gebhart/patrepeval huggingface dataset:
Macrophages cultured in vitro release leukotriene B4 and neutrophil attractant/activation protein (interleukin 8) sequentially in response to stimulation with lipopolysaccharide and zymosan. (1990)

The capacity of lipopolysaccharide (LPS), zymosan, and calcium ionophore A23187 to induce neutrophil chemotactic activity (NCA), leukotriene B4 (LTB4), and neutrophil attractant/activation protein (NAP-1) release from human alveolar macrophages (AM) retrieved from normal nonsmokers was evaluated. LPS induced a dose-dependent release of LTB4 that began by 1 h, 4.0 +/- 3.2 ng/10(6) viable AM; peaked at 3 h, 24.7 +/- 13.5 ng/10(6) viable AM; and decreased by 24 h, 1.2 +/- 1.0 ng/10(6) viable AM (n = 8). Quantities of LTB4 in cell-free supernatants of AM stimulated with LPS were determined by reverse-phase high-performance liquid chromatography and corresponded well with results obtained by radioimmunoassay. By contrast, NAP-1 release began approximately 3-5 h after stimulation of AM with LPS, 197 +/- 192 ng/ml, and peaked at 24 h, 790 +/- 124 ng/ml. Release of NAP-1 was stimulus specific because A23187 evoked the release of LTB4 but not NAP-1, whereas LPS and zymosan induced the release of both LTB4 and NAP-1. The appearance of neutrophil chemotactic activity in supernatants of AM challenged with LPS for 3 h could be explained completely by the quantities of LTB4 present. After stimulation with LPS or zymosan for 24 h, AM had metabolized almost all generated LTB4. Preincubation of AM with nordihydroguiaretic acid (10(-4) M) completely abolished the appearance of NCA, LTB4, and NAP-1 in supernatants of AM challenged with LPS. Therefore, LPS and zymosan particles were potent stimuli of the sequential release of LTB4 and NAP-1 from AM.
Further Characterization of a Human Sperm Coating Antigen (gp12) (1986)

In our previous paper, we identified a novel sperm-coating antigen with molecular weight of approximately 12,000 daltons that is highly specific to sperm, seminal plasma, and milk from the plasma membrane fraction of human spermatozoa by using rabbit antiseminal plasma antiserum. In the present study, this 12,000-daltons component, termed gp12, has been investigated for its tissue distribution and antigenic stability. The largest amounts of the antigen are found in seminal plasma, although individual variation is rather high. In seminal plasma, the gp12 molecule presents in a large form with a molecular weight of approximately 50,000 daltons. Its antigenicity is stable when treated with acid, alkali, heat, and various protein denaturants.
Adrenergic, cholinergic, and inactive human neuroblastoma cell lines with the action-potential Na+ ionophore. (1977)

Cultured human neuroblastoma cell lines were assayed for biochemical characteristics of neuonal function. Cell lines studied included LA-N-1, LA-N-2, IMR-32, SK-N-SH, and SK-N-MC. Veratridine-dependent uptake of 22Na+ implied the presence of the action potential Na+ ionophore in LA-N-1, LA-N-2, IMR-32, and SK-N-SH. The time course of 22Na+ uptake and inhibition of uptake by tetrodotoxin supported this. SK-N-MC had no veratridine-dependent 22Na+ uptake. Tyrosine hydroxylase (EC 1.14.10.), glutamic acid decarboxylase (EC 4.1.1.15), and acetylcholine contents in neuroblastoma cells were compared to those in brain. LA-N-1 and IMR-32 contained 15 and 5 times as much tyrosine hydroxylase, respectively, whereas LA-N-2, SK-N-SH, and SK-N-MC contained only 0.5 to 5% of that in brain. Acetylcholine was present in -LA-N-2 in 15- to 20-fold greater quantities than in brain; other lines had only 10 to 50% of that in brain. None of the cell lines contained glutamic acid decarboxylase. Thus, continuously propogated human neuroblastoma cell lines may have the action potential Na+ ionophore and may be adrenergic (LA-N-1 and IMR-32), cholinergic (LA-N-2), or inactive (SK-N-SH and SK-N-MC). This is the first demonstration of the action potential Na+ ionophore and of acetylcholine production in human neuroblastoma cell lines.
Micromachined piezoelectric force sensors based on PZT thin films (1996)

A micromachined lead zirconate titanate (PZT) force sensor for scanning force microscope (SFM) is conceptualized by its piezoelectricity. The fabrication procedure is interpreted, and mechanical characteristics of the micromachined PZT force sensors with various lengths are studied in this paper. A compact SFM is constructed by using the piezoelectric PZT sensor. A very clear image is taken by this SFM. The current study of the micromachined PZT force sensor can be considered as a breakthrough of design of SFM as well as a good example of integrated piezoelectric microdevices.
Linker Tailing: Unphosphorylated Linker Oligonucleotides for Joining DNA Termini (1984)

Current procedures for inserting linker oligonucleotides between DNA termini involve terminal addition of linker duplexes followed by restriction enzyme cleavage and religation . Such methods have the disadvantage that target DNA molecules containing internal recognition sites are cut during the linker cleavage step. We describe a method for adding linker oligonucleotides to DNA termini which eliminates the requirement for subsequent restriction enzyme treatment. Nonphosphorylated linker duplexes are ligated to target DNA termini on one strand alone. Removal of the unligated strand generates a single-stranded protrusion at each terminus. Two such tailed termini may now be linked by annealing their single-stranded complementary tails, resulting in a hybrid DNA molecule containing a single linker insertion. Each step of the procedure has been studied to optimize the recovery of recombinant molecules, and we present examples of how the method may be applied.
Cutting Edge: Opposite Effects of IL-1 and IL-2 on the Regulation of IL-17+ T Cell Pool IL-1 Subverts IL-2-Mediated Suppression (2007)

In this report, we show that IL-17(+)CD4(+) and IL-17(+)CD8(+) T cells are largely found in lung and digestive mucosa compartments in normal mice. Endogenous and exogenous IL-1 dramatically contribute to IL-17(+) T cell differentiation mediated by TGFbeta and IL-6. IL-1 is capable of stimulating IL-17(+) T cell differentiation in the absence of IL-6. Furthermore, although IL-2 reduces IL-17(+) T cell differentiation, IL-1 completely disables this effect. Mechanistically, IL-1 and IL-2 play opposite roles in regulating the expression of several molecules regulating Th17 cell differentiation, including the orphan nuclear receptor ROR gamma t, the IL-1 receptor, and the IL-23 receptor. IL-1 subverts the effects of IL-2 on the expression of these gene transcripts. Altogether, our work demonstrates that IL-6 is important but not indispensable for IL-17(+) T cell differentiation and that IL-1 plays a predominant role in promoting IL-17(+) T cell induction. Thus, the IL-17(+) T cell pool may be controlled by the local cytokine profile in the microenvironment.
Identification of a second mutation in the protein-coding sequence of the Z type alpha 1-antitrypsin gene. (1986)

This study reports the entire nucleotide sequence of the protein coding region sequence of the alpha 1-antitrypsin (alpha 1AT) Z gene, a common form of the alpha 1AT gene associated with serum alpha 1AT deficiency. In addition to Glu342 to Lys342 mutation in exon V which has been previously identified by peptide analysis, another point mutation (GTG to GCG in exon III) in the gene sequence predicts a second amino acid substitution (Val213 to Ala213) in the Z protein. This Val213 to Ala213 mutation was confirmed to be a general finding in Z type alpha 1AT gene by evaluating genomic DNA from 40 Z haplotypes using synthetic oligonucleotide gene probes directed toward the mutated exon III sequences in the Z gene. Furthermore, the exon III Val213 to Ala213 mutation eliminates a BstEII restriction endonuclease site in the alpha 1AT Z gene, allowing rapid identification of this Val213 to Ala213 substitution at the genomic DNA level. Surprisingly, when genomic DNA samples from individuals thought to be homozygous for the M1 gene (the most common alpha 1AT normal haplotype) were evaluated with BstEII, 23% of the M1 haplotypes were BstEII site negative, thus identifying a new form of M1 (i.e. M1(Ala213], likely identical to M1 but with an isoelectric focusing "silent" amino acid substitution (Val213 to Ala213). Although the relative importance of the newly identified exon III Val213 to Ala213 mutation to the pathogenesis of the abnormalities associated with the Z gene is not known, it is likely that M1(Ala213) gene represents a common "normal" polymorphism of the alpha 1AT gene that served as an evolutionary intermediate between the M1(Val213) and Z genes.
Vaccination of Monkeys with RecombinantPlasmodium falciparumApical Membrane Antigen 1 Confers Protection against Blood-Stage Malaria (2002)

A major challenge facing malaria vaccine development programs is identifying efficacious combinations of antigens. To date, merozoite surface protein 1 (MSP1) is regarded as the leading asexual vaccine candidate. Apical membrane antigen 1 (AMA1) has been identified as another leading candidate for an asexual malaria vaccine, but without any direct in vivo evidence that a recombinant form of Plasmodium falciparum AMA1 would have efficacy. We evaluated the efficacy of a form of P. falciparum AMA1, produced in Pichia pastoris, by vaccinating Aotus vociferans monkeys and then challenging them with P. falciparum parasites. Significant protection from this otherwise lethal challenge with P. falciparum was observed. Five of six animals had delayed patency; two of these remained subpatent for the course of the infection, and two controlled parasite growth at <0.75% of red blood cells parasitized. The protection induced by AMA1 was superior to that obtained with a form of MSP1 used in the same trial. The protection induced by a combination vaccine of AMA1 and MSP1 was not superior to the protection obtained with AMA1 alone, although the immunity generated appeared to operate against both vaccine components.
SoxR, a [2Fe-2S] transcription factor, is active only in its oxidized form. (1996)

SoxR protein is known to function both as a sensor and as a transcriptional activator for a superoxide response regulon in Escherichia coli. The activity of SoxR was tested by its ability to enable the transcription of its target gene, soxS, in vitro. The activity of the oxidized form was lost when its [2Fe-2S] clusters were reduced by dithionite under anaerobic conditions, and it was rapidly restored by autooxidation. This result is consistent with the hypothesis that induction of the regulon is effected by the univalent oxidation of the Fe-S centers of SoxR. In vivo, this oxidation may be caused by an alteration of the redox balance of electron chain intermediates that normally maintains soxR in an inactive, reduced state. Oxidized SoxR was about twice as effective as reduced SoxR in protecting the soxS operator from endonucleolytic cleavage. However, this difference could not account for a greater than 50-fold difference in their activities and therefore could not support a model in which oxidation activates SoxR by enabling it to bind to DNA. NADPH, ferredoxin, flavodoxin, or ferredoxin (flavodoxin):NADP+ reductase could not reduce SoxR directly in vitro at a measurable rate. The midpoint potential for SoxR was measured at -283 mV.
Alterations in chromatin conformation are accompanied by reorganization of nonchromatin domains that contain U-snRNP protein p28 and nuclear protein p107. (1985)

The intranuclear distribution of nuclear matrix-associated protein p107 and the 28-kD Sm antigen of U-snRNPs have been studied using double-label immunofluorescence and immunoperoxidase electron microscopy. In interphase nuclei of HeLa cells, Novikoff hepatoma cells, and rat kangaroo kidney cells, p107 was confined to discrete interchromatin domains. The domains had an irregular contour, with an average diameter of 1-1.5 micron. Each domain appeared to be composed of interconnected granules. The Sm antigen colocalized and appeared concentrated in these domains but also showed some general nucleoplasmic distribution. During mitosis, the interchromatin domains disassembled such that the Sm portion redistributed to the perichromosomal and spindle regions and the p107 component redistributed throughout the mitotic cytoplasm. During anaphase, p107 assembled into discrete clusters throughout the mitotic cytoplasm. The Sm antigen was not a component of these clusters. Double-label immunofluorescence with anti-p107 and the anti-DNA tight-binding protein, AhNa1, showed that the extranuclear p107 domains assumed an interchromatin localization only after the chromosomes had decondensed. The correlation between chromosome decondensation and the occurrence of p107 within interchromatin domains was also observed during chicken erythrocyte nuclear reactivation. We propose that the discrete interchromatin domains that contain p107 and p28 may be important for processing and splicing of RNA and that their structural assembly within nuclei is sensitive to the presence of the transcriptionally active conformation of chromatin.
Tung Tree DGAT1 and DGAT2 Have Nonredundant Functions in Triacylglycerol Biosynthesis and Are Localized to Different Subdomains of the Endoplasmic Reticulum (2006)

Seeds of the tung tree (Vernicia fordii) produce large quantities of triacylglycerols (TAGs) containing approximately 80% eleostearic acid, an unusual conjugated fatty acid. We present a comparative analysis of the genetic, functional, and cellular properties of tung type 1 and type 2 diacylglycerol acyltransferases (DGAT1 and DGAT2), two unrelated enzymes that catalyze the committed step in TAG biosynthesis. We show that both enzymes are encoded by single genes and that DGAT1 is expressed at similar levels in various organs, whereas DGAT2 is strongly induced in developing seeds at the onset of oil biosynthesis. Expression of DGAT1 and DGAT2 in yeast produced different types and proportions of TAGs containing eleostearic acid, with DGAT2 possessing an enhanced propensity for the synthesis of trieleostearin, the main component of tung oil. Both DGAT1 and DGAT2 are located in distinct, dynamic regions of the endoplasmic reticulum (ER), and surprisingly, these regions do not overlap. Furthermore, although both DGAT1 and DGAT2 contain a similar C-terminal pentapeptide ER retrieval motif, this motif alone is not sufficient for their localization to specific regions of the ER. These data suggest that DGAT1 and DGAT2 have nonredundant functions in plants and that the production of storage oils, including those containing unusual fatty acids, occurs in distinct ER subdomains.
Detection of endotoxins and other pyrogens using human whole blood. (1999)

When cells of the immune system, i.e. primarily blood monocytes and macrophages, come into contact with pyrogens (fever-inducing contaminations) they release mediators transmitting the fever reaction through the organism to the thermoregulatory centres of the brain. The new test discussed here exploits this reaction for the detection of pyrogens: human whole blood taken from healthy volunteers is incubated in the presence of the test sample. If there is pyrogen contamination, the endogenous pyrogen interleukin-1 is released, which is then determined by ELISA. According to the pharmacopoeia, the rabbit pyrogen test determines the fever reaction following injection of a test sample. In comparison, the new whole blood assay is more sensitive, less expensive and determines the reaction of the targeted species. Compared to the well established in vitro alternative, i.e. the limulus amebocyte lysate assay (LAL), the new blood assay is not restricted to endotoxins of gram-negative bacteria, it is not affected by endotoxin-binding blood proteins and it reflects the potency of different endotoxin preparations in mammals. Here, interim results of the ongoing optimization and pre-validation are reported and the present state of the evaluation for biological and pharmaceutical drugs are presented.
The CRISPRdb database and tools to display CRISPRs and to generate dictionaries of spacers and repeats (2007)

It is hoped that availability of a public database, regularly updated and which can be queried on the web will help in further dissecting and understanding CRISPR structure and flanking sequences evolution. Subsequent analyses of the intra-species CRISPR polymorphism will be facilitated by CRISPRFinder and the dictionary creator. CRISPRdb is accessible at http://crispr.u-psud.fr/crispr.
Topical glycopyrrolate should not be overlooked in treatment of focal hyperhidrosis (2006)

Conflicts of interest: none declared. Sir, The recent review article by Lowe et al.1 on the place of botulinum toxin type A in the treatment of focal hyperhidrosis omits the topical antimuscarinic agent, glycopyrronium bromide. Topical glycopyrrolate (0·5–4% cream, solution or pads) is indicated mainly for the head and neck2, 3 and various types of gustatory sweating (compensatory,4 diabetic5 and Frey's)6 and, in our experience, is effective and well tolerated. EP and USP grade glycopyrrolate powder can be imported into the U.K. and the desired formulation prepared by ‘Special Order Manufacturers’ (SOMs). The cream formulation should use an acidic base, e.g. Unguentum M, to reduce drug hydrolysis and extend stability; a 3‐month expiry is given by some SOMs. The solution, on the other hand, has a shorter expiry, of 1 month, if pH‐stabilized and refrigerated. Glycopyrrolate may be used twice daily, but it is more usually applied at night. Care should be taken to avoid the nose, mouth, and particularly the eyes, where an inadvertent splash can cause failure to accommodate. Patients often experience a dry mouth and throat, and should be warned about that also. We advise not to wash treated skin for 3–4 h after application, and to store the drug in a cool place. If local prescribing authorities do not allow for provision of glycopyrrolate, it may be obtained by mail from Canada (at http://www.pharmacy.ca).
Durable Clinical Response of Refractory Hepatocellular Carcinoma to Orally Administered Thalidomide (2000)

Thalidomide, a sedative agent previously associated with severe fetal malformations, has anti-angiogenic activity. We describe the antitumor effects of thalidomide in a patient with hepatocellular carcinoma that was refractory to systemic and intraarterial therapy.
Expression of the hypoxia marker carbonic anhydrase IX is critically dependent on SP1 activity. Identification of a novel type of hypoxia-responsive enhancer. (2003)

In the present study, we further studied mechanisms of transcriptional regulation of the tumor-associated carbonic anhydrase IX (CAIX). We identified PR5 in the CA9 promoter as another SP1/SP3-binding site. As shown by electromobility shift assays and block-replacement mutagenesis, PR5 is functionally equivalent to the SP1/SP3-binding PR1 identified previously. However, there is a strong requirement for SP1/SP3 activity in the PR1 position, and SP1/SP3 activity from the PR5 position cannot compensate for this. In various cell lines, the expression of endogenous CAIX and activity of CA9 promoter constructs depend on SP1/SP3 activity as demonstrated by the dose-dependent inhibitory effect of the SP1 inhibitor mithramycin A. The two conditions of the induction of CAIX expression described previously differ in their sensitivity to mithramycin A inhibition; the hypoxia-mimic-induced expression is less sensitive than the cell density (mild hypoxia)-induced expression. Our present study highlights the importance of SP1/SP3 activity for CAIX expression and provides additional evidence for distinct mechanisms responsible for true and mild hypoxia-induced CAIX expression. The presence of a SP1/SP3-binding element in the PR1 position is absolutely required for mild hypoxia-induced activity, and it significantly up-regulates the true hypoxic induction. The SP1/SP3 and hypoxia-response element in the CA9 promoter thus may represent a novel type of enhancer capable of mounting responses to a wider range of hypoxic conditions.
Pattern Recognition Experiments in the Mandala/Cosine Domain (1983)

The problem of recognition of objects in images is investigated from the simultaneous viewpoints of image bandwidth compression and automatic target recognition. A scenario is suggested in which recognition is implemented on features in the block cosine transform domain which is useful for data compression as well. While most image frames would be processed by the automatic recognition algorithms in the compressed domain without need for image reconstruction, this still allows for visual image classification of targets with poor recognition rates (by human viewing at the receiving terminal). It has been found that the Mandala sorting of the block cosine domain results in a more effective domain for selecting target identification parameters. Useful features from this Mandala/cosine domain are developed based upon correlation parameters and homogeneity measures which appear to successfully discriminate between natural and man-made objects. The Bhattacharyya feature discriminator is used to provide a 10:1 compression of the feature space for implementation of simple statistical decision surfaces (Gaussian and minimum distance classification). Imagery sensed in the visible spectra with a resolution of approximately 5-10 ft is used to illustrate the success of the technique on targets such as ships to be separated from clouds. A data set of 38 images is used for experimental verification with typical classification results ranging from the high 80's to low 90 percentile regions depending on the options choosen.
Calcitroic acid, end product of renal metabolism of 1,25-dihydroxyvitamin D3 through the C-24 oxidation pathway (1989)

About a decade ago calcitroic acid was isolated as a major side chain cleaved water-soluble metabolite of 1,25-dihydroxyvitamin D3 [Esvelt, R. P., Schnoes, H. K., & Decula, H. F. (1979) Biochemistry 18, 3977]. Presently, calcitroic acid is being considered as the major excretory form of 1,25-dihydroxyvitamin D3. However, the exact site or sites of calcitroic acid production and the possible side chain modified intermediary metabolites that may be formed during the conversion of 1,25-dihydroxyvitamin D3 into calcitroic acid are not fully understood. In the mean time there have been many advances in our understanding of the side-chain metabolism of 1,25-dihydroxyvitamin D3. It is now well established that both the kidney and the intestine metabolize 1,25-dihydroxyvitamin D3 through the C-24 oxidation pathway according to the following steps: 1,25-dihydroxyvitamin D3----1,24,25-trihydroxyvitamin D3----1,25-dihydroxy-24-oxovitamin D3-----1,23,25-trihydroxy-24-oxovitamin D3. Recently, we identified 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3 (C-23 alcohol) as a major side chain cleaved lipid-soluble metabolite of 1,25-dihydroxyvitamin D3 and further extended the aforementioned C-24 oxidation pathway in the kidney by demonstrating 1,23,25-trihydroxy-24-oxovitamin D3 as the precursor of C-23 alcohol [Reddy, G. S., Tserng, K. Y., Thomas, B. R., Dayal, R., & Norman, A. W. (1987) Biochemistry 26, 324]. In this present study, we investigated the metabolic fate of 1,25-dihydroxyvitamin D3 (3 X 10(-10) M) in the perfused rat kidney and identified calcitroic acid as the major water-soluble metabolite of 1,25-dihydroxyvitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)