gebhart/patrepeval huggingface dataset:
Bacterial Toxin–Antitoxin Systems: More Than Selfish Entities? (2009)

Bacterial toxin-antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes.
Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. (1993)

Immunohistochemical analysis for the epidermal growth factor receptor (EGFR), EGF and transforming growth factor-alpha (TGF-alpha) was performed in 87 human pancreatic carcinomas. Expression frequencies for EGFR, EGF, and TGF-alpha were 43%, 46% and 54%, respectively. Coexpression of the receptor and at least one of its ligands occurred in 38% of the tumors, and correlated with large tumor size, advanced clinical staging, and decreased survival period. In situ hybridization revealed that the respective mRNAs were also overexpressed in the carcinomas. These findings suggest that coexpression of EGFR and its ligands may contribute to the aggressiveness of human pancreatic cancer.
Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. (1985)

Cachectin/TNF (tumor necrosis factor), an endotoxin-induced murine macrophage hormone implicated in the pathogenesis of cachexia and shock, has been found capable of stimulating collagenase and prostaglandin E2 (PGE2) production by isolated human synovial cells and dermal fibroblasts. This bioactivity associated with cachectin is comparable to that observed with the monokine interleukin 1 (IL-1), previously suggested as the major mediator of proteolysis. The ability of cachectin/TNF to stimulate collagenase and PGE2 production suggests that it may play a role in tissue destruction and remodelling, as these processes occur in inflammatory diseases.
Handbook of Corynebacterium glutamicum (2005)

One of the most important organisms in biotechnology, Corynebacterium glutamicum is currently used to produce 2 million tons of amino acids per year for a rapidly expanding market. Until now, research and information have been scattered among individual papers which are often difficult to locate in a timely manner.As the first complete comp
Antioxidant studies need a change of direction. (2004)

A major flaw of the studies to date is that they failed to measure changes in levels of oxidative stress.
Target-based agents against ErbB receptors and their ligands: a novel approach to cancer treatment. (2003)

The ErbB receptors and their cognate ligands that belong to the epidermal growth factor (EGF) family of peptides are involved in the pathogenesis of different types of carcinomas. In fact, the ErbB receptors and the EGF-like growth factors are frequently expressed in human tumors. These proteins form a complex system that regulates the proliferation and the survival of cancer cells. Therefore, ErbB receptors and their ligands might represent suitable targets for novel therapeutic approaches in human carcinomas. In this regard, different target-based agents that are directed against the ErbB receptors have been developed in the past two decades. One of these compounds, the humanized anti-ErbB-2 monoclonal antibody trastuzumab has been approved for the treatment of patients with metastatic breast cancer. The anti-EGF receptor (EGFR) antibody C225, as well as EGFR tyrosine kinase inhibitors ZD1839 and OSI-774 are currently in phase III clinical development. Several other ErbB tyrosine kinase inhibitors are in phase I/II studies. These compounds have generally been shown to have an acceptable toxicity profile and promising anti-tumor activity in heavily pretreated patients. The mechanisms of action of these compounds, as well as the potential therapeutic strategies to improve their efficacy are discussed in this review with particular regard to the combinations of anti-ErbB agents with cytotoxic drugs, or combinations of different ErbB-targeting agents.
MIA (melanoma inhibitory activity): a potential serum marker for rheumatoid arthritis (1999)

In addition to RF, MIA might therefore be useful in the differential diagnosis of RA vs non-destructive rheumatic diseases, and the presence of elevated levels of MIA in serum very likely reflects joint destruction in RA.
Cosmid vectors for rapid genomic walking, restriction mapping, and gene transfer. (1987)

We have designed cosmid vectors for rapid genomic "walking" and restriction mapping. These vectors contain the transcription promoters from either bacteriophage SP6, T7, or T3 flanking a unique BamHI cloning site. Mammalian expression modules encoding the dominant marker neomycin phosphotransferase or the amplifiable dihydrofolate reductase gene expressed from SV40 promoters were inserted for use in gene transfer studies. Restriction sites for the enzymes Not I and Sfi I, which cut mammalian DNA very infrequently, have been engineered near the transcriptional promoters to enable the excision of most inserts as single, full-length fragments. Genomic libraries representative of mouse, human, and hamster genomes were constructed by inserting 33- to 44-kilobase-pair (kbp) DNA fragments, generated by partial cleavage of genomic DNA with Mbo I or Sau3A, into the unique BamHI site. Digestion of recombinant cosmids with restriction enzymes that cleave frequently but do not disrupt the transcriptional promoters generates two small DNA templates for the synthesis of end-specific RNA probes to facilitate directional "walking." Cosmid restriction maps can be determined rapidly by one of several methods. The cosmids and methods we describe should have wide utility in determining the functional and structural organization of complex eukaryotic genomes and for physically linking distant genetic loci.
Complementation of class II A alleles in the immune response to (GluLysTyr) polymers. (1986)

The proliferative T cell responses to poly(GluLysTyr) (GLT) and poly(GLULysPhe) (GLPhe) are restricted by the E alpha E beta class II MHC molecule (E) in most responded strains. Some nonresponder strains that carry responder E beta, but cannot express cell surface E molecules, can complement with other nonresponder strains that provide the missing E alpha chain needed for the expression of E molecules and for responsiveness to GLT and GLPhe. Here another type of complementation is described between two E-nonexpressor haplotypes, H-2f and H-2s, which result in E-nonexpressor F1 hybrids, which are responders to GLT. The restriction element involved in this response is an Af/As hybrid molecule. The data support the hypothesis that conformational determinants resulting from the free association of alpha and beta chains in heterozygotes can increase the immune potential of the individual.
Reperfusion induced injury: manifestations, mechanisms, and clinical relevance (1992)

Although reperfusion is an absolute prerequisite for the survival of ischaemic tissue, it is not necessarily without hazard. Many (but not all) cardiologists are of the opinion that some component of reperfusion may be detrimental and able to inflict injury over and above that attributable to the ischaemia. In this article we define four sequelae of reperfusion which might be designated as "reperfusion injury", we identify possible underlying mechanisms, and consider whether any of these forms of reperfusion injury are of clinical relevance.
Growth inhibition of human leukemic cells by WT1 (Wilms tumor gene) antisense oligodeoxynucleotides: implications for the involvement of WT1 in leukemogenesis (1996)

We have previously reported expression of WT1 in acute leukemia. To elucidate its biological significance, we examined the effect of the suppression of the WT1 expression by WT1 antisense oligomers on the growth of the leukemic cells expressing WT1. When 20 different WT1 antisense (AS) oligomers covering from the 5' cap sites of the WT1 gene to the 3' end were examined for the inhibitory effect on the growth of K562 cells expressing WT1, four WT1 AS oligomers inhibited the cell growth, whereas WT1 sense and random sequence oligomers had no effect on the cell growth of K562. Moreover, WT1 AS oligomers significantly inhibited the growth of the clonogenic cells of fresh leukemic cells in six of 14 patients with acute myeloid leukemia, in one of two patients with chronic myelogenous leukemia (CML) chronic phase, and in one of one patient with CML blastic crisis. However, these oligomers did not inhibit normal colony-forming unit-granulocyte-macrophage. Western blot analysis clearly demonstrated the significant reduction in the WT1 protein levels in the K562 and fresh leukemic cells that were treated with the WT1 AS oligomers, confirming that the inhibitory effect of the WT1 AS oligomers on the cell growth operates via the reduction in the WT1 protein levels. These results show that WT1 plays an important role in leukemogenesis.
Hybrid in-car speech recognition for mobile multimedia applications (2003)

This paper presents a speech recognition system that is particularly suited for drivers and passengers in a vehicle environment. The requirements of such a system are quite unique. Some applications require small vocabulary with a quick response time while others demand a large vocabulary, however, they can sustain a larger latency in response. The idea of our approach is to complement the scope of an in-car speech recognizer with a large vocabulary recognizer running on a server using a client/server architecture without increasing the overall costs. Apart from the recognizing concept, the paper describes a hybrid speech interface (HSI), in which the back-end recognizer is embedded. The HSI architecture is an open architecture for in-car clients and their underlying infrastructure. It allows the integration of different applications (NewsReader, Route Guidance, etc.) into a homogeneous user interface.
Increased epidermal growth factor receptor in multidrug‐resistant human neuroblastoma cells (1988)

Multidrug-resistant human neuroblastoma cell lines obtained by selection with vincristine or actinomycin D from two independent clonal lines, SH-SY5Y and MC-IXC, have 3- to 30-fold more cell surface epidermal growth factor (EGF) receptors than the drug-sensitive parental cells as indicated by EGF binding assays and immunoprecipitation, affinity-labeling, and phosphorylation studies. Reversion to drug sensitivity in one line was accompanied by a return to the parental level of EGF receptor. SH-EP cells, a clone derived from the same neuroblastoma cell line as SH-SY5Y but which displays melanocyte rather than neuronal lineage markers, also express significantly more EGF receptor than SH-SY5Y cells. By nucleic acid hybridization analysis with a molecularly cloned probe, increased receptor level in multidrug-resistant cells was shown to be the result of higher levels of EGF receptor mRNA in drug-resistant than in drug-sensitive cells. The increased steady state amount of specific RNA did not result from amplification of receptor-encoding genes. A small difference was observed in the electrophoretic mobility under denaturing conditions of EGF receptor immunoprecipitated from drug-resistant and drug-sensitive cells. Quantitative and qualitative modulation of the EGF receptor might reflect alterations in the transformation and/or differentiation phenotype of the resistant cells or might result from unknown selective pressures associated with the development of multidrug resistance.
The Arabidopsis Cdc2a‐interacting protein ICK2 is structurally related to ICK1 and is a potent inhibitor of cyclin‐dependent kinase activity in vitro (2000)

Cyclin-dependent kinases (CDKs) are important regulators of the eukaryotic cell division cycle. To study protein-protein interactions involving plant CDKs, the Arabidopsis thaliana Cdc2aAt was used as bait in the yeast two-hybrid system. Here we report on the isolation of ICK2, and show that it interacts with Cdc2aAt, but not with a second CDK from Arabidopsis, Cdc2bAt. ICK2 contains a carboxy-terminal domain related to that of ICK1, a previously described CDK inhibitor from Arabidopsis, and to the CDK-binding domain of the mammalian inhibitor p27Kip1. Outside of this domain, ICK2 is distinct from ICK1, p27Kip1, and other proteins. At nanogram levels (8 nM), purified recombinant ICK2 inhibits p13Suc1-associated histone H1 kinase activity from Arabidopsis tissue extracts, demonstrating that it is a potent inhibitor of plant CDK activity in vitro. ICK2 mRNA was present in all tissues analysed by Northern hybridization, and its distribution was distinct from that of ICK1. These results demonstrate that plants possess a family of differentially regulated CDK inhibitors that contain a conserved carboxy terminal but with distinct amino terminal regions.
Roles of Specific Extracellular Domains of the Glucagon Receptor in Ligand Binding and Signaling (2002)

To identify structural determinants of ligand binding in the glucagon receptor, eight receptor chimeras and additional receptor point mutants were prepared and studied. Amino acid residues 103-117 and 126-137 in the extracellular N-terminal tail and residues 206-219 and 220-231 in the first extracellular loop of the glucagon receptor were replaced with the corresponding segments of the glucagon-like peptide-1 receptor or the secretin receptor. Specific segments of both the N-terminal tail and the first extracellular loop of the glucagon receptor are required for hormone binding. The 206-219 segment of the first loop appears to be important for both glucagon binding and receptor activation. Functional studies with a synthetic chimeric peptide consisting of the N-terminal 14 residues of glucagon and the C-terminal 17 residues of glucagon-like peptide 1 suggest that hormone binding specificity may involve this segment of the first loop. The binding selectivity may arise in part from aspartic acid residues in this segment. Mutation of R-202 located at the junction between the second transmembrane helix and the first loop resulted in a mutant receptor that failed to bind glucagon or signal. We conclude that high-affinity glucagon binding requires multiple contacts with residues in the N-terminal tail and first extracellular loop domain of the glucagon receptor, with hormone specificity arising primarily from the amino acid 206-219 segment. The data suggest a model whereby glucagon first interacts with the N-terminal domain of the receptor followed by more specific interactions between the N-terminal half of the peptide and the first extracellular loop of the receptor, leading to activation.
Characterization of Monoclonal Antibodies Raised against Solubilized Thyrotropin Receptors in a Cytochemical Bioassay for Thyroid Stimulators* (1985)

Selected clones of monoclonal antibodies from mice immunized with solubilized preparations of bovine TSH receptors have been characterized in a cytochemical bioassay (CBA) for thyroid stimulators. This assay is based upon quantification of changes in naphthylamidase activity of sections of guinea pig thyroids with use of a chromogenic substrate. Monoclonal 22A6 is a thyroid-stimulating antibody directed at a site within the TSH receptor. Thus, although it is a weak inhibitor of 125I-TSH binding to thyroid membranes, 22A6 is inhibited from binding to membranes by TSH, exhibits a more than additive agonist effect on adenylate cyclase activity when tested at low TSH concentrations in thyroid cells, and is a competitive antagonist of TSH enhancement of adenylate cyclase activity at high TSH concentrations. In the CBA, 22A6 is a stimulator whose maximal activity is obtained with 77 pg/ml (3-min exposure). Dose-response curves of a long acting thyroid stimulator (LATS)-B standard and 22A6 have slopes which are not significantly different; as anticipated, the response to LATS-B is inhibited by antihuman immunoglobulin G (IgG) and that due to 22A6 by antimouse IgG. In contrast to 22A6, monoclonal 11E8 is a relatively potent inhibitor of 125I-TSH binding as well as TSH stimulation of adenylate cyclase activity, while failing to act as a stimulator itself. 11E8 is itself inactive as a stimulator in the CBA over a wide dose range; it does, however, inhibit TSH stimulation in the CBA. This inhibition is abolished by antimouse IgG. The transient peak of response observed in time courses to TSH occurs later in the presence of 11E8. Unlike its effect on TSH 11E8 shows relatively low potency (greater than 10,000-fold lower) when inhibiting stimulation by the thyroid stimulating antibodies, 22A6 or LATS-B. Since this difference cannot be explained by quantitative differences in the ability of 22A6 or 11E8 to bind to thyroid membranes, the CBA data suggest that the stimulating antibodies, 22A6 and LATS-B, may interact with different determinants on TSH receptors then either TSH or the blocking antibody, 11E8. This also implies that in Graves' disease blocking antibodies may be incompletely expressed in the presence of stimulating antibodies, although they may be potent inhibitors of TSH binding, as measured in receptor assays.
Zeolite, clay, and heteropoly acid in organic reactions (1992)

Zeolites, clays and heteropoly acid are unique materials with remarkable catalytic properties. Their characteristic features have enabled chemists to develop novel synthetic methods, which hold promise of new frontiers in synthetic and industrial organic chemistry. Written by leading experts on petrochemistry, catalysis, and organic synthesis, this book describes novel synthetic applications and reaction-promoting functions of zeolites, clays and heteropoly acid. Emphasis is put on the excellent catalytic performance of these materials in various organic reactions. Research chemists, process engineers and graduate students interested in new catalyst materials will value this book as an indispensable guide to the uses of zeolites, clay and heteropoly acid in organic synthesis. (orig.)
FI/SI on-line solvent extraction/back extraction preconcentration coupled to direct injection nebulization inductively coupled plasma mass spectrometry for determination of copper and lead (2002)

An automated sequential injection on-line preconcentration procedure for determination of trace levels of copper and lead via solvent extraction/back extraction coupled to ICP-MS is described. In citrate buffer of pH 3, neutral complexes between the analytes and the chelating reagent, ammonium pyrrolidinedithiocarbamate (APDC), are extracted into isobutyl methyl ketone (IBMK). The organic phase is separated from the aqueous one by means of a dual-conical gravitational phase separator, and stored in a PTFE holding coil. Afterwards, the organic phase is propelled and mixed with an aqueous back extractant of nitric acid containing Pd(II) ions as stripping agent, thereby facilitating a rapid metal exchange reaction with the APDC ligand and transfer of the analytes back into the aqueous phase. The aqueous phase is separated in a second dual-conical gravitational phase separator, and 30 µl is entrapped in a sample loop, the content of which is subsequently introduced into the ICP-MS, via a direct injection high efficiency nebulizer (DIHEN), for quantification. Enrichment factors of 29.6 (Cu) and 23.3 (Pb), detection limits of 17 ng l−1 (Cu) and 11 ng l−1 (Pb), along with a sampling frequency of 13 h−1 were obtained at a sample flow rate of 6.0 ml min−1. The precisions (RSD) at the 0.2 µg l−1 level were 4.4% (Cu) and 4.8% (Pb), respectively. The applicability of the procedure is demonstrated for the determination of copper and lead in three certified reference materials and a urine sample.
Temperature-insensitive multipoint strain-sensing system based on fiber Bragg gratings and optical power detection scheme (2006)

This work presents a new temperature-insensitive multipoint strain sensor based on fiber Bragg gratings. A divider circuit at the post detection port compensates for optical power variation and thermal instability induced by the nonflatness of the source spectrum. Experimental results show a measurement resolution of /spl plusmn/0.35 /spl mu/S and a temperature stability of /spl plusmn/0.005% for no strain (/spl plusmn/0.48% for a strain of <400 /spl mu/S) in an example with two sensing points. A measurement linearity of /spl plusmn/0.17% is estimated in the range 0 to 350 /spl mu/S with no crosstalk.
Coating Single-Walled Carbon Nanotubes with Tin Oxide (2003)

Single-walled carbon nanotubes coated with crystalline tin oxide by a simple chemical-solution route are reported. The room-temperature chemical treatment results in a nominally complete and uniform coating over the entire outer surface of singular nanotubes, nanotube bundles, and also fullerene-like nanoparticles. The samples have been characterized by high-resolution transmission electron microscopy, energy-dispersive X-ray spectrometry, and X-ray diffraction. The coating is composed of interconnected SnO2 nanoparticles of sizes between 1−6 nm. Typically, the coatings have a total thickness on the order of the constituent nanoparticle size.
Carbamoyl Pyridone HIV-1 Integrase Inhibitors. 2. Bi- and Tricyclic Derivatives Result in Superior Antiviral and Pharmacokinetic Profiles (2013)

This work is a continuation of our initial discovery of a potent monocyclic carbamoyl pyridone human immunodeficiency virus type-1 (HIV-1) integrase inhibitor that displayed favorable antiviral and pharmacokinetic properties. We report herein a series of bicyclic carbamoyl pyridone analogues to address conformational issues from our initial SAR studies. This modification of the core unit succeeded to deliver low nanomolar potency in standard antiviral assays. An additional hydroxyl substituent on the bicyclic scaffold provides remarkable improvement of antiviral efficacies against clinically relevant resistant viruses. These findings led to additional cyclic tethering of the naked hydroxyl group resulting in tricyclic carbamoyl pyridone inhibitors to address remaining issues and deliver potential clinical candidates. The tricyclic carbamoyl pyridone derivatives described herein served as the immediate leads in molecules to the next generation integrase inhibitor dolutegravir which is currently in late stage clinical evaluation.
Random Forests--Random Features (1999)

Random forests are a combination of tree predictors such that each tree depends on the values of a random vector sampled independently and with the same distribution for all trees in the forest. The generalization error for forests converges a.s. to a limit as the number of trees in the forest becomes large. The error of a forest of tree classifiers depends on the strength of the individual trees in the forest and the correlation between them. Using a random selection of features to split each node yields error rates that compare favorably to Adaboost, but are more robust with respect to noise. Internal estimates monitor error, strength, and correlation and these are used to show the response to increasing the number of features used in the splitting. These ideas are al;so applicable to regression. 2 1. Random Forests 1.1 Introduction Significant improvements in classification accuracy have resulted from growing an ensemble of trees and letting them vote for the most popular class...