gebhart/patrepeval huggingface dataset:
Crystal Structure of α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase: Insight into the Active Site and Catalytic Mechanism of a Novel Decarboxylation Reaction , (2006)

Alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) is a widespread enzyme found in many bacterial species and all currently sequenced eukaryotic organisms. It occupies a key position at the branching point of two metabolic pathways: the tryptophan to quinolinate pathway and the bacterial 2-nitrobenzoic acid degradation pathway. The activity of ACMSD determines whether the metabolites in both pathways are converted to quinolinic acid for NAD biosynthesis or to acetyl-CoA for the citric acid cycle. Here we report the first high-resolution crystal structure of ACMSD from Pseudomonas fluorescens which validates our previous predictions that this enzyme is a member of the metal-dependent amidohydrolase superfamily of the (beta/alpha)(8) TIM barrel fold. The structure of the enzyme in its native form, determined at 1.65 A resolution, reveals the precise spatial arrangement of the active site metal center and identifies a potential substrate-binding pocket. The identity of the native active site metal was determined to be Zn. Also determined was the structure of the enzyme complexed with cobalt at 2.50 A resolution. The hydrogen bonding network around the metal center suggests that Arg51 and His228 may play important roles in catalysis. The metal center configuration of PfACMSD is very similar to that of Zn-dependent adenosine deaminase and Fe-dependent cytosine deaminase, suggesting that ACMSD may share certain similarities in its catalytic mechanism with these enzymes. These data enable us to propose possible catalytic mechanisms for ACMSD which appear to be unprecedented among all currently characterized decarboxylases.
Planning and deploying a SONET-based metro network (1991)

It is demonstrated that metropolitan networks can be analyzed to develop an architectural strategy that provides both cost-effective bandwidth management and survivability. The planning and deployment considerations, methodologies, and planning tools are discussed. An example of a planned synchronous optical network (SONET) metropolitan network, including the transition from an asynchronous network, is presented. It is shown that the most effective deployment strategy for SONET is built around an infrastructure of survivable SONET rings and automated facility management based on a combination of SONET cross-connects and distributed bandwidth management in SONET ring terminals. This SONET infrastructure will provide the framework for the predicted expansion in communications services, and will meet expanding telecommunication needs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Atom transfer radical addition and polymerization reactions catalyzed by ppm amounts of copper complexes (2008)

Over the past decade, copper-catalyzed atom transfer radical polymerization (ATRP) has had a tremendous impact on the synthesis of polymeric materials with well defined compositions, architectures and functionalities. Apart from synthetic aspects of ATRP, considerable effort has also been devoted to structural and mechanistic understanding of copper complexes involved in ATRP, as well as development of methodologies to decrease the amount of catalyst needed in these systems. This tutorial review reports on recent advances in the area of catalyst regeneration in ATRP and mechanistically similar atom transfer radical addition (ATRA) using environmentally benign reducing agents. The outlined processes termed ARGET (activators regenerated by electron transfer) and ICAR (initiators for continuous activator regeneration) ATRP enable the synthesis of well-defined (co)polymers and single addition adducts using very low concentrations of copper catalysts (1-100 ppm). Recent developments in this area could have profound industrial implications on the synthesis of well-defined polymeric materials and small organic molecules.
Large memory embedded ASICs (2003)

Application-specific integrated circuits (ASICs) with high-performance embedded memory array with suitable design route have considerable merits in terms of system speed, scalability with technology and system cost. The choice of design approach according to applications is critical. For highly memory-rich applications, one of the recently developed memory ASICs, an integrated cache memory is described. Another example suited for large-size random logic and high-density memory is a structure array approach. A recently developed 72 K track-free gate array with 1 Mb DRAM is described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Slanted Hole Array Beam Profiler (SHArP) - A highresolution portable beam profiler based on a slanted linear aperture array (2006)

A high-resolution portable beam profiler based on a linear aperture array fabricated on a metal coated CMOS imaging sensor is introduced. With single linear scan, it establishes a dense virtual sensing grid for beam profiling.
Comparison of O-Linked Carbohydrate Chains in MUC-1 Mucin from Normal Breast Epithelial Cell Lines and Breast Carcinoma Cell Lines: (1996)

MUC-1 mucin is considered to be aberrantly glycosylated in breast, ovary, and other carcinomas in comparison with mucin from corresponding normal tissues. In order to clarify these differences in glycosylation, we have compared the O-linked carbohydrate chains from MUC-1 immunoprecipitated from [3H]GlcN-labeled breast epithelial cell lines (MMSV1-1, MTSV1-7, and HB-2) derived from cells cultured from human milk, with three breast cancer cell lines (MCF-7, BT-20, and T47D). Analysis by high pH anion chromatography showed that the normal cell lines had a higher ratio of GlcN/GalN and more complex oligosaccharide profiles than the cancer cell lines. Structural analyses were carried out on the oligosaccharides from MTSV1-7 and T47D MUC-1, and the following structures were proposed. MUC-1 from T47D had rather a simple glycosylation pattern, with NeuAcalpha2-3Galbeta1-3GalNAc-ol, Galbeta1-3GalNAc-ol, and GalNAc-ol predominating; in contrast, MUC-1 from MTSV1-7 had more complex structures, including a number of disialo, core 2 species, i.e. NeuAcalpha2-3Galbeta1-4GlcNAcbeta1-6[NeuAcalpha2 -3Galbeta1-3]GalNAc- ol and NeuAcalpha2-3Galbeta1-4GlcNAcbeta1-6[NeuAcalpha2 -3Galbeta1-4GlcNAcbet a1-3Galbeta1-3]GalNAc-ol. Double-labeling experiments with [3H]GlcN and 14C-aminoacids and analysis of GalNAc or GalNAc-ol:protein ratios in MUC-1 showed that there was also a significant difference in the degree of glycosylation of the mucin between the two cell types. We conclude that MUC-1 from breast cancer cell lines has simpler, and fewer, carbohydrate chains than MUC-1 from normal breast epithelial cells, and that these differences, combined or separately, explain the differential tumor specificity of some MUC-1 antibodies and T cells.
Macroporous Polyacrylamide/Poly(ethylene glycol) Matrixes as Stationary Phases in Capillary Electrochromatography (1997)

A one-step method is described for in situ preparation of macroporous polymeric matrixes to be used as stationary phases for capillary electrochromatography. The monomers (acrylamide, bisacrylamide, and acrylic or vinylsulfonic acid), including hydrophobic ligands (C4, C6, or C12), and poly(ethylene glycol) have been polymerized in formamide (or N-methylformamide) aqueous solutions inside the capillary. The capillary wall had been activated first by a bifunctional reagent, to couple covalently the resulting gel inside the fused-silica tubing. Thus, no frit is necessary to keep the stationary phase in place. High efficiencies were obtained for a mixture of alkyl phenones (up to 398 000 plates/m). Good separations are achieved in less than 5 min. The migration time reproducibility is better than 1% (RSD) from run to run and 2.5% from day to day. The gel is stable up to at least 50% acetonitrile used as a mobile phase. On-column UV and fluorescence detection can readily be employed. Applications to peptides and carbohydrates are also shown.
An associate-predict model for face recognition (2011)

Handling intra-personal variation is a major challenge in face recognition. It is difficult how to appropriately measure the similarity between human faces under significantly different settings (e.g., pose, illumination, and expression). In this paper, we propose a new model, called “Associate-Predict” (AP) model, to address this issue. The associate-predict model is built on an extra generic identity data set, in which each identity contains multiple images with large intra-personal variation. When considering two faces under significantly different settings (e.g., non-frontal and frontal), we first “associate” one input face with alike identities from the generic identity date set. Using the associated faces, we generatively “predict” the appearance of one input face under the setting of another input face, or discriminatively “predict” the likelihood whether two input faces are from the same person or not. We call the two proposed prediction methods as “appearance-prediction” and “likelihood-prediction”. By leveraging an extra data set (“memory”) and the “associate-predict” model, the intra-personal variation can be effectively handled. To improve the generalization ability of our model, we further add a switching mechanism - we directly compare the appearances of two faces if they have close intra-personal settings; otherwise, we use the associate-predict model for the recognition. Experiments on two public face benchmarks (Multi-PIE and LFW) demonstrated that our final model can substantially improve the performance of most existing face recognition methods.
Distance determination by GIY-YIG intron endonucleases: discrimination between repression and cleavage functions (2006)

GIY-YIG homing endonucleases are modular proteins, with conserved N-terminal catalytic domains connected by linkers to C-terminal DNA-binding domains. I-TevI, the T4 phage GIY-YIG intron endonuclease, functions both in promoting td intron homing, and in acting as a transcriptional autorepressor. Repression is achieved by binding to an operator, which is cleaved at 100-fold reduced efficiency relative to the intronless homing site. The linker includes a zinc finger, which functions in distance determination, to constrain the catalytic domain to cleave the homing site at a fixed position. Here we show that I-BmoI, a related GIY-YIG endonuclease lacking a zinc finger, also possesses some cleavage distance discrimination. Furthermore, hybrid endonucleases constructed by swapping the domains of I-BmoI and I-TevI are active, precise and demonstrate that features other than the zinc finger facilitate distance determination. Most importantly, I-TevI zinc finger mutants cleave the operator more efficiently than the homing site, the converse of wild-type protein. These results are consistent with the zinc finger acting as a measuring device, directing efficient cleavage of the homing site to promote intron mobility, while reducing cleavage at the operator to ensure transcriptional autorepression and phage viability.
Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors (2009)

Subnormal plasma levels of high-density lipoprotein cholesterol (HDL-C) constitute a major cardiovascular risk factor; raising low HDL-C levels may therefore reduce the residual cardiovascular risk that frequently presents in dyslipidaemic subjects despite statin therapy. Cholesteryl ester transfer protein (CETP), a key modulator not only of the intravascular metabolism of HDL and apolipoprotein (apo) A-I but also of triglyceride (TG)-rich particles and low-density lipoprotein (LDL), mediates the transfer of cholesteryl esters from HDL to pro-atherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein to HDL. Cholesteryl ester transfer protein activity is elevated in the dyslipidaemias of metabolic disease involving insulin resistance and moderate to marked hypertriglyceridaemia, and is intimately associated with premature atherosclerosis and high cardiovascular risk. Cholesteryl ester transfer protein inhibition therefore presents a preferential target for elevation of HDL-C and reduction in atherosclerosis. This review appraises recent evidence for a central role of CETP in the action of current lipid-modulating agents with HDL-raising potential, i.e. statins, fibrates, and niacin, and compares their mechanisms of action with those of pharmacological agents under development which directly inhibit CETP. New CETP inhibitors, such as dalcetrapib and anacetrapib, are targeted to normalize HDL/apoA-I levels and anti-atherogenic activities of HDL particles. Further studies of these CETP inhibitors, in particular in long-term, large-scale outcome trials, will provide essential information on their safety and efficacy in reducing residual cardiovascular risk.
Lactose metabolism in Lactobacillus bulgaricus: analysis of the primary structure and expression of the genes involved (1991)

The genes coding for the lactose permease and beta-galactosidase, two proteins involved in the metabolism of lactose by Lactobacillus bulgaricus, have been cloned, expressed, and found functional in Escherichia coli. The nucleotide sequences of these genes and their flanking regions have been determined, showing the presence of two contiguous open reading frames (ORFs). One of these ORFs codes for the lactose permease gene, and the other codes for the beta-galactosidase gene. The lactose permease gene is located in front of the beta-galactosidase gene, with 3 bp in the intergenic region. The two genes are probably transcribed as one operon. Primer extension studies have mapped a promoter upstream from the lactose permease gene but not the beta-galactosidase gene. This promoter is similar to those found in E. coli with general characteristics of GC-rich organisms. In addition, the sequences around the promoter contain a significantly higher number of AT base pairs (80%) than does the overall L. bulgaricus genome, which is rich in GC (GC content of 54%). The amino acid sequences obtained from translation of the ORFs are found to be highly homologous (similarity of 75%) to those from Streptococcus thermophilus. The first 460 amino acids of the lactose permease shows homology to the melibiose transport protein of E. coli. Little homology was found between the lactose permease of L. bulgaricus and E. coli, but the residues which are involved in the binding and the transport of lactose are conserved. The carboxy terminus is similar to that of the enzyme III of several phosphoenolpyruvate-dependent phosphotransferase systems.
Development a Knowledge-based Medical Diagnosing System for Thyroid Disorders (1990)

In this study, we will present a knowledge-based consulting system, called THYCONS, for diagnosing thyroid disorders. It has been developed to make the knowledge and expertise of the human expert more widely available, therefore achieving a high-quality diagnosis. Frames will be used to represent the medical knowledge of thyroid disorders, and several rules are attached in each slot of a frame. The uncertainty of diagnostic processes is manipulated by the subjective Bayesian method under the assumption that the pieces of evidence are conditionally independent. Searching for the group of diagnostic tests to be carried out and their optimum sequences will be established in order to infer a more correct diagnosis on the basis of maximum information gain with cost and time restrictions. Additionally. differential diagnosis will be carried out based on the information gained.
Toxicology of chemical mixtures : case studies, mechanisms, and novel approaches (1994)

Introduction to the toxicology of chemical mixtures real life case studies or special problem-related situations - love canal - the development of the toxicologic evaluation of its complex chemical contamination toxicological studies on mixtures of chemical contaminants in the great lakes health effect studies on recycled drinking water from secondary waste water assessing the carcinogenic potency of coal tar toxicology of chemical mixtures derived from hazardous waste sites or applications of pesticides and fertilizers diesel exhaust - an approach for the study of the toxicity of chemical mixtures toxicologic problems associated with pesticide mixtures and pesticide impurities - identification of potential carcinogenic hazards associated with consuming seafood contaminated with mixtures of diverse and unknown chemical composition target organ toxicity or special toxicologic responses related to chemical mixture exposures - immune alterations resulting from exposure to chemical mixtures cytogenetic effects from chemical mixture exposures multiple chemical exposure and risks of adverse reproductive function and outcome mechanism of the interactive amplification of halomethane hepatotoxicity and lethality by other chemicals nephrotoxicity resulting from multiple chemical exposures and chemical interactions effects of low dose level exposure to multiple carcinogens in combination contemporary issues - new approaches to bioassay - and biomarker - directed identification and mutation spectra physiologically based pharmacokinetic modelling of chemical mixtures the application of physico-chemical concepts to mechanistic elucidation of toxicologic interactions defining populations potentially exposed to chemical waste mixtures using computer-aided mapping and analysis challenges for in situ bioremediation of chemical mixtures chemical mixture toxicity assessment using an alternative-species model - applications, opportunities, and perspectives regulatory approaches and problems in risk assessments of chemical mixtures statistical methods for the toxicological evaluation of the additivity assumption analysis of chemical combinations - relating isobolograms to response surfaces the potential effects of chemical mixtures on the carcinogenic process within the context of the mathematical multistage model.
Classic and New Animal Models of Parkinson's Disease (2012)

Neurological disorders can be modeled in animals so as to recreate specific pathogenic events and behavioral outcomes. Parkinson's Disease (PD) is the second most common neurodegenerative disease of an aging population, and although there have been several significant findings about the PD disease process, much of this process still remains a mystery. Breakthroughs in the last two decades using animal models have offered insights into the understanding of the PD disease process, its etiology, pathology, and molecular mechanisms. Furthermore, while cellular models have helped to identify specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are useful for testing new neuroprotective or neurorestorative strategies. Moreover, significant advances in the modeling of additional PD features have come to light in both classic and newer models. In this review, we try to provide an updated summary of the main characteristics of these models as well as the strengths and weaknesses of what we believe to be the most popular PD animal models. These models include those produced by 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydropiridine (MPTP), rotenone, and paraquat, as well as several genetic models like those related to alpha-synuclein, PINK1, Parkin and LRRK2 alterations.
The V617F JAK2 mutation and the myeloproliferative disorders (2005)

The discovery this year of a single mutation in the Janus Kinase (JAK)-2 gene in a high percentage of cases of polycythaemia vera (PV), essential thrombocythaemia (ET) and myelofibrosis suggests that it maybe the underlying molecular mechanism for these disorders. Different approaches from the inhibition of the tyrosine kinase JAK2, widespread search for mutations in tyrosine kinases, and investigation of the short arm of chromosome 9 where JAK2 is located all led to the discovery of the V617F JAK2 mutation. Substitution of a valine for a phenylalanine destabilizes the JH2 domain of JAK2 causes loss of the auto-inhibitory activity of this domain and explains some of the biological phenomena observed in patients with myeloproliferative disorders (MPD). The V617F JAK2 mutation can be detected by PCR-direct sequencing using DNA from the granulocyte lineage or with increased sensitivity by the amplification refractory mutation system using DNA from unfractionated blood. Pyrosequencing assays can be used to quantitate allele ratios to accurately define homozygote and heterozygote status. This single mutation is widespread having been detected in related MPD and other haematological malignancies. This leads to a number of further questions about the role of this single mutation in the clinical pattern of disease.
Cationic Liposome-mediated Intravenous Gene Delivery (1995)

Systemic gene transfer provides new opportunities for the analysis of gene function and gene regulation in vivo, as well as for human gene therapy. We used the chloramphenicol acetyltransferase reporter gene to examine several parameters important for the development of efficient, cationic liposome-mediated, intravenous (IV) gene transfer in mice. We then demonstrated that this approach can produce high level expression of biologically important genes. Specifically, we assessed the relationship of expression vector design to the level of systemic gene expression produced, and compared transfection levels produced by intravenously injecting DNA alone versus DNA-liposome complexes. We found that both the position of the heterologous intron, and the promoter element used in the expression plasmid, significantly affected the level of systemic gene expression produced. Although intravenous injection of plasmid DNA alone transfected every tissue analyzed, liposome-mediated delivery was much more efficient. We also established that repeated i.v. injection of DNA-liposome complexes produced high level systemic transfection. The second injection of DNA-liposome complexes produced levels of gene expression at least as high as those following a single i.v. injection. Thus, unlike some viral vectors, a neutralizing host-immune response does not limit re-expression, following reinjection of DNA-liposome complexes. Finally, we showed that the expression vectors which produced the highest levels of chloramphenicol acetyltransferase reporter gene expression could also produce high level expression of two colony stimulating factor genes in mice. Specifically, i.v. injection of liposomes complexed to expression vectors into which we had inserted either the murine granulocyte-macrophage-colony stimulating factor cDNA or the human granulocyte-CSF cDNA, produced circulating levels of the corresponding colony stimulating factor gene product comparable to levels which have been shown previously to be both biologically and therapeutically significant.