gebhart/patrepeval huggingface dataset:
PLASMA LIPID TRANSFER PROTEINS (1995)

The plasma lipid transfer proteins mediate the transfer and exchange of phospholipids and neutral lipids between the plasma lipoproteins. The cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) are members of the lipid transfer/lipopolysaccharide binding gene family. The CETP contains binding sites for cholesteryl ester and triglycerides and probably acts by a carrier-mediated mechanism. The CETP mediates catabolism of HDL cholesteryl esters, with secondary decreases in HDL size and protein content. The CETP plays a central role in reverse cholesterol transport i.e. the centripetal movement of cholesterol from the periphery back to the liver. CETP gene expression is upregulated in response to increased dietary cholesterol or endogenous hypercholesterolemia. Although CETP reduces HDL levels, its role in reverse cholesterol transport suggests a dominant anti-atherogenic action in vivo.
JavaScript instrumentation for browser security (2007)

It is well recognized that JavaScript can be exploited to launch browser-based security attacks. We propose to battle such attacks using program instrumentation. Untrusted JavaScript code goes through a rewriting process which identifies relevant operations, modifies questionable behaviors, and prompts the user (a web page viewer) for decisions on how to proceed when appropriate. Our solution is parametric with respect to the security policy-the policy is implemented separately from the rewriting, and the same rewriting process is carried out regardless of which policy is in use. Be-sides providing a rigorous account of the correctness of our solution, we also discuss practical issues including policy management and prototype experiments. A useful by-product of our work is an operational semantics of a core subset of JavaScript, where code embedded in (HTML) documents may generate further document pieces (with new code embedded) at runtime, yielding a form of self-modifying code.
Mechanisms of Monophosphoryl Lipid A Augmentation of Host Responses to Recombinant HagB fromPorphyromonas gingivalis (2002)

Porphyromonas gingivalis, a gram-negative, black-pigmented anaerobe, is among the microorganisms implicated in the etiology of adult periodontal disease. This bacterium possesses a number of factors, including hemagglutinins, of potential importance in virulence. Our laboratory has shown the induction of protection to P. gingivalis infection after subcutaneous immunization with recombinant hemagglutinin B (rHagB). The purpose of this study was to determine if humoral antibody responses are induced after intranasal (i.n.) immunization of rHagB and if monophosphoryl lipid A (MPL), a nontoxic derivative of the lipid A region of lipopolysaccharide, acts as a mucosal adjuvant and potentiates responses to rHagB. Further, the effects of MPL on the nature of the response to HagB and on the costimulatory molecules B7-1 and B7-2 on different antigen-presenting cells (APC) were evaluated. Groups of BALB/c mice were immunized three times (2-week intervals) by the i.n. route with HagB (20 microg) alone or with MPL (25 microg). A group of nonimmunized mice served as control. Serum and saliva samples were collected prior to immunization and at approximately 2-week intervals and evaluated for serum immunoglobulin G (IgG) and IgG subclass and for salivary IgA antibody activity by enzyme-linked immunosorbent assay. Mice immunized with rHagB plus MPL had significantly higher salivary IgA (P < 0.05) and serum IgG (P < 0.05) anti-HagB responses than mice immunized with rHagB alone. The IgG1 and IgG2a subclass responses seen in mice immunized with rHagB plus MPL were significantly higher (P < 0.05) than those seen in mice immunized with rHagB only. Further, the IgG2a/IgG1 ratio in the latter group was approximately 1, whereas in mice immunized with rHagB plus MPL the ratio was <1. These results provide evidence for the participation of T helper (Th) 1 and Th2 cells in responses to rHagB and that MPL potentiates a type 2 response to HagB. MPL was also shown to preferentially up-regulate B7-2 expression on B cells, whereas a preferential increase in B7-1 costimulatory molecule was seen on macrophages and dendritic cells. These results provide evidence that MPL exerts a differential regulation in the expression of costimulatory molecules on APC.
Increased Incidence of Metabolic Syndrome after Hematopoietic Stem Cell Transplantation. (2005)

Abstract Metabolic syndrome (MS), formerly known as X-syndrome, is a clinical and laboratory entity involving obesity, hypertension, and borderline fasting glucose, high triglyceride and low HDL cholesterol levels, that is considered to be a counterpart of insulin resistance with overweight playing a key role; increased insulin, leptin, adiponectin and resistin levels link its various features and some common flanking findings such as hypercholesterolemia, hyperuricemia and hyperferritinemia. Clinical and laboratory data reminiscent of metabolic syndrome are commonly observed after hematopoietic stem cell transplantation (HSCT). We evaluated the body mass index (BMI), routine lipid and glucidic markers, and common endocrinologic parameters in 37 HSCT recipients (19 males; median age 45 years, range 26–60; 22 autologous, 15 allogeneic) whose continuous CR lasted at least five years; insulin (baseline and after an oral glucose test), leptin, resistin, TNF-alpha and adiponectin levels were also detemined. Diabetic HSCT recipients were excluded. The control group consisted of 23 healthy volunteers of comparable age and sex without a family history of diabetes. In comparison with the controls, the HSCT recipients had significantly increased levels of TNF (median 10.05 vs 9.3 pg/mL, p=0.034), insulin (13.6 vs 10.1 mIU/mL, p=0.029) and leptin (13.71 vs 3.69 ng/mL, p= 0.02); there were no significant differences in adiponectin and resistin levels, BMI or the other considered parameters. In comparison with the other HSCT recipients, the 16 patients with higher baseline insulin levels (&amp;gt;15 mIU/mL) had significantly higher leptin levels (median 23.665 vs 8.3, p&amp;lt;0.001), and also different total cholesterol (231 vs 202 mg/dL, p&amp;lt;0.01), HDL-cholesterol (58 vs 68 mg/dL, p&amp;lt;0.01), triglyceride (150 vs 92 mg/dL, p&amp;lt;0.01) and ferritin levels (635 vs 491 ng/mL, p&amp;lt;0.01). This preliminary investigation show an increased prevalence of MS findings in HSCT recipients, and a relationship between baseline insulin levels and some common laboratory features of MS. Unlike in spontaneously occurring cases, obesity does not seem to play a primary role; furthermore, BMI and adiponectin were not significantly increased. However, the significant increase in TNF (another inducer of insulin resistance) suggests a possible pathogenetic sequence of post-HSCT MS linking TNF, insulin and leptin. The association between MS and the development of cardiovascular diseases is well known, but HSCT may, in alternative ways, induce a long-term metabolic derangement that affects the life expectancy of patients already cured of their baseline neoplastic disease.
Irinophore C: A Liposome Formulation of Irinotecan with Substantially Improved Therapeutic Efficacy against a Panel of Human Xenograft Tumors (2008)

Irinophore C improved CPT-11/SN-38 pharmacokinetics, promoted tumor drug accumulation, and increased therapeutic efficacy in a panel of five distinct human tumor xenografts.
Ursodeoxycholic Acid Therapy in Treatment of Primary Sclerosing Cholangitis (1994)

The beneficial effects of ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis led to therapeutic trials with this bile acid for the treatment of PSC. In two prospective placebo-controlled trials, UDCA led to a significant improvement of AP, GGT, ALT, AST, and, in one study, also of serum bilirubin. In both studies liver histology improved significantly, mainly due to a decrease of cellular infiltrates in portal triads. Pruritus and fatigue improved in approximately one-third of the patients, but, compared to placebo, this effect was not significant. In a follow-up study after on average 3.1 years of UDCA treatment, 7/43 of the patients with stages I-IV disease developed a stenosis of the common bile duct which was effectively treated by endoscopic dilatations. Of 57 patients with PSC included since 1987 in the study, 14 dropped out and of these in 10 information on the outcome is available. In patients treated by UDCA and, whenever necessary, by endoscopic dilatations, the frequency of transplantations was significantly reduced in comparison to patients who dropped out of the study. Bile duct carcinoma developed in 5% of our patients. The data indicate that treatment of patients with PSC with UDCA and by endoscopic dilatations of common duct stenoses is promising. In patients with endstage disease, the only effective therapy is liver transplantation. Therefore, the early diagnosis of the disease seems very important.
Induction of antigen-specific hyporesponsiveness by transplantation of hemopoietic cells containing an MHC class I transgene regulated by a lymphocyte-specific promoter. (1998)

We explored a novel approach to tolerance induction by the transplantation of bone marrow (BM) cells (BMCs) that themselves do not express a foreign histocompatibility Ag, but which give rise to mature lymphocytes that do so. Lines of transgenic (FVB) mice were generated that contained an MHC class I Dd cDNA regulated by a CD2 promoter. Because the CD2 promoter is lymphocyte-specific and activated relatively late in lymphocyte ontogeny, Dd is expressed on most mature lymphocytes in the periphery but only on developing B cells in the BM of transgenic mice. Transgenic BMCs are tolerogenic and reproducibly engraft in nontransgenic mice using a conditioning regimen that is nonpermissive for the engraftment of conventional (MHC promoter) Dd-transgenic BMCs. Engrafted BMCs generate transgene-expressing lymphocytes and confer a state of Ag-specific hyporesponsiveness on the host that is primarily attributable to a peripheral mechanism. The strategies by which tolerance can be optimized in this system are discussed.
Transcription Factors GATA-3 and RORγt Are Important for Determining the Phenotype of Allergic Airway Inflammation in a Murine Model of Asthma (2013)

In refractory asthma, neutrophils, rather than eosinophils, often predominate in the airways. Neutrophilic airway inflammation appears to be resistant to steroids and may be related to the Th17, rather than the Th2, cytokine milieu. However, the role of GATA-3 and RORγt, transcription factors for Th2 and Th17 cell differentiation, respectively, in the pathogenesis of steroid-insensitive asthma remains unclear. To examine the effect of GATA-3- and RORγt-overexpression backgrounds on airway inflammation and steroid sensitivity, we generated two strains of transgenic mice overexpressing GATA-3 or RORγt. Mice were sensitized and challenged with OVA. Some OVA-sensitized/challenged mice were treated with dexamethasone, anti-IL-17 Ab, CXCR2 antagonist, or anti-IL-6R Ab to demonstrate their therapeutic effects on airway inflammation. Although Ag-specific airway inflammation and hyperresponsiveness were induced in each mouse, the phenotype of inflammation showed a distinct difference that was dependent upon the genotype. GATA-3-overexpressing mice exhibited steroid-sensitive eosinophilic inflammation with goblet cell hyperplasia and mucus hyperproduction under Th2-biased conditions, and RORγt-overexpressing mice developed steroid-insensitive neutrophilic inflammation under Th17-biased conditions. The levels of keratinocyte-derived chemokine, MIP-2, IL-6, and other neutrophil chemotaxis-related mediators were significantly elevated in OVA-exposed RORγt-overexpressing mice compared with wild-type mice. Interestingly, airway hyperresponsiveness accompanied by neutrophilic airway inflammation in RORγt-overexpressing mice was effectively suppressed by anti-IL-17 Ab, CXCR2 antagonist, or anti-IL-6R Ab administration. In conclusion, our results suggest that the expression levels of GATA-3 and RORγt may be important for determining the phenotype of asthmatic airway inflammation. Furthermore, blockade of the Th17-signaling pathway may be a treatment option for steroid-insensitive asthma.
Structure, organization, and expression of the lct gene for lacticin 481, a novel lantibiotic produced by Lactococcus lactis (1993)

The structural gene for the lactococcal lantibiotic lacticin 481 (lct) has been identified and cloned using a degenerated 20-mer DNA oligonucleotide based on the amino-terminal 7 amino acid residues of the purified protein. The transcription of the lct gene was analyzed, and its promoter was mapped. DNA sequence analysis of the lct gene revealed an open reading frame encoding a peptide of 51 amino acids. Comparison of its deduced amino acid sequence with the amino-terminal sequence and the amino acid composition of lacticin 481 indicates that the 51-residue peptide is prelacticin 481, containing a 27-residue carboxyl-terminal propeptide and a 24-residue amino-terminal leader peptide which lacks the properties of a typical signal sequence and which is significantly different from the leaders of other lantibiotics. The predicted amino acid sequence of prolacticin 481 contains 3 cysteines, 2 serines, and 2 threonines which were not detectable in amino acid analyses of mature lacticin 481. Based on these results and on characterization by two-dimensional NMR techniques, a structural model is proposed in which 2 cysteine residues are involved in lanthionine and one in beta-methyllanthionine formation, and a 4th threonine residue is dehydrated. This model predicts a molecular mass for lacticin 481 of 2,901, which is in excellent agreement with that obtained from mass spectrometry.
CLE peptide signaling during plant development (2009)

Peptide signaling in plants is a rapid developing area of research which focuses on so called peptide hormones. These signaling molecules are utilized for inter-cellular communication in different developmental processes, beside the usage of the more well-known phytohormones. Probably the best studied peptide ligands in plants are the CLAVATA3 (CLV3)/ENDOSPERM SURROUNDING REGION (ESR)-related (CLE) proteins. This family of signaling polypeptides is comprised of 32 members in Arabidopsis and, with the exception of the presence of related proteins in some parasitic worms, is restricted to the plant kingdom. CLV3 is one of the founding CLE genes and is involved in stem cell niche maintenance in apical meristems during plant development. While the CLV signaling pathway is well characterized with the identification of three receptors and a stem-cell-promoting transcription factor as target, the functioning of other family members is not or poorly understood. The recent discoveries of a new type of receptor involved in CLV signaling and a functional pathway for CLE40 in root development mark the rapid progress that is made in the area of CLE peptide signaling. This review gives an overview how CLE peptides are used as signaling molecules, and how they are involved in cell-to-cell communication in concert with different known and unknown receptors in a range of developmental processes during plant development.
Clarification of the Oxidation State of Cobalt Corroles in Heterogeneous and Homogeneous Catalytic Reduction of Dioxygen (2008)

Co(III) corroles were investigated as efficient catalysts for the reduction of dioxygen in the presence of perchloric acid in both heterogeneous and homogeneous systems. The investigated compounds are (5,10,15-tris(pentafluorophenyl)corrole)cobalt (TPFCor)Co, (10-pentafluorophenyl-5,15-dimesitylcorrole)cobalt (F 5PhMes 2Cor)Co, and (5,10,15-trismesitylcorrole)cobalt (Mes 3Cor)Co, all of which contain bulky substituents at the three meso positions of the corrole macrocycle. Cyclic voltammetry and rotating ring-disk electrode voltammetry were used to examine the catalytic activity of the compounds when adsorbed on the surface of a graphite electrode in the presence of 1.0 M perchloric acid, and this data is compared to results for the homogeneous catalytic reduction of O 2 in benzonitrile containing 10 (-2) M HClO 4. The corroles were also investigated as to their redox properties in nonaqueous media. A reversible one-electron oxidation occurs at E 1/2 values between 0.42 and 0.89 V versus SCE depending upon the solvent and number of fluorine substituents on the compounds, and this is followed by a second reversible one-electron abstraction at E 1/2 = 0.86 to 1.18 V in CH 2Cl 2, THF, or PhCN. Two reductions of each corrole are also observed in the three solvents. A linear relationship is observed between E 1/2 for oxidation or reduction and the number of electron-withdrawing fluorine groups on the compounds, and the magnitude of the substituent effect is compared to what is observed in the case of tetraphenylporphyrins containing meso -substituted C 6F 5 substituents. The electrochemically generated forms of the corrole can exist with Co(I), Co(II), or Co(IV) central metal ions, and the site of the electron-transfer in each oxidation or reduction of the initial Co(III) complex was examined by UV-vis spectroelectrochemistry. ESR characterization was also used to characterize singly oxidized (F 5PhMes 2Cor)Co, which is unambiguously assigned as a Co(III) radical cation rather than the expected Co(IV) corrole with an unoxidized macrocyclic ring.
Nonsteroidal antiinflammatory drug‐induced gastroduodenal injury in children (1995)

We conclude that NSAID use in children with arthritis frequently leads to gastroduodenal injury, with an estimated incidence and relative risk that are comparable to the rates found in adults with arthritis taking NSAIDs, but that hospitalization or death as a result of this injury is uncommon.
SqueezeNext: Hardware-Aware Neural Network Design (2018)

One of the main barriers for deploying neural networks on embedded systems has been large memory and power consumption of existing neural networks. In this work, we introduce SqueezeNext, a new family of neural network architectures whose design was guided by considering previous architectures such as SqueezeNet, as well as by simulation results on a neural network accelerator. This new network is able to match AlexNet's accuracy on the ImageNet benchmark with 112× fewer parameters, and one of its deeper variants is able to achieve VGG-19 accuracy with only 4.4 Million parameters, (31× smaller than VGG-19). SqueezeNext also achieves better top-5 classification accuracy with 1.3× fewer parameters as compared to MobileNet, but avoids using depthwise-separable convolutions that are inefficient on some mobile processor platforms. This wide range of accuracy gives the user the ability to make speed-accuracy tradeoffs, depending on the available resources on the target hardware. Using hardware simulation results for power and inference speed on an embedded system has guided us to design variations of the baseline model that are 2.59×/8.26× faster and 2.25×/7.5× more energy efficient as compared to SqueezeNet/AlexNet without any accuracy degradation.
Nanostructures and Functional Materials Fabricated by Interferometric Lithography (2010)

Interferometric lithography (IL) is a powerful technique for the definition of large-area, nanometer-scale, periodically patterned structures. Patterns are recorded in a light-sensitive medium, such as a photoresist, that responds nonlinearly to the intensity distribution associated with the interference of two or more coherent beams of light. The photoresist patterns produced with IL are a platform for further fabrication of nanostructures and growth of functional materials and are building blocks for devices. This article provides a brief review of IL technologies and focuses on various applications for nanostructures and functional materials based on IL including directed self-assembly of colloidal nanoparticles, nanophotonics, semiconductor materials growth, and nanofluidic devices. Perspectives on future directions for IL and emerging applications in other fields are presented.
Bronchial reactivity pattern in nonasthmatic parents of asthmatics. (1988)

Genetic mechanisms have been proposed to explain the presence of asthma in families. A methacholine challenge can identify individuals with bronchial reactivity (a hallmark of asthma). It may then be possible to determine whether the presence of non-specific bronchial reactivity, as detected by a methacholine response, has potential as a genetic marker. Thirty-one non-asthmatic parent pairs of asthmatic children were selected from asthma (AF) families enrolled in a Natural History of Asthma study. Parent pairs were chosen if both gave negative responses to a modified National Heart, Lung and Blood Institute questionnaire on asthma. The methacholine response of these parents of asthmatic children had a bimodal distribution. These results show that the methacholine response can mark bronchial reactivity without the presence of clinical asthma and that a familial component of bronchial reactivity exists which may be transmitted from one generation to the next.
Mechanism-Based Inactivation (MBI) of Cytochrome P450 Enzymes: Structure–Activity Relationships and Discovery Strategies To Mitigate Drug–Drug Interaction Risks (2012)

ADVERTISEMENT RETURN TO ISSUEPREVPerspectiveNEXTMechanism-Based Inactivation (MBI) of Cytochrome P450 Enzymes: Structure–Activity Relationships and Discovery Strategies To Mitigate Drug–Drug Interaction RisksSuvi T. M. Orr†, Sharon L. Ripp‡, T. Eric Ballard†, Jaclyn L. Henderson†, Dennis O. Scott§, R. Scott Obach‡, Hao Sun‡, and Amit S. Kalgutkar*§View Author Information‡ †Worldwide Medicinal Chemistry and ‡Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States§ Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, 620 Memorial Drive, Cambridge, Massachusetts 02139, United States*Phone: (617) 551-3336. E-mail: [email protected]Cite this: J. Med. Chem. 2012, 55, 11, 4896–4933Publication Date (Web):March 12, 2012Publication History Received15 January 2012Published online27 March 2012Published inissue 14 June 2012https://pubs.acs.org/doi/10.1021/jm300065hhttps://doi.org/10.1021/jm300065hreview-articleACS PublicationsCopyright © 2012 American Chemical SocietyRequest reuse permissionsArticle Views13560Altmetric-Citations168LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Bioinorganic chemistry,Genetics,Inhibitors,Metabolism,Peptides and proteins Get e-Alerts
Metastatic Potential Is Positively Correlated with Cell Surface Sialylation of Cultured Murine Tumor Cell Lines (1981)

The ability of murine tumor cells to metastasize spontaneously from subcutaneous sites is positively correlated with the total sialic acid content of the cells in culture, the degree to which the sialic acid is exposed on the tumor cell surface, and, most strongly, with the degree of sialylation of galactosyl and N-acetylgalactosaminyl residues in cell surface glycoconjugates. These findings suggest that sialic acid on the cell surface may play a role in tumor cell metastasis.