gebhart/patrepeval huggingface dataset:
Genetics of serine pathway enzymes in Methylobacterium extorquens AM1: phosphoenolpyruvate carboxylase and malyl coenzyme A lyase (1993)

Methylobacterium extorquens AM1 is a facultative methylotrophic bacterium that uses the serine pathway for formaldehyde incorporation as its assimilation pathway during growth on one-carbon compounds. A DNA region from M. extorquens AM1 previously shown to contain genes for the serine pathway enzymes malyl coenzyme A (CoA) lyase and hydroxypyruvate reductase has been characterized in more detail. Insertion mutagenesis revealed an additional region required for growth on one-carbon compounds, and all of the insertion mutants in this region lacked activity for another serine pathway enzyme, the acetyl-CoA-independent phosphoenolpyruvate (PEP) carboxylase. Expression analysis with Escherichia coli of DNA fragments that included the malyl-CoA lyase and PEP carboxylase regions identified five polypeptides, all transcribed in the same direction. Three of these polypeptides were expressed from the region necessary for the acetyl-CoA-independent PEP carboxylase, one was expressed from the region containing the malyl-CoA lyase gene, and the fifth was expressed from a region immediately downstream from the gene encoding hydroxypyruvate reductase. All six genes are transcribed in the same direction, but the transposon insertion data suggest that they are not all cotranscribed.
An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. (1997)

We developed a set of informant-based items describing performance of activities of daily living (ADL) by patients with Alzheimer's disease (AD) to identify which ADL are useful for assessment of patients in clinical trials. Evaluation of ADL is an important outcome measure in AD clinical trials. For clinical trial measurement, ADL should have broad applicability, good test-retest reliability, scaling to cover a range of performance, and sensitivity to detect change in disease progression. A total of 45 ADL items developed from literature review and clinical experience were administered to informants of 242 AD patients and 64 elderly controls as part of the multicenter Alzheimer's Disease Cooperative Study Instrument protocol. Half of the subjects were re-evaluated at 1 and 2 months and all at 6 and 12 months. Controls performed virtually all ADL items optimally at baseline and at 12 months. Among subjects with AD, 27 of the 45 ADL were widely applicable, i.e., performed at baseline or premorbidly by > 90% of subjects; showed good test-retest reliability between baseline and 1 and 2 months; correlated with MMSE scores of AD patients cross-sectionally; and showed a decline in performance from baseline to 12 months in at least 20% of AD patients. ADL could be identified that capture change in functional ability in patients across the entire range of the MMSE. The remaining 18 ADL included several that may be useful for trials that target specific populations, e.g., women with AD. Because change on specific items depends on baseline MMSE, ADL evaluation should include items relevant to the severity of dementia of patients enrolled in a clinical trial.
Reduced Paneth cell α-defensins in ileal Crohn's disease (2005)

The pathogenesis of Crohn's disease (CD), an idiopathic inflammatory bowel disease, is attributed, in part, to intestinal bacteria that may initiate and perpetuate mucosal inflammation in genetically susceptible individuals. Paneth cells (PC) are the major source of antimicrobial peptides in the small intestine, including human alpha-defensins HD5 and HD6. We tested the hypothesis that reduced expression of PC alpha-defensins compromises mucosal host defenses and predisposes patients to CD of the ileum. We report that patients with CD of the ileum have reduced antibacterial activity in their intestinal mucosal extracts. These specimens also showed decreased expression of PC alpha-defensins, whereas the expression of eight other PC products either remained unchanged or increased when compared with controls. The specific decrease of alpha-defensins was independent of the degree of inflammation in the specimens and was not observed in either CD of the colon, ulcerative colitis, or pouchitis. The functional consequence of alpha-defensin expression levels was examined by using a transgenic mouse model, where we found changes in HD5 expression levels, comparable to those observed in CD, had a pronounced impact on the luminal microbiota. Thus, the specific deficiency of PC defensins that characterizes ileal CD may compromise innate immune defenses of the ileal mucosa and initiate and/or perpetuate this disease.
Fluorine-19 NMR studies on the mechanism of riboflavin synthase. Synthesis of 6-(trifluoromethyl)-7-oxo-8-(D-ribityl)lumazine and 6-(trifluoromethyl)-7-methyl-8-(D-ribityl)lumazine (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorine-19 NMR studies on the mechanism of riboflavin synthase. Synthesis of 6-(trifluoromethyl)-7-oxo-8-(D-ribityl)lumazine and 6-(trifluoromethyl)-7-methyl-8-(D-ribityl)lumazineMark Cushman, Hemantkumar H. Patel, Johannes Scheuring, and Adelbert BacherCite this: J. Org. Chem. 1992, 57, 21, 5630–5643Publication Date (Print):October 1, 1992Publication History Published online1 May 2002Published inissue 1 October 1992https://pubs.acs.org/doi/10.1021/jo00047a015https://doi.org/10.1021/jo00047a015research-articleACS PublicationsRequest reuse permissionsArticle Views277Altmetric-Citations32LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
CCR6, a CC Chemokine Receptor that Interacts with Macrophage Inflammatory Protein 3α and Is Highly Expressed in Human Dendritic Cells (1997)

Dendritic cells initiate immune responses by ferrying antigen from the tissues to the lymphoid organs for presentation to lymphocytes. Little is known about the molecular mechanisms underlying this migratory behavior. We have identified a chemokine receptor which appears to be selectively expressed in human dendritic cells derived from CD34+ cord blood precursors, but not in dendritic cells derived from peripheral blood monocytes. When stably expressed as a recombinant protein in a variety of host cell backgrounds, the receptor shows a strong interaction with only one chemokine among 25 tested: the recently reported CC chemokine macrophage inflammatory protein 3alpha. Thus, we have designated this receptor as the CC chemokine receptor 6. The cloning and characterization of a dendritic cell CC chemokine receptor suggests a role for chemokines in the control of the migration of dendritic cells and the regulation of dendritic cell function in immunity and infection.
Design of Enzyme Systems for Selective Product Release from Microbial Cells; Isolation of a Recombinant Protein from Yeast (1988)

The development of expression systems for recombinant proteins and recombinant protein particles that cannot be secreted and that are located in specific cell locations necessitates the development of novel, more selective, techniques for cell disruption. Mechanical cell disruption methods do not discriminate the release of the desired product from among a host of other contaminating molecules and cell debris, and they also may damage the protein product. In contrast, the use of lytic enzyme systems, which can provide biological specificity to the process of cell lysis and disruption, shows an interesting potential for controlled lysis. In this report, the design and the use of lytic enzyme systems for differential product release from microbial cells have been reviewed. Lytic enzyme systems are usually specific either for yeast or for different types of bacteria. Moreover, the activity profile of a lytic system will have an effect on the product distribution. This profile can be manipulated at the genetic, physiological, production reactor, enzyme purification, and lysis reactor levels. Alternative process designs that will allow the sequential release of products from different cell locations have been reviewed and discussed. Alternatives have been explored by process modeling, process simulation, and optimization techniques. These studies show that the use of lytic enzyme systems has tremendous promise as a method of controlled lysis and differential product release. Finally, the release of a specific recombinant protein, human serum albumin (HSA) from yeast cells, has been investigated. The low levels of wall-lytic protease present in the Oerskovia lytic enzyme system have no deleterious effect on the protein product, and the level of HSA extracted from two positive yeast clones using lytic enzymes is similar to that extracted after bead breakage.
Miniature six-DOF inertial system for tracking HMDs (1998)

Current HMD applications are hampered by the limitations of head-tracking technologies now in use. Commercially available magnetic, optical, acoustic, and mechanical head- trackers suffer form various problems such as vulnerability to interference, line-of-sight restrictions, jitter, latency, small range, and high cost. This paper presents inertial-sensor-based hybrid tracking technology that was developed to combat all these problems. Two commercially available products, the IS-300 and the IS-600, are described, both based on the same miniature triaxial inertial sensor device. The IS-300 is a sourceless 3-DOF orientation tracker, using gravimetric tilt-sensing to prevent any gyroscopic drift in pitch and roll, and optical geo-magnetic compassing to prevent any gyroscopic drift in yaw. The IS-600 is a hybrid acousto-inertial 6-DOF position and orientation tracking system. It tracks changes in orientation and position by integrating the outputs of its gyros and accelerometers, and corrects drift using a room- referenced ultrasonic time-of-flight range measuring system. The is paper overviews the theory of operation of both systems, and reports bench-testing results designed to evaluate the resolution, accuracy, and latency of each system.
Integration of Colloidal Nanocrystals into Lithographically Patterned Devices (2004)

We report a facile method for reproducibly fabricating large-scale device arrays, suitable for nanoelectronics or nanophotonics, that incorporate a controlled number of sub-50-nm-diameter nanocrystals at lithographically defined precise locations on a chip and within a circuit. The interfacial capillary force present during the evaporation of a nanocrystal suspension forms the basis of the assembly mechnism. Our results demonstrate for the first time that macromolecule size particles down to 2-nm diameter and complex nanostructures such as nanotetrapods can be effectively organized by the capillary interaction. This approach integrates the merits of bottom-up solution-processed nanostructures with top-down lithographically prepared devices and has the potential to be scaled up to wafer size for a large number of functional nanoelectronics and nanophotonics applications.
Supervised Learning Combined with an Actor-Critic Architecture TITLE2: (2002)

To address the shortcomings of reinforcement learning (RL) a number of researchers have focused recently on ways to take advantage of structure in RL problems and on ways to make domain knowledge part of RL algorithms. In this paper we examine a {\em supervised} actor-critic architecture, whereby a supervisor adds structure to a learning problem and supervised learning makes that structure part of an actor-critic framework for reinforcement learning. We provide a steepest descent algorithm for real-valued actions such that the actor adjusts its policy in accordance with gradient information from both supervisor and critic. We also illustrate the approach with two kinds of supervisors: a feedback controller that is easily designed yet sub-optimal, and a human operator providing intermittent control of a simulated robotic arm.
A Multipotential Leukemia Cell Line (K-562) of Human Origin (1981)

The K-562 leukemia cell line, originally established in our laboratory, has been characterized as an early precursor of the granulocytic series with a block for differentiation. Since K-562 blasts did not differentiate when cultured for 7-8 days in liquid media or 14-16 days in agar-gel an attempt was made to stimulate their potential for spontaneous differentiation by prolonging the time in culture. Inducers of differentiation were not added to the cultures and the cells were studied when they reached the steady state rather than during exponential growth. The cultivation of K-562 cells for 10 to 11 days in media gradually depleted of the essential nutrients needed for cell division induced their differentiation into early precursors of the monocytic, granulocytic, and erythrocytic series. Thus, the peroxidase reaction for hemoglobin demonstrates benzidine-positive material limited to the region of the Golgi apparatus. Analysis of the hemoglobin by isoelectric focusing indicated major bands in the region of embryonic hemoglobin. Most cells (80-90%) give a strong reaction for α-naphthyl acetate esterase typical of monocytes and as many as 30 to 40% of the cells have abundant red cytoplasmic granules of naphthol AS-D chloroacetate esterase characteristic of granulocytic precursors. Myeloperoxidase activity was found in 5 to 10% of the cells. Polyploid cells (5-8%) and early myelomonocytic precursors have PAS-positive material, were stained with Sudan black, and possessed abundant acid phosphatase. The data support the conclusion that K-562 is, indeed, a multipotential leukemia cell line of human origin.
A new affinity reagent for the site-specific, covalent attachment of DNA to active-site nucleophiles: application to theEcoRI andRsrl restriction and modification enzymes (1992)

A modified oligodeoxyribonucleotide duplex containing an unnatural internucleotide trisubstituted 3' to 5' pyrophosphate bond in one strand [5'(oligo1)3'-P(OCH3)P-5'(oligo2) 3'] reacts with nucleophiles in aqueous media by acting as a phosphorylating affinity reagent. When interacted with a protein, a portion of the oligonucleotide [--P-5'(oligo2)3'] becomes attached to an amino acid nucleophilic group through a phosphate of the O-methyl-modified pyrophosphate linkage. We demonstrate the affinity labeling of nucleophilic groups at the active sites of the EcoRI and RsrI restriction and modification enzymes with an oligodeoxyribonucleotide duplex containing a modified scissile bond in the EcoRI recognition site. With the EcoRI and RsrI endonucleases in molar excess approximately 1% of the oligonucleotide becomes attached to the protein, and with the companion methyltransferases the yield approaches 40% for the EcoRI enzyme and 30% for the RsrI methyltransferase. Crosslinking proceeds only upon formation of a sequence-specific enzyme-DNA complex, and generates a covalent bond between the 3'-phosphate of the modified pyrophosphate in the substrate and a nucleophilic group at the active site of the enzyme. The reaction results in the elimination of an oligodeoxyribonucleotide remnant that contains the 3'-O-methylphosphate [5'(oligo1)3'-P(OCH3)] derived from the modified phosphate of the pyrophosphate linkage. Hydrolysis properties of the covalent protein-DNA adducts indicate that phosphoamide (P-N) bonds are formed with the EcoRI endonuclease and methyltransferase.
Cu(II)-Catalyzed Functionalizations of Aryl C−H Bonds Using O2 as an Oxidant (2006)

Cu(II)-catalyzed acetoxylation and halogenation of aryl C−H bonds are developed. ortho-Selectivity was observed with a wide range of 2-arylpyridine substrates. Both mono- and difunctionalizations are achieved by tuning the reaction conditions. Excellent functional group tolerance and use of O2 as a stoichiometric oxidant are significant advantages over our recently developed Pd-catalyzed C−H functionalization reactions. These newly discovered reaction conditions are also applicable for cyanation, amination, etherification, and thioetherification of aryl C−H bonds. Mechanistic investigations are carried out to gain insights into the Cu(II)-catalyzed C−H functionalization reactions.
Exciting Prospects for Precise Engineering of Caenorhabditis elegans Genomes with CRISPR/Cas9 (2013)

With remarkable speed, the CRISPR-Cas9 nuclease has become the genome-editing tool of choice for essentially all genetically tractable organisms. Targeting specific DNA sequences is conceptually simple because the Cas9 nuclease can be guided by a single, short RNA (sgRNA) to introduce double-strand DNA breaks (DSBs) at precise locations. Here I contrast and highlight protocols recently developed by eight different research groups, six of which are published in GENETICS, to modify the Caenorhabditis elegans genome using CRISPR/Cas9. This reverse engineering tool levels the playing field for experimental geneticists.
Probing the performance limits of the Escherichia coli metabolic network subject to gene additions or deletions (2001)

An optimization-based procedure for studying the response of metabolic networks after gene knockouts or additions is introduced and applied to a linear flux balance analysis (FBA) Escherichia coli model. Both the gene addition problem of optimally selecting which foreign genes to recombine into E. coli, as well as the gene deletion problem of removing a given number of existing ones, are formulated as mixed-integer optimization problems using binary 0-1 variables. The developed modeling and optimization framework is tested by investigating the effect of gene deletions on biomass production and addressing the maximum theoretical production of the 20 amino acids for aerobic growth on glucose and acetate substrates. In the gene deletion study, the smallest gene set necessary to achieve maximum biomass production in E. coli is determined for aerobic growth on glucose. The subsequent gene knockout analysis indicates that biomass production decreases monotonically, rendering the metabolic network incapable of growth after only 18 gene deletions. In the gene addition study, the E. coli flux balance model is augmented with 3,400 non-E. coli reactions from the KEGG database to form a multispecies model. This model is referred to as the Universal model. This study reveals that the maximum theoretical production of six amino acids could be improved by the addition of only one or two genes to the native amino acid production pathway of E. coli, even though the model could choose from 3,400 foreign reaction candidates. Specifically, manipulation of the arginine production pathway showed the most promise with 8.75% and 9.05% predicted increases with the addition of genes for growth on glucose and acetate, respectively. The mechanism of all suggested enhancements is either by: 1) improving the energy efficiency and/or 2) increasing the carbon conversion efficiency of the production route.
Constitutive Expression of the β-Ketothiolase Gene in Transgenic Plants. A Major Obstacle for Obtaining Polyhydroxybutyrate-Producing Plants (2002)

Polyhydroxybutyrate (PHB) is a member of a class of thermoelastic polymers called polyhydroxyalkanoates that serve many bacteria as intracellular storage molecules for carbon and energy. Transgenic plants provide a potential means of producing this polymer cost-effectively. To date, however, few reports of the successful production of this polymer have been published, with the exception of work with transgenic Arabidopsis. Using a variety of chimeric constructs, we have determined that the constitutive, chloroplast-localized expression of one of the genes involved in PHB production-the beta-ketothiolase (phbA) gene-is detrimental to the efficient production of transgenic PHB. The alternate use of either inducible or somatically activated promoters allowed the construction of transgenic PHB-producing potato (Solanum tuberosum) and tobacco (Nicotiana tabacum) plants, although the amount of PHB formed was still rather low. Taking advantage of an inducible promoter, the maximal amount of PHB produced in transgenic potato was 0.09 mg g(-1) dry weight. In transgenic tobacco using a somatically activated promoter, up to 3.2 mg g(-1) dry weight was accumulated. In Arabidopsis, the formation of high levels of PHB had previously been shown to be accompanied by severe negative effects on growth and development of the plant. Phasins are proteins known from PHB-producing bacteria speculated to serve as protectants against the highly hydrophobic surface of the PHB granules in the bacterial intracellular milieu. Co-expression of the phasin gene in parallel with the PHB synthesis genes, however, did not lead to reduced symptom development.
Extension of a training set for artificial neural networks and its application to brain source localization (2002)

The problem of training sets with inadequate training patterns is addressed. Learning based on such sets results in poor generalizations. We introduce an extension procedure to augment training sets in order to provide improved generalization. The original training set is used to provide hints, along with some statistical information, in the extension procedure. We show that if a mathematical model is available for a poorly observed physical process, then the extension of the inadequate training set is possible. The procedure is applied to the brain source localization problem. Our experiments results show that learning based on the extended training set is superior, with robust generalization, to learning based on the initial training set.