gebhart/patrepeval huggingface dataset:
IL-7 and IL-15: Biology and Roles in T-Cell Immunity in Health and Disease (2008)

Cytokines IL-7 and IL-15 are essentially involved in T-cell homeostasis. IL-7 is required for developing mature T cells in the thymus, whereas in the periphery, it promotes the survival of naïve and memory T cells by upregulating the antiapoptotic molecule Bcl-2. IL-15 potently induces the proliferation of memory CD8+ T cells independently of antigen and augments their effector function. Although IL-7 and IL-15 may help to defend the host against microorganisms and tumors by promoting T-cell immunity, dysregulated production of IL-7 and IL-15 can be harmful. In fact, increased levels of IL-15 in the circulation and inflamed tissues have been reported in various autoimmune diseases, including rheumatoid arthritis (RA), possibly contributing to the pathogenesis. In addition, IL-7, which may induce the production of inflammatory cytokines from T cells and monocytes, are found to be elevated in the joints of patients with RA. Here, we review what is currently known about the roles of these cytokines in T-cell immunity, in general, as well as in RA, in particular, focusing on recent discoveries.
Piceatannol Inhibits TNF-Induced NF-κB Activation and NF-κB-Mediated Gene Expression Through Suppression of IκBα Kinase and p65 Phosphorylation (2002)

Piceatannol is an anti-inflammatory, immunomodulatory, and anti-proliferative stilbene that has been shown to interfere with the cytokine signaling pathway. Previously, we have shown that resveratrol suppresses the activation of the nuclear transcription factor NF-kappaB. Piceatannol, previously reported as a selective inhibitor of protein tyrosine kinase Syk, is structurally homologous to resveratrol. Whether piceatannol can also suppress NF-kappaB activation was investigated. The treatment of human myeloid cells with piceatannol suppressed TNF-induced DNA binding activity of NF-kappaB. In contrast, stilbene or rhaponticin (another analog of piceatannol) had no effect, suggesting the critical role of hydroxyl groups. The effect of piceatannol was not restricted to myeloid cells, as TNF-induced NF-kappaB activation was also suppressed in lymphocyte and epithelial cells. Piceatannol also inhibited NF-kappaB activated by H(2)O(2), PMA, LPS, okadaic acid, and ceramide. Piceatannol abrogated the expression of TNF-induced NF-kappaB-dependent reporter gene and of matrix metalloprotease-9, cyclooxygenase-2, and cyclin D1. When examined for the mechanism, we found that piceatannol inhibited TNF-induced IkappaBalpha phosphorylation, p65 phosphorylation, p65 nuclear translocation, and IkappaBalpha kinase activation, but had no significant effect on IkappaBalpha degradation. Piceatannol inhibited NF-kappaB in cells with deleted Syk, indicating the lack of involvement of this kinase. Overall, our results clearly demonstrate that hydroxyl groups of stilbenes are critical and that piceatannol, a tetrahydroxystilbene, suppresses NF-kappaB activation induced by various inflammatory agents through inhibition of IkappaBalpha kinase and p65 phosphorylation.
High-field cross polarization NMR from laser-polarized xenon to a polymer surface (1993)

Surface-selective characterization of materials with NMR has been quite useful in the few cases where sufficient sensitivity and selectivity have been achieved.1 In this communication we report the use of laser-polarized xenon as the source of magnetization for a high-field cross polarization experiment, obtaining surfaceselective magnetization transfer. Gas-phase xenon with nuclear spin polarization several orders of magnitude higher than thermal Boltzmann levels in a high magnetic field can be produced using optically pumped rubidium vapor according to the pioneering work of Happer and co-workers.1 2 The angular momentum of circularly polarized laser light is transferred, via the rubidium electron spins, to the (slowly relaxing) xenon nuclear spin system. We have previously used xenon, with a large polarization enhancement («10 000), as a probe of low surface area materials.3 More recently, using thermal mixing in low field,4 polarization has been transferred between xenon isotopes5 and from xenon to 13C02 occluded in solid xenon.6 The approach of low-field mixing has the disadvantages of nonselective magnetization transfer, typically very short spin-lattice relaxation times in low field, and the necessity of rapid field switching or mechanical transport of the sample to high field for detection. High-field cross polarization methods should be advantageous in allowing nuclear spin selectivity in the transfer step as well as circumventing relaxation and transport problems. In the present work, contact between laser-polarized xenon and surface spins was achieved in high field by Hartmann-Hahn matching of the energy levels in the rotating frame with direct NMR detection of the polarized species.7-8 Proton spins are observed due to their abundance at the surface and the dominant dipolar interactions with adsorbed xenon.
Cellulose degradation byClostridium thermocellum: From manure to molecular biology (1992)

Clostridium thermocellum, a Gram-positive, thermophilic anaerobe produces a highly active cellulase system. This system, termed the cellulosome, is a complex composed of at least 14–18 different types of components organized around a large, cellulose-binding protein. Combining recombinant DNA technology and protein biochemistry has proved to be a successful approach in unravelling some important features of the system.
Deception in Honeynets: A Game-Theoretic Analysis (2007)

Recently, honeynets became one of the main tools for understanding the characteristics of malicious attacks and the behavior of the attackers. However the attackers may identify the honeypots and avoid attacking them. Thus the honeynet administrators must be able to deceive the attackers and induce them to attack the honeypots. In this paper we propose a game theoretic framework for modeling deception in honeynets. The framework is based on extensive games of imperfect information. We study the equilibrium solutions of these games and show how they are used to determine the strategies of the attacker and the honeynet system.
Families of transmembrane sugar transport proteins (2000)

We describe here 20 families of secondary (pmf-driven) carriers which, in addition to nine families within the ATP-dependent ABC superfamily, and seven families of Gram-negative bacterial outer membrane porins, largely account for the stereospecific transport of sugars and their derivatives into and out of all living cells on earth. Family characteristics as well as struc-tural and functional properties of the family constituents are described. By reference to our website (http://www-biology.ucsd.edu/ approximately msaier/transport/), phylogenetic relationships, detailed substrate specificity information and both primary and secondary references are also available. This review provides a comprehensive guide to the diversity of carriers that mediate the transport of sugar-containing molecules across cell and organellar membranes.
TIME‐RESOLVED FLUORESCENCE DETECTION OF SHIGA‐LIKE TOXINS PRODUCED BY ESCHERICHIA COLI O157 AND NON‐O157 IN GROUND BEEF1 (2004)

ABSTRACT An immunomagnetic bead time‐resolved fluorescence assay (IMB‐TRF) was developed for the detection of Shiga‐like toxins I and II (SLT I and II) from Shiga‐like toxin‐producing Escherichia coli (STEC). Twenty‐five gram of ground beef patties were inoculated with 1 CFU/g of O157 or non‐O157 (STEC) stored at 7C for 5 h and incubated with 100 mL added EC broth at 37C and 140 r.p.m. shaking for 20 h. Ten µg/mL of ofloxacin was added to the EC broth after 20 h of incubation to enhance toxin production. After 4 more hours of incubation, samples were removed and centrifuged for 10 min at 5000 r.p.m. The supernatant was removed and saved and a bacterial protein extraction reagent was used to lyse the cells in the pellet and release intracellular SLTs (Fraction I) which were then recombined with extracellular SLTs (Fraction II) present in the supernatant. Immunomagnetic beads coated with monoclonal antibodies specific to Shiga‐like toxins I and II were applied to capture and concentrate the toxins and captured toxins were labeled with lanthanide‐tagged antitoxin antibodies to from sandwiched complexes prior to detection by a TRF reader. TRF pathogen detection levels, defined as signals ≥ 2× uninoculated samples, were achieved in all STEC inoculated samples and no cross‐reactivity was observed with either nonpathogenic microflora present on the meat or nontoxin‐producing E. coli K12 inoculated samples.
Experimental Chemonucleolysis With Chondroitinase ABC in Monkeys (1996)

The results confirm that selective degradation is achieved with chondroitinase ABC in vivo in monkeys and that chondroitinase ABC is less toxic to discs than chymopapain is. From these considerations, chondroitinase ABC is believed to have a high potential for clinical application.
Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis (2007)

Results from this mouse model would suggest accumulation of triglycerides may be a protective mechanism to prevent progressive liver damage in NAFLD.
Design space exploration for 3D architectures (2006)

As technology scales, interconnects have become a major performance bottleneck and a major source of power consumption for microprocessors. Increasing interconnect costs make it necessary to consider alternate ways of building modern microprocessors. One promising option is 3D architectures where a stack of multiple device layers with direct vertical tunneling through them are put together on the same chip. As fabrication of 3D integrated circuits has become viable, developing CAD tools and architectural techniques is imperative to explore the design space to 3D microarchitectures. In this article, we give a brief introduction to 3D integration technology, discuss the EDA design tools that can enable the adoption of 3D ICs, and present the implementation of various microprocessor components using 3D technology. An industrial case study is presented as an initial attempt to design 3D microarchitectures.
Different CD40-mediated signaling events require distinct CD40 structural features (1996)

Signals delivered to B cells through CD40 are critical to the development of humoral immune responses. In this study we characterize regions of the 62-amino acid cytoplasmic domain of human CD40 (hCD40) that are essential for signal transduction and examine the functional consequences of mutations in these regions. A panel of mutant hCD40 molecules was stably expressed in mouse B cell lines and tested for its ability to stimulate Ab secretion, homotypic adhesion, and increased surface expression of B7, Fas, CD23, LFA-1, and intracellular adhesion molecule-1. Our results indicate that CD40 contains at least two major signaling determinants in the cytoplasmic domain: one disrupted by a truncation of 22 amino acids, and a second disrupted by the removal of 10 additional amino acids. The second determinant includes threonine 234, a residue previously shown to be important in CD40 signal transduction. Our functional analysis of alanine and serine substitutions at position 234 indicates that phosphorylation of this residue may be important for full CD40 signaling activity.
Protein-Dependent Translocation of Aminophospholipids and Asymmetric Transbilayer Distribution of Phospholipids in the Plasma Membrane of Ram Sperm Cells (1994)

We have investigated the transbilayer movement of phospholipids in the plasma membrane of ram sperm cells using spin- and fluorescence-labeled lipid analogues. After incorporation into the outer leaflet, phosphatidylcholine (PC) and sphingomyelin (SM) moved slowly to the inner cytoplasmic leaflet, whereas phosphatidylserine (PS) and phosphatidylethanolamine (PE) rapidly disappeared from the exoplasmic monolayer. Variation of the initial velocity of the relocation kinetics vs the amount of analogue incorporated into the membrane suggests a saturability of the transbilayer movement of aminophospholipids. ATP depletion or pretreatment with N-ethylmaleimide of ram sperm cells reduced the fast inward motion of PS and PE, indicating a protein-mediated aminophospholipid translocation. The results suggest for the plasma membrane of ram sperm cells the presence of an aminophospholipid translocase and an asymmetric transversal lipid distribution with aminophospholipids preferentially located in the inner leaflet and choline-containing phospholipids in the outer leaflet. The relevance of the transversal segregation of phospholipids for membrane fusion processes occurring during fertilization is discussed.
Cartilage‐specific constitutive expression of TSG‐6 protein (product of tumor necrosis factor α–stimulated gene 6) provides a chondroprotective, but not antiinflammatory, effect in antigen‐induced arthritis (2002)

TSG-6 protein is known to form a complex with inter-alpha-inhibitor (IalphaI), a potent serine protease inhibitor, which may be immobilized via the hyaluronan (HA)-binding domain of TSG-6 protein in the HA-rich extracellular matrix of cartilage. Thus, the local accumulation of TSG-6 protein and TSG-6 protein-bound IalphaI in tsg6/tnfip6 transgenic mice may inhibit serine proteases and subsequent activation of MPs. It is suggested that this mechanism might protect cartilage from extensive degradation even in the presence of acute inflammation.
Detecting semantic cloaking on the web (2006)

By supplying different versions of a web page to search engines and to browsers, a content provider attempts to cloak the real content from the view of the search engine. Semantic cloaking refers to differences in meaning between pages which have the effect of deceiving search engine ranking algorithms. In this paper, we propose an automated two-step method to detect semantic cloaking pages based on different copies of the same page downloaded by a web crawler and a web browser. The first step is a filtering step, which generates a candidate list of semantic cloaking pages. In the second step, a classifier is used to detect semantic cloaking pages from the candidates generated by the filtering step. Experiments on manually labeled data sets show that we can generate a classifier with a precision of 93% and a recall of 85%. We apply our approach to links from the dmoz Open Directory Project and estimate that more than 50,000 of these pages employ semantic cloaking.
Atypical protein disulfide isomerases (PDI): Comparison of the molecular and catalytic properties of poplar PDI-A and PDI-M with PDI-L1A (2017)

Protein disulfide isomerases are overwhelmingly multi-modular redox catalysts able to perform the formation, reduction or isomerisation of disulfide bonds. We present here the biochemical characterization of three different poplar PDI isoforms. PDI-A is characterized by a single catalytic Trx module, the so-called a domain, whereas PDI-L1a and PDI-M display an a-b-b'-a' and a°-a-b organisation respectively. Their activities have been tested in vitro using purified recombinant proteins and a series of model substrates as insulin, NADPH thioredoxin reductase, NADP malate dehydrogenase (NADP-MDH), peroxiredoxins or RNase A. We demonstrated that PDI-A exhibited none of the usually reported activities, although the cysteines of the WCKHC active site signature are able to form a disulfide with a redox midpoint potential of -170 mV at pH 7.0. The fact that it is able to bind a [Fe2S2] cluster upon Escherichia coli expression and anaerobic purification might indicate that it does not have a function in dithiol-disulfide exchange reactions. The two other proteins were able to catalyze oxidation or reduction reactions, PDI-L1a being more efficient in most cases, except that it was unable to activate the non-physiological substrate NADP-MDH, in contrast to PDI-M. To further evaluate the contribution of the catalytic domains of PDI-M, the dicysteinic motifs have been independently mutated in each a domain. The results indicated that the two a domains seem interconnected and that the a° module preferentially catalyzed oxidation reactions whereas the a module catalyzed reduction reactions, in line with the respective redox potentials of -170 mV and -190 mV at pH 7.0. Overall, these in vitro results illustrate that the number and position of a and b domains influence the redox properties and substrate recognition (both electron donors and acceptors) of PDI which contributes to understand why this protein family expanded along evolution.
Capecitabine: a novel, orally administered, tumour-activated treatment for colorectal cancer (2001)

Objective. To provide a comprehensive review of the preclinical and clinical pharmacology and toxicology of the fluoropyrimidine, capecitabine, with particular reference to its use in its new indication, advanced colorectal cancer. Data sources. A MEDLINE search was conducted using the term ‘‘capecitabine’’ for the period 1995 -2001. The reference lists from retrieved articles were reviewed and other relevant papers identified. The abstract books from the annual meetings of the American Society of Clinical and Oncology and the European Society of Medical Oncology were also reviewed. Data extraction. The aim of the review was to be comprehensive and descriptive. All studies containing information deemed to be of interest were reviewed by the author, none were excluded on grounds of quality. Data synthesis. Capecitabine is a prodrug of the widely used cytotoxic agent 5-fluorouracil (5-FU). Unlike 5-FU it is extensively and reliably absorbed after oral administration and does not require folinate (FA) potentiation. Activation of capecitabine is a three-step enzymatic process. The final activating enzyme, thymidine phosphorylase, is found in unusually high concentrations in many solid tumours, resulting in preferential delivery of 5-FU to tumour tissues, including that of colorectal cancers, suggesting therapeutic potential in this malignancy. Large, randomized trials have demonstrated that capecitabine fulfils this potential—compared with the widely used ‘‘Mayo’’ regimen of intravenous 5-FU and folinic acid, oral capecitabine (1250 mg/m 2 twice daily) produced a superior response rate and a similar time to disease progression and duration of survival. It was also better tolerated than 5-FU/FA—of seven common fluoropyrimidine-induced toxicities, four were significantly less common with capecitabine. Capecitabine also produced significantly less grade 4 toxicity or toxicity requiring hospitalization, though the hand -foot syndrome that characterizes prolonged, continuous exposure to 5-FU was more common after capecitabine.
Alert correlation in a cooperative intrusion detection framework (2005)

This paper presents the work we have done within the MIRADOR project to design CRIM, a cooperative module for intrusion detection systems (IDS). This module implements functions to manage, cluster, merge and correlate alerts. The clustering and merging functions recognize alerts that correspond to the same occurrence of an attack and create a new alert that merge data contained in these various alerts. Experiments show that these functions significantly reduce the number of alerts. However, we also observe that alerts we obtain are still too elementary to be managed by a security administrator. The purpose of the correlation function is thus to generate global and synthetic alerts. This paper focuses on the approach we suggest to design this function.
RNA Editome Imbalance in Hepatocellular Carcinoma (2014)

Adenosine-to-inosine conversion (A-to-I editing), a posttranscriptional modification on RNA, contributes to extensive transcriptome diversity. A-to-I editing is a hydrolytic deamination process, catalyzed by adenosine deAminase acting on double-stranded RNA (ADAR) family of enzymes. ADARs are essential for normal mammalian development, and disturbance in RNA editing has been implicated in various pathologic disorders, including cancer. Thanks to next-generation sequencing, rich databases of transcriptome evolution for cancer development at the resolution of single nucleotide have been generated. Extensive bioinformatic analysis revealed a complex picture of RNA editing change during transformation. Cancer displayed global hypoediting of Alu-repetitive elements with gene-specific editing pattern. In particular, hepatocellular carcinoma editome is severely disrupted and characterized by hyper- and hypoediting of different genes, such as hyperedited AZIN1 (antizyme inhibitor 1) and FLNB (filamin B, β) and hypoedited COPA (coatomer protein complex, subunit α). In hepatocellular carcinoma, not only the recoding editing in exons, but also the editing in noncoding regions (e.g., Alu-repetitive elements and microRNA) displays such complex editing pattern with site-specific editing trend. In this review, we will discuss current research progress on the involvement of abnormal A-to-I editing in cancer development, more specifically on hepatocellular carcinoma.
Correction of Sickle Cell Disease in Transgenic Mouse Models by Gene Therapy (2001)

Sickle cell disease (SCD) is caused by a single point mutation in the human betaA globin gene that results in the formation of an abnormal hemoglobin [HbS (alpha2betaS2)]. We designed a betaA globin gene variant that prevents HbS polymerization and introduced it into a lentiviral vector we optimized for transfer to hematopoietic stem cells and gene expression in the adult red blood cell lineage. Long-term expression (up to 10 months) was achieved, without preselection, in all transplanted mice with erythroid-specific accumulation of the antisickling protein in up to 52% of total hemoglobin and 99% of circulating red blood cells. In two mouse SCD models, Berkeley and SAD, inhibition of red blood cell dehydration and sickling was achieved with correction of hematological parameters, splenomegaly, and prevention of the characteristic urine concentration defect.
Summary and Recommendations of the Third International Workshop-Conference on Gestational Diabetes Mellitus (1991)

The Third International Workshop-Conference on Gestational Diabetes Mellitus (GDM) was convened in Chicago, Illinois, on 8 November 1990 as an invitational meeting sponsored by the American Diabetes Association with the cooperation of the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the National Diabetes Advisory Board, the Centers for Disease Control, and the Diabetic Pregnancy Study Group of the European Association for the Study of Diabetes. The meeting provided a forum for the review of new information concerning GDM in the areas of diagnosis and prevalence, perinatal and long-range implications, and management strategies.