gebhart/patrepeval huggingface dataset:
CD4 T Cell Cytokine Differentiation: The B Cell Activation Molecule, OX40 Ligand, Instructs CD4 T Cells to Express Interleukin 4 and Upregulates Expression of the Chemokine Receptor, Blr-1 (1998)

This report investigates the role of OX40 ligand (OX40L) and its receptor, OX40, expressed on activated B and T cells, respectively, in promoting the differentiation of T helper type 2 (Th2) CD4 T cells. These molecules are expressed in vivo by day 2 after priming with T cell- dependent antigens. Their expression coincides with the appearance of immunoglobulin (Ig)G switch transcripts and mRNA for interleukin (IL)-4 and interferon (IFN)-gamma, suggesting that this molecular interaction plays a role in early cognate interactions between B and T cells. In vitro, we report that costimulation of naive, CD62Lhigh CD4 T cells through OX40 promotes IL-4 expression and upregulates mRNA for the chemokine receptor, blr-1, whose ligand is expressed in B follicles and attracts lymphocytes to this location. Furthermore, T cell stimulation through OX40 inhibits IFN-gamma expression in both CD8 T cells and IL-12-stimulated CD4 T cells. Although this signal initiates IL-4 expression, IL-4 itself is strongly synergistic. Our data suggest that OX40L on antigen-activated B cells instructs naive T cells to differentiate into Th2 cells and migrate into B follicles, where T cell-dependent germinal centers develop.
Molecular cloning of a mouse submaxillary gland renin cDNA fragment. (1981)

The mRNA encoding mouse renin has been partially purified from total poly(A)-containing RNA of submaxillary glands of male Swiss mice. Corresponding cDNAs were cloned in the Pst I site of pBR322. Recombinants have been characterized by differential screening and hybrid-arrested translation. The DNA of clone pRn3-5 has been used to study the expression of renin mRNA in the submaxillary gland and in the kidney of different mouse strains. The renin mRNA from submaxillary gland and kidney have the same length (1600 nucleotides) and appear to be the products of the same gene. In vitro translation of mRNAs and RNA blotting experiments have shown that renin mRNA sequences are accumulated in the submaxillary gland of males of AKR and Swiss strains but not in the gland of male BALB/c.
Single-Nucleotide Polymorphisms and Haplotype Analysis in β -Defensin Genes in Different Ethnic Populations (2002)

Beta-defensins are cationic antimicrobial peptides expressed by epithelial cells and exhibit antibacterial, antifungal, and antiviral properties. The defensins are part of the innate host defense network and may have a significant protective role in the oral cavity and other mucosa. Defects or alteration in expression of the beta-defensins may be associated with susceptibility to infection and mucosal disorders. We examined the occurrence of single-nucleotide polymorphisms (SNPs) in the human beta-defensin genes DEFB1 and DEFB2 encoding human beta-defensin-1 and -2 (hBD-1, hBD-2), respectively, in five ethnic populations and defined haplotypes in these populations. Fifteen SNPs were identified in both DEFB1 and DEFB2. Coding region SNPs were found in very low frequency in both genes. One nonsynonymous DEFB1 SNP, G1654A (Val --> Ile), and one nonsynonymous DEFB2 SNP, T2312A (Leu --> His), were identified. Seven sites in each gene exhibited statistically significant differences in frequency between ethnic groups, with the greatest variation in the promoter and in the 5'-untranslated region of DEFB1. DEFB1 displayed 10 common haplotypes, including one cosmopolitan haplotype. Eight common haplotypes were found in DEFB2, including one cosmopolitan haplotype shared among all five ethnic groups. Our results show that genotypic variability among ethnic groups will need to be addressed when performing associative genetic studies of innate defense mechanisms and susceptibility to disease.
Single-chain Fv with manifold N-glycans as bifunctional scaffolds for immunomolecules (1998)

Unlike natural antibodies, single-chain Fv (sFv) proteins normally lack asparagine-linked glycosylation. Many designed immunoconjugates and other therapeutics currently employ the advantageous conjugation chemistry or targeting properties provided by the glycoprotein oligosaccharide domain. sFv proteins with engineered N-glycan designs were evaluated in Pichia pastoris for glycosylation efficiency, expression level, oligosaccharide chain length and composition, and affinity. In contrast to nearly all natural glycoproteins, the engineered attachment of N-glycans conveniently near the polypeptide C-terminus was found to produce the optimal results. Furthermore, the percentage modification and chain length of the attached mannose chains were controllable by the use of tandem and overlapping Asn-X-Thr tripeptide sites. The glycosylated sFv mannose chains could be effectively conjugated to polyethylene glycol and the resulting conjugate displayed a 10-fold increased circulating life in mice. The potential to control polymer:sFv or drug:sFv molar ratios by site-specific conjugation may substantially improve the therapeutic efficacy of these minimal antigen-binding molecules.
The synthesis of β-amyrin (1968)

18α-Olean-12-ene, which is in acid-catalysed equilibrium with olean-13(18)-ene (δ-amyrene), has been converted in several steps into olean-12-ene (β-amyrene). Transformation of this hydrocarbon into its 11α-hydroxyderivative and photolysis of the nitrite of the latter gave 11α-hydroxy-1-oximino-olean-12-ene. This oxime has been hydrolysed and further processed to furnish olean-12-en-1-one. Several methods have been developed to change the 1-oxo into a 3-oxo-function and vice versa. Since olean-12-en-3-one has already been reduced to β-amyrin and olean-13(18)-ene has been synthesised, our work constitutes a synthesis of β-amyrin.Related studies on the photolysis of 11β-hydroxyolean-12-ene nitrite and on the interrelationship of the 1- and 3-oxo-groups in the lanostane series are also recorded.
Legionella pneumophilaReplication in Macrophages Inhibited by Selective Immunomodulatory Effects on Cytokine Formation by Epigallocatechin Gallate, a Major Form of Tea Catechins (2001)

Epigallocatechin gallate (EGCg) is a major form of tea catechin and has a variety of biological activities, including antitumor as well as antimicrobial activity against some pathogens. Although the biological activities of EGCg have been extensively studied, its immunological effects are not well known. In the present study, the ability of EGCg to modulate macrophage immune functions in an in vitro Legionella pneumophila infection model of macrophages was examined. The study showed that EGCg inhibited the growth of L. pneumophila in macrophages at a concentration as low as 0.5 microg/ml without any direct antibacterial effect on the organisms. The EGCg selectively upregulated the production of interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-alpha) and downregulated IL-10 production of macrophages induced by L. pneumophila infection in a dose-dependent manner, but did not alter IL-6 production even at a high dose. The upregulation of the levels of macrophage gamma interferon (IFN-gamma) mRNA by EGCg was also demonstrated. Treatment of macrophage cultures with anti-TNF-alpha and anti-IFN-gamma monoclonal antibodies markedly abolished the anti-L. pneumophila activity of macrophages induced by the EGCg treatment. These results indicate that EGCg selectively alters the immune responses of macrophages to L. pneumophila and leads to an enhanced anti-L. pneumophila activity of macrophages mediated by enhanced production of both TNF-alpha and IFN-gamma. However, the enhancement of in vitro anti-L. pneumophila activity by EGCg may not be directly mediated by IL-10 and IL-12 production modulation. Thus, the results of this study revealed the immunomodulatory effect of EGCg on macrophages, which have a critical role in infections.
Mutual Synchronization of Geographically Separated Oscillators (1966)

A control scheme for synchronizing the frequencies of geographically separated oscillators connected by communication links consists of averaging the phases received at each station from remote oscillators, comparing the result with the local phase, and applying the filtered error signal as a correction to the local oscillator frequency. The system was studied by V. E. Beneš who found a sufficient condition for the stability of the system using advanced mathematical techniques. In this paper, the stability condition is derived (for a slightly more general control scheme) using only the transfer function concept of linear systems and some properties of determinants. A practical difficulty regarding the final frequency of the oscillators is discussed and a modification of the control scheme is shown to alleviate the difficulty. Also examined are the questions of sensitivity to parameter changes, the effect of jitter noise on the performance of the system, and the effect of failure of an oscillator or transmission link.
Cloning and high‐level expression of a chloroperoxidase gene from Pseudomonas pyrrocinia in Escherichia coli (1988)

A chloroperoxidase gene from Pseudomonas pyrrocinia was cloned into Escherichia coli using the cosmid vector pJB8. The gene coding for the chloroperoxidase could be localized to a 1.5 kb fragment of DNA which was subcloned into the high-copy-number plasmid pUC18. In one subclone increased halogenating activity could be found which was 570-fold greater than in P. pyrrocinia. The halogenating enzyme was identified as the chloroperoxidase by SDS-polyacrylamide gel electrophoresis.
Peptidylarginine Deiminase Inhibition Reduces Vascular Damage and Modulates Innate Immune Responses in Murine Models of Atherosclerosis (2014)

Pharmacological interventions that block NET formation can reduce atherosclerosis burden and arterial thrombosis in murine systems. These results support a role for aberrant NET formation in the pathogenesis of atherosclerosis through modulation of innate immune responses.
Synthesis and biological evaluation of substituted benzo[h]cinnolinones and 3H-benzo[6,7]cyclohepta[1,2-c]pyridazinones: higher homologs of the antihypertensive and antithrombotic 5H-indeno[1,2-c]pyridazinones (1989)

Several substituted benzo[h]cinnolinones 3 and 3H-benzo[6,7]cyclohepta[1,2-c]pyridazinones 4, which were designed as less rigid congeners of 5H-indeno[1,2-c]pyridazinones 2, were synthesized and tested as antihypertensive, inotropic, antithrombotic, antiinflammatory, and antiulcer agents. While the seven-membered ring derivatives displayed only antithrombotic properties, which were comparable to that of acetylsalicylic acid, most of the benzo[h]cinnolinones exhibited significant antihypertensive, inotropic, and antithrombotic properties. In this respect, the 8-amino (3b) and 8-acetylamino (3c) together with the 4,4a-dehydro analogue of 3c (11) were found to possess the most potent and long-lasting antihypertensive activity. In particular, the dextro isomer of 3c was more active than the racemic form, with lower tachycardiac effects. Unlike the lower homologues 2, none of the compounds showed significant antiinflammatory or antiulcer activity.
2,3,5-Tri-O-benzyl-D-ribosyl and -L-arabinosyl Bromides (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT2,3,5-Tri-O-benzyl-D-ribosyl and -L-arabinosyl BromidesROBERT BARKER and HEWITT G. FLETCHER Jr.Cite this: J. Org. Chem. 1961, 26, 11, 4605–4609Publication Date (Print):November 1, 1961Publication History Published online1 May 2002Published inissue 1 November 1961https://doi.org/10.1021/jo01069a095RIGHTS & PERMISSIONSArticle Views1635Altmetric-Citations196LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (664 KB) Get e-Alerts Get e-Alerts
NetSTAT: a network-based intrusion detection approach (2002)

Network-based attacks have become common and sophisticated. For this reason, intrusion detection systems are now shifting their focus from the hosts and their operating systems to the network itself. Network-based intrusion detection is challenging because network auditing produces large amounts of data, and different events related to a single intrusion may be visible in different places on the network. This paper presents NetSTAT, a new approach to network intrusion detection. By using a formal model of both the network and the attacks, NetSTAT is able to determine which network events have to be monitored and where they can be monitored.
Distinct Effects of Surfactant Protein A or D Deficiency During Bacterial Infection on the Lung (2000)

Mice lacking surfactant protein (SP)-A (SP-A-/-) or SP-D (SP-D-/-) and wild-type mice were infected with group B streptococcus or Haemophilus influenzae by intratracheal instillation. Although decreased killing of group B streptococcus and H. influenzae was observed in SP-A-/- mice but not in SP-D-/- mice, deficiency of either SP-A or SP-D was associated with increased inflammation and inflammatory cell recruitment in the lung after infection. Deficient uptake of bacteria by alveolar macrophages was observed in both SP-A- and SP-D-deficient mice. Isolated alveolar macrophages from SP-A-/- mice generated significantly less, whereas those from SP-D-/- mice generated significantly greater superoxide and hydrogen peroxide compared with wild-type alveolar macrophages. In SP-D-/- mice, bacterial killing was associated with increased lung inflammation, increased oxidant production, and decreased macrophage phagocytosis. In contrast, in the absence of SP-A, bacterial killing was decreased and associated with increased lung inflammation, decreased oxidant production, and decreased macrophage phagocytosis. Increased oxidant production likely contributes to effective bacterial killing in the lungs of SP-D-/- mice. The collectins, SP-A and SP-D, play distinct roles during bacterial infection of the lung.
Use of progesterone and progestin analogs for inhibition of preterm birth and other uterine contractility disorders. (2012)

In this paper we focus on preterm birth as a uterine contractility disorder caused by hypercontractility of the -myometrium. We describe changes in uterine function during term and preterm labor and delivery. We also examine the usefulness of measurement of uterine electromyographic (EMG) activity, noninvasively monitored from the -abdominal surface of pregnant patients. The use of progesterone treatment for preterm birth is discussed and we conclude that present therapies with progesterone could be improved by changing the route of administration. -Finally we show the results of recent studies that show that progesterone injections completely inhibit uterine EMG activity when given several days to hours before normal delivery. These studies illustrate how progesterone suppresses labor at term or preterm, probably through repression of genes which control excitability and conduction of electrical activity. However, direct profusion of soluble progesterone into the uterine cavity has little immediate inhibitory action and this may demonstrate that progesterone has no direct, nongenomic effects, at least in the rat model used. Further studies are required to determine the effects of progesterone on human uterine EMG activity and whether progesterone treatments will prevent preterm birth.
The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of RO5068760, an MEK Inhibitor, in Healthy Volunteers: Assessment of Target Suppression (2010)

RO5068760, a substituted hydantoin, represents a new class of potent, highly selective, non-adenosine triphosphate (ATP)-competitive MEK1/2 inhibitors. The study aimed to determine the safety/tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of RO5068760 in human healthy volunteers. All participants received a single dose followed by 48 hours of pharmacokinetics, pharmacodynamics, and safety/tolerability assessments. The pharmacodynamics were measured by changes in ERK phosphorylation (pERK) in peripheral blood mononuclear cells, ex vivo stimulated by phorbol 12-myristate 13-acetate (PMA). Forty-eight participants received 6 doses (50, 100, 200, 400, 600, 800 mg). RO5068760 was well tolerated up to 800 mg. There were no clinically significant safety findings, including laboratory, electrocardiogram, ophthalmological assessment, and fecal occult blood tests. Of the total 13 adverse events (n = 12), 11 were mild, 2 were moderate, and none were severe, and only 5 were considered by the investigator as possibly related to treatment. RO5068760 was absorbed with a t(max), of 2 hours. Disposition appeared to be biphasic with a terminal elimination t(1/2) of 5 to 9 hours. The variability was moderate to high, ranging from 38% to 62% for C(max) and 41% to 69% AUC. Within the dose range tested, pERK inhibition was relatively modest with a mean maximal pERK suppression of 55%.
Ultra-early clot aspiration after lysis with tissue plasminogen activator in a porcine model of intracerebral hemorrhage: edema reduction and blood-brain barrier protection (1999)

Hematomas were quickly and easily aspirated after treatment with tPA, resulting in significant reductions in mass effect. Hematoma aspiration after fibrinolysis with tPA enabled removal of the bulk of the hematoma (> 70%), markedly reduced perihematomal edema, and prevented the development of vasogenic edema. These findings in a large-animal model of ICH provide support for clinical trials that include the use of fibrinolytic agents and ultra-early stereotactically guided clot aspiration for treating ICH.
Identification of thrombin activatable fibrinolysis inhibitor (TAFI) in human platelets (2003)

Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme that after activation down-regulates fibrinolysis. Platelets are known to contain antifibrinolytic factors that are secreted during platelet activation. Therefore, the presence of TAFI in platelets was analyzed. TAFI was identified in platelets in a concentration of about 50 ng/1 x 109 platelets and was secreted on platelet activation. Thrombin-mediated activation of platelet-derived TAFI resembled that of plasma-derived TAFI with respect to stimulation by thrombomodulin and spontaneous loss of activity at 37 degrees C. The different glycosylation of platelet-derived TAFI compared with plasma-derived TAFI suggests that platelet-derived TAFI is synthesized in the megakaryocyte. This suggestion was substantiated by the detection of mRNA in the megakaryocytic cell lines DAMI and CHRF, representing the intermediate and late stages of megakaryocyte development. These results establish the presence of TAFI in platelets and suggest a role for platelet-derived TAFI in the protection of the clot against fibrinolysis.
The Pan-B Cell Marker CD22 Is Expressed on Gastrointestinal Eosinophils and Negatively Regulates Tissue Eosinophilia (2011)

CD22 is currently recognized as a B cell-specific Siglec and has been exploited therapeutically with humanized anti-CD22 mAb having been used against B cell leukemia. In this study, tissue-specific eosinophil mRNA microarray analysis identified that CD22 transcript levels of murine gastrointestinal (GI) eosinophils are 10-fold higher than those of lung eosinophils. To confirm the mRNA data at the protein level, we developed a FACS-based protocol designed to phenotype live GI eosinophils isolated from the murine lamina propria. Indeed, we found that jejunum eosinophils expressed remarkably high levels of surface CD22, similar to levels found in B cells across multiple mouse strains. In contrast, CD22 was undetectable on eosinophils from the colon, blood, thymus, spleen, uterus, peritoneal cavity, and allergen-challenged lung. Eosinophils isolated from newborn mice did not express CD22 but subsequently upregulated CD22 expression to adult levels within the first 10 d after birth. The GI lamina propria from CD22 gene-targeted mice harbored more eosinophils than wild type control mice, whereas the GI eosinophil turnover rate was unaltered in the absence of CD22. Our findings identify a novel expression pattern and tissue eosinophilia-regulating function for the "B cell-specific" inhibitory molecule CD22 on GI eosinophils.
Turbidimetric assessment of the compatibility of taxol with selected other drugs during simulated Y-site injection (1992)

The compatibility of taxol in 5% dextrose injection with each of 17 other drugs during simulated Y-site injection was studied through visual and turbidimetric assessment. A 4-mL sample of taxol 1.2 mg/mL in 5% dextrose injection was combined with a 4-mL sample of each of 17 drugs at concentrations that are used clinically. Each combination was prepared in duplicate, with the order of mixing reversed between the two samples. The samples were inspected visually in normal fluorescent light, in high-intensity light, and against light and dark backgrounds with a 3-diopter magnification lens initially and at 30 minutes, one hour, and four hours. A turbidimeter was used to measure the turbidity of each drug combination in triplicate initially and at one and four hours after mixing. None of the drug combinations resulted in visual evidence of precipitation, color change, or gas production, and the turbidity was essentially unchanged over the four-hour observation period. Taxol 1.2 mg/mL in 5% dextrose injection exhibited no visual or turbidimetric evidence of incompatibility when combined with each of 17 other drugs during simulated Y-site injection. However, drug combinations for which no visual or turbidimetric incompatibility is apparent may not be chemically stable; therefore, practitioners should be cautious in applying these findings to the clinical setting.
Rural “expert” system (1987)

A university course offered to rural teachers of the gifted was the medium through which a parent/teacher organization was formed. The Respond/Read/Replicate/Report System was used to develop course objectives, methods, and evaluative means reflective of the individual needs of the teachers, their gifted students, and their parents in rural Madison, Florida. The unique characteristics of the delivery system and the unusual collaborative efforts of university and community officials are described.