gebhart/patrepeval huggingface dataset:
A Glu-urea-Lys Ligand-conjugated Lipid Nanoparticle/siRNA System Inhibits Androgen Receptor Expression In Vivo (2016)

The androgen receptor plays a critical role in the progression of prostate cancer. Here, we describe targeting the prostate-specific membrane antigen using a lipid nanoparticle formulation containing small interfering RNA designed to silence expression of the messenger RNA encoding the androgen receptor. Specifically, a Glu-urea-Lys PSMA-targeting ligand was incorporated into the lipid nanoparticle system formulated with a long alkyl chain polyethylene glycol-lipid to enhance accumulation at tumor sites and facilitate intracellular uptake into tumor cells following systemic administration. Through these features, and by using a structurally refined cationic lipid and an optimized small interfering RNA payload, a lipid nanoparticle system with improved potency and significant therapeutic potential against prostate cancer and potentially other solid tumors was developed. Decreases in serum prostate-specific antigen, tumor cellular proliferation, and androgen receptor levels were observed in a mouse xenograft model following intravenous injection. These results support the potential clinical utility of a prostate-specific membrane antigen-targeted lipid nanoparticle system to silence the androgen receptor in advanced prostate cancer.
Fast and Convenient Divergent Synthesis of Aliphatic Ester Dendrimers by Anhydride Coupling (2001)

A novel divergent approach was developed for the synthesis of dendritic aliphatic polyester structures using an acetal-protected anhydride derivative of 2,2-bis(hydroxymethyl)propionic acid as the acylating agent. This divergent synthesis is remarkable, because unlike all others, it only requires a small excess of reagent to achieve quantitative growth, and it requires no means of purification other than a simple solvent extraction or precipitation. A monodisperse sixth generation dendrimer with molecular weight of 30 711 Dalton and 192 masked hydroxyl groups was prepared in high yield and purity using 1,1,1-tris(hydroxyphenyl)ethane as the core molecule. Linear and star-shaped poly(ethylene glycol) (PEG) derivatives of narrow polydispersity were also used as core molecules in the divergent synthesis of dendritic-linear copolymer hybrids up to the fourth generation without requiring any chromatographic purification.
A Possible Role of Ursodeoxycholic Acid in Liver Transplantation (1994)

There are many different causes of graft dysfunction and cholestasis after liver transplantation. These include non-primary function, preservation and reperfusion injury, acute rejection, artery thrombosis, drug toxicity, bile leakage, and bile duct stenosis. Medication with ursodeoxycholic acid (UDCA) has beneficial effects in different cholestatic conditions. The initial rationale for its use after liver transplantation was to alter the bile acid pool to a more atoxic composition, as liver transplantation can be associated with cholestasis and can stimulate the initial bile production. We have consecutively treated 41 patients with primary graft function with UDCA. During the first postoperative month, 17% of the UDCA treated patients had an episode of acute rejection compared with 75% of a historical control group of 8 patients. The results suggest that adjuvant treatment with UDCA reduces acute liver graft rejection. This has to be confirmed by controlled prospective trials; one is presently being carried out in the Nordic countries. Several studies have indicated an immunomodulating capacity of this bile acid and we have recently reported our results from a heart transplant model in the rat, where treatment with UDCA prolonged graft survival. Improvement in surgical technique and postoperative care as well as immunosuppressive treatment has improved the results of liver transplantation. Acute rejection is nowadays a dominating problem after liver transplantation and the inclusion of UDCA may reduce morbidity.
Novel Asn-linked oligosaccharides terminating in GaINAc (1->4)[Fuca(1->3)]GlcNAcB(1-> ) are present in recombinant human Protein C expressed in human kidney 293 cells (1993)

Recombinant human Protein C (rHPC), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC, while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein. In seeking to elucidate the molecular basis for the improved efficacy of the recombinant antithrombotic drug, we focused on the carbohydrate moiety of rHPC. Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites. Glycosyl composition analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC. In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc. The Asn-linked oligosaccharides of rHPC were released by N-glycanase and separated into 25 fractions by high-pH anion-exchange chromatography. The most abundant oligosaccharides were structurally characterized by glycosyl composition and linkage analysis, in conjunction with 1H-NMR spectroscopy at 600 MHz. The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.), in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.), and/or in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.). Since the latter trisaccharide was first [Yan, S.B., Chao, B.Y. and Van Halbeek,H. (1992) J. Cell. Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.) terminal trisaccharide the PC-293 determinant. The PC-293-containing oligosaccharides may contribute to the higher anticoagulant activity of rHPC as compared to plasma HPC.
Extracting structured data from Web pages (2003)

Many web sites contain large sets of pages generated using a common template or layout. For example, Amazon lays out the author, title, comments, etc. in the same way in all its book pages. The values used to generate the pages (e.g., the author, title,...) typically come from a database. In this paper, we study the problem of automatically extracting the database values from such template-generated web pages without any learning examples or other similar human input. We formally define a template, and propose a model that describes how values are encoded into pages using a template. We present an algorithm that takes, as input, a set of template-generated pages, deduces the unknown template used to generate the pages, and extracts, as output, the values encoded in the pages. Experimental evaluation on a large number of real input page collections indicates that our algorithm correctly extracts data in most cases.
Hydrogenolysis of Cellulose over Cu‐Based Catalysts—Analysis of the Reaction Network (2014)

A series of polyols, carbohydrates, and cellulose were tested in the aqueous, CuO/ZnO/Al2O3-catalyzed hydrogenolysis reaction at 245 °C and 50 bar H2. The compositions of liquid-phase products were analyzed; based on these results a unified reaction mechanism is proposed that accounts for the observed product distribution. Elementary transformations such as dehydration, dehydrogenation/hydrogenation, Lobry de Bruyn-van Ekenstein isomerization and retro-aldol cleavage were identified as most important for controlling the selectivity of simple polyols and carbohydrates. For cellulose the product distribution is considerably different than for glucose or sorbitol, indicating a change in the reaction pathway. Therefore, next to the traditional hydrolysis of the glycosidic bond, an additional depolymerization mechanism involving only the reducing ends of cellulose oligomers is proposed to account for this observation.
Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombinant ALR and demonstration of tissue distribution. (1994)

A full-length cDNA clone encoding a purified augmenter of liver regeneration (ALR) factor prepared from the cytosol of weanling rat livers was isolated. The 1.2-kb cDNA included a 299-bp 5' untranslated region, a 375-bp coding region, and a 550-bp 3' untranslated region. It encoded a protein consisting of 125 amino acids. The molecular weight of ALR calculated from the cDNA was 15,081, which is consistent with the size estimated by SDS/PAGE under reducing conditions. The molecular weight of the purified native ALR estimated by SDS/PAGE under nonreducing conditions was approximately 30,000; thus ALR apparently has a homodimeric structure. The recombinant ALR produced by expression of the cDNA in COS cells was tested in vivo in the canine Eck fistula model and found to have potency equivalent to the purified native ALR. The 125-aa sequence deduced from the rat ALR cDNA shows 50% homology to the amino acid sequence of the gene for oxidative phosphorylation and vegetative growth in the yeast Saccharomyces cerevisiae.
Square-ring microstrip antenna with a cross strip for compact circular polarization operation (1999)

A novel design of square-ring microstrip antenna with a cross strip for achieving compact circular polarization (CP) operation is proposed and experimentally studied. The cross strip can be placed in the centerlines or diagonals of the square-ring patch. Either design can make its excited fundamental mode patch surface current path much longer than that in a conventional square microstrip antenna with same antenna size. By incorporating a small tuning stub for splitting the fundamental mode into two near-degenerate resonant modes with equal amplitudes and 90/spl deg/ phase-difference compact CP operation for the proposed design can he obtained.
Glycogen Synthase Kinase-3:  Properties, Functions, and Regulation (2001)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGlycogen Synthase Kinase-3: Properties, Functions, and RegulationAdnan Ali, Klaus P. Hoeflich, and James R. WoodgettView Author Information Division of Experimental Therapeutics, Ontario Cancer Institute, 610-University Avenue, Toronto, Ontario, Canada M5G 2M9 Cite this: Chem. Rev. 2001, 101, 8, 2527–2540Publication Date (Web):July 4, 2001Publication History Received21 December 2000Published online4 July 2001Published inissue 1 August 2001https://pubs.acs.org/doi/10.1021/cr000110ohttps://doi.org/10.1021/cr000110oresearch-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views4054Altmetric-Citations313LEARN 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:Cell and molecular biology,Cell signaling,Genetics,Peptides and proteins,Post-translational modification Get e-Alerts
Adapting ranking SVM to document retrieval (2006)

The paper is concerned with applying learning to rank to document retrieval. Ranking SVM is a typical method of learning to rank. We point out that there are two factors one must consider when applying Ranking SVM, in general a "learning to rank" method, to document retrieval. First, correctly ranking documents on the top of the result list is crucial for an Information Retrieval system. One must conduct training in a way that such ranked results are accurate. Second, the number of relevant documents can vary from query to query. One must avoid training a model biased toward queries with a large number of relevant documents. Previously, when existing methods that include Ranking SVM were applied to document retrieval, none of the two factors was taken into consideration. We show it is possible to make modifications in conventional Ranking SVM, so it can be better used for document retrieval. Specifically, we modify the "Hinge Loss" function in Ranking SVM to deal with the problems described above. We employ two methods to conduct optimization on the loss function: gradient descent and quadratic programming. Experimental results show that our method, referred to as Ranking SVM for IR, can outperform the conventional Ranking SVM and other existing methods for document retrieval on two datasets.
New insights into the role of cytokines in asthma (2001)

Asthma is a triad of intermittent airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. From an aetiological standpoint, asthma is a heterogeneous disease, but often appears as a form of immediate hypersensitivity. Many patients with asthma have other manifestations of atopy, such as rhinitis or eczema. Even among non-atopic patients with asthma, the pathophysiology of airway constriction is similar, raising the hypothesis that alternative mechanisms of mast cell degranulation may underlie the disease. The primary inflammatory lesion of asthma consists of accumulation of CD4(+) T helper type 2 (TH2) lymphocytes and eosinophils in the airway mucosa. TH2 cells orchestrate the asthmatic inflammation through the secretion of a series of cytokines, particularly interleukin 4 (IL-4), IL-13, IL-5, and IL-9. IL-4 is the major factor regulating IgE production by B cells, and is required for optimal TH2 differentiation. However, blocking IL-4 is not sufficient to inhibit the development of asthma in experimental models. In contrast, inhibition of IL-13, another TH2 cytokine whose signal transduction pathway overlaps with that of IL-4, completely blocks airway hyperreactivity in mouse asthma models. IL-5 is a key factor for eosinophilia and could therefore be responsible for some of the tissue damage seen in chronic asthma. IL-9 has pleiotropic activities on allergic mediators such as mast cells, eosinophils, B cells and epithelial cells, and might be a good target for therapeutic interventions. Finally, chemokines, which can be produced by many cell types from inflamed lungs, play a major role in recruiting the mediators of asthmatic inflammation. Genetic studies have demonstrated that multiple genes are involved in asthma. Several genome wide screens point to chromosome 5q31--33 as a major susceptibility locus for asthma and high IgE values. This region includes a cluster of cytokine genes, and genes encoding IL-3, IL-4, IL-5, IL-9, IL-13, granulocyte macrophage colony stimulating factor, and the beta chain of IL-12. Interestingly, for some of these cytokines, a linkage was also established between asthma and their receptor. Another susceptibility locus has been mapped on chromosome 12 in a region that contains other potential candidate cytokine genes, including the gene encoding interferon gamma, the prototypical TH1 cytokine with inhibitory activities for TH2 lymphocytes. Taken together, both experimental and genetic studies point to TH2 cytokines, such as IL-4, IL-13, IL-5, and IL-9, as important targets for therapeutic applications in patients with asthma.
Cell dynamics in the germinal center of the human tonsil. (1996)

Apoptosis of the human tonsillar germinal center was studied by means of immunocytochemical methods. It is generally accepted that the germinal center of the lymphoid tissues plays an important role both in cell proliferation and cell death. Although many studies on cell proliferation have been reported, the cell death mechanism is not yet well understood. According to recent studies, apoptosis is the result of programmed, not pathological cell death, and it plays an important role in the maintenance, immunity and development of life. The present study showed that the tingible body was a mass of nuclear chromatin of dead cells, and that cells with a tingible body are macrophages, called tingible-body macrophages. The purpose of this study was to examine the relationship between tingible-body macrophages and apoptosis. The structure of tingible-body macrophages were observed by immunostaining methods.
Informatics-based, highly accurate, noninvasive prenatal paternity testing (2012)

A noninvasive paternity test using informatics-based analysis of single-nucleotide polymorphism array measurements accurately determined paternity early in pregnancy.
Inhibition of the production and effects of interleukins‐1 and tumor necrosis factor α in rheumatoid arthritis (1995)

This review has summarized information published over the last 5 years on the presence and pathophysiologic role of IL-1 and TNF alpha in RA. The evidence to date shows that 5 of 6 criteria for identifying mediators of tissue damage in human autoimmune diseases are satisfied (Table 1). The last criterion, prevention of clinical progression in patients with RA, is currently being evaluated. Many new therapeutic approaches are currently being developed, including the use of soluble receptors to IL-1 or TNF, monoclonal antibodies to TNF alpha, a specific IL-1 receptor antagonist, and gene therapy with the latter molecule. It should be emphasized that both IL-1 and TNF alpha play important roles in normal host defense; the possible complications of blocking their production or effects need to be carefully evaluated in long-term studies. A recent review has emphasized that although IL-1 and TNF alpha have many overlapping biologic properties, each may exhibit distinct effects in joint disease (99). Anti-TNF treatment may be primarily antiinflammatory but blocking IL-1 may be more effective in preventing cartilage destruction (100). The possibility exists that simultaneous inhibition of TNF alpha and IL-1 may be more therapeutically efficacious than blockade of either agent alone, as was recently demonstrated with IL-1ra and soluble TNF receptors in bacterial cell wall-induced arthritis in rats (101). The next level of clinical studies in rheumatoid arthritis should include the use of two biologic response modifiers together, or one agent combined with a more traditional form of therapy.
Amyloid-β Deposits Lead to Retinal Degeneration in a Mouse Model of Alzheimer Disease (2008)

Amyloid-beta deposits accumulate with age in the retina of a transgenic mouse model of AD. The amyloid-beta loads are accompanied by increased immunoreactivity for MCP-1, F4/80, and TUNEL-positive profiles in the RGC layer. The results suggest that amyloid-beta causes neurodegeneration in the retina of the doubly mutant transgenic mouse model of AD.
Characterization of the integrin alpha v beta 6 as a fibronectin-binding protein. (1992)

Integrins are a complex family of divalent cation-dependent cell adhesion receptors composed of one alpha and one beta subunit noncovalently bound to one another. A subset of integrins contains the alpha v subunit in association with one of several beta subunits (e.g. beta 3, beta 5, beta 1). We have recently identified a novel integrin beta subunit, beta 6, that is present in a number of epithelial cell lines. Using a polyclonal antibody raised against the carboxyl-terminal peptide of beta 6, we have now identified the integrin heterodimer, alpha v beta 6, on the surface of two human carcinoma cell lines. Using affinity chromatography of lysates from the pancreatic carcinoma cell line, FG-2, we demonstrate that alpha v beta 6 binds to fibronectin, but not to vitronectin or collagen I. In contrast, the alpha v beta 5 integrin, which is also expressed on FG-2 cells, binds exclusively to vitronectin. Immobilized collagen I does not interact with alpha v integrins, but binds beta 1-containing integrins. Both alpha v beta 6 and alpha v beta 5 are eluted from their respective immobilized ligands by a hexa-peptide containing the sequence Arg-Gly-Asp (RGD). RGD is highly effective in the presence of Ca2+, somewhat less effective in Mg2+, and virtually inactive in Mn2+. These results suggest that alpha v beta 6 functions as an RGD-dependent fibronectin receptor in FG-2 carcinoma cells. In agreement with this notion, cell adhesion assays show that FG-2 cell attachment to fibronectin is only partially inhibited by anti-beta 1 integrin antibodies, implying that other fibronectin receptors may be involved. Taken together with recent reports on the vitronectin receptor function of alpha v beta 5, our results suggest that the previously described carcinoma cell integrin, alpha v beta x (Cheresh, D. A., Smith, J. W., Cooper, H. M., and Quaranta, V. (1989) Cell 57, 59-69), is a mixture of at least two different receptors: alpha v beta 5, mediating adhesion to vitronectin, and alpha v beta 6, mediating adhesion to fibronectin.
Identification of a Drosophila activin receptor. (1993)

Activins are cytokines of the transforming growth factor beta superfamily that control various events during vertebrate embryo development and cell differentiation in the adult, and act through transmembrane receptors that contain a cytoplasmic protein-serine/threonine kinase domain. We describe the identification, deduced primary structure, and expression pattern of Atr-II, a receptor serine/threonine kinase found in Drosophila. With the exception of the spacing of 10 cysteine residues, the extracellular domain of Atr-II is very dissimilar from those of vertebrate activin receptors, yet it binds activin with high affinity and specificity. The kinase domain sequence of Atr-II is 60% identical to those of activin receptors from vertebrates, suggesting similarities in their signaling mechanisms. Maternal Atr-II transcript and its product are abundant in the oocyte. During development, the highest levels of Atr-II transcript and protein are observed in the mesoderm and gut. The possible role of an activin signaling system in Drosophila development is discussed.
Regulation of the lipidation of β-secretase by statins (2007)

Statins inhibit the dimerization of beta-secretase [BACE (beta-site amyloid precursor protein-cleaving enzyme)] by inhibiting the lipidation of BACE and associated proteins. Our studies have demonstrated a clearly defined temporal sequence for these reactions in the assembly of the BACE complex, which may provide targets for the treatment of Alzheimer's disease.
Human Estrogen Receptor β-Gene Structure, Chromosomal Localization, and Expression Pattern1 (1997)

The estrogen receptor (ER) is a ligand-activated transcription factor that mediates the effects of the steroid hormone 17 beta-estradiol, in both males and females. Since the isolation and cloning of ER, the consensus has been that only one such receptor exists. The finding of a second subtype of ER (ER beta) has caused considerable excitement amongst endocrinologists. In this article, we present data regarding the genomic structure and chromosomal localization of the human ER beta gene, demonstrating that two independent ER genes do exist in the human. Furthermore, we present data regarding the tissue distribution of human ER beta, showing that this receptor is expressed in multiple tissues. For instance, ER beta is found in developing spermatids of the testis, a finding of potential relevance for the ongoing debate on the effects of environmental estrogens on sperm counts. In addition, we find ER beta in ovarian granulosa cells, indicating that estrogens also participate in the regulation of follicular growth in the human.