gebhart/patrepeval huggingface dataset:
Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide prevent inducible nitric oxide synthase transcription in macrophages by inhibiting NF-kappa B and IFN regulatory factor 1 activation. (1999)

High-output nitric oxide (NO) production from activated macrophages, resulting from the induction of inducible NO synthase (iNOS) expression, represents a major mechanism for macrophage cytotoxicity against pathogens. However, despite its beneficial role in host defense, sustained high-output NO production was also implicated in a variety of acute inflammatory diseases and autoimmune diseases. Therefore, the down-regulation of iNOS expression during an inflammatory process plays a significant physiological role. This study examines the role of two immunomodulatory neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP), on NO production by LPS-, IFN-gamma-, and LPS/IFN-gamma-stimulated peritoneal macrophages and the Raw 264.7 cell line. Both VIP and PACAP inhibit NO production in a dose- and time-dependent manner by reducing iNOS expression at protein and mRNA level. VPAC1, the type 1 VIP receptor, which is constitutively expressed in macrophages, and to a lesser degree VPAC2, the type 2 VIP receptor, which is induced upon macrophage activation, mediate the effect of VIP/PACAP. VIP/PACAP inhibit iNOS expression and activity both in vivo and in vitro. Two transduction pathways appear to be involved, a cAMP-dependent pathway that preferentially inhibits IFN regulatory factor-1 transactivation and a cAMP-independent pathway that blocks NF-kappa B binding to the iNOS promoter. The down-regulation of iNOS expression, together with previously reported inhibitory effects on the production of the proinflammatory cytokines IL-6, TNF-alpha, and IL-12, and the stimulation of the anti-inflammatory IL-10, define VIP and PACAP as "macrophage deactivating factors" with significant physiological relevance.
Surface plasmon polariton excitation by electrostatic modulation and phase grating in indium-tin-oxide coated lithium niobate slabs (2015)

Excitation of surface plasmon polaritons (SPPs) in a non-metal system in visible regime is discussed. With the assistance of phase grating resulted from photorefractive effect and electrostatic modulation of ITO induced by strong photovoltaic effect in iron-doped LiNbO3, phase matching condition could be satisfied for SPP excitation in this semiconductor/dielectric system. Both the phase grating instead of metal grating and electrostatic modulation of semiconductor could be used for the design of tunable plasmonic devices based on nonlinear photorefractive crystals.
gp130 AND THE INTERLEUKIN-6 FAMILY OF CYTOKINES (1997)

Receptors for most interleukins and cytokines that regulate immune and hematopoietic systems belong to the class I cytokine receptor family. These molecules form multichain receptor complexes in order to exhibit high-affinity binding to, and mediate biological functions of, their respective cytokines. In most cases, these functional receptor complexes share common signal transducing receptor components that are also in the class I cytokine receptor family, i.e. gp130, common beta, and common gamma molecules. Interleukin-6 and related cytokines, interleukin-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin-1 are all pleiotropic and exhibit overlapping biological functions. Functional receptor complexes for this interleukin-6 family of cytokines share gp130 as a component critical for signal transduction. Unlike cytokines sharing common beta and common gamma chains that mainly function in hematopoietic and lymphoid cell systems, the interleukin-6 family of cytokines function extensively outside these systems as well, e.g. from the cardiovascular to the nervous system, owing to ubiquitously expressed gp130. Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. Although gp130 and its dimer partners possess no intrinsic tyrosine kinase domain, the dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. This paper reviews recent progress in the study of the interleukin-6 family of cytokines and gp130.
DNA-dependent protein kinase is activated by nicks and larger single-stranded gaps (1994)

DNA-PK is a DNA-activated serine/threonine protein kinase capable of phosphorylating a number of nuclear DNA-binding proteins. Purified human DNA-PK has two subunits, a 350-kDa polypeptide, Prkdc, which binds ATP and is presumed to contain the catalytic site, and the Ku autoantigen which mediates DNA binding and activation. Previous studies have shown that DNA-PK is activated in vitro by linear double-stranded DNA fragments; however, the Ku subunit binds a broader range of DNA structures. Here we show that EBP-80, a protein originally isolated as a transcription factor for a retroviral long terminal repeat element and subsequently found to be similar to if not identical with Ku, also mediates kinase activation. The EBP-80-Prkdc complex is activated by nanomolar concentrations of DNA constructs containing single-to-double strand transitions, including a closed stem-loop structure and single strand gaps of 0 (nick), 6, and 30 nucleotides. Kinase activation parallels the ability of EBP-80 to bind these and other constructs. Our results extend the range of DNA configurations known to activate DNA-PK and are consistent with the participation of this enzyme complex in several nuclear functions.
White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer (2020)

Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.
Preparation of immunotherapeutic autologous tumor cell vaccines from solid tumors. (1979)

Abstract Comparisons of mechanical and various enzymatic methods of disaggregation of solid tumor were made for the purpose of producing a tumor cell suspension, which would be effective as an immunotherapeutic, autologous tumor cell vaccine when admixed with Bacillus Calmette-Guerin (BCG). Transplantable L10 hepatocarcinoma, syngeneic in strain 2 guinea pigs, grows in either ascites or solid form. The solid tumor grown in the muscle was used for evaluation of dissociation procedures. Trypsin, collagenase type I, collagenase type III, collagenase type I combined with hyaluronidase, and mechanical procedures were used under various conditions, and the cell suspensions were compared for cell yield per g tumor, percentage of viability, and membrane tumor-specific antigen. Of the methods tested, the enzymatic procedure utilizing collagenase type I exhibited the greatest potential to dissociate solid tumor with the least destruction or loss of tumor cell surface antigen. A vaccine of BCG admixed with irradiated solid tumor dissociated L10 cells had a therapeutic effect on subclinical, disseminated micrometastasis. Inbred strain 2 guinea pigs given i.v. injections of either 10 4 , 10 5 , or 10 6 syngeneic L10 hepatocarcinoma cells were treated with the BCG plus tumor cell vaccine after metastatic foci were established in the lung parenchyma. The results show that under defined conditions of preparation and administration, the nontumorigenic vaccines of BCG and tumor cells dissociated from solid tumors effect a highly significant survival rate in animals bearing otherwise lethal visceral metastasis.
Domain Structure of the NRIF3 Family of Coregulators Suggests Potential Dual Roles in Transcriptional Regulation (2001)

The identification of a novel coregulator for nuclear hormone receptors, designated NRIF3, was recently reported (D. Li et al., Mol. Cell. Biol. 19:7191-7202, 1999). Unlike most known coactivators, NRIF3 exhibits a distinct receptor specificity in interacting with and potentiating the activity of only TRs and RXRs but not other examined nuclear receptors. However, the molecular basis underlying such specificity is unclear. In this report, we extended our study of NRIF3-receptor interactions. Our results suggest a bivalent interaction model, where a single NRIF3 molecule utilizes both the C-terminal LXXIL (receptor-interacting domain 1 [RID1]) and the N-terminal LXXLL (RID2) modules to cooperatively interact with TR or RXR (presumably a receptor dimer), with the spacing between RID1 and RID2 playing an important role in influencing the affinity of the interactions. During the course of these studies, we also uncovered an NRIF3-NRIF3 interaction domain. Deletion and mutagenesis analyses mapped the dimerization domain to a region in the middle of NRIF3 (residues 84 to 112), which is predicted to form a coiled-coil structure and contains a putative leucine zipper-like motif. By using Gal4 fusion constructs, we identified an autonomous transactivation domain (AD1) at the C terminus of NRIF3. Somewhat surprisingly, full-length NRIF3 fused to the DNA-binding domain of Gal4 was found to repress transcription of a Gal4 reporter. Further analyses mapped a novel repression domain (RepD1) to a small region at the N-terminal portion of NRIF3 (residues 20 to 50). The NRIF3 gene encodes at least two additional isoforms due to alternative splicing. These two isoforms contain the same RepD1 region as NRIF3. Consistent with this, Gal4 fusions of these two isoforms were also found to repress transcription. Cotransfection of NRIF3 or its two isoforms did not relieve the transrepression function mediated by their corresponding Gal4 fusion proteins, suggesting that the repression involves a mechanism(s) other than the recruitment of a titratable corepressor. Interestingly, a single amino acid residue change of a potential phosphorylation site in RepD1 (Ser(28) to Ala) abolishes its transrepression function, suggesting that the coregulatory property of NRIF3 (or its isoforms) might be subjected to regulation by cellular signaling. Taken together, our results identify NRIF3 as an interesting coregulator that possesses both transactivation and transrepression domains and/or functions. Collectively, the NRIF3 family of coregulators (which includes NRIF3 and its other isoforms) may play dual roles in mediating both positive and negative regulatory effects on gene expression.
O01 TRANSCRIPTION FACTOR XBP1 REGULATES PANETH CELL FUNCTION AND INFLAMMATION IN THE INTESTINE (2007)

Although infliximab (IFX) is used in clinical practice for >7 years, only few data are available on the efficacy long-term. Aims: To determine efficacy of IFX in Crohn' s disease (CD) long-term. Methods: In the first 440 out of 562 CD patients treated with IFX for luminal (n=359) or fistulizing (n=81) CD, long-term follow-up was completed up to June 2006. Treatment was episodic in 213 (48%), scheduled in 108 (25%) and episodic with switch to maintenance in 119 patients (27%). Concomitant medication was AZA in 228 (52%), MTX in 46 (10.5%) and corticosteroids (CS) in 162 patients (37%). Shortening of the interval between infusions or increase of dose of IFX were considered therapeutic intervention. Results: A total of 5.029 IFX infusions (median per patient 8, IQR 3-16) were administered over a median of 41 months (IQR 21-69). Median disease duration until 1st IFX was 7.7 years (IQR 3.1-14.7). A long-term benefit to IFX was observed in 60% of patients (n=262), of whom 42% (n=186) had a sustained benefit on ongoing IFX and in 17% (n=76) IFX could be stopped. Of the latter, 91% were still in remission at latest follow-up (n=46 on AZA, n=11 on MTX and 12 no therapy). The majority (64%) did not need interventions to maintain continued response, 28% needed 1 or 2 and only 7% needed 3 or more. Once patients started with IFX and responded initially, median duration of continued response was 132 weeks (IQR 57-239). Of all patients on CS at 1st IFX, 73% were weaned completely and did not need retreatment. Only 8% were judged primary non-responders after a maximum of 3 infusions. 40 patients (9%) had to stop IFX definitely due to side effects (19 severe infusion reactions, 20 delayed hypersensitivity, 14 other severe adverse events). In 85 patients (19%), a definitive change in therapy was necessary primarily due to loss of response. Of the 35 primary non-responders, 18 (51%) needed major abdominal surgery, compared to 21% (87/405) of the responders (Odds ratio 3.87 (95%CI 1.91-7.83), p<0.001). Conclusions: This is the largest single center experience on the long-term outcome of IFX in patients with CD. With a median follow-up of 41 months, 60% of patients report a sustained benefit with IFX and 73% could completely stop steroids. Loss of response is usually managed with therapeutic intervention with need for discontinuation in only 19% of patients so far. Almost one third of patients with sustained benefit (29%) were able to discontinue IFX, with sustained disease control for a median of 23.6 months after stop of IFX . Primary non-response to IFX was associated with increased risk of abdominal complications needing surgical intervention.
Characterization of a Corynebacterium glutamicum Lactate Utilization Operon Induced during Temperature-Triggered Glutamate Production (2005)

Gene expression changes of glutamate-producing Corynebacterium glutamicum were identified in transcriptome comparisons by DNA microarray analysis. During glutamate production induced by a temperature shift, C. glutamicum strain 2262 showed significantly higher mRNA levels of the NCgl2816 and NCgl2817 genes than its non-glutamate-producing derivative 2262NP. Reverse transcription-PCR analysis showed that the two genes together constitute an operon. NCgl2816 putatively codes for a lactate permease, while NCgl2817 was demonstrated to encode quinone-dependent l-lactate dehydrogenase, which was named LldD. C. glutamicum LldD displayed Michaelis-Menten kinetics for the substrate l-lactate with a K(m) of about 0.51 mM. The specific activity of LldD was about 10-fold higher during growth on l-lactate or on an l-lactate-glucose mixture than during growth on glucose, d-lactate, or pyruvate, while the specific activity of quinone-dependent d-lactate dehydrogenase differed little with the carbon source. RNA levels of NCgl2816 and lldD were about 18-fold higher during growth on l-lactate than on pyruvate. Disruption of the NCgl2816-lldD operon resulted in loss of the ability to utilize l-lactate as the sole carbon source. Expression of lldD restored l-lactate utilization, indicating that the function of the permease gene NCgl2816 is dispensable, while LldD is essential, for growth of C. glutamicum on l-lactate.
Bloat in Cattle and Composition of Rumen Gases (1943)

Summary The hydrogen sulfide content of the rumen gas of bloated and nonbloated cows on alfalfa pasture was measured in 8 trials by an iodometric method especially adapted for this purpose. The rumen gas contained, on the average of 26 titrations, 0.11 ± 0.01 per cent hydrogen sulfide by volume. There was no relation between hydrogen sulfide concentration and bloat. The rumen gas contained on the average 67 per cent carbon dioxide, 26 per cent methane, and less than 1 per cent oxygen. The concentration of these gases was not related to bloat. This result supports the theory that bloat is caused, not by abnormal gas formation, but by a lack of belching.
Differential Interactions Between Beclin 1 and Bcl-2 Family Members (2007)

Autophagy, a cellular degradation system, promotes both cell death and survival. The interaction between Bcl-2 family proteins and Beclin 1, a Bcl-2 interacting protein that promotes autophagy, can mediate crosstalk between autophagy and apoptosis. We investigated the interaction between anti-and pro-apoptotic Bcl-2 proteins with Beclin 1. Our results show that Beclin 1 directly interacts with Bcl-2, Bcl-x(L), Bcl-w and to a lesser extent with Mcl-1. Beclin 1 does not bind the pro-apoptotic Bcl-2 proteins. The interaction between Beclin 1 and the anti-apoptotic protein Bcl-x(L) was inhibited by BH3-only proteins, but not by multi-domain proteins. Sequence alignment and structural modeling suggest that Beclin 1 contains a putative BH3-like domain which may interact with the hydrophobic grove of Bcl-x(L). Mutation of the Beclin 1 amino acids predicted to mediate this interaction inhibited the association of Beclin 1 with Bcl-x(L). Our results suggest that BH3 only proapoptotic Bcl-2 proteins may modulate the interactions between Bcl-x(L) and Beclin 1.
Paracellin-1, a Renal Tight Junction Protein Required for Paracellular Mg 2+ Resorption (1999)

Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Tight junctions constitute the barrier to paracellular conductance; however, little is known about the specific molecules that mediate paracellular permeabilities. Renal magnesium ion (Mg2+) resorption occurs predominantly through a paracellular conductance in the thick ascending limb of Henle (TAL). Here, positional cloning has identified a human gene, paracellin-1 (PCLN-1), mutations in which cause renal Mg2+ wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into Mg2+ homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of a selective paracellular conductance.
Targeting the WNT Signaling Pathway in Cancer Therapeutics (2015)

The WNT signaling cascade is integral in numerous biological processes including embryonic development, cell cycle regulation, inflammation, and cancer. Hyperactivation of WNT signaling secondary to alterations to varying nodes of the pathway have been identified in multiple tumor types. These alterations converge into increased tumorigenicity, sustained proliferation, and enhanced metastatic potential. This review seeks to evaluate the evidence supporting the WNT pathway in cancer, the therapeutic strategies in modulating this pathway, and potential challenges in drug development.
Antibodies to DNA (1988)

Abstract Antibodies that are specific for DNA provide an excellent system for studying the protein‐nucleic acid interactions that allow proteins to recognize specific DNA structures or sequences.
New radio networks for tactical communication (1990)

A packet-switched radio system designed and developed for the Norwegian Army is presented. In particular, the development of an overall network concept, the network and access protocols, and the routing strategy are examined. Network synchronization and radio process protocols are discussed, and simulation results are given. A radio design allowing integration of electronic countermeasures (ECM) protected data and voice channels is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Venom coagglutinin for detection of von Willebrand factor activity in animal plasmas. (1983)

Platelet-aggregating vWF activity in several animal species is difficult to detect with either the ristocetin co-factor test or the PAF test using human platelets, indicating considerable species restriction in applicability of these procedures. VCA, a recently described second "activator" of vWF, was found not to be restrictive as to species and readily elicited the vWF response in all 13 animal plasmas tested. For any one of the animal plasmas, the vWF-dependent platelet aggregation reaction can be demonstrated by using VCA with either homologous or heterologous species of platelets. VCA was employed with lyophilized platelets in two types of platelet aggregating test systems, a macroscopic procedure and an aggregometric method. Many of the animal plasmas (dog, rabbit, horse, cow, cat, sheep, and goat) had about three to five times the plasma vWF content of human plasma. Pig and rat plasmas had vWF levels approximating those of human plasma. Guinea pig plasma had about half as much vWF as human plasma. VCA also caused a well-defined vWF-dependent platelet response in PRPs. The data suggest considerable differences in the rate of aggregation of platelets from different species. Bioassay of vWF can be performed with the different animal plasmas if the source of platelets and the VCA concentration are controlled. VCA thus appears to provide a broad-spectrum probe for vWF and is effective in the various species combinations of plasma and platelets.
Comparison between bronchial response to inhaled hypoosmolar and isoosmolar solutions of sodium cromoglycate after exercise challenge. (1990)

The effectiveness of a sodium cromoglycate isoosmolar solution (288 mOsmol/L) versus hypoosmolar commercial solution (40 mOsmol/L) was studied in 14 asthmatic children with exercise-induced asthma. The mean FEV1 after exercise in patients pretreated with a sodium cromoglycate hypotonic solution compared with FEV1 at rest was -2% +/- 10%. The mean FEV1 after exercise in patients pretreated with an isotonic solution compared with FEV1 at rest was 3% +/- 6%. This statistically significant difference (P less than .01) proves that the effectiveness of sodium cromoglycate can be improved by raising the osmolarity to isotonic levels.
Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock* (2009)

Initial serum lactate was associated with mortality independent of clinically apparent organ dysfunction and shock in patients admitted to the ED with severe sepsis. Both intermediate and high serum lactate levels were independently associated with mortality.
Reflections on NoteCards (2001)

NoteCards, developed by a team at Xerox PARC, was designed to support the task of transforming a chaotic collection of unrelated thoughts into an integrated, orderly interpretation of ideas and their interconnections. This article presents NoteCards as a foil against which to explore some of the major limitations of the current generation of hypermedia systems, and characterizes the issues that must be addressed in designing the next generation systems.