)

The recent explosion of newly described species of Nocardia results from the impact in the last decade of newer molecular technology, including PCR restriction enzyme analysis and 16S rRNA sequencing. These molecular techniques have revolutionized the identification of the nocardiae by providing rapid and accurate identification of recognized nocardiae and, at the same time, revealing new species and a number of yet-to-be-described species. There are currently more than 30 species of nocardiae of human clinical significance, with the majority of isolates being N. nova complex, N. abscessus, N. transvalensis complex, N. farcinica, N. asteroides type VI (N. cyriacigeorgica), and N. brasiliensis. These species cause a wide variety of diseases and have variable drug susceptibilities. Accurate identification often requires referral to a reference laboratory with molecular capabilities, as many newer species are genetically distinct from established species yet have few or no distinguishing phenotypic characteristics. Correct identification is important in deciding the clinical relevance of a species and in the clinical management and treatment of patients with nocardial disease. This review characterizes the currently known pathogenic species of Nocardia, including clinical disease, drug susceptibility, and methods of identification.
ARE- and TRE-mediated Regulation of Gene Expression (1995)

Antioxidant response elements (AREs) containing 12-O-tetradecanoylphorbol-13-acetate response element (TRE) (perfect AP1) and TRE-like (imperfect AP1) elements mediate high basal transcription of the NAD(P)H:quinone oxidoreductase1 (NQO1) and glutathione S-transferase Ya genes in tumor cells and its induction in response to xenobiotics and antioxidants. Mutations in the human NQO1 gene ARE (hARE) revealed the requirement for two TRE or TRE-like elements arranged in inverse orientation at the interval of three base pairs and a GC box for optimal expression and beta-naphthoflavone induction of the NQO1 gene. A single TRE element from the human collagenase gene failed to respond to beta-naphthoflavone. These results demonstrate that ARE (2 x TRE or TRE-like elements)-containing detoxifying enzyme genes and not genes that contain 1 x TRE are responsive to xenobiotics and antioxidants. Bandshift assays showed shifting of a complex of more or less similar mobility with hARE and TRE that could be competed by each other. Mutations in the 3'-TRE of the NQO1 gene hARE eliminated binding of nuclear proteins to the hARE and resulted in the loss of basal and induced expression, indicating that 3'-TRE is the most important element within the hARE. 5'-TRE-like element within the NQO1 gene hARE is required for xenobiotic response but may not bind to the nuclear proteins by itself. The GC box located immediately following the 3'-TRE is required for optimal expression and induction of the NQO1 gene. The comparison of AREs from several different genes indicated the requirement for specific arrangement and spacing of two TRE and TRE-like elements within the AREs.
Novel Cyclic Ketones for Catalytic Oxidation Reactions (1998)

In our effort to search for C2 symmetric and conformationally rigid chiral ketones as catalysts for asymmetric epoxidation, a series of cyclic ketones 4−10 were prepared from the corresponding diacids. Compared with acyclic ketones for epoxidation of trans-stilbene, those 9-, 10-, and 11-membered-ring cyclic ketones were found to have much higher catalytic activities, which were attributed to steric effects, electronic effects, and ring strains. By using the homogeneous acetonitrile−water solvent system, unfunctionalized olefins with various substitution patterns (with 5 mol % of ketone 9) and strongly electron-deficient olefins (with a 1:1 ketone 9:substrate ratio) were epoxidized with Oxone as terminal oxidant in 75−96% yield at room temperature and neutral pH. In addition, oxidation of alcohols (with 20 mol % of ketone 9) was carried out successfully with good isolated yields of aldehydes or ketones (75−88%).
Inhibition of the phosphatidylinositol 3'-kinase-AKT pathway induces apoptosis in pancreatic carcinoma cells in vitro and in vivo. (2002)

The phosphatidylinositol 3'-kinase (PI3k)-AKT survival pathway is activated in many malignancies. We observed constitutive AKT phosphorylation (on S473) consistent with pathway activation in seven of nine human pancreatic carcinoma cell lines in vitro. Exposure of the cells to two structurally distinct inhibitors of PI3k (worthmannin and LY294002) resulted in a dose-dependent induction of apoptosis in six of seven of the cell lines that displayed constitutive AKT phosphorylation but not in either of the cell lines that did not. The mitogen-activated protein/extracellular signal-regulated kinase kinase-mitogen-activated protein kinase inhibitor PD98059 also induced apoptosis in two of the cell lines, including one of the LY294002-insensitive lines (AsPC-1). Exposure of orthotopic L3.6pl pancreatic tumors to LY294002 resulted in dose-dependent inhibition of tumor growth, and decreased peritoneal and liver metastases, effects that were associated with an inhibition of AKT phosphorylation and increased terminal deoxynucleotidyl transferase-mediated nick end labeling staining characteristic of apoptosis. Furthermore, a suboptimal dose of LY294002 (25 mg/kg) produced additive inhibition of tumor growth when combined with a suboptimal dose of gemcitabine (62 mg/kg). Together, our results establish that the PI3k/AKT pathway is constitutively activated in a majority of human pancreatic cancer cell lines and establish that the pathway is a promising target for therapeutic intervention.
Uneven fatty replacement of the pancreas: evaluation with CT. (1995)

Fatty replacement is more severe in the anterior aspect of the head of the pancreas. The posterior aspect of the head of the pancreas and the area around the CBD tended to be spared.