gebhart/patrepeval huggingface dataset:
Substrate specificity of the Escherichia coli endonuclease III: Excision of thymine- and cytosine-derived lesions in DNA produced by radiation-generated free radicals (1993)

The excision of modified bases from DNA by Escherichia coli endonuclease III was investigated. Modified bases were produced in DNA by exposure of dilute buffered solutions of DNA to ionizing radiation under oxic or anoxic conditions. The technique of gas chromatography/mass spectrometry (GC/MS) was used to identify and quantify 16 pyrimidine- and purine-derived DNA lesions. DNA substrates were incubated either with the native enzyme or with the heat-inactivated enzyme. Subsequently, DNA was precipitated. Pellets were analyzed by GC/MS after hydrolysis and derivatization. Supernatant fractions were analyzed after derivatization without hydrolysis. The results provided unequivocal evidence for the excision by E. coli endonuclease III of a number of thymine- and cytosine-derived lesions from DNA. These were 5,6-dihydrothymine, 5-hydroxy-5-methylhydantoin, thymine glycol, 5-hydroxy-6-hydrothymine, 5,6-dihydrouracil, alloxan, uracil glycol, and 5-hydroxy-6-hydrouracil. None of the purine-derived lesions was excised by endonuclease III. The present work extends the substrate specificity of E. coli endonuclease III to another thymine-derived and four cytosine-derived lesions. It is the first investigation of the substrate specificity of this repair enzyme in the context of a large number of pyrimidine- and purine-derived lesions in DNA.
Therapeutic Use of Heparin beyond Anticoagulation (2009)

Heparin has been used as an anticoagulant for decades. Recently, attention has been drawn to the non-anticoagulant activities of heparin. Experimentally and clinically those non-anticoagulant properties of heparin inhibit inflammation and metastatic spread of tumor cells. On the molecular level, heparin inhibits the function, expression and/or synthesis of adhesion molecules, cytokines, angiogenic factors and complement. However, despite a similar anticoagulant activity, those non-anticoagulant effects of heparin differ greatly among the different heparin preparations. The same holds true for the most common adverse events of heparin treatment. The incidence of immune mediated heparin-induced thrombocytopenia and cutaneous hypersensitivity responses is greatly, but not exclusively, influenced by the heparin preparation used. As the structure-function relationship of the anti-inflammatory and anti-metastatic effects of heparins are understood in more detail, and as the risk profile of different heparin preparations regarding the induction of adverse events have been identified, we propose to use the different heparin preparations according to the individual needs of each patient.
A configurable system for automation programming and control (1986)

This paper discusses an environment for configuration, programming, and control of robot workcells. The controller is intended to support research in automation programming and motion control, and to provide a vehicle for conveniently integrating new sensors and other devices into a workcell in a useful way. The system consists of an interactive Programming System connected through a shared memory to a multiple-processor Real Time System that performs time-critical operations. The Programming System executes programs written in an enhanced version of AML and transmits high level commands, called verbs, to the Real Time System for execution. Verbs may either be simple, consisting essentially of a process specification and termination conditions, or they may be compositions of other verbs. The processes themselves are specified in terms of lower level entities called real time application subroutines, state vector variables, and data flow graphs which describe computations to be performed in the Real Time System.
The Kallikrein-Kinin System: Current and Future Pharmacological Targets (2005)

The kallikrein-kinin system is an endogenous metabolic cascade, triggering of which results in the release of vasoactive kinins (bradykinin-related peptides). This complex system includes the precursors of kinins known as kininogens and mainly tissue and plasma kallikreins. The pharmacologically active kinins, which are often considered as either proinflammatory or cardioprotective, are implicated in many physiological and pathological processes. The interest of the various components of this multi-protein system is explained in part by the multiplicity of its pharmacological activities, mediated not only by kinins and their receptors, but also by their precursors and their activators and the metallopeptidases and the antiproteases that limit their activities. The regulation of this system by serpins and the wide distribution of the different constituents add to the complexity of this system, as well as its multiple relationships with other important metabolic pathways such as the renin-angiotensin, coagulation, or complement pathways. The purpose of this review is to summarize the main properties of this kallikrein-kinin system and to address the multiple pharmacological interventions that modulate the functions of this system, restraining its proinflammatory effects or potentiating its cardiovascular properties.
Intranasal Corticosteroids for Allergic Rhinitis (2002)

Intranasal corticosteroids are accepted as safe and effective first-line therapy for allergic rhinitis. Several intranasal corticosteroids are available: beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, mometasone furoate, and triamcinolone acetonide. All are efficacious in treating seasonal allergic rhinitis and as prophylaxis for perennial allergic rhinitis. In general, they relieve nasal congestion and itching, rhinorrhea, and sneezing that occur in the early and late phases of allergic response, with studies showing almost complete prevention of late-phase symptoms. The rationale for topical intranasal corticosteroids in the treatment of allergic rhinitis is that adequate drug concentrations can be achieved at receptor sites in the nasal mucosa. This leads to symptom control and reduces the risk of systemic adverse effects. Adverse reactions usually are limited to the nasal mucosa, such as dryness, burning and stinging, and sneezing, together with headache and epistaxis in 5-10% of patients regardless of formulation or compound. Differences among agents are limited to potency, patient preference, dosing regimens, and delivery, device and vehicle.
Expression of carcinoembryonic antigen and its predicted immunoglobulin-like domains in HeLa cells for epitope analysis. (1992)

Carcinoembryonic antigen (CEA) is a member of the immunoglobulin gene superfamily with one predicted variable domain-like region (N domain; 108 amino acids) and three sets of constant domain-like regions (A1B1, A2B2, and A3B3; 92 amino acids for A domains and 86 amino acids for B domains). In addition, CEA possesses two signal peptides, one at the amino terminus and one at the carboxyl terminus. Both are removed during posttranslational processing, with the one at the carboxyl terminus being replaced by a glycosylphosphatidylinositol (GPI) moiety. We have previously expressed the full length complementary DNA clone for CEA in Chinese hamster ovary cells and murine L cells, demonstrating proper processing of nascent polypeptide chains to mature, fully glycosylated CEA including the GPI anchor. Using the same full length CEA complementary DNA clone and the polymerase chain reaction, we have now constructed expression clones for secreted versions of the N domain, the A3B3 domain, and the A3 and B3 subdomains. The clones were expressed in HeLa cells using the beta-actin promoter. A stop codon was introduced at the end of the A3B3 and the A3 and B3 domains to allow secretion instead of retention on plasma membranes with the GPI anchor. Expressed products were purified to homogeneity by affinity chromatography using monoclonal antibodies specific for each domain and by reversed phase high pressure liquid chromatography. Purified domains were characterized by Western blotting, antibody binding and inhibition studies, amino-terminal sequence and amino acid analyses, and laser desorption/time of flight mass spectrometry. These analyses revealed that the monomeric N domain is of size 15,990, with a glycosylation mass of about 4100, in good agreement with two N-linked glycosyl units of about mass 2100. There is some evidence that the N domain forms dimers. The N domain reacted with antibodies specific for this domain with an affinity similar to that of intact CEA. The A3B3 domain had a mass of 34,462, with a glycosylation mass of 14,900, in good agreement with seven N-linked glycosylation sites of average mass 2100. The A3B3 domain reacted only with antibodies specific for this domain, with a slightly lower affinity than that of native CEA. The amino-terminal sequences of the N domain and A3B3 domain proteins demonstrated proper processing of the signal peptide.(ABSTRACT TRUNCATED AT 400 WORDS)
Working with process variation aware caches (2007)

Deep-submicron designs have to take care of process variation effects as variations in critical process parameters result in large variations in access latencies of hardware components. This is severe in the case of memory components as minimum sized transistors are used in their design. In this work, by considering on-chip data caches, we study the effect of access latency variations on performance. We discuss performance losses due to the worst-case design, wherein the entire cache operates with the worst-case process variation delay, followed by process variation aware cache designs which work at set-level granularity. We then propose a technique called block rearrangement to minimize performance loss incurred by a process variation aware cache which works at set-level granularity. Using block rearrangement technique, we rearrange the physical locations of cache blocks such that a cache set can have its n blocks (assuming a n-way set-associative cache) in multiple rows instead of a single row as in the case of a cache with conventional addressing scheme. By distributing blocks of a cache set over multiple sets, we minimize the number of sets being affected by process variation. We evaluate our technique using SPEC2000 CPU benchmarks and show that our technique achieves significant performance benefits over caches with conventional addressing scheme
Intracellular expression profiles measured by real-time PCR tomography in the Xenopus laevis oocyte (2007)

Real-time PCR tomography is a novel, quantitative method for measuring localized RNA expression profiles within single cells. We demonstrate its usefulness by dissecting an oocyte from Xenopus laevis into slices along its animal-vegetal axis, extracting its RNA and measuring the levels of 18 selected mRNAs by real-time RT-PCR. This identified two classes of mRNA, one preferentially located towards the animal, the other towards the vegetal pole. mRNAs within each group show comparable intracellular gradients, suggesting they are produced by similar mechanisms. The polarization is substantial, though not extreme, with around 5% of vegetal gene mRNA molecules detected at the animal pole, and around 50% of the molecules in the far most vegetal section. Most animal pole mRNAs were found in the second section from the animal pole and in the central section, which is where the nucleus is located. mRNA expression profiles did not change following in vitro fertilization and we conclude that the cortical rotation that follows fertilization has no detectable effect on intracellular mRNA gradients.
The Synthesis of the 1,2,4-Thiadiazine-1,1-dioxides (1972)

Abstract N-(2-Phenylethene-1-sulfonyl)-N′-monoalkyl S-methylisothioureas, 2, were ring-closed to yield Michael cycloadducts, 3-methylthio-4-alkyl-5-phenyl-1,1-dioxo-5,6-dihydro-1,2,4-thiadiazines, 3. Bulky N′-alkyl groups hindered the cycloaddition. The base-catalyzed hydrolysis of 3 and 3-chloro-derivatives 4 gave 4-methyl-5-phenyl-2,3,5,6-tetrahydro-1,1,3-trioxo-1,2,4-thiadiazines, 5, which in turn underwent N-alkylation to give 6. The reaction of 4 with amines or with sodium methoxide yielded 3-amino-, 7, or 3-methoxy-thiadiazine derivatives, 9.
Expression of a human cytomegalovirus gp58 antigenic domain fused to the hepatitis B virus nucleocapsid protein (1996)

Hepatitis B virus core antigen (HBcAg) has been used as a carrier for expression and presentation of a variety of heterologous viral epitopes in particulate form. The aim of this study was to produce hybrid antigens comprising HBcAg and an immunogenic epitope of human cytomegalovirus (HCMV). A direct comparison was made of amino and carboxyl terminal fusions in order to investigate the influence of position of the foreign epitope on hybrid core particle formation, antigenicity and immunogenicity. HCMV DNA encoding a neutralising epitope of the surface glycoprotein gp58 was either inserted at the amino terminus or fused to the truncated carboxyl terminus of HBcAg and expressed in Escherichia coli. The carboxyl terminal fusion (HBc3−144–HCMV) was expressed at high levels and assembled into core like particles resembling native HBcAg. Protein with a similar fusion at the amino terminus (HCMV—HBc1−183) could not be purified or characterised immunologically, although it formed core like particles. HBc3−144-HCMV displayed HBc antigenicity but HCMV antigenicity could not be detected by radioimmunoassay or western blotting using anti-HCMV monoclonal antibody 7−17 or an anti-HCMV human polyclonal antiserum. Following immunisation of rabbits with HBc3−144—HCMV, a high titre of anti-HBc specific antibody was produced along with lower titres of HCMV/gp58 specific antibody.
The ras/cholesterol connection: implications for ras oncogenicity. (1992)

The frequent detection of mutated ras genes in a variety of cancers (reviewed in Bos, 1988, 1989; Der, 1988) suggests that ras makes a significant contribution to human malignancies (reviewed in Barbacid, 1987; Lacal and Tronick, 1988; Der, 1989). While the role of ras in malignancy is unclear, it is well-established that the association of ras protein with the inner surface of the plasma membrane is critical for triggering ras oncogenicity. The trafficking of ras proteins to the plasma membrane requires a series of three closely linked posttranslational modifications (farnesylation, proteolysis, and carboxymethylation) that are signaled by the consensus C-terminal CAAX motif present on all ras proteins (reviewed in Rine and Kim, 1990; Gibbs, 1991; Der and Cox, 1991). THe recent discovery that an essential intermediate in cholesterol biosynthesis, the isoprenoid farnesol, is attached covalently to ras proteins has stimulated considerable interest and has identified important new directions for studies of ras function. First, understanding the role of farnesol-linked interactions with the plasma membrane may identify the biochemical basis for the oncogenic actions of ras proteins. Second, the enzymes that catalyze the processing steps that trigger membrane association of ras proteins are promising targets for pharmacologic intervention in ras-associated disease. In this review, we summarize our current knowledge of the role of posttranslational processing in ras-membrane interaction and transforming activity. We also provide an update of recent studies addressing the role of isoprenoid modification in the function of ras and of other isoprenoid-modified proteins (reviewed in James and Olson, 1990; Glomset et al., 1990; Maltese, 1990). While this role is likely to be specific for each protein, ras proteins can provide an excellent prototype for understanding the role of isoprenoid modification in protein function.
Anisotropic Metal Nanoparticles:  Synthesis, Assembly, and Optical Applications (2005)

This feature article highlights work from the authors' laboratories on the synthesis, assembly, reactivity, and optical applications of metallic nanoparticles of nonspherical shape, especially nanorods. The synthesis is a seed-mediated growth procedure, in which metal salts are reduced initially with a strong reducing agent, in water, to produce approximately 4 nm seed particles. Subsequent reduction of more metal salt with a weak reducing agent, in the presence of structure-directing additives, leads to the controlled formation of nanorods of specified aspect ratio and can also yield other shapes of nanoparticles (stars, tetrapods, blocks, cubes, etc.). Variations in reaction conditions and crystallographic analysis of gold nanorods have led to insight into the growth mechanism of these materials. Assembly of nanorods can be driven by simple evaporation from solution or by rational design with molecular-scale connectors. Short nanorods appear to be more chemically reactive than long nanorods. Finally, optical applications in sensing and imaging, which take advantage of the visible light absorption and scattering properties of the nanorods, are discussed.
Synthesis of Rh Fv phage‐antibodies using VH and VL germline genes (1999)

Antibodies to the D antigen of the Rh system use a restricted set of immunoglobulin V and J gene segments, especially VH DP50 and DP63, JH6, Vlambda DPL16 and Jlambda 2/3. These gene segments may confer a natural affinity on the antibodies for the D antigen and this hypothesis has been tested by constructing two single-chain Fv phage-antibody libraries based on the germline gene segments DP50 and DP63; structural variability was obtained by insertion of 11 amino acids in random sequence in the VHCDR3. 10 anti-D antibodies were selected from these libraries, each with a unique VHCDR3. In contrast, selections with the CcEe antigens produced antibodies reacting with the Rh polypeptide molecules but without strict blood group specificity. One of these latter DP50-based antibodies was converted into 12 different antibodies with specificity for E by replacing the original germline light chain with chains from a rearranged L chain library. The CDR1 and CDR2 sequences of the DP50-based antibodies were common to both anti-D and anti-E molecules; differentiation between D and E specificity was dependent on VHCDR3 sequences and their correct pairing with an appropriate L chain.
Enhancement of Homologous Recombination Efficiency by Homologous Oligonucleotides (2012)

as mammalian somatic cells and higher plant cells. Furthermore, in multiploid somatic cells, simultaneous gene targeting is required, making complete gene replacement extremely difficult. Even in embryonic stem (ES) cells, where homologous recombination occurs with high efficiency, some genes are difficult to target and subject to homologous recombination. To overcome these problems, the development of efficient and versatile methods that can artificially increase the efficiency of homologous recombination is needed. Figure 1. Schematic diagram of principle of Gene Targeting When extracellular DNA fragment is introduced into cell, gene replacement rarely occurs by homologous recombination. Utilizing this phenomenon, one can 'target' a gene of interest and change its DNA alignment at will.
Herpes Simplex Virus Type 1 Infection Stimulates p38/c-Jun N-terminal Mitogen-activated Protein Kinase Pathways and Activates Transcription Factor AP-1 (1999)

Cells respond to environmental stress and proinflammatory cytokines by stimulating the Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase cascades. Infection of eukaryotic cells with herpes simplex virus type 1 (HSV-1) resulted in stimulation of both JNK/SAPK and p38 mitogen-activated protein kinase after 3 h of infection, and activation reached a maximum of 4-fold by 9 h post-infection. By using a series of mutant viruses, we showed that the virion transactivator protein VP16 stimulates p38/JNK, whereas no immediate-early, early, or late viral expressed gene is involved. We identified the stress-activated protein kinase kinase 1 as an upstream activator of p38/JNK, and we demonstrated that activation of AP-1 binding proceeded p38/JNK stimulation. During infection, the activated AP-1 consisted mainly of JunB and JunD with a simultaneous decrease in the cellular levels of Jun protein. We suggest that activation of the stress pathways by HSV-1 infection either represents a cascade triggered by the virus to facilitate the lytic cycle or a defense mechanism of the host cell against virus invasion.
Theory of Models of Electromagnetic Systems (1948)

Most model measurements are made on models which simulate only the geometrical configurations of the lines of force in the fields of the full-scale system, and thus yield only relative results for many of the properties of the system. It is possible, however, to devise models in which the measurements are on a quantitative or absolute basis in terms of the full-scale system. The conditions to be satisfied in an absolute model for accurate simulation are derived. The limitations imposed on practical models are discussed.
Towards Trojan-Free Trusted ICs: Problem Analysis and Detection Scheme (2008)

There have been serious concerns recently about the security of microchips from hardware trojan horse insertion during manufacturing. This issue has been raised recently due to outsourcing of the chip manufacturing processes to reduce cost. This is an important consideration especially in critical applications such as avionics, communications, military, industrial and so on. A trojan is inserted into a main circuit at manufacturing and is mostly inactive unless it is triggered by a rare value or time event; then it produces a payload error in the circuit, potentially catastrophic. Because of its nature, a trojan may not be easily detected by functional or ATPG testing. The problem of trojan detection has been addressed only recently in very few works. Our work analyzes and formulates the trojan detection problem based on a frequency analysis under rare trigger values and provides procedures to generate input trigger vectors and trojan test vectors to detect trojan effects. We also provide experimental results.
Reversing Bacterial Resistance to Antibiotics by Phage-Mediated Delivery of Dominant Sensitive Genes (2011)

Pathogen resistance to antibiotics is a rapidly growing problem, leading to an urgent need for novel antimicrobial agents. Unfortunately, development of new antibiotics faces numerous obstacles, and a method that resensitizes pathogens to approved antibiotics therefore holds key advantages. We present a proof of principle for a system that restores antibiotic efficiency by reversing pathogen resistance. This system uses temperate phages to introduce, by lysogenization, the genes rpsL and gyrA conferring sensitivity in a dominant fashion to two antibiotics, streptomycin and nalidixic acid, respectively. Unique selective pressure is generated to enrich for bacteria that harbor the phages carrying the sensitizing constructs. This selection pressure is based on a toxic compound, tellurite, and therefore does not forfeit any antibiotic for the sensitization procedure. We further demonstrate a possible way of reducing undesirable recombination events by synthesizing dominant sensitive genes with major barriers to homologous recombination. Such synthesis does not significantly reduce the gene's sensitization ability. Unlike conventional bacteriophage therapy, the system does not rely on the phage's ability to kill pathogens in the infected host, but instead, on its ability to deliver genetic constructs into the bacteria and thus render them sensitive to antibiotics prior to host infection. We believe that transfer of the sensitizing cassette by the constructed phage will significantly enrich for antibiotic-treatable pathogens on hospital surfaces. Broad usage of the proposed system, in contrast to antibiotics and phage therapy, will potentially change the nature of nosocomial infections toward being more susceptible to antibiotics rather than more resistant.