gebhart/patrepeval huggingface dataset:
Antipeptide antibodies against conserved regions of human interferon-alpha: evidence for conformational variations between IFN-alpha subtypes. (1990)

Antibodies to two conserved regions (residues 29-36 and 139-151) of human interferon-alpha were raised by immunizing rabbits with four short synthetic peptides coupled to carriers. The antibodies were tested for reactivity with recombinant interferon-alpha by ELISA. Despite the amino acid conservation of the two regions, there are significant variations in the reactivity of the antibodies with the IFN-alpha subtypes. The reactivity is enhanced significantly when the disulfide bonds of the interferon molecule are reduced. The results indicate that there are subtype-specific differences in the presentation of the epitopes in these conserved regions of human interferon-alpha.
Rationale for Probiotic and Antibiotic Treatment Strategies in Inflammatory Bowel Diseases (2003)

Inflammatory bowel diseases (IBD), commonly referred to as Crohn's disease and ulcerative colitis are chronic aggressive disorders which share many similarities concerning pathomechanism and clinical course, but have very distinct features. Both entities are mainly located in areas with high bacterial concentrations, such as the terminal ileum and cecum in Crohn's disease and the rectum in ulcerative colitis. In recent years, overwhelming evidence accumulated, supporting the hypothesis that IBD are characterized by a genetically determined, overly aggressive immune response towards ubiquitous luminal antigens, especially commensal bacteria and their products. Trials in both human IBD and experimental colitis have demonstrated that broad-spectrum antibiotics may influence the course of ulcerative colitis and Crohn's disease and antibiotics with narrow activity against the anaerobic fraction of the flora can prevent relapse in Crohn's disease after surgically induced remission. Since relevant antibiotic strategies can be associated with some side effects, the ongoing research recently focused on alternative methods to modify the intestinal flora in patients with IBD. Clinical observations including few controlled trials, basic research, and animal studies have suggested a potential role for probiotic bacteria within the treatment regimens for IBD. However, the mode of action of these organisms is still largely unclear and in vitro studies are inconclusive. This review summarizes recent in vitro and in vivo data regarding the role of the intestinal microflora in the pathogenesis of chronic intestinal inflammation and possible therapeutic mechanisms of probiotic bacteria relevant to IBD. Furthermore, we will review clinical trials examining the efficacy of antibiotic and probiotic treatment strategies in IBD.
An environment-friendly synthesis of 4(3H)-quinazolinones (2015)

4(3H)-Quinazolinones, a class of important heterocycles, are used extensively in various fields. Although there are a number of synthetic approaches, all of them use catalysts, solvents, chemical oxidants, and/or reagents harmful to the environment when released in large quantities. An environment-friendly, catalyst-free, solventless, one-step synthesis of 4(3H)-quinazolinones is presented. The process involves heating of aldehydes and anthranilamides under air as cheap oxidant and as key promoter of reaction. The protocol is suitable for both aromatic and aliphatic aldehydes. This novel synthetic method may be applied to a wide range of educts, offering high yields at low cost while characterized by minimum environmental impact.
A Multicenter, Single-Arm, Open-Label Study To Evaluate the Efficacy and Safety of Single-Agent Lenalidomide in Patients with Relapsed and Refractory Multiple Myeloma; Prelininary Results. (2005)

Abstract INTRODUCTION: Lenalidomide (REVLIMID®; CC-5013) is a novel, orally active immunomodulatory drug under investigation for the treatment of multiple myeloma (MM). Phase 1 dose-escalation studies in patients (pts) with relapsed and refractory MM determined that the maximum tolerated dose (MTD) of lenalidomide was 25 mg/day, based upon myelosuppression encountered beyond 28 days, which was manageable with growth factor support and dose reduction. In a multicenter phase 2 study to determine optimal dose and schedule, 102 pts with relapsed or refractory MM were randomized to receive lenalidomide at either 15 mg bid (n=34) or 30 mg qd (n=68), for 21 days every 4 wks. Both treatment arms showed significant activity with manageable toxicity. An increased incidence of cytopenia was noted in the 15-mg bid group and thus the 30 mg qd schedule was taken forward. METHODS: The objective of this multicenter, phase 2, open-label study (CC-5013-MM-014) was to further evaluate the effectiveness and safety of single-agent lenalidomide administered at a dose of 30 mg qd for 21 days every 28 days (28-day cycle) in pts with relapsed and refractory MM. Eligible patients included those who had received prior thalidomide, bortezomib, or SCT. RESULTS: 222 pts were enrolled into the study. All patients had received at least 2 prior anti-myeloma treatments, including bortezomib (41%), thalidomide (80%), and SCT (44%). Table 1 shows Best Response data, excluding patients in whom responses were not evaluable (n=10). Partial response or better occurred in 25% of patients and SD or better in 71%. Time to Progression was a median of 22.4 wks (range 1.8– 66 wks). The median survival has not been reached (the lower bound of the 95% CI exceeds 15 months). The most common treatment-related AEs (those reported in ≥10% of patients overall) included upper respiratory tract infection, neutropenia and thrombocytopenia. AEs that most frequently led to dose reduction or interruption by percentage of cases were neutropenia (40%), thrombocytopenia (23%), fatigue (5%), and anemia (5%). CONCLUSION: Oral lenalidomide in relapsed and refractory MM patients achieved PR+CR in 25%, stable disease or better in 71%, a median TTP of approximately 6 months and a median survival that has not been reached. Toxicity has been manageable with a very low incidence of DVT and minimal treatment-emergent neuropathy. Table 1. Best Response Best Response* n (%) *Excluding patients not evaluable (n=10); CR=complete response and PR=partial response (EBMT criteria) ≥PR (CR + PR) 53 (25) Stable disease 152 (71)
Characterization of Conductive Polymeric Nickel(II) Tetrakis(3‐methoxy‐4‐hydroxy‐phenyl)Porphyrin as an Anodic Material for Electrocatalysis (1991)

Highly conductive film has been obtained by oxidative polymerization of nickel(II) tetrakis(3‐methoxy‐4‐hydroxy‐phenyl)porphyrin, Ni(II)TMHPP. This material was characterized by voltammetry, ac impedance, UV‐visible spectroscopy, and x‐ray photoelectron spectroscopy. The application of polymeric Ni(II)TMHPP as an anode for catalytic oxidation of water, methanol, and hydrazine in basic media is discussed.
Triplex formation with 2'-O,4'-C-ethylene-bridged nucleic acids (ENA) having C3'-endo conformation at physiological pH (2003)

Antigenes, which are substances that inhibit gene expression by binding to double-stranded DNA (dsDNA) in a sequence-specific manner, are currently sought for the treatment of various gene-related diseases. As such antigenes, we developed new nuclease-resistant oligopyrimidine nucleotides that are partially modified with 2'-O,4'-C-ethylene nucleic acids (ENA), which are constrained in the C3'-endo conformation and can form a triplex with dsDNA at physiological pH. It was found that these oligonucleotides formed triplexes similarly to those partially modified with 2'-O,4'-C-methylene nucleic acids (2',4'-BNA or LNA), as determined by UV melting analyses, electromobility shift assays, CD spectral analyses and restriction enzyme inhibition assays. In our studies, oligonucleotides fully modified with ENA have delta torsion angle values that are marginally higher than those of 2',4'-BNA/LNA. ENA oligonucleotides present in 10-fold the amount of dsDNA were found to be favorable in forming triplexes. These results provide useful information for the future design of triplex-forming oligonucleotides fully modified with such nucleic acids constrained in the C3'-endo conformation considering that oligonucleotides fully modified with 2',4'-BNA/LNA do not form triplexes.
Selenium, isoflavones, and AR‐regulated genes in rat prostate (2007)

This study aimed to identify potential prostate cancer chemopreventive effects of combined high intake of Se and isoflavones. Subjects were Noble male rats born to breeders fed stock diets containing low (10 ppm) or high (600 ppm) isoflavones, with or without a supplement of 3 ppm Se as Se‐methylselenocysteine. Pups continued consuming the same diets as their parents until sacrifice at 200 days. Liver glutathione peroxidase activity was unaffected by diets. Serum isoflavone (equol+genistein+daidzein) concentrations averaged 23.5 + 2.4 ng/ml (mean + SD) in rats fed 10 ppm isoflavones, and 1457 + 273 ng/ml in rats fed 600 ppm diets. Dietary Se had no effect on serum isoflavones. Steady state mRNA levels in dorsolateral prostates were determined for genes which previous data mining (Zhang 2005) showed to be 1) differentially regulated in prostate cancer; 2) androgen receptor (AR)‐regulated; and 3) for which high Se countered AR effects. These genes included Abcc4, Dhcr24, Ascl3, and Gucyla3. Levels of mRNA for Akr1c6 and AR (large) were also assayed. High isoflavones decreased expression of Akr1c6, Ascl3, and Gucy1a3 (p=.000–.003). High Se decreased expression of AR, Abcc4, and Dhcr24 (p=.000–.012). Combined intake of high Se and high isoflavones may achieve a greater chemopreventive effect that either compound supplemented individually. (Supported by NIH CA122235).
The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically? (2004)

Macrophages play important roles in the clearance of dying and dead cells. Typically, and perhaps simplistically, they are viewed as the professional phagocytes of apoptotic cells. Clearance by macrophages of cells undergoing apoptosis is a non-phlogistic phenomenon which is often associated with actively anti-inflammatory phagocyte responses. By contrast, macrophage responses to necrotic cells, including secondarily necrotic cells derived from uncleared apoptotic cells, are perceived as proinflammatory. Indeed, persistence of apoptotic cells as a result of defective apoptotic-cell clearance has been found to be associated with the pathogenesis of autoimmune disease. Here we review the mechanisms by which macrophages interact with, and respond to, apoptotic cells. We suggest that macrophages are especially important in clearing cells at sites of histologically visible, high-rate apoptosis and that, otherwise, apoptotic cells are removed largely by non-macrophage neighbours. We challenge the view that necrotic cells, including persistent apoptotic cells are, of necessity, proinflammatory and immunostimulatory and suggest that, under appropriate circumstances, persistent apoptotic cells can provide a prolonged anti-inflammatory stimulus.
An Altered Immunity Hypothesis for the Development of Symptomatic Bacterial Vaginosis (2007)

The hypothesis is advanced that the transition from a Lactobacillus-dominated vaginal microflora to a microflora characteristic of bacterial vaginosis (BV), as well as development of the adverse consequences of BV in some women but not in others, are due to alterations in innate immunity. A microbial-induced inhibition of Toll-like receptor expression and/or activity may block induction of proinflammatory immunity and lead to the proliferation of atypical vaginal bacteria. A lack of 70-kDa heat-shock protein production and release in response to abnormal flora would compound this failure to activate antimicrobial immune responses. A deficit in vaginal mannose-binding lectin concentrations would further decrease the capacity for microbial killing and increase the likelihood of bacterial migration from the vagina to the upper genital tract.
An Engineered Rare Codon Device for Optimization of Metabolic Pathways (2016)

Rare codons generally arrest translation due to rarity of their cognate tRNAs. This property of rare codons can be utilized to regulate protein expression. In this study, a linear relationship was found between expression levels of genes and copy numbers of rare codons inserted within them. Based on this discovery, we constructed a molecular device in Escherichia coli using the rare codon AGG, its cognate tRNA (tRNA(Arg) (CCU)), modified tRNA(Asp) (GUC → CCU), and truncated aspartyl-tRNA synthetase (TDRS) to switch the expression of reporter genes on or off as well as to precisely regulate their expression to various intermediate levels. To underscore the applicability of our work, we used the rare codon device to alter the expression levels of four genes of the fatty acid synthesis II (FASII) pathway (i.e. fabZ, fabG, fabI, and tesA') in E. coli to optimize steady-state kinetics, which produced nearly two-fold increase in fatty acid yield. Thus, the proposed method has potential applications in regulating target protein expression at desired levels and optimizing metabolic pathways by precisely tuning in vivo molar ratio of relevant enzymes.
Mammalian Staufen Is a Double-Stranded-RNA- and Tubulin-Binding Protein Which Localizes to the Rough Endoplasmic Reticulum (1999)

Staufen (Stau) is a double-stranded RNA (dsRNA)-binding protein involved in mRNA transport and localization in Drosophila. To understand the molecular mechanisms of mRNA transport in mammals, we cloned human (hStau) and mouse (mStau) staufen cDNAs. In humans, four transcripts arise by differential splicing of the Stau gene and code for two proteins with different N-terminal extremities. In vitro, hStau and mStau bind dsRNA via each of two full-length dsRNA-binding domains and tubulin via a region similar to the microtubule-binding domain of MAP-1B, suggesting that Stau cross-links cytoskeletal and RNA components. Immunofluorescent double labeling of transfected mammalian cells revealed that Stau is localized to the rough endoplasmic reticulum (RER), implicating this RNA-binding protein in mRNA targeting to the RER, perhaps via a multistep process involving microtubules. These results are the first demonstration of the association of an RNA-binding protein in addition to ribosomal proteins, with the RER, implicating this class of proteins in the transport of RNA to its site of translation.
Adaptive assistants for customized E-shopping (2002)

Shopping bots today are biased toward vendors who pay to be listed. To make user-centered business models viable, we developed IntelliShopper, which learns shoppers' individual preferences and autonomously monitors vendor sites for items matching those preferences.
Prostacyclin deficiency in a young woman with recurrent thrombosis. (1986)

A young woman with recurrent deep venous thromboses and spontaneous abortions was studied. She suffered an ovarian infarction followed by aortic thrombosis and renal failure. Evidence for deficient prostacyclin production was found and she responded to treatment with a prostacyclin infusion. This syndrome is identical with that seen in women with the lupus anticoagulant, but the lupus anticoagulant was not detected and no other cause was identified.
Identification of B7-H1 as a Novel Mediator of the Innate Immune/Proinflammatory Response as well as a Possible Myeloid Cell Prognostic Biomarker in Sepsis (2013)

Identifying relevant mediators responsible for the pathogenesis during sepsis may lead to finding novel diagnostic and therapeutic targets. Recent studies indicate programmed cell death receptor (PD)-1 plays a significant role in the development of immune suppression associated with sepsis. In this study, we determine whether B7-H1, the primary ligand of PD-1, contributes to the pathogenesis of sepsis. We report that B7-H1 is upregulated extensively on various immune cells during sepsis and B7-H1 gene deficiency protects mice from the lethality of sepsis. In terms of the histological development of multiple organ damage and inflammatory cytokine levels in circulation or at infectious site, B7-H1-deficient mice showed a remarkable reduction in these indices when compared with wild-type mice. However, B7-H1 gene-deficient mice did not exhibit a lower bacterial burden when compared with wild-type mice, although they recruited more macrophages and neutrophils into infectious site. In addition, we found that, during sepsis, whereas there were no marked differences affecting ex vivo macrophage cytokine productive capacity between PD-1 and B7-H1 gene-deficient mice, preservation of ex vivo macrophage phagocytic function was only seen in septic PD-1 knockout mouse cells. Finally, higher percentage B7-H1(+) neutrophils in peripheral blood correlated not only with higher levels of pro- and anti-inflammatory cytokines/chemokines (CCL2, IL-6, CXCL2, KC, TNF-α, and IL-10), but with lethal outcome as well. Together, these results indicate B7-H1 contributes to septic morbidity in fashion distinct from PD-1 and suggest B7-H1 expression on neutrophils could be used as a biomarker of septic severity.
Development of a Completely Encapsulated Intraocular Pressure Sensor (2000)

A completely encapsulated intraocular pressure (IOP) sensor equipped with telemetric signal and energy transfer is introduced integrated into a silicone disc for implantation into the eye. After implantation into enucleated pig eyes and into rabbit eyes in vivo, the IOP was recorded and compared to established techniques of IOP measurement. Pressure chamber tests showed that the sensor functioned correctly after biocompatible encapsulation in polydimethylsiloxane. In vivo and in vitro tests in rabbit and pig eyes demonstrated that the implanted system worked with the same precision as established techniques for IOP determination. The correlation between the measurements with the implanted device and pneumotonometry in several experiments was between 0.9 and 0.99. This device serves as a functioning model for the realization of a telemetric IOP sensor for integration into an artificial intraocular lens. Such a device will open new perspectives, not only in the management of glaucoma, but also in basic research for mechanisms of glaucoma.
Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene (2005)

Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious heat. These strain differences are shown here to reflect differential responsiveness of primary afferent thermal nociceptors to heat stimuli. We further present convergent behavioral and electrophysiological evidence that the variable responses to noxious heat are due to strain-dependence of CGRP expression and sensitivity. Strain differences in behavioral response to noxious heat could be abolished by peripheral injection of CGRP, blockade of cutaneous and spinal CGRP receptors, or long-term inactivation of CGRP with a CGRP-binding Spiegelmer. Linkage mapping supports the contention that the genetic variant determining variable heat pain sensitivity across mouse strains affects the expression of the Calca gene that codes for CGRPalpha.
Efficient Routability Checking for Global Wires in Planar Layouts (1997)

In VLSI and printed wiring board design, routing process usually consists of two stages: the global routing and the detailed routing. The routability checking is to decide whether the global wires can be transformed into the detailed ones or not. In this paper, we propose two graphs, the capacity checking graph and the initial flow graph, for the efficient routability checking.
P-GaN/N-InGaN/N-GaN Double-Heterostructure Blue-Light-Emitting Diodes (1993)

P-GaN/n-InGaN/n-GaN double-heterostructure (DH) blue-light-emitting diodes (LEDs) were fabricated successfully for the first time. The output power was 125 µW and the external quantum efficiency was as high as 0.22% at a forward current of 20 mA at room temperature. The peak wavelength and the full width at half-maximum (FWHM) of the electroluminescence (EL) were 440 nm and 180 meV, respectively. This value FWHM of was the smallest ever reported for blue GaN LEDs.
Implications of Serum Pepsinogen I in Early Endoscopic Diagnosis of Gastric Cancer and Dysplasia (2000)

We conclude that assay of SPGI followed by endoscopy is an approach which can enable the early diagnosis of gastric cancer at a curable stage.
One-Way Traffic of a Viral Motor Channel for Double-Stranded DNA Translocation (2010)

Linear double-stranded DNA (dsDNA) viruses package their genome into a procapsid using an ATP-driven nanomotor. Here we report that bacteriophage phi29 DNA packaging motor exercises a one-way traffic property for dsDNA translocation from N-terminal entrance to C-terminal exit with a valve mechanism in DNA packaging, as demonstrated by voltage ramping, electrode polarity switching, and sedimentation force assessment. Without the use of gating control as found in other biological channels, the observed single direction dsDNA transportation provides a novel system with a natural valve to control dsDNA loading and gene delivery in bioreactors, liposomes, or high throughput DNA sequencing apparatus.
Introduction (2011)

In March 1984, a foreign correspondent for the Washington Post tracked down Pierre Poujade, the stationery salesman who had led a political revolt of French shopkeepers three decades earlier. Poujade's movement, the Union de Défense Commerçants et Artisans (Union for the Defense of Tradesmen and Artisans, UDCA), did not survive beyond a single parliamentary term in the French National Assembly and serves as a classic example of a “flash” party. But the ideology of Poujadism – the defense of small business interests and traditional values against the forces of modernization – appeared to be making a comeback in the form of Jean-Marie Le Pen's Front National (National Front, FN). Le Pen had first entered parliament as a twenty-eight-year-old deputy of the UDCA, and although he was now well into his sixth decade, Poujade still spoke of him as a protégé. “A handsome kid with a fine gift of gab” was his estimation of the FN's leader. Le Pen was attracting national attention after his party, with the cooperation of two mainstream conservative parties, won several council seats in the town of Dreux. This led to a series of television appearances and increased visibility, and by the time of the interview with Poujade the FN was polling between 10% and 15% for the upcoming elections to the European Parliament.
Graphical search and replace (1988)

Graphical search is a technique for finding all instances of a graphical pattern in a synthetic picture in which objects are regions bounded by lines and curves. The pattern may descirbe shape, color and other properties. Matched objects may be allowed to differ from the pattern in rotation and scale or may differ in shape by a specified tolerance. Graphical replace is a technique for replacing the shape, color, or other properties of matched objects with new properties described in a replacement pattern. Combined, the two techniques are similar to textual search and replace in text editors. Graphical search and replace can be used to make global changes to illustrations with repetitive patterns, independent of the means used to make those patterns. It can also be used to create a class of iterative or recursive shapes that can be specified by replacement rules.