gebhart/patrepeval huggingface dataset:
Epilepsy and psychiatric comorbidity: A nationally representative population‐based study (2012)

Psychiatric and neurodevelopmental conditions were overrepresented in people with epilepsy. These associations were stronger than with other nonneurologic chronic conditions, and not explained by confounding. Some overlap in the psychopathology observed in epilepsy and migraine cannot rule out the presence of common pathways of psychiatric comorbidity in neurologic conditions. However, associations of epilepsy with conditions such as autism spectrum disorders point to comorbidities specific to epilepsy that may not be shared by other neurologic conditions.
Strong antitumor activities of IgG3 antibodies to a human melanoma-associated ganglioside. (1985)

Three mouse monoclonal IgG3 antibodies, 2B2, IF4, and MG-21, recognize a GD3 ganglioside antigen that is expressed at the cell surface of most human melanomas. All three antibodies mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro when tested with human lymphocytes as effector cells in a 2-hr or 4-hr 51Cr-release test, and one antibody, MG-21, also gives strong complement-dependent cytotoxicity with human serum. Antibody 2B2, which gives ADCC also in the presence of mouse lymphocytes, inhibited the outgrowth of a human melanoma in nude mice, but antibody IF4, which showed no ADCC with mouse lymphocyte effectors, did not.
Refractive index of Irtran 2 as a function of wavelength and temperature (1978)

Data are presented for the refractive index of Irtran 2, a hot-pressed microcrystalline compact of ZnS, made by the Eastman Kodak Company, from 1 microm to 15 microm and from 93 K to 283 K. The values range from 2.35 at both high temperatures and short wavelengths to 2.12 at the opposite extremes. The average value of dn/dT is about 4 x 10(-5) K(-1) at 104 K for all wavelengths, with a value of 2 x 10(-7) K(-2) for the temperature variation of dn/dT.
Catalytic Pyrolysis of High Density Polyethylene on a HZSM-5 Zeolite Catalyst in a Conical Spouted Bed Reactor (2007)

HDPE has been pyrolysed at 450 °C and 500 °C using HZSM-5 zeolite as a catalyst. Batch runs have been carried out at atmospheric pressure in a conical spouted bed reactor. Product analysis has been carried out by means of a GC, connected on-line with a thermostated line. The degradation rate of the plastic is slightly faster at 500 °C than at 450 °C and much faster than thermal pyrolysis in both cases. Products have been grouped into five lumps: the lump of light olefins, C2-C4; light alkanes, C1-C4; the gasoline fraction, C5-C11 compounds; C11+ hydrocarbons; and the coke deposited on the catalyst. An HZSM-5 catalyst is appropriate to obtain light olefins; about 55 wt% in both cases. The yield of gasoline fraction is also considerable and although its composition is not suitable for commercial gasoline, is interesting for its use in petrochemistry. The catalyst deactivation rate is low.
Design and conformational analysis of several highly potent bradykinin receptor antagonists (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign and conformational analysis of several highly potent bradykinin receptor antagonistsDonald J. Kyle, Jennifer A. Martin, Stephen G. Farmer, and Ronald M. BurchCite this: J. Med. Chem. 1991, 34, 3, 1230–1233Publication Date (Print):March 1, 1991Publication History Published online1 May 2002Published inissue 1 March 1991https://pubs.acs.org/doi/10.1021/jm00107a052https://doi.org/10.1021/jm00107a052research-articleACS PublicationsRequest reuse permissionsArticle Views100Altmetric-Citations74LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Evolution, genomic analysis, and reconstruction of isobutanol tolerance in Escherichia coli (2010)

Escherichia coli has been engineered to produce isobutanol, with titers reaching greater than the toxicity level. However, the specific effects of isobutanol on the cell have never been fully understood. Here, we aim to identify genotype-phenotype relationships in isobutanol response. An isobutanol-tolerant mutant was isolated with serial transfers. Using whole-genome sequencing followed by gene repair and knockout, we identified five mutations (acrA, gatY, tnaA, yhbJ, and marCRAB) that were primarily responsible for the increased isobutanol tolerance. We successfully reconstructed the tolerance phenotype by combining deletions of these five loci, and identified glucosamine-6-phosphate as an important metabolite for isobutanol tolerance, which presumably enhanced membrane synthesis. The isobutanol-tolerant mutants also show increased tolerance to n-butanol and 2-methyl-1-butanol, but showed no improvement in ethanol tolerance and higher sensitivity to hexane and chloramphenicol than the parental strain. These results suggest that C4, C5 alcohol stress impacts the cell differently compared with the general solvent or antibiotic stresses. Interestingly, improved isobutanol tolerance did not increase the final titer of isobutanol production.
Monte Carlo simulation of particle acceleration at astrophysical shocks (1989)

A Monte Carlo code was developed for the simulation of particle acceleration at astrophysical shocks. The code is implemented in Turbo Pascal on a PC. It is modularized and structured in such a way that modification and maintenance are relatively painless. Monte Carlo simulations of particle acceleration at shocks follow the trajectories of individual particles as they scatter repeatedly across the shock front, gaining energy with each crossing. The particles are assumed to scatter from magnetohydrodynamic (MHD) turbulence on both sides of the shock. A scattering law is used which is related to the assumed form of the turbulence, and the particle and shock parameters. High energy cosmic ray spectra derived from Monte Carlo simulations have observed power law behavior just as the spectra derived from analytic calculations based on a diffusion equation. This high energy behavior is not sensitive to the scattering law used. In contrast with Monte Carlo calculations diffusive calculations rely on the initial injection of supra-thermal particles into the shock environment. Monte Carlo simulations are the only known way to describe the extraction of particles directly from the thermal pool. This was the triumph of the Monte Carlo approach. The question of acceleration efficiency is an important one in the shock acceleration game. The efficiency of shock waves efficient to account for the observed flux of high energy galactic cosmic rays was examined. The efficiency of the acceleration process depends on the thermal particle pick-up and hence the low energy scattering in detail. One of the goals is the self-consistent derivation of the accelerated particle spectra and the MHD turbulence spectra. Presumably the upstream turbulence, which scatters the particles so they can be accelerated, is excited by the streaming accelerated particles and the needed downstream turbulence is convected from the upstream region. The present code is to be modified to include a better description of particle scattering (pitch-angle instead of hard-sphere) and as iterative procedure for treating the self-excitation of the MHD turbulence.
Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme (1989)

The conversion of cholesterol into bile acids in the liver represents the major catabolic pathway for the removal of cholesterol from the body. In this complex biosynthetic pathway, at least 10 enzymes modify both the ring structure and side chain of cholesterol, resulting in the formation of the primary bile acids, cholic acid, and chenodeoxycholic acid. To gain insight into the details and regulation of this pathway, we have used protein sequencing and molecular cloning techniques to isolate and characterize a cDNA encoding the rabbit mitochondrial sterol 26-hydroxylase. This enzyme catalyzes the first step in the oxidation of the side chain of sterol intermediates in the biosynthesis of bile acids. The structure of the sterol 26-hydroxylase, as deduced by both DNA sequence analysis of the cDNA and protein sequence analysis, reveals it to be a mitochondrial cytochrome P-450. A signal sequence of 36 residues precedes a coding region of 499 amino acids, predicting a molecular weight of 56,657 for the mature protein. The identity of the 26-hydroxylase cDNA was further confirmed by expression in monkey COS cells employing a versatile eukaryotic expression vector. Blotting experiments revealed that the mRNA for this enzyme is expressed in many tissues and that it is encoded by a low copy number gene in the rabbit genome.
Shaking the Ivory Tower, or "When I Think of All I Could Have Learned" (1985)

Often we have a misconception of the relationship between ourselves as students and our instructors. Frequently we feel it's "us versus them", and too often it seems the instructors view things the same way. This is detrimental to the learning process. It also leads to a rift in communication between students and instructors. The function of an instructor, however, is not to become a thorn in our flesh. The instructor, rather, is to fulfill the role of a trusted servant who leads his or her charges (that's us) down the pathway of knowledge to the place where we intelligent and hard-working students can become competent veterinarians. The fact that few of us stray from this path is testimony to the abilities of instructors to keep our goal in mind. It may even be that the success of these "institutions of higher learning" which we attend may be due to the instructors spending many long hours in their ivory towers gazing out over the pathway of knowledge looking for potholes to fix and detours to avoid so we can work unhindered (unhindered, at least, by the teacher).
Evaluation of the Fibrin Binding Profile of two Anti-fibrin Monoclonal Antibodies (1996)

Two anti-fibrin monoclonal antibodies, MAbs 1H10 and 5F3, raised to human freeze-fractured fibrin and thrombin-treated N-terminal disulphide knot (T-NDSK), respectively, were compared for epitope binding to various domains of the fibrinogen/fibrin moiety. Using plasmin-mediated fibrinogen digests, immunoblots showed that both MAbs crossreacted strongly with fragments X and Y, weakly with fragment-E and not at all with fragment D. Purified fragments D and E used in an ELISA confirmed that MAbs 1H10 and 5F3 cross-reacted in a dose-response fashion with the isolated fragment-E, while there was no reaction with fragment-D. The two MAbs were similarly shown to react with fibrin-derived fragment-E. Surface Plasmon Resonance (SPR) technology, employed to further evaluate the epitopes in fibrin, showed that MAb 1H10 had a higher affinity for fragment-E (KD = 8.04 x 10(-9) M) than MAb 5F3 (KD = 1.13 x 10(-8) M). Individual association and dissociation rate constants of 7.97 x 10(5) M-1s-1 and 3.97 x 10(-3)s-1, respectively, for MAb 1HAb 1H10, and 5.16 x 10(5) M-1s-1 and 3.62 x 10(-3)s-1, respectively, for MAb 5F3 were also obtained. A SPR inhibition assay confirmed that MAb 1H10 had a greater affinity for fragment-E than MAb 5F3. However individual isolated polypeptide chains of fibrinogen fragment E (E-A alpha, E-B beta, E-gamma) showed no reaction with the two antibodies in ELISA, immunoblot or SPR analysis procedures. Furthermore, SPR pair-wise epitope mapping analysis revealed that MAbs 1H10 and 5F3 have in fact distinct epitopes on fragment-E. These distinct epitopes appeared to be a conformational amalgam of linear sequences in two or three of the polypeptide chains of fragment-E, or distinct conformational epitopes on one of the three subunit chains alone.
Potent tumor killing and inhibition of tumor growth by CEA/CD3-bispecific single chain antibodies that are resistant to inhibition by soluble CEA (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4106 

Introduction: 

Carcinoembryonic antigen (CEA) is a well-characterized target antigen for antibody-based cancer therapy. Expression of CEA on normal adult tissue is restricted to the luminal surface of intestinal epithelia, where it is inaccessible to systemically administered antibodies. In contrast, CEA is highly expressed in a non-polarized fashion on various adenocarcinomas, including colorectal, pancreatic and gastric cancer. As a novel therapeutic approach for treatment of CEA-expressing tumors we constructed bispecific single-chain antibodies (scFv) of the BiTE format by combining human anti-CEA scFvs with a single deimmunized anti-human CD3 scFv, respectively.

Experimental Procedures: 

Dose dependency of redirected lysis of CEA-expressing human tumor cell lines was investigated by a 51Cr-release assay. Unstimulated human PBMC, or stimulated CD8+ T cells from healthy donors were used as effector cells. Human CEA/mouse CD3-specific BiTE molecules were tested for inhibition of lung tumor growth in immunocompetent Balb/C mice.

Results: 

Various CEA-specific BiTE molecules were constructed from CEA-specific scFvs and efficiently redirected the cytotoxic activity of human T cells to kill CEA-positive tumor cell lines without the need for T cell costimulation. BiTE molecules selected for further development showed half-maximal tumor cell lysis at concentrations as low as of 5 pg/mL with activated human CD8+ T cells, and 0.5 ng/mL with unstimulated human PBMC as effector cells. The cytotoxic activity of certain CEA-specific BiTE molecules were resistant to concentrations of soluble CEA of up to 1 µg/mL, a level higher than found in the serum of most cancer patients. For in vivo proof of concept studies, selected anti-human CEA scFvs were combined with a scFv specific for murine CD3 to generate BiTE molecules capable of recruiting murine T cells for redirected tumor lysis in immunocompetent mice. Untreated mice developed on average 100 tumor colonies in the lung after intravenous inoculation with a syngeneic murine colorectal cancer cell line transfected with human CEA. In contrast, treatment of tumor bearing mice with 1 µg murine-specific CEA-BiTE once daily for 5 days almost completely inhibited outgrowth of lung tumors.

Conclusions: 

Novel CEA-specific BiTE molecules with potent in vitro and in vivo anti-tumor activity were generated; a subset were resistant to inhibition by soluble CEA. In light of its potent efficacy, CEA-specific BiTE molecules may prove a useful and novel approach for the treatment of CEA-expressing human adenocarcinomas.
Theory of Electron-Transfer Reactions and of Related Phenomena (1965)

Data on electron exchange reactions have provided insight into factors influencing rates of electron-transfer reactions in solution. The present paper has the twofold purpose of discussing some of these factors and of describing applications of these exchange data and theory to other phenomena. The reaction rate depends upon the extent of reorganization of bond lengths (angles) in the reactants and of solvent reorientation outside them. The reorganization is facilitated or hindered in a comparatively simple way by a favorable or unfavorable standard free energy of reaction. The rate depends, too, on coulombic and other interactions, as evidenced perhaps by certain salt effects, though probably only by a few orders of magnitude typically. The observed variation of rates of some 15 orders of magnitude is best attributed primarily 10&#13;\ndifferences in the vibrational reorganization term, a factor calculable from bond lengths and force constants&#13;\nwhen known. A remaining factor, non-adiabaticity, is at present of uncertain importance. Arrhenius frequency&#13;\nfactors in chemical and electrochemical exchange rate constants would provide the most direct information,&#13;\nbut can be complicated or even dwarfed by solvent reordering effects in the coulombic interaction. Available&#13;\ndata are few. They provide examples where a non-adiabatic effect is minor. There appear to be no known examples where it is major (Fe2+ - Fe3+ could be a candidate but its mechanism is apparently uncertain). Reorganization in reactants and in solvent occurs in a variety of related phenomena, and related concepts will be applied to treat them. In turn, chemical exchange data have useful applications to the latter. These areas include electrochemical exchange reactions, chemiluminescent electron-transfer reactions (between positive and negative aromatic ions, for example), and redox reactions of the solvated electron. An explanation for the chemiluminescent reactions will be based on the possible "inverse ΔF" effect, discussed several years ago by the author. A related phenomenon involving solvent "orientation strain" occurs in light absorption or emission by polar solutes in polar solvents, and the theoretical approach used by the author for treating it is closely related to that used for the exchange reactions.
Malignant transformation by the eukaryotic translation initiation factor 3 subunit p48 (eIF3e) (2002)

Several components of translation, e.g. eIF4E and PKR, are implicated in cancer. The e-subunit (p48) of mammalian initiation factor 3 is encoded by the Int6 gene, a common site for integration of the mouse mammary tumor virus genome, leading to the production of a truncated eukaryotic initiation factor-3e (eIF3e). Stable expression of a truncated eIF3e in NIH 3T3 cells causes malignant transformation by four criteria: foci formation; anchorage independent growth; accelerated growth; and lack of contact inhibition. Stable expression of full-length eIF3e does not cause transformation. The truncated eIF3e also inhibits the onset of apoptosis caused by serum starvation.
Nontraditional Reactions of Azomethine Ylides: Decarboxylative Three-Component Couplings of α-Amino Acids (2010)

New reactions of azomethine ylides with nontraditional dipolarophiles are reported. Azomethine ylides, formed in situ via decarboxylative condensations of alpha-amino acids with aldehydes, undergo reactions with naphthols, indoles, alkynes, and nitroalkanes.
Strategy Toward the Total Synthesis of Epothilones A and B (1999)

Abstract : Having accomplished total syntheses of epothilone A and B, we have been engaged in a new stage of investigation that involves development of efficient strategies for a large scale epothilone preparation and search for more potent analogues. Efficient and processable syntheses of key building blocks of l2,l3-desoxyepothilone B (dEpoB) by catalytic asymmetric induction has been achieved. dEpoB is a potent anticancer agent, showing a highly promising therapeutic potential in the currently undergoing phase I study. The syntheses of two epothilone analogues, 15(S)-aza-l2,13-desoxyepothilone B and the epimeric l5(R)-aza-12,l3- desoxyepothilone B have been accomplished. Tubulin binding and cytotoxicity profiles of these analogues have also been investigated. Another epothilone, l2,l3-desoxyepothilone F (dEpoF), was synthesized and evaluated for antitumor potential. The results from an in vitro assay reveal that this new analogue is highly active against various tumor cell lines with a potency comparable to that of dEpoB. In particular, the growth of resistant tumor cells is inhibited by dEpoF at concentrations where paclitaxel (Taxol) is basically ineffective. A preliminary assessment of its in vivo activity is also promising. The new analogue, containing an additional hydroxyl group at C21, provides advantages over other epothilones in terms of water solubility and can serve as a readily functionalizable handle to produce other useful compounds for pertinent biological studies.
Glucose sensing in pancreatic islet beta cells: the key role of glucokinase and the glycolytic intermediates. (1993)

The beta cells of the pancreatic islets of Langerhans respond to changes in glucose concentration by varying the rate of insulin synthesis and secretion. Beta cells sense glucose concentration by the levels of the products of glucose catabolism. Distinctive beta-cell proteins glucose transporter 2 and glucokinase catalyze the first two steps in beta-cell glucose catabolism. To test whether either protein controls the sensitivity of the beta cell to glucose by controlling the rate of glucose catabolism, we used gene-transfer techniques to express the isoenzymes glucose transporter 1 and hexokinase I in beta cells and measured the response to glucose of the insulin gene promoter. Cells expressing glucose transporter 1 do not differ significantly from control cells, but in cells expressing hexokinase I, insulin promoter activity increases, reaches a maximum by 1 mM glucose, and does not respond to changes in glucose concentration within the physiologic range. We conclude that glucokinase catalyzes the rate-limiting step of glucose catabolism in beta cells and, therefore, acts as the glucose sensor. Pyruvate, the end product of anaerobic glycolysis, is readily oxidized by mitochondria in normal beta cells but cannot substitute for glucose as a stimulator of insulin synthesis and secretion. We found that pyruvate can stimulate the insulin promoter in cells expressing the bacterial gluconeogenic enzyme phosphoenolpyruvate carboxykinase, which allows the conversion of pyruvate to phosphoenolpyruvate and the earlier intermediates of glycolysis. We conclude that the intermediates of anaerobic glycolysis between fructose 1,6-diphosphate and phosphoenolpyruvate are essential for beta-cell glucose sensing.
SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions (2009)

Much of the information on the Cytochrome P450 enzymes (CYPs) is spread across literature and the internet. Aggregating knowledge about CYPs into one database makes the search more efficient. Text mining on 57 CYPs and drugs led to a mass of papers, which were screened manually for facts about metabolism, SNPs and their effects on drug degradation. Information was put into a database, which enables the user not only to look up a particular CYP and all metabolized drugs, but also to check tolerability of drug-cocktails and to find alternative combinations, to use metabolic pathways more efficiently. The SuperCYP database contains 1170 drugs with more than 3800 interactions including references. Approximately 2000 SNPs and mutations are listed and ordered according to their effect on expression and/or activity. SuperCYP (http://bioinformatics.charite.de/supercyp) is a comprehensive resource focused on CYPs and drug metabolism. Homology-modeled structures of the CYPs can be downloaded in PDB format and related drugs are available as MOL-files. Within the resource, CYPs can be aligned with each other, drug-cocktails can be 'mixed', SNPs, protein point mutations, and their effects can be viewed and corresponding PubMed IDs are given. SuperCYP is meant to be a platform and a starting point for scientists and health professionals for furthering their research.