gebhart/patrepeval huggingface dataset:
Interleukin‐7 in the skin of Schistosoma mansoni‐infected mice is associated with a decrease in interferon‐γ production and leads to an aggravation of the disease (1997)

The effect of recombinant interleukin-7 (rIL-7) on the course of murine schistosomiasis and the development of the accompanying immune response were investigated. We demonstrated that IL-7 expression could be detected in the skin of infected mice from 1 to 21 days following infection. We here report that intradermal injection of exogenous human IL-7, prior to the penetration of the parasite into the skin, leads to a more severe liver pathology and an increased number of surviving adult parasites. In addition, injection of rIL-7 alters parasite migration (estimation of burdens of young larvae in lungs and liver). Administration of rIL-7 led to a decrease of IL-12 and interferon-gamma-(IFN-gamma) specific messengers RNA in skin and, more markedly, in skin-draining lymph nodes. The number of B220 expressing cells was increased, and T-cell number was reduced, in IL-7-treated infected mice. In addition, levels of IFN-gamma and IL-4 in sera were significantly reduced, whereas there was a shift from a Th1 to a Th2 type associated humoral response towards the egg antigens. Our experimental observation illustrate that the exogenous administration of rIL-7 affects both the development of the host's immune response and the behaviour of the parasite within the infected host. The early and specific production of IL-7 in the host skin, following infection with Schistosoma mansoni, raises fascinating questions concerning the relationships between the parasite and its host at the very beginning of their interaction.
Chromatographic analysis of the chiral and covalent instability of S-adenosyl-L-methionine (1986)

The chirality of biologically active S-adenosyl-L-methionine (AdoMet) is S,S, where the designations refer to the sulfur and the alpha-carbon, respectively. This paper describes a cation-exchange high-performance liquid chromatographic (HPLC) method for separating (S,S)-AdoMet from the biologically inactive (R,S)-AdoMet that results from racemization at the sulfur. This method was used to measure the rates of the degradation reactions of (S,S)-AdoMet as a function of pH. These reactions and the first-order rate constants, which were found at 37 degrees C and pH 7.5, are racemization, 1.8 X 10(-6) s-1; cleavage to homoserine lactone and 5'-(methylthio)adenosine, 4.6 X 10(-6) s-1; and hydrolysis to adenine and S-pentosylmethionine, 3 X 10(-6) s-1. Racemization showed no change in rate over the pH range from 7.5 to 1.5. The cleavage reaction persisted until the pH was lowered to 1.5, but hydrolysis ceased at pH 6. Commercial samples of nonradioactive AdoMet contained 20-30% (R,S)-AdoMet, while a sample of [methyl-3H]AdoMet had less than 1% (R,S)-AdoMet. Preparing enzyme substrates by mixing such samples will cause an underestimate of specific activity and an overestimate of the amount of product. The (R,S)-AdoMet/(S,S)-AdoMet ratio in mouse liver was 0.03, much less than the value of 0.19 calculated from the above rate constants. An enzyme extract from mouse liver did not degrade (R,S)-AdoMet, but a more thorough search may find such an activity. In any event, the cleavage and hydrolysis reactions partially balance the racemization of (S,S)-AdoMet in vivo and prevent excessive accumulation of (R,S)-AdoMet.
2  Surfactants and their applications (2003)

Surfactants form a unique class of chemical compounds. This review provides an introduction to the nature and physical properties of surfactants, emphasizing their ability to radically alter surface and interfacial properties and to self-associate and solubilize themselves in micelles. These properties provide the means to apply surfactants in wettability modification, detergency, and the displacement of liquid phases through porous media on one hand, and to stabilize dispersions (including foams, froths and emulsions), or to destabilize dispersions (again including foams and emulsions) on the other hand. These in turn lead to a vast array of practical application areas which are illustrated in terms of mineral and petroleum processing, biological systems, health and personal care products, foods, and crop protection.
Single-Cell TCR and Transcriptome Analysis: An Indispensable Tool for Studying T-Cell Biology and Cancer Immunotherapy (2021)

T cells have been known to be the driving force for immune response and cancer immunotherapy. Recent advances on single-cell sequencing techniques have empowered scientists to discover new biology at the single-cell level. Here, we review the single-cell techniques used for T-cell studies, including T-cell receptor (TCR) and transcriptome analysis. In addition, we summarize the approaches used for the identification of T-cell neoantigens, an important aspect for T-cell mediated cancer immunotherapy. More importantly, we discuss the applications of single-cell techniques for T-cell studies, including T-cell development and differentiation, as well as the role of T cells in autoimmunity, infectious disease and cancer immunotherapy. Taken together, this powerful tool not only can validate previous observation by conventional approaches, but also can pave the way for new discovery, such as previous unidentified T-cell subpopulations that potentially responsible for clinical outcomes in patients with autoimmunity or cancer.
KINECT 3: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Valbenazine (NBI-98854) for Tardive Dyskinesia (PL02.003) (2016)

Objective: To assess the efficacy, safety and tolerability of valbenazine (NBI-98854) for Tardive Dyskinesia (TD). Background: Valbenazine is a novel, highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor with favorable efficacy and safety profiles in Phase 1 and 2 studies. Methods: In this Phase 3, double-blind, parallel-group, six-week, placebo-controlled trial, subjects with moderate or severe neuroleptic-induced TD and underlying schizophrenia, schizoaffective disorder, or mood disorder were randomized 1:1:1 (placebo: 40mg valbenazine: 80mg valbenazine, once daily). The primary outcome was an intention-to-treat (ITT) analysis of change from baseline on the Abnormal Involuntary Movement Scale (AIMS) total score, assessed by blinded central raters, for the 80mg dose vs. placebo. Safety assessments included adverse event (AE) rates, laboratory, ECG, and psychiatric assessments. Results: Sixty-four sites randomized 234 subjects. Most subjects had schizophrenia (66[percnt]), and 86[percnt] were receiving stable doses of concomitant antipsychotic medications (16[percnt] typical, 77[percnt] atypical). The mean baseline AIMS score (SD) was 10.0 (4.0). Valbenazine 80mg resulted in a significant improvement in AIMS score vs. placebo (LS Mean change from baseline -3.2 vs. -0.1; P<0.0001). The AIMS score was also reduced in the 40mg group vs. placebo (LS Mean change from baseline -1.9 vs. -0.1; P=0.0021; full description of supportive analyses to be presented). Adverse events were similar among all groups and were consistent with those of prior studies; the most commonly reported AE was somnolence (80mg: 5[percnt], 40mg: 4[percnt], placebo: 4[percnt]). Three percent of subjects discontinued due to treatment-emergent AEs (80mg: 4[percnt], 40mg: 3[percnt], placebo: 3[percnt]). Conclusions: Once-daily administration of valbenazine 80mg was associated with a significant improvement in TD vs. placebo in subjects with schizophrenia, schizoaffective disorder or mood disorder. Both valbenazine doses were generally well tolerated, even as patients were taking a wide range of concomitant medications (including antipsychotic agents). Valbenazine is a promising therapy for TD.
DNA sequence variation in a negative control region 5' to the beta- globin gene correlates with the phenotypic expression of the beta s mutation (1992)

The clinical diversity of sickle cell anemia is strongly related to the degree of intracellular hemoglobin S (Hb S) polymerization, which in turn is dependent on the intracellular concentration of Hb S. We have recently defined a region of DNA approximately 500 bp 5' to the human beta-globin gene that acts as a silencer for the transcription of this gene and have shown that a polymorphism in this sequence is associated with a thalassemic phenotype of the beta-globin gene. In this work we have examined the correlation of DNA sequence polymorphisms in this silencer with binding of a previously identified putative repressor protein, BP1, and with the expression of Hb S in individuals heterozygous for the beta s allele. It was found that specific configurations of the motif, (AT)x(T)y, are homogeneous for the major haplotypes of the beta-globin gene cluster described on beta s chromosomes. Binding of BP1 was measured to DNA of three haplotypes: Indian, Benin, and Bantu. BP1 binds most tightly to DNA of the Indian haplotype, and these patients produce less beta s protein than Benin patients, whose DNA exhibits weaker affinity for BP1. Binding of BP1 is the weakest to DNA of the Bantu haplotype, which is associated with clinically more severe sickle cell symptoms. These data are consistent with the hypothesis that these polymorphisms may not be neutral and that the DNA sequence at this site may affect the expression of the beta s gene. Such an effect may be synergistic with other genetic variables, such as fetal hemoglobin levels, F-cell numbers, and the number of alpha-globin genes, in determining intracellular polymerization and, thus, the severity of the sickle cell syndromes.
Interleukin-1β-induced Cyclooxygenase-2 Expression Requires Activation of Both c-Jun NH2-terminal Kinase and p38 MAPK Signal Pathways in Rat Renal Mesangial Cells (1998)

The inflammatory cytokine interleukin-1beta (IL-1beta) induces cyclooxygenase-2 (Cox-2) expression with a concomitant release of prostaglandins from glomerular mesangial cells. We reported previously that IL-1beta rapidly activates the c-Jun NH2-terminal/stress-activated protein kinases (JNK/SAPK) and p38 mitogen-activated protein kinase (MAPK) and also induces Cox-2 expression and prostaglandin E2 (PGE2) production. The current study demonstrates that overexpression of the dominant negative form of JNK1 or p54 JNK2/SAPKbeta reduces Cox-2 expression and PGE2 production stimulated by IL-1beta. Similarly, overexpression of the kinase-dead form of p38 MAPK also inhibits IL-1beta-induced Cox-2 expression and PGE2 production. These results suggest that activation of both JNK/SAPK and p38 MAPK is required for Cox-2 expression after IL-1beta activation. Furthermore, our experiments confirm that IL-1beta activates MAP kinase kinase-4 (MKK4)/SEK1, MKK3, and MKK6 in renal mesangial cells. Overexpression of the dominant negative form of MKK4/SEK1 decreases IL-1beta- induced Cox-2 expression with inhibition of both JNK/SAPK and p38 MAPK phosphorylation. Overexpression of the kinase-dead form of MKK3 or MKK6 demonstrated that either of these two mutant kinases inhibited IL-1beta-induced p38 MAPK phosphorylation and Cox-2 expression but not JNK/SAPK phosphorylation and activation. This study suggests that the activation of both JNK/SAPK and p38 MAPK signaling cascades is required for IL-1beta-induced Cox-2 expression and PGE2 synthesis.
Binding of Adeno-associated Virus Type 5 to 2,3-Linked Sialic Acid Is Required for Gene Transfer (2001)

Recombinant adeno-associated viruses (AAV) are promising gene therapy vectors. Whereas AAV serotype 2-mediated gene transfer to muscle has partially replaced factor IX deficiency in hemophilia patients, its ability to mediate gene transfer to the lungs for cystic fibrosis is hindered by lack of apical receptors. However, AAV serotype 5 infects human airway epithelia from the lumenal surface. We found that in contrast to AAV2, the apical membrane of airway epithelia contains abundant high affinity receptors for AAV5. Binding and gene transfer with AAV5 was abolished by genetic or enzymatic removal of sialic acid from the cell surface. Furthermore, binding and gene transfer to airway epithelia was competed by lectins that specifically bind 2,3-linked sialic acid. These observations suggest that 2,3-linked sialic acid is either a receptor for AAV5 or it is a necessary component of a receptor complex. Further elucidation of the receptor for this virus should enhance understanding of parvovirus biology and expand the therapeutic targets for AAV vectors.
Oxidations of 17β-estradiol and estrone and their interconversions catalyzed by liver, mammary gland and mammary tumor after acute and chronic treatment of rats with indole-3-carbinol or β-naphthoflavone (2001)

Altered cytochrome P450-catalyzed metabolism of 17β-estradiol (E2) and estrone (E1) in the liver and (or) extrahepatic tissues may affect estrogen-sensitive tumorigenesis. We examined the effects of oral treatments of (i) indole-3-carbinol (I3C) at 250 or 500 mg/kg or β-naphthoflavone (β-NF) at 40 mg/kg of body weight (bw)/day from 51 to 54 days of age (acute regimen), and (ii) I3C at 250 mg/kg or β-NF at 20 mg/kg bw given 3x/week from 10 to 22 weeks of age (chronic regimen) in female Sprague-Dawley rats. We determined the effects of these treatments on the P450 content and P450 (CYP)-specific activities in the liver, P450-dependent metabolism of E2 and E1 by the liver and mammary gland, and interconversion of E1 and E2 catalyzed by 17β-hydroxysteroid dehydrogenase (17β-HSD) in these tissues and malignant mammary tumors. I3C at the two levels of acute regimen elicited similar responses. Acute and chronic treatments with I3C, but not β-NF, increased P450 content ~2-fold. I3C, and to a lesser extent β-NF, increased CYP1A1 and CYP1A2 probe activities in liver up to 117- and 27- fold, respectively, and after acute regimens, that of CYP3A by ~1.8-fold. I3C also increased activity of CYP2B up to 100-fold. Overall hepatic metabolism of E2 and E1, which was ~2-fold greater at 55 than 155 days of age, was increased (~2.8-fold) by I3C with 2-, 4-, 16α-, 6α-, 6β-, and 15α-hydroxy (OH) comprising [Formula: see text]54, 3, 2, ~2, ~5, 7, and 2%, respectively, of E1 and E2 metabolites. Acute regimens of β-NF increased 2- and 15α-OH-E2 (62 and 5% of total) from E2 and 2-, 4-, and 6α-OH-E1 + 6β-OH-E1 (32, 13, and 4% of total) from E1. Mammary gland metabolized E2 to E1 and small amounts of 15α-, 4-, 16α-, 6β-, and 6α-OH-E2. After the acute IC3 regimen, E2 was also converted to 2-OH-E2. 17β-HSD-catalyzed oxidation of E2 was favored in the liver and reduction of E1 was favored in mammary gland and tumor (= 1% of hepatic activity). An increased (~2-fold) ratio of reductive to oxidative activities in malignant mammary tumors by chronic I3C regimen may stimulate tumor growth. This is the first report showing that after chronic oral regimens, the I3C-, but not β-NF-, induced changes in CYP complement led to elevated E2 and E1 metabolism. The persistent effects of increased putative carcinogenic and estrogenic 4- and 16α-OH as well as 6α- and 6β-OH-E2 and 6β-OH-E1 might counteract those of the less estrogenic 2-OH metabolites, thus accounting for the lack of suppression of mammary tumorigenesis by I3C in our previous study.Key words: estrogen metabolism, P450, 17β-hydroxysteroid dehydrogenase, indole-3-carbinol, β-naphthoflavone.
Regulation and characterization of Thermobifida fusca carbohydrate‐binding module proteins E7 and E8 (2008)

E7, a single domain Family 33 cellulose binding module (CBM) protein, and E8, a non-catalytic, three-domain protein consisting of a Family 33 CBM, a FNIII domain, followed by a Family 2 CBM, were cloned, expressed, purified, and characterized. Western blots showed that E7 and E8 were induced and secreted when Thermobifida fusca was grown on cellobiose, Solka floc, switchgrass, or alfalfa as well as on beta-1,3 linked glucose molecules such as laminaribiose or pachyman. E8 bound well to alpha- and beta-chitin and bacterial microcrystalline cellulose (BMCC) at all pHs tested. E7 bound strongly to beta-chitin, less well to alpha-chitin and more weakly to BMCC than E8. Filter paper binding assays showed that E7 was 28% bound, E8 was 39% bound, a purified CBM2 binding domain from Cel6B was 88% bound, and only 5% of the Cel5A catalytic domain was bound. A C-terminal 6xHis tag influenced binding of both E7 and E8 to these substrates. Filter paper activity assays showed enhanced activity of T. fusca cellulases when E7 or E8 was present. This effect was observed at very low concentrations of cellulases or at very long times into the reaction and was mainly independent of the type of cellulase and the number of cellulases in the mixture. E8, and to a lesser extent E7, significantly enhanced the activity of Serratia marscescens Chitinase C on beta-chitin.
NDR1, a locus of Arabidopsis thaliana that is required for disease resistance to both a bacterial and a fungal pathogen. (1995)

We have employed Arabidopsis thaliana as a model host plant to genetically dissect the molecular pathways leading to disease resistance. A. thaliana accession Col-0 is susceptible to the bacterial pathogen Pseudomonas syringae pv. tomato strain DC3000 but resistant in a race-specific manner to DC3000 carrying any one of the cloned avirulence genes avrB, avrRpm1, avrRpt2, and avrPph3. Fast-neutron-mutagenized Col-0 M2 seed was screened to identify mutants susceptible to DC3000(avrB). Disease assays and analysis of in planta bacterial growth identified one mutant, ndr1-1 (nonrace-specific disease resistance), that was susceptible to DC3000 expressing any one of the four avirulence genes tested. Interestingly, a hypersensitive-like response was still induced by several of the strains. The ndr1-1 mutation also rendered the plant susceptible to several avirulent isolates of the fungal pathogen Peronospora parasitica. Genetic analysis of ndr1-1 demonstrated that the mutation segregated as a single recessive locus, located on chromosome III. Characterization of the ndr1-1 mutation suggests that a common step exists in pathways of resistance to two unrelated pathogens.
Equidistant path generation for improving scanning efficiency in layered manufacturing (2002)

Path generation is an important factor that affects the quality and efficiency of most laminated manufacturing processes such as SLS, SLA and FDM. This paper introduces an efficient path generation algorithm. The principle of the algorithm and its implementation are presented. A comparative study is used to analyze the effectiveness of this method. The results of comparison on both path length and processing time between the traditional method and the proposed method are discussed.
Analysis of the mechanisms of T cell-dependent polyclonal activation of human B cells. Induction of human B cell responses by fixed activated T cells (1991)

Coculture of resting human B cells with T cells stimulated with immobilized mAb to the CD3 molecular complex induces polyclonal activation and the production of Ig of all isotypes. The current experiments were carried out to determine the nature of the signals provided to B cells by the anti-CD3-activated T cells. For these experiments, fresh T cells or T cell clones were activated with immobilized mAb to CD3 and then fixed with 1% paraformaldehyde. Upon coculture, the fixed activated T cells or T cell clones induced B cell RNA synthesis and IL-2R expression, but only minimal DNA synthesis and no Ig production. Induction of B cell RNA synthesis by fixed activated T cells was not inhibited by mAb to the alpha-chain of the IL-2R, and was not enhanced by supplementing cultures with IL-2, IL-4, IL-6, or supernatants of mitogen-activated T cells. Upon the addition of IL-2, but not IL-4 or IL-6, to cultures of B cells and fixed activated T cells, sustained proliferation was noted along with the production of Ig. Control fixed T cells or T cell clones did not induce any of these responses. The presence of cycloheximide or cyclosporin A during the activation with anti-CD3 prevented T cells from developing the capacity to provide help for B cells. The use of mAb to a variety of cell surface molecules indicated that several T cell surface molecules including CD11a/CD18, CD44, CD54, and class I MHC molecules are involved in the induction of B cell responses. Among the mAb that inhibited B cell DNA synthesis and/or Ig production, only mAb to CD11a, CD18, or CD54 inhibited initial B cell activation as assessed by RNA synthesis. Even though mAB to CD11a/CD18 inhibited the capacity of fixed activated T cells to induce B cell responses, the finding that fixed activated CD18 deficit clones provided help for B cells indicated that expression of the beta 2 family of integrins by T cells was not necessary. These results indicate that activated T cells acquire the capacity to stimulate B cells polyclonally and induce cytokine responsiveness, proliferation, and Ig production by utilization of a variety of surface molecules. Moreover, these results indicate that the initial activation of the B cell is independent of the metabolic activity of the T cell and the production of cytokines.
Crystal structure of the catalytic domain of human tumor necrosis factor-α-converting enzyme (1998)

Tumor necrosis factor-alpha (TNFalpha) is a cytokine that induces protective inflammatory reactions and kills tumor cells but also causes severe damage when produced in excess, as in rheumatoid arthritis and septic shock. Soluble TNFalpha is released from its membrane-bound precursor by a membrane-anchored proteinase, recently identified as a multidomain metalloproteinase called TNFalpha-converting enzyme or TACE. We have cocrystallized the catalytic domain of TACE with a hydroxamic acid inhibitor and have solved its 2.0 A crystal structure. This structure reveals a polypeptide fold and a catalytic zinc environment resembling that of the snake venom metalloproteinases, identifying TACE as a member of the adamalysin/ADAM family. However, a number of large insertion loops generate unique surface features. The pro-TNFalpha cleavage site fits to the active site of TACE but seems also to be determined by its position relative to the base of the compact trimeric TNFalpha cone. The active-site cleft of TACE shares properties with the matrix metalloproteinases but exhibits unique features such as a deep S3' pocket merging with the S1' specificity pocket below the surface. The structure thus opens a different approach toward the design of specific synthetic TACE inhibitors, which could act as effective therapeutic agents in vivo to modulate TNFalpha-induced pathophysiological effects, and might also help to control related shedding processes.
Read Channel and Format for High-Density Magneto-Optical Disk System (1993)

Read/write technologies for the second-generation magneto-optical disk are developed. A large capacity of 1 GB on a 130-mm-diameter disk and high transfer rate of 2∼4 MB/s are attained by mark length recording and the zoned constant angular velocity (zoned CAV) method. Read technologies such as slice level adjustment in the direct slice detection method, the independent edge detection and resync patterns for DC free are combined with the (1-7) run-length limited (RLL) code to provide sufficient edge jitter margin of over 60% of the detection window.