gebhart/patrepeval huggingface dataset:
Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells (2001)

Edited by Louis J. Ignarro, University of California, Los Angeles School of Medicine, Los Angeles, CA, and approved August 27, 2001 (received for review May 16, 2001)
Osmium Bipyridyl Redox Polymers Used in Enzyme Electrodes (1995)

A review of the background of biosensors which utilise osmium complexes for monitoring the glucose levels in diabetic patients is presented. An electrochemical system, based on an osmium redox polymer, is described; the system is aimed at being a reliable, compact and miniature in vivo sensor for implantation into diabetic patients for continuous monitoring of their blood glucose levels. The sensor is about to begin trials on human volunteers.
Effects of Bacterial ACC Deaminase onBrassica napusGene Expression (2012)

Plants in association with plant growth-promoting rhizobacteria can benefit from lower plant ethylene levels through the action of the bacterial enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase. This enzyme cleaves the immediate biosynthetic precursor of ethylene, ACC. Ethylene is responsible for many aspects of plant growth and development but, under stressful conditions, it exacerbates stress symptoms. The ACC deaminase-containing bacterium Pseudomonas putida UW4 is a potent plant growth-promoting strain and, as such, was used to elaborate the detailed role of bacterial ACC deaminase in Brassica napus (canola) plant growth promotion. Transcriptional changes in bacterially treated canola plants were investigated with the use of an Arabidopsis thaliana oligonucleotide microarray. A heterologous approach was necessary because there are few tools available at present to measure global expression changes in nonmodel organisms, specifically with the sensitivity of microarrays. The results indicate that the transcription of genes involved in plant hormone regulation, secondary metabolism, and stress response was altered in plants by the presence of the bacterium, whereas the upregulation of genes for auxin response factors and the downregulation of stress response genes was observed only in the presence of bacterial ACC deaminase. These results support the suggestion that there is a direct link between ethylene and the auxin response, which has been suggested from physiological studies, and provide more evidence for the stress-reducing benefits of ACC deaminase-expressing plant growth-promoting bacteria.
RNA Interference (RNAi)-Based Therapeutics: Delivering on the Promise? (2016)

A resurgence in clinical trials using RNA interference (RNAi) occurred in 2012. Although there were initial difficulties in achieving efficacious results with RNAi without toxic side effects, advances in delivery and improved chemistry made this resurgence possible. More than 20 RNAi-based therapeutics are currently in clinical trials, and several of these are Phase III trials. Continued positive results from these trials have helped bolster further attempts to develop clinically relevant RNAi therapies. With a wide variety of disease targets to choose from, the first RNAi therapeutic to be clinically approved is not far off. This review covers recently established and completed clinical trials.
CD27 expression by a distinct subpopulation of human B lymphocytes (1990)

CD27 is present on the surface of a major subset of peripheral blood T lymphocytes. In this report we show that CD27 is also expressed on a subpopulation of the normal human B cell lineage which is absent from cord blood but present in tonsils and in the peripheral blood of adult individuals. CD27+ B lymphocytes are characterized by the following criteria: (a) in terms of physical properties, the CD27+ B cells form a population with an increased cell size combined with a decreased cell density; (b) the CD27 expression of tonsillar B lymphocytes is postively correlated with mIgA but negatively correlated with membrane IgM/membrane IgD positivity; (c) CD27 on B cells can be induced selectively by the combination of Staphylococcus aureus plus interleukin 2, but not by either treatment alone, and (d) CD27+ B lymphocytes express high levels of the adhesion structures LFA-1 (CD11a), ICAM-1 (CD54), LFA-3 (CD58) and of the lymphocyte homing receptor CD44. These latter findings suggest that CD27+ B cells are predispose to form cell-cell interactions. Accordingly, within 3 h of cell culture CD27+, but not CD27-, B lymphocytes were found to form LFA-1-mediated homotypic B cell clusters.
Cytokine modulation in sepsis and septic shock (2002)

Sepsis and septic shock are a major cause of morbidity and mortality in patients admitted to the intensive care unit. Since the introduction of antibiotic therapy, the mortality associated with sepsis has remained within the 30- 50% range. Sepsis constitutes the systemic response to infection. This response encompasses both pro-inflammatory and anti-inflammatory phases that are marked by the sequential generation of pro- and anti-inflammatory cytokines. Among the most important pro-inflammatory cytokines are TNF-alpha and IL-1beta. The pro-inflammatory effects of such cytokines are inhibited by soluble receptors/receptor antagonists and anti-inflammatory cytokines including IL-10 and transforming growth factor-beta. Modulation of the activity of both pro- and anti-inflammatory cytokines to improve outcome in patients with sepsis has been subject of multiple clinical studies. This review will examine clinical trials evaluating several strategies for blocking or attenuating TNF-alpha and IL-1beta activity. This review will also survey the current state of experimental therapies involving IL-10, transforming growth factor-beta, granulocyte colony-stimulating factor and IFN-phi. Finally, newer developments related to less known cytokines such as macrophage migration inhibitory factor and high mobility group 1 protein will be evaluated.
Regulation of 5'-adenosine monophosphate deaminase in the freeze tolerant wood frog, Rana sylvatica (2008)

Maintenance of long term viability under the ischemic conditions in frozen muscle requires attention to the control of cellular energetics. Differential regulatory controls on AMPD by mechanisms including binding to muscle proteins, actions allosteric effectors, glucose and temperature effects and reversible phosphorylation adjust enzyme function for an optimal role in controlling cellular adenylate levels in ischemic frozen muscle. Stable modification of AMPD properties via freeze-responsive phosphorylation may contribute both to AMPD control and to coordinating AMPD function with other enzymes of energy metabolism in cold ischemic muscle.
Conformational differences between linear .alpha.(2.fwdarw.8)-linked homosialooligosaccharides and the epitope of the group B meningococcal polysaccharide (1987)

The alpha-(2----8)-linked sialic acid oligosaccharides (NeuAc)n exhibit an unusual degree of heterogeneity in the conformation of their linkages. This was diagnosed by observation in their 13C NMR spectra of an equivalent and unique heterogeneity in the chemical shifts of their anomeric carbons and subsequently confirmed by more comprehensive 1H and 13C NMR studies. In these studies both one-dimensional and two-dimensional experiments were carried out on the trisaccharide (NeuAc)3 and colominic acid. In addition to the unambiguous assignment of the signals in the spectra, these experiments demonstrated that both linkages of (NeuAc)3 differed in conformation from each other and from the inner linkages of colominic acid. The NMR data indicate that these conformational differences extend to both terminal disaccharides of oligosaccharides larger than (NeuAc)5, a result that has considerable physical and biological significance. In the context of the group B meningococcal polysaccharide, it provides an explanation for the conformational epitope of the group B meningococcal polysaccharide, which was proposed on the evidence that (NeuAc)10, larger than the optimum size of an antibody site, was the smallest oligosaccharide able to bind to group B polysaccharide specific antibodies. Because the two terminal disaccharides of (NeuAc)10 differ in conformation to its inner residues, the immunologically functional part of (NeuAc)10 resides in its inner six residues. This number of residues is now consistent with the maximum size of an antibody site.
DRL INTERRESPONSE‐TIME DISTRIBUTIONS: QUANTIFICATION BY PEAK DEVIATION ANALYSIS (1993)

Peak deviation analysis is a quantitative technique for characterizing interresponse-time distributions that result from training on differential-reinforcement-of-low-rate schedules of reinforcement. It compares each rat's obtained interresponse-time distribution to the corresponding negative exponential distribution that would have occurred if the rat had emitted the same number of responses randomly in time, at the same rate. The comparison of the obtained distributions with corresponding negative exponential distributions provides the basis for computing three standardized metrics (burst ratio, peak location, and peak area) that quantitatively characterize the profile of the obtained interresponse-time distributions. In Experiment 1 peak deviation analysis quantitatively described the difference between the interresponse-time distributions of rats trained on variable-interval 300-s and differential-reinforcement-of-low-rate 72-s schedules of reinforcement. In Experiment 2 peak deviation analysis differentiated between the effects of the psychomotor stimulant d-amphetamine, the anxiolytic compound chlordiazepoxide, and the antidepressant desipramine. The results suggest that peak deviation analysis of interresponse-time distributions may provide a useful behavioral assay system for characterizing the effects of drugs.
Protease-Mediated Ligation of Abiotic Oligomers (2005)

We demonstrate that proteases can catalyze the ligation of peptidomimetic oligomers. The enzyme clostripain was used to facilitate the native ligation of N-substituted glycine oligomers, or peptoids. In addition to mediating the efficient condensation of two peptoid fragments, iterative ligation events were also performed, giving rise to concatenation products with molecular weights up to 20 kDa. Efficient ligation of peptoid foldamers may enable the chemical synthesis of biomimetic macromolecules capable of forming complex tertiary structures.
Partial-encryption technique for intellectual property protection of FPGA-based products (2000)

The configuration-data sequence of a field-programmable gate array (FPGA) is an intellectual property (IP) of the original designer. This paper proposes a partial-encryption (PE) technique for IP protection of configuration-data sequences by means of increasing the reverse-engineering cost. The PE technique encrypts a few selected data of the sequence. These data are selected in a judicious way such that, when a rival competitor copies the partially encrypted sequence into a cloned product, the cloned product performs the expected task to a certain degree of correctness but not absolutely error-free. Debugging is required. It is shown that, without an initial knowledge that a reverse-engineering countermeasure is employed, the PE technique outperforms the full-encryption technique in terms of the reverse-engineering cost. This paper describes implementation details of the proposed PE technique. Issues regarding system designs that embed hidden imperfections are also discussed.
Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi (2011)

Antibiotics have varying effects on the different morphological forms of B. burgdorferi. Persistence of viable organisms in round body forms and biofilm-like colonies may explain treatment failure and persistent symptoms following antibiotic therapy of Lyme disease.
Synthesis of double-stranded DNA complementary to lysozyme, ovomucoid, and ovalbumin mRNAs. Optimization for full length second strand synthesis by Escherichia coli DNA polymerase I. (1978)

Sequential reverse transcriptase, DNA polymerase, and S1 nuclease reactions can be employed to synthesize double-stranded DNA representing messenger RNA. Using reverse transcriptase products made from partially purified lysozyme, ovomucoid, and ovalbumin messengers from hen oviduct, we have characterized the Escherichia coli DNA polymerase I reaction. We have optimized for a high yield of full length second strands under conditions which require only a small amount of mRNA. The effects of several parameters (time, enzyme levels, salt concentration, monovalent cation, and temperature) on the length of products synthesized by DNA polymerase I have been investigated. Each has a significant influence on the proportion of products which are full length. Under our conditions the three reactions are efficient in synthesizing full length duplex DNA from partially purified mRNA fractions or from total poly(A)-containing RNA.
The mature bone morphogenetic protein-2 is aberrantly expressed in non-small cell lung carcinomas and stimulates tumor growth of A549 cells (2003)

To help identify genes, which may regulate metastasis in lung cancer, we performed representational difference analysis between a patient-derived non-small cell lung carcinoma (NSCLC) and immortalized normal human bronchial epithelial cells. This analysis revealed that bone morphogenetic proteins-2/4 (BMP) mRNA was expressed in the lung carcinoma. BMP-2/4 are known to induce pluripotent cell differentiation, enhance cell migration and stimulate proliferation during embryonic development. Despite being powerful morphogens it is not known whether BMP-2/4 have significant biological activity in human carcinomas. Furthermore, it has not been established whether the mature active BMP-2/4 protein is aberrantly expressed in patient-derived tumors. The purpose of this study was to determine whether the expression of the mature BMP-2/4 protein is disregulated in human lung carcinomas and to establish whether it has adverse biological activity. This study reveals that the mature BMP-2 protein, but not BMP-4, is highly over-expressed in human NCSLC with little to no expression in normal lung tissue or benign lung tumors. The expression of BMP-2 localized specifically to the cancer cells. Recombinant BMP-2 stimulated in vitro, the migration and invasiveness of the A549 and H7249 human lung cancer cell lines. In vivo, recombinant BMP-2 enhanced the growth of tumors formed from A549 cells injected subcutaneously into nude mice. Furthermore, inhibition of BMP-2 activity with either recombinant noggin or anti-BMP-2 antibody resulted in a significant reduction in tumor growth. This study shows that expression of the mature BMP-2 protein is disregulated in the majority of NSCLC. BMP-2 enhancement of tumor cell migration and invasion, as well as stimulating tumor growth in vivo, suggests it has important biological activity in lung carcinomas.
Fas and Fas ligand system may mediate antiproliferative activity of gonadotropin-releasing hormone receptor in endometrial cancer cells. (1998)

Gonadotropin-releasing hormone (GnRH) receptor-bearing tumors undergo apoptosis in vivo and in vitro with GnRH analogs. We recently showed that GnRH stimulation induces intratumoral expression of the apoptosis-inducing Fas ligand in human reproductive tract tumors. To provide a potential association of Fas/Fas ligand system with the antiproliferative signaling process of GnRH receptor, we evaluated a correlation between the Fas ligand expression and the number of viable cells in two types of GnRH receptor-bearing endometrial carcinomas that differ in Fas content. Surgically removed uterine endometrial carcinomas had been screened for the presence of GnRH receptor and Fas before analyses. Fas ligand protein was characterized by immunoblotting of membrane proteins with the specific antibody. After a lag time of 2 days, incubation with a GnRH analog leuprolide (10 microM) induced significant growth inhibition of the Fas- and GnRH receptor-bearing cells (p<0.01). Time course analysis showed that Fas ligand production, which was already observed at day 2 (p<0.01), precedes the onset of reduction in viable cell number. The stimulatory effect of GnRH on Fas ligand expression and reduction of viable cells revealed dose-dependency. The analog at concentration of 10 microM induced up to 90% reduction in cell number. In contrast, the growth of Fas-negative cells was not affected by the analog, although Fas ligand appeared in response to the GnRH analog (p<0.01). These data demonstrate that the co-presence of Fas could be essential for GnRH to promote antiproliferative action in endometrial cancer cells carrying GnRH receptor. The hormone may act through intratumor Fas and Fas ligand system to induced growth inhibition in GnRH-sensitive tumors.
Clinical significance of early non‐response in depressed patients (1994)

Abstract Many authorities recommend a 6‐week trial of an antidepressant before deciding whether the patient will have a favorable response. However, this length of time is frequently impractical, especially for hospitalized patients. Some data suggests that ultimate response to a tricyclic antidepressant may be predicted from improvement within the first few weeks. To investigate this issue the authors analyzed data from six 6‐week double‐blind, controlled trials of selective serotonin reuptake inhibitors. Five studies included a placebo control group and all had an active antidepressant control. Overall the data showed that if there is no improvement early in treatment the chance of meaningful response by week 6 is poor. If a patient on active drug does not have at least a 20% improvement in the HAMD score at any point during the first 4 weeks the chance of 6‐week response was 3.7%. If a patient did not have a 20% improvement at 4 weeks but did at one or more previous weeks the chance of 6‐week response was 23.1%. The overall response rate for the whole sample was 60.7%. Very similar results were obtained using the Clinical Global Impressions Scale. These data suggest that a full 6‐week trial of an antidepressant is usually not warranted if there is not at least some improvement during the first 4 weeks of the trial. Depression 2:32–35 (1994). © 1994 Wiley‐Liss, Inc.
Digital recording and numerical reconstruction of holograms (2002)

This article describes the principles and major applications of digital recording and numerical reconstruction of holograms (digital holography).
Regulation of quorum sensing in Vibrio harveyi by LuxO and Sigma‐54 (2000)

The bioluminescent marine bacterium Vibrio harveyi controls light production (lux) by an elaborate quorum-sensing circuit. V. harveyi produces and responds to two different autoinducer signals (AI-1 and AI-2) to modulate the luciferase structural operon (luxCDABEGH) in response to changes in cell-population density. Unlike all other Gram-negative quorum-sensing organisms, V. harveyi regulates quorum sensing using a two-component phosphorylation-dephosphorylation cascade. Each autoinducer is recognized by a cognate hybrid sensor kinase (called LuxN and LuxQ). Both sensors transduce information to a shared phosphorelay protein called LuxU, which in turn conveys the signal to the response regulator protein LuxO. Phospho-LuxO is responsible for repression of luxCDABEGH expression at low cell density. In the present study, we demonstrate that LuxO functions as an activator protein via interaction with the alternative sigma factor, sigma54 (encoded by rpoN). Our results suggest that LuxO, together with sigma54, activates the expression of a negative regulator of luminescence. We also show that phenotypes other than lux are regulated by LuxO and sigma54, demonstrating that in Vibrio harveyi, quorum sensing controls multiple processes.
Statistical considerations for linkage analysis using recombinant inbred strains and backcrosses. (1986)

Recombinant inbred (RI) mouse strains are extremely useful for gene mapping, especially for establishing preliminary map positions for new loci. However, the usual statistical analysis applied to such experiments may lead to erroneous conclusions about linkage unless unusually stringent criteria are adopted for rejecting the null hypothesis. We describe a Bayesian statistical approach for determining the probability of linkage when no prior information is available about the location of the gene to be mapped (the test locus). We present a table that gives the probability of linkage, the most likely position of the test locus with respect to a marker locus, and the interval around the marker locus that has a 95% chance of containing the test locus, for all possible experimental results suggesting linkage in sets of up to 40 RI strains. These results show that for the probability of linkage to be greater than 95%, the number of RI strains inheriting chromosomes recombinant for the test and marker loci must be smaller than previously assumed. The formulas derived for RI strains can be applied, with only minor modifications, to the analysis of Mendelian backcrosses. Differences between the Bayesian approach advocated here and the more traditional analysis of linkage are discussed in detail.
The application of semi-conductivity measurements in the study of catalysis on copper oxide (1949)

Abstract An apparatus has been constructed to measure the electrical conductivity of thin films of oxides in order to study the effects of adsorbed gases and reactions between them. This has been applied to the cuprous-cupric oxide system.
Contribution of Linker Stability to the Activities of Anticancer Immunoconjugates (2008)

The linker component of antibody-drug conjugates (ADC) is a key feature in developing optimized therapeutic agents that are highly active at well tolerated doses. For maximal intratumoral drug delivery, linkers are required that are highly stable in the systemic circulation, yet allow for efficient drug release at the target site. In this respect, amide bond-based technologies constitute a technological advancement, since the linker half-lives in circulation ( t 1/2 approximately 7 days) are much longer than earlier generation linkers that break down within 1-2 days. The amide linkers, some of which contain peptides, are appended to the mAb carriers through thioether/maleimide adducts. Here, we describe that use of a bromoacetamidecaproyl (bac) in place of the maleimidocaproyl (mc) increases the plasma stability of resulting thioether ADCs. One such ADC, 1F6-C4v2-bac-MMAF, which is directed against the CD70 antigen on lymphomas and renal cell carcinoma, was prepared containing a bac thioether spacer between the drug (MMAF) and the mAb carrier (1F6-C4v2). There was no measurable systemic drug release from this ADC for 2 weeks postadministration in mice. In order to assess the impact of improving linker stability beyond mc containing ADCs, a series of mc and bac-linked 1F6-MMAF conjugates were compared for tolerability, intratumoral drug delivery, and therapeutic efficacy in nude mice with renal cell carcinoma xenografts. There were no statistically significant efficacy differences between sets of mc and bac containing ADCs, although the bac linker technology led to 25% higher intratumoral drug exposure over a 7 day period compared to the corresponding mc linker. The mechanism of drug release from maleimide-adducts likely involves a retro-Michael reaction that takes place in plasma, based on in vitro studies demonstrating that some of the released drug-maleimide derivative became covalently bound to cysteine-34 of serum albumin. In summary, the data indicate that new linkers can be obtained with improved in vivo stability by replacing the maleimide with an acetamide, but the resulting ADCs had similar tolerability and activity profiles.
What can we learn about the need for transfusion from patients who refuse blood? The experience with Jehovah's Witnesses (1994)

These data have significant limitations but suggest that survival, without transfusion, is possible at low hemoglobin concentrations, while mortality with an unknown incidence is encountered at hemoglobin concentrations below 5 g per dL (50 g/L).