gebhart/patrepeval huggingface dataset:
Dual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomas (2010)

Primary effusion lymphoma (PEL) constitutes a subset of non-Hodgkin lymphoma whose incidence is highly increased in the context of HIV infection. Kaposi sarcoma-associated herpesvirus is the causative agent of PEL. The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a critical role in cell proliferation and survival, and this pathway is dysregulated in many different cancers, including PEL, which display activated PI3K, Akt, and mammalian target of rapamycin (mTOR) kinases. PELs rely heavily on PI3K/Akt/mTOR signaling, are dependent on autocrine and paracrine growth factors, and also have a poor prognosis with reported median survival times of less than 6 months. We compared different compounds that inhibit the PI3K/Akt/mTOR pathway in PEL. Although compounds that modulated activity of only a single pathway member inhibited PEL proliferation, the use of a novel compound, NVP-BEZ235, that dually inhibits both PI3K and mTOR kinases was significantly more efficacious in culture and in a PEL xenograft tumor model. NVP-BEZ235 was effective at low nanomolar concentrations and has oral bioavailability. We also report a novel mechanism for NVP-BEZ235 involving the suppression of multiple autocrine and paracrine growth factors required for lymphoma survival. Our data have broad applicability for the treatment of cytokine-dependent tumors with PI3K/mTOR dual inhibitors.
Insulin Receptor Knockout Mice (2003)

To examine the role of the insulin receptor in fuel homeostasis, we and others have carried out genetic ablation studies in mice. Mice lacking insulin receptors are born with normal features, but develop early postnatal diabetes and die of ketoacidosis. In contrast, mice lacking insulin receptors in specific cell types as a result of conditional mutagenesis develop mild metabolic and reproductive abnormalities. These experiments have uncovered novel functions of insulin receptors in tissues such as brain and pancreatic beta-cells. Combined knockout studies of insulin and Igf1 receptors indicate that the insulin receptor also promotes embryonic growth. Experimental crosses of mice with insulin receptor haploinsufficiency have been instrumental to the genetic analysis of insulin action by enabling us to assign specific roles to different insulin receptor substrates and identify novel elements in insulin signaling.
Hereditary nonpolyposis colorectal cancer: Review of clinical, molecular genetics, and counseling aspects (1996)

Lynch syndrome, or hereditary nonpolyposis colon cancer (HNPCC), is an autosomal-dominant disease accounting for approximately 1-5% of all colorectal cancer cases. Due to the lack of pathognomonic morphological or biomolecular markers, HNPCC has traditionally posed unique problems to clinicians and geneticists alike, both in terms of diagnosis and clinical management. Recently, novel insight into the pathogenesis of this syndrome has been provided by the identification of its molecular basis. In HNPCC families, germline mutations in any of four genes encoding proteins of a specialized DNA repair system, the mismatch repair, predispose to cancer development. Mutations in mismatch repair genes lead to an overall increase of the mutation rate and are associated with a phenotype of length instability of microsatellite loci. The present report summarizes the clinicopathological aspects of HNPCC and reviews the most recent molecular and biochemical findings.
Distribution of organic anion-transporting polypeptide 2 (oatp2) and oatp3 in the rat retina. (2002)

These results reveal that oatp2 is localized mainly in the RPE, suggesting a role for organic anion transport in this specialized ocular tissue. In contrast, oatp3 is localized mainly in optic nerve fibers, suggesting that oatp3 is a specific transporter in the visual nervous system. In conclusion, these data suggest that oatp2 and -3 may be involved in the transport of thyroid hormone in the rat retina.
Activation of Pro-gelatinase B by Endometase/Matrilysin-2 Promotes Invasion of Human Prostate Cancer Cells (2003)

This work has explored a putative biochemical mechanism by which endometase/matrilysin-2/matrix metalloproteinase-26 (MMP-26) may promote human prostate cancer cell invasion. Here, we showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular tissues. The role of MMP-26 in prostate cancer progression is unknown. MMP-26 was capable of activating pro-MMP-9 by cleavage at the Ala(93)-Met(94) site of the prepro-enzyme. This activation proceeded in a time- and dose-dependent manner, facilitating the efficient cleavage of fibronectin by MMP-9. The activated MMP-9 products generated by MMP-26 appeared more stable than those cleaved by MMP-7 under the conditions tested. To investigate the contribution of MMP-26 to cancer cell invasion via the activation of MMP-9, highly invasive and metastatic human prostate carcinoma cells, androgen-repressed prostate cancer (ARCaP) cells were selected as a working model. ARCaP cells express both MMP-26 and MMP-9. Specific anti-MMP-26 and anti-MMP-9 functional blocking antibodies both reduced the invasiveness of ARCaP cells across fibronectin or type IV collagen. Furthermore, the introduction of MMP-26 antisense cDNA into ARCaP cells significantly reduced the MMP-26 protein level in these cells and strongly suppressed the invasiveness of ARCaP cells. Double immunofluorescence staining and confocal laser scanning microscopic images revealed that MMP-26 and MMP-9 were co-localized in parental and MMP-26 sense-transfected ARCaP cells. Moreover, MMP-26 and MMP-9 proteins were both expressed in the same human prostate carcinoma tissue samples examined. These results indicate that MMP-26 may be a physiological and pathological activator of pro-MMP-9.
THE MEMBRANE PROTEASES ADAMS AND HEPSIN ARE DIFFERENTIALLY EXPRESSED IN RENAL CELL CARCINOMA. ARE THEY POTENTIAL TUMOR MARKERS? (2004)

The differential expression of hepsin and ADAMs suggests early and late involvement of membrane proteases in the development of RCC. Their association with the clinical outcome illustrates their potential usefulness as biomarkers for RCC.
Using hybrid branch predictors to improve branch prediction accuracy in the presence of context switches (1996)

Pipeline stalls due to conditional branches represent one of the most significant impediments to realizing the performance potential of deeply pipelined, superscalar processors. Many branch predictors have been proposed to help alleviate this problem, including the Two-Level Adaptive Branch Predictor, and more recently, two-component hybrid branch predictors.In a less idealized environment, such as a time-shared system, code of interest involves context switches. Context switches, even at fairly large intervals, can seriously degrade the performance of many of the most accurate branch prediction schemes. In this paper, we introduce a new hybrid branch predictor and show that it is more accurate (for a given cost) than any previously published scheme, especially if the branch histories are periodically flushed due to the presence of context switches.
EGFR-TKI in non-small cell lung cancer treatment (2012)

The epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)is a kind of high-efficiency and low-toxicity tumor molecular targeted drugs.It becomes a research hotspot in non-small cell lung cancer (NSCLC)treatment because of its unique curative effect and well tolerance.EGFR-TKI is mainly applied to the second and third line treatment of patients with advanced NSCLC or first line treatment of EGFR mutation patients.With the development of research,the indications of EGFR-TKI expand unceasingly.The preoperative neoadjuvant therapy is likely to become a new kind of treatment mode.

Key words: 
Carcinoma, non-small-cell lung; Receptor, epidermal growth factor; Enzyme inhibitors
Spiro[1H-indene-1,4‘-piperidine] Derivatives As Potent and Selective Non-Peptide Human Somatostatin Receptor Subtype 2 (sst2) Agonists (1998)

ADVERTISEMENT RETURN TO ISSUELetterNEXTSpiro[1H-indene-1,4'-piperidine] Derivatives As Potent and Selective Non-Peptide Human Somatostatin Receptor Subtype 2 (sst2) AgonistsLihu Yang, Liangqin Guo, Alexander Pasternak, Ralph Mosley, Susan Rohrer, Elizabeth Birzin, Forrest Foor, Kang Cheng, James Schaeffer, and Arthur A. PatchettView Author Information Departments of Medicinal Chemistry and Biochemistry & Physiology, Merck Research Laboratories, Rahway, New Jersey 07065 Cite this: J. Med. Chem. 1998, 41, 13, 2175–2179Publication Date (Web):June 3, 1998Publication History Received30 March 1998Published online3 June 1998Published inissue 1 June 1998https://pubs.acs.org/doi/10.1021/jm980194hhttps://doi.org/10.1021/jm980194hrapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1520Altmetric-Citations49LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Agonists,Monomers,Peptides and proteins,Receptors,Selectivity Get e-Alerts
Candida albicans intralesional injection immunotherapy of warts. (2002)

Often, the treatment of verrucae is frustrating for both the physician and patient. Treatment may be painful, scarring, ineffective, and costly. The object of this study was to compare the clinical outcomes and safety of Candida albicans intralesional injection immunotherapy (CI) versus conventional wart treatment. The results of a prospective, nonrandomized, open-label, comparison study are presented. CI is a novel, simple, and inexpensive modality for the treatment of verruca vulgaris (VV), including the plantar wart (PW) type. CI appears safe and well tolerated and is well suited for multiple warts on hands and fingers, PWs, and recalcitrant warts. Uninjected warts also may regress during CI. The new phenomenon of postimmunotherapy-revealed cicatrix (PIRC) is described. CI represents an off-label usage of Candida extract.
Hemagglutinin-neuraminidase enhances F protein-mediated membrane fusion of reconstituted Sendai virus envelopes with cells (1993)

Reconstituted Sendai virus envelopes containing both the fusion (F) protein and the hemagglutinin-neuraminidase (HN) (F,HN-virosomes) or only the F protein (F-virosomes) were prepared by solubilization of the intact virus with Triton X-100 followed by its removal by using SM2 Bio-Beads. Viral envelopes containing HN whose disulfide bonds were irreversibly reduced (HNred) were also prepared by treating the envelopes with dithiothreitol followed by dialysis (F,HNred-virosomes). Both F-virosomes and F,HNred-virosomes induced hemolysis of erythrocytes in the presence of wheat germ agglutinin, but the rates and extents were markedly lower than those for hemolysis induced by F,HN-virosomes. Using an assay based on the relief of self-quenching of a lipid probe incorporated in the Sendai virus envelopes, we demonstrate the fusion of both F,HN-virosomes and F-virosomes with cultured HepG2 cells containing the asialoglycoprotein receptor, which binds to a terminal galactose moiety of F. By desialylating the HepG2 cells, the entry mediated by HN-terminal sialic acid receptor interactions was bypassed. We show that both F-virosomes and F,HN-virosomes fuse with desialylated HepG2 cells, although the rate was two- to threefold higher if HN was included in the viral envelope. We also observed enhancement of fusion rates when both F and HN envelope proteins were attached to their specific receptors.
Plasmapheresis Treatment in Guillain-Barré Syndrome: Potential Benefit over Intravenous Immunoglobulin (2010)

Guillain-Barré syndrome includes acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, Miller Fisher syndrome and acute pandysautonomia. Plasma exchange was the first treatment in Guillain-Barrd syndrome proven to be superior to supportive treatment alone and intravenous immunoglobulin was subsequently shown to be equally effective and is now commonly used as first-line treatment. We describe a 78-year-old woman who presented with a two-day history of progressive generalised weakness and left facial nerve palsy, preceded by a flu-like illness lasting for one week. A five-day course of daily immunoglobulin (0.4 g/kg/day) was commenced without benefit and progressive clinical deterioration. Seven days after completion of immunoglobulin treatment, plasma exchange was started with an exchange of about three litres of plasma every day for three days and every second day on two further occasions. A gradual improvement of respiratory function and peripheral muscle strength was observed after the first plasma exchange and on the eighth day the patient was weaned off mechanical ventilation. This case suggests that patients with severe Guillain-Barrd syndrome may benefit from plasma exchange after immunoglobulin treatment in refractory cases. Plasma exchange should be considered early in Guillain-Barrć syndrome cases with axonal involvement, and in the recurrent or familial Guillain-Barré syndrome forms.
Phase Ib study evaluating a self-adjuvanted mRNA cancer vaccine (RNActive®) combined with local radiation as consolidation and maintenance treatment for patients with stage IV non-small cell lung cancer (2014)

Clinicaltrials.gov: NCT01915524/EudraCT No.: 2012-004230-41.
Y1 receptors for neuropeptide Y are coupled to mobilization of intracellular calcium and inhibition of adenylate cyclase (1990)

Two types of binding sites have previously been described for neuropeptide Y (NPY), called Y1 and Y2 receptors. The intracellular events following Y1 receptor activation was studied in the human neuroblastoma cell line SK-N-MC. Both NPY and the specific Y1 receptor ligand, [Leu31,Pro34]-NPY, caused a rapid and transient increase in the concentration of free calcium in the cytoplasm as measured by the fluorescent probe, Fura-2. The effect of both peptides was independent of extracellular calcium as addition of EGTA or manganese neither changed the size nor the shape of the calcium response. The calcium response to NPY was abolished by pretreatment with thapsigargin, which can selectively deplete a calcium store in the endoplasmic reticulum. Y1 receptor stimulation, by both NPY and [Leu31,Pro34]NPY, also inhibited the forskolin-stimulated cAMP production with an EC50 of 3.5 nM. There was a close relation between the receptor binding and the cellular effects as half-maximal displacement of [125I-Tyr36]monoiodoNPY from the receptor was obtained with 2.1 nM NPY. The Y2-specific ligand NPY(16-36)peptide had no effect on either intracellular calcium or cAMP levels in the SK-N-MC cells. It is concluded that Y1 receptor stimulation is associated with both mobilization of intracellular calcium and inhibition of adenylate cyclase activity.
Immunization with a Lentivector That Targets Tumor Antigen Expression to Dendritic Cells Induces Potent CD8 + and CD4 + T-Cell Responses (2007)

Lentivectors stimulate potent immune responses to antigen transgenes and are being developed as novel genetic vaccines. To improve safety while retaining efficacy, we constructed a lentivector in which transgene expression was restricted to antigen-presenting cells using the mouse dectin-2 gene promoter. This lentivector expressed a green fluorescent protein (GFP) transgene in mouse bone marrow-derived dendritic cell cultures and in human skin-derived Langerhans and dermal dendritic cells. In mice GFP expression was detected in splenic dectin-2(+) cells after intravenous injection and in CD11c(+) dendritic cells in the draining lymph node after subcutaneous injection. A dectin-2 lentivector encoding the human melanoma antigen NY-ESO-1 primed an NY-ESO-1-specific CD8(+) T-cell response in HLA-A2 transgenic mice and stimulated a CD4(+) T-cell response to a newly identified NY-ESO-1 epitope presented by H2 I-A(b). As immunization with the optimal dose of the dectin-2 lentivector was similar to that stimulated by a lentivector containing a strong constitutive viral promoter, targeting antigen expression to dendritic cells can provide a safe and effective vaccine.
Pasture Establishment (1995)

Pasture establishment involves considerations such as site preparation, time of sowing, seed mixtures, seed coating, method of sowing and subsequent management. The recommendations which follow relate mostly to the initial development of native tussock grassland
Total Synthesis of the Glycopeptide Recognition Domain of the P‐Selectin Glycoprotein Ligand 1 (2008)

Block glycosylation of a T antigen–threonine conjugate with a sialyl Lewisx trichloroacetimidate was used to synthesize a sialyl Lewisx–T antigen–threonine building block. Selective protecting-group manipulations furnished a compound with exclusively acetyl-protected functions in the carbohydrate portion; this intermediate is sufficiently acid-stable that it is applicable to the solid-phase synthesis of binding site A of the P-selectin ligand PSGL-1.
Effect of Ligand Modification on Rhodium-Catalyzed Homogeneous Hydroformylation in Supercritical Carbon Dioxide (1999)

Several fluoroalkyl- and fluoroalkoxy-substituted tertiary arylphosphines were synthesized and investigated in the homogeneous catalytic hydroformylation of 1-octene using HRh(CO)L3 (L = tertiary arylphosphine). The activity of the rhodium complex (formed in situ from Rh(CO)2(acac) and L) increased with decreasing basicity of the phosphine according to the series [3,5-(CF3)2C6H3]3P > [4-CF3C6H4]3P ≈ [3-CF3C6H4]3P > [4-CF3OC6H4]3P > [4-F(CF2)4(CH2)3C6H4]3P. The very weakly basic phosphine (C6F5)3P did not complex with Rh(CO)2(acac), most likely due to a combination of electronic and steric factors. Steric effects did not play a role in either the activity or selectivity of the rhodium catalysts that were formed under hydroformylation conditions.
A New Indole Synthesis1 (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA New Indole Synthesis1R. R. Lorenz, B. F. Tullar, C. F. Koelsch, and S. ArcherCite this: J. Org. Chem. 1965, 30, 8, 2531–2533Publication Date (Print):August 1, 1965Publication History Published online1 May 2002Published inissue 1 August 1965https://pubs.acs.org/doi/10.1021/jo01019a007https://doi.org/10.1021/jo01019a007research-articleACS PublicationsRequest reuse permissionsArticle Views630Altmetric-Citations39LEARN 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 Get e-Alerts
Genes, chromosomes, and rhabdomyosarcoma (1999)

Rhabdomyosarcomas are a heterogeneous group of malignant tumors and are the most common soft-tissue sarcoma of childhood. Rhabdomyosarcomas resemble developing skeletal muscle, notably in their expression of the MRF family of transcription factors and the PAX3 and PAX7 genes. These PAX genes are also involved through specific translocations, t(2;13)(q35;q14) and variant t(1;13)(p36;q14) in the alveolar subtype, which result in PAX3-FKHR and PAX7-FKHR fusion genes, respectively. The fusion genes are thought critically to affect downstream targets of PAX3 and PAX7 or possibly have novel targets. Similar downstream changes may also be involved in embryonal and fusion gene negative cases. Genomic amplification of such genes as MYCN, MDM2, CDK4, and PAX7-FKHR is a feature mainly of the alveolar subtype, while specific chromosomal gains, including chromosomes 2, 8, 12, and 13, are associated with the embryonal subtype. Loss of alleles and imprinting at 11p15.5 and disruption of genes such as IGF2, ATR, PTC, P16, and TP53 have also been implicated in rhabdomyosarcoma development. Whereas there is now a realistic possibility of cure in the majority of cases, there remains a subset that is resistant to multimodality therapy, including high-dose chemotherapy. Characterization of the defining molecular features of tumors that are likely to behave aggressively represents a particular challenge. Current research is leading toward a better understanding of rhabdomyosarcoma tumorigenesis, which may ultimately result in novel therapeutic strategies that increase the overall cure. Genes Chromosomes Cancer 26:275-285, 1999.
Genetics of cell and axon migrations in Caenorhabditis elegans (1987)

The Caenorhabditis elegans epidermis comprises 78 cells which cover the external surface of the embryo as a single cell layer. These cells secrete the cuticle from their exterior faces and support the body wall muscles and most of the nervous system on their interior faces. The epidermal cells arise by autonomous embryonic cell lineages but show regulative interactions after their assembly into an epithelium. It is believed that the various epidermal cells express different kinds or amounts of surface molecules that govern their mutual assembly and also guide the attachments and migrations of the underlying body muscles and neurones. The first muscles and neurones may in turn express new surface molecules that refine later cell movements. Mutations in some 30 known genes disrupt the movements of cells or axons along the body wall.
Using SSL/TLS in authentication and key agreement procedures of future mobile networks (2003)

Existing security schemes in 2G and 3G systems are inadequate, as there is a greater demand to provide a more flexible, reconfigurable and scalable security mechanism that can advance as fast as mobile hosts are evolving into full-IP enabled devices. Work has already begun on such an "all-IP" end-to-end solution, commonly referred to as 4G systems. Fully-fledged integration between mobile networks and the Internet demands fully compatible, time-tested and reliable mechanisms to depend on. SSL/TLS protocol has proved its effectiveness in wired Internet and it will probably be the most promising candidate for future wireless environments. We discuss existing problems related to authentication and key agreement procedures (AKA), such as compromised authentication vectors attacks, as they appear in 2G and 3G systems, and propose how SSL/TLS can be used to overcome these inefficiencies. Further on, we mark down additional benefits that stem from the introduction of SSL/TLS combined with the appropriate PKI elements in the 4G wireless environment.