gebhart/patrepeval huggingface dataset:
Distinct Classes of Phosphatidylinositol 3′-Kinases Are Involved in Signaling Pathways That Control Macroautophagy in HT-29 Cells (2000)

3-Methyladenine which stops macroautophagy at the sequestration step in mammalian cells also inhibits the phosphoinositide 3-kinase (PI3K) activity raising the possibility that PI3K signaling controls the macroautophagic pathway (Blommaart, E. F. C., Krause, U., Schellens, J. P. M., Vreeling-Sindelárová, H., and Meijer, A. J. (1997) Eur. J. Biochem. 243, 240-246). The aim of this study was to identify PI3Ks involved in the control of macroautophagic sequestration in human colon cancer HT-29 cells. An increase of class I PI3K products (phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-triphosphate) caused by either feeding cells with synthetic lipids (dipalmitoyl phosphatidylinositol 3, 4-bisphosphate and dipalmitoyl phosphatidylinositol 3,4, 5-triphosphate) or by stimulating the enzymatic activity by interleukin-13 reduced macroautophagy. In contrast, an increase in the class III PI3K product (phosphatidylinositol 3-phosphate), either by feeding cells with a synthetic lipid or by overexpressing the p150 adaptor, stimulates macroautophagy. Transfection of a specific class III PI3K antisense oligonucleotide greatly inhibited the rate of macroautophagy. In accordance with a role of class III PI3K, wortmannin (an inhibitor of PI3Ks) inhibits macroautophagic sequestration and protein degradation in the low nanomolar range (IC(50) 5-15 nM). Further in vitro enzymatic assay showed that 3-methyladenine inhibits the class III PI3K activity. Dipalmitoyl phosphatidylinositol 3-phosphate supplementation or p150 overexpression rescued the macroautophagic pathway in HT-29 cells overexpressing a GTPase-deficient mutant of the Galpha(i3) protein suggesting that both class III PI3K and trimeric G(i3) protein signaling are required in the control macroautophagy in HT-29 cells. In conclusion, our results demonstrate that distinct classes of PI3K control the macroautophagic pathway in opposite directions. The roles of PI3Ks in macroautophagy are discussed in the context of membrane recycling.
Immunosuppressive activity of [MeBm2t]1-, D-diaminobutyryl-8-, and D-diaminopropyl-8-cyclosporin analogues correlates with inhibition of calcineurin phosphatase activity (1993)

Calcineurin, a Ca2+/calmodulin-dependent phosphatase, has recently been identified as a common target for cyclophilin A-cyclosporin A and FK506 binding protein 12-FK506 complexes. This study has examined the structure activity relationships of cyclosporin A (CsA) and three functionally distinct analogues, [MeBm2t]1-CsA, D-diaminobutyryl-8-CsA (Dab8-CsA), and D-diaminopropyl-8-CsA (Dap8-CsA). Immunosuppressive potency in T cell activation models, NF kappa B activation, and IL-2 mRNA transcription has been compared with analogue affinity for cyclophilin A and inhibition of calcineurin phosphatase activity. CsA, Dap8-CsA, and Dab8-CsA bind to cyclophilin A with a similar affinity (Ki 4 to 5 nM as measured by inhibition of prolyl cis-trans isomerase activity), however, Dap8-CsA and Dab8-CsA inhibit T cell activation less than CsA. Although [MeBm2t]-CsA has weak affinity for cyclophilin A (Ki 540 nM), its immunosuppressive potency is similar to that of CsA. Both cyclophilin A-CsA and cyclophilin A-[MeBm2t]1-CsA complexes inhibit calcineurin phosphatase activity in vitro (Ki 114 and 67 nM, respectively). In Jurkat cells exposed to CsA or the analogues for 2 h, endogenous calcineurin phosphatase activity in cell lysates was inhibited by CsA and [MeBm2t]1-CsA (drug concentrations causing 50% reduction in 32PO4 release of 8 and 55 nM, respectively) in proportion to inhibition of T cell activation, IL-2 mRNA transcription, and NF kappa B activation. Dap8-CsA and Dab8-CsA had a minimal effect on endogenous calcineurin phosphatase activity in Jurkat cell lysates. These findings correlate the functional activity of CsA and structural analogues with calcineurin phosphatase activity and support calcineurin as a target for drug action. The Dap8 and Dab8 modifications of CsA, occurring in residue 8, which is exposed to solvent in the cyclophilin A-CsA complex, appears to significantly alter complex affinity for calcineurin.
Symmetric light emitting devices from poly(p-di ethynylene phenylene) (p-di phenylene vinylene) derivatives (1995)

Light emitting devices were fabricated from 2,5-dialkoxy derivatives of poly(p-di ethynylene phenylene-p-di phenylene vinylene) (PDEPDPV) sandwiched between indium tin oxide (ITO) and Al. The current–voltage (I–V) curve, electroluminescence (EL) intensity-voltage (IEL–V) curve, and the EL spectra were identical in forward and reverse bias. The I–V curves were also symmetric under illumination, with I≊0 and V=0, suggesting a negligibly small internal electric field. At high bias voltage, carrier injection was found to be dominated by tunneling at the interfaces. At low bias voltage, tunneling among localized states at the Fermi level prevailed. The behavior is discussed in relation to Fermi-level pinning at defect states in the interfaces with the ITO and Al.
Studies on oriented and reversible immobilization of glycoprotein using novel boronate affinity gel (1996)

The authors have previously synthesized a novel boronate affinity ligand, catechol [2-(diethylamino)carbonyl-4-bromomethyl]phenylboronate. When this ligand was coupled to cellulose beads, it bound horseradish peroxidase (HRP), a glycoprotein, at pH 7.0. In comparison, commercial m-aminophenylboronic acid-agarose did not bind HRP below pH 8.0. HRP was immobilized in an oriented and reversible fashion using this gel. The immobilized enzyme retained 90.12 per cent of its original activity, probably due to its attachment via the carbohydrate moiety of the enzyme. After repeated use, the activity remaining on the new gel was twice as high as that on conventional m-aminophenylboronic acid-agarose. The column was regenerated easily by washing with dilute acid because of reversibility of the boronate glycol bond.
Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity (2008)

A new regulatory T (T reg) cell-specific, FoxP3-GFP-hCre bacterial artificial chromosome transgenic mouse was crossed to a conditional Dicer knockout (KO) mouse strain to analyze the role of microRNAs (miRNAs) in the development and function of T reg cells. Although thymic T reg cells developed normally in this setting, the cells showed evidence of altered differentiation and dysfunction in the periphery. Dicer-deficient T reg lineage cells failed to remain stable, as a subset of cells down-regulated the T reg cell-specific transcription factor FoxP3, whereas the majority expressed altered levels of multiple genes and proteins (including Neuropilin 1, glucocorticoid-induced tumor necrosis factor receptor, and cytotoxic T lymphocyte antigen 4) associated with the T reg cell fingerprint. In fact, a significant percentage of the T reg lineage cells took on a T helper cell memory phenotype including increased levels of CD127, interleukin 4, and interferon gamma. Importantly, Dicer-deficient T reg cells lost suppression activity in vivo; the mice rapidly developed fatal systemic autoimmune disease resembling the FoxP3 KO phenotype. These results support a central role for miRNAs in maintaining the stability of differentiated T reg cell function in vivo and homeostasis of the adaptive immune system.
Platelet aggregation inhibitors. IX. Chemical transformation of adenosine into 2-thioadenosine derivatives. (1977)

A facile synthesis of 2-thioadenosine (IX) and its derivatives from adenosine (I) was described. Treatment of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide O-benzyloxime (IV), obtained via 3 steps from I, with CS2-MeOH-pyridine at room temperature gave N1-benzyloxy-2-thioadenosine (VII) which was readily transformed into 2-benzylthioadenosine N-oxide (VIII) by heating. Treatment of IV with CS2-MeOH-NaOH at 180°in an autoclave gave a mixture of 2-thioadenosine (IX), 2-methylthioadenosine (X) and 2-benzylthioadenosine (XI). Reaction of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamidoxime (XV) obtained from I with CS2-MeOH-H2O at 120°in an autoclave gave IX in an overall yield of 60% (practically 2 steps). Treatment of XV with CS2-MeOH-pyridine at room temperature yielded 2-thioadenosine N-oxide (XVIII) which was subsequently transformed into IX by H2S. Adenines (XX) were also transformed into 2-thioadenine or 9-benzyl-2-thioadenine (XXV) by treatment of the intermediate compounds (XXII) of carboxamidoxime-type with CS2-MeOH-H2O at 120°.
Internet based remote camera control system (2002)

The intelligent transportation system (ITS) or the intelligent vehicle-highway system (IVHS) concept, as part of the US National Transportation Program, applies real-time data, live video, and wireless communication techniques to improve real-time traffic monitoring, provide integrated control, and support advanced control operations. This paper illustrates a prototype system, Remote Integrated Camera Operation System (RICOS), developed by the Integrated Transportation Management Center (ITMC), Texas Transportation Institute (TTI) and Texas A&M University System, to improve the system efficiency and operational safety.
Training Referential Communicative Skills to Individuals with Autism Spectrum Disorder: A Pilot Study (2011)

The present study reports the effects of referential communication training in individuals formally diagnosed with autism spectrum disorder (ASD). Participants were 20 children with ASD (M age = 14.3 yr., SD = 4.2; 6 girls, 14 boys) in the role of speakers and 20 control children, who acted as listeners. They were all enrolled in mainstream compulsory education. Inclusion/exclusion criteria were defined according to the clinical diagnosis of ASD, the presence or absence of additional or associated disability, previous training in referential communication, and any drug treatment. Speakers were randomly assigned to one of two groups (trained vs untrained). Linguistic age, cognitive level and autistic symptoms were analyzed, respectively, with the Peabody Picture Vocabulary Test (PPVT), the Wechsler Intelligence Scale (WISC-R or WAIS-III), and the Autistic Behavior Checklist (ABC). Communicative abilities were analyzed through two indexes related to message complexity and self-regulation. The trained group was trained in referential communication tasks (task analysis, role taking, and task evaluation), while the untrained group took part in a communicative game but without any specific communicative training. The results showed that the complexity of emitted messages had improved statistically significantly in the trained group as an effect of training. Ecological referential communication is shown to be an appropriate paradigm for studying the communicative process and its products and could be used to develop and implement a training program focused on those skills in which individuals with ASD are most deficient.
Abstract 4576: IMGN853, an anti-Folate Receptor I antibody-maytansinoid conjugate for targeted cancer therapy (2011)

Abstract Previously we reported (O. Ab; EORTC, 2010) that an antibody-maytansinoid conjugate (AMC) composed of an anti-FOLR1 antibody conjugated to the cytotoxic maytansinoid, DM4, via the disulfide-containing linker, SPDB, was potent in killing FOLR1-expressing cancer cells in vitro and in vivo. In light of the favorable results noted, we assessed the optimal antibody, linker, and maytansinoid agent for an AMC targeting FOLR1, as reported here. Antibody selection. Anti-FOLR1 antibodies were generated by immunizing mice with human FOLR1-expressing cells, and a panel of FOLR1-specific antibodies was identified by flow cytometry binding assay. Several FOLR1-antibodies with high binding affinity to both human and monkey FOLR1 were chosen for further evaluation and were humanized using ImmunoGen's resurfacing technology. Antibodies were conjugated to DM1 via the non-cleavable SMCC linker and the conjugates tested for activity against FOLR1-positive KB cells in vitro and in vivo. All conjugates had comparable cytotoxic potencies in vitro. However, the in vivo anti-tumor activity of one conjugate, M9346A-SMCC-DM1, was significantly better than that of SMCC-DM1 conjugates of other FOLR1 antibodies. Based on this finding, the M9346A antibody was chosen for further development. Linker/maytansinoid selection. The M9346A antibody was linked to DM1 or DM4 via the disulfide-containing cleavable linkers SPP, SPDB or sulfo-SPDB, or via the non-cleavable SMCC linker. We compared the in vitro cytotoxic activities of these conjugates on KB, Igrov-1 and Jeg-3 cell lines. The conjugates with cleavable linkers displayed markedly greater in vitro activities than the SMCC conjugate. We then examined the in vivo activities of the conjugates in FOLR1-positive KB- and Ovcar 3-tumor models. Again, we found that the conjugates with cleavable linkers were more active in vivo than the noncleavable conjugate. Among the conjugates with cleavable linkers, the sulfo-SPDB-DM4 conjugate was the most active conjugate against the Ovcar-3 model, it had activity comparable to that of the SPDB-DM4 conjugate against KB tumors, and both were more active than the SPP-DM1 conjugate in the two xenograft models. Taking into consideration that sulfo-SPDB-DM4 was the most efficacious design in vivo and the potential of the hydrophilic sulfo-SPDB-linker to enable better activity against PgP-expressing cells (previously reported data), M9346A-sulfo-SPDB-DM4 was selected to be the candidate for development and designated IMGN853. IMGN853 is a promising candidate for the treatment of FOLR1-expressing tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4576. doi:10.1158/1538-7445.AM2011-4576
Identification of metastasis-associated genes in prostate cancer by genetic profiling of human prostate cancer cell lines. (2005)

DNA microarray technology offers the possibility of screening a large number of genes with regard to alterations in the expression level or mutations. In this study, we identified 14 genes that are most probably associated with the higher metastatic potential of LNCaP C4-2 cells as compared to LNCaP cells. Eight of these 14 genes are potential new molecular markers for assessing the metastatic potential of PCa, or may serve as therapeutical targets.
A review of head-mounted displays (HMD) technologies and applications for consumer electronics (2013)

We review in this paper the various architectures that have been proposed in industry to implement see-through head-mounted display (HMD), especially for the consumer electronics market.
Removal of Leukocytes from Whole Blood and ErythrocyteSuspensions by Filtration Through Cotton Wool (1975)

1,820 units of leukocyte- and platelet-poor erythrocyte suspensions were prepared by filtration through cotton wool. On the average more than 98% of the leukocytes and 90-95% of the platelets could be removed. The red cell recovery was 96%. 97% of the units given to polytransfused patients did not cause febrile reactions. Serological follow-up of future transplantation recipients indicated that immunization may be avoided by using erythrocyte suspensions of fresh, filtered blood.
Binding of Nonphysiological Protein and Peptide Substrates to Proteases:  Differences between Urokinase-Type Plasminogen Activator and Trypsin and Contributions to the Evolution of Regulated Proteolysis (2003)

Understanding the regulation of physiological processes requires detailed knowledge of the recognition of substrates by enzymes. One of the most productive model systems for the study of enzyme-substrate interactions is the serine protease family; however, most studies of protease action have used small substrates that contain an activated, non-natural scissile bond. Because few kinetic or structural studies have used protein substrates, the physiologically relevant target of most proteases, it seems likely that important mechanisms of substrate recognition and processing by proteases have not yet been fully elucidated. Consistent with this hypothesis, we have observed that K(m) values for protein substrates are reduced as much as 200-15000-fold relative to those of analogous peptide substrates. Here we examine the thermodynamic consequences of interactions between proteases and their substrates using staphylococcal nuclease (SNase) and SNase variants as model protein substrates. We have obtained values for enthalpy, entropy, and K(d) for binding of proteins and peptides by the nonspecific protease trypsin and the highly specific protease urokinase-type plasminogen activator (u-PA). To avoid cleavage of substrates during these measurements, we used inactive variants of trypsin and u-PA whose catalytic serine S195 had been replaced by alanine. Differences in the K(d) values for binding of protein and peptide substrates closely approximate the large differences observed in the corresponding K(m) values. Improved binding of protein substrates is due to decreased enthalpy, and this effect is pronounced for the selective protease u-PA. Fundamental differences in recognition of analogous protein and peptide substrates may have influenced the evolution of protease specificity.
Expression of apoptosis regulators in cutaneous malignant melanoma. (1998)

Metastatic malignant melanoma (MM) is usually incurable and responds poorly to chemotherapy. Because many cytotoxic drugs cause cell death by inducing apoptosis, an imbalance of apoptosis regulatory proteins may contribute to MM treatment resistance. We have previously shown reduced expression of Bcl-2 protein, a negative regulator of apoptosis, in MM as compared with benign nevi. It is hypothesized that other apoptosis regulators may be involved in survival of MM cells. We examined the expression of Bax, Bcl-2, Bcl-X, and Mcl-1 in human benign nevi, primary MM, and metastatic MM using immunohistochemistry. Results were confirmed with Western blotting. The proapoptotic protein, Bax, was surprisingly overexpressed in all MM samples compared with benign nevi. Interestingly, in most MM samples there was overexpression of Mcl-1 or Bcl-XL, both negative regulators of apoptosis. Increased expression of Mcl-1 and Bcl-XL was first observed in thin primary melanomas, suggesting that up-regulation of these proteins represents a relatively early event associated with malignant transformation in MM. As published previously, the majority of primary and metastatic MM exhibited reduced Bcl-2 levels. We conclude that the apoptosis inhibitors Bcl-XL or Mcl-1, alone or in combination, may circumvent the normal cell death pathway, contributing to the pathogenesis and treatment resistance in metastatic MM.
Isolation, Chemical, and Biotransformation Routes of Labdane-type Diterpenes (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTIsolation, Chemical, and Biotransformation Routes of Labdane-type DiterpenesLuís M. T. Frija*†, Raquel F. M. Frade*†, and Carlos A. M. Afonso*†‡View Author Information† CQFM - Centro de Química-Física Molecular and IN - Institute of Nanoscience and Nanotechnology, Departamento de Engenharia Química e Biológica Instituto Superior Técnico, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal‡ i-Med.UL, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, PortugalPhone: +351 218417627. Fax: +351 218464455. E-mail: [email protected] (L.M.T.F.); [email protected] (R.F.M.F.); [email protected] (C.A.M.A.).Cite this: Chem. Rev. 2011, 111, 8, 4418–4452Publication Date (Web):May 27, 2011Publication History Received11 August 2010Published online27 May 2011Published inissue 10 August 2011https://pubs.acs.org/doi/10.1021/cr100258khttps://doi.org/10.1021/cr100258kreview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views5793Altmetric-Citations93LEARN 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:Biotransformation,Hydrocarbons,Ketones,Oxides,Vinyl Get e-Alerts
AGEing and osteoarthritis: a different perspective (2003)

The reviewed literature demonstrates that the age-related accumulation of advanced glycation end products in articular cartilage may provide a molecular mechanism capable of (at least in part) explaining the age-related increase in the incidence of osteoarthritis. This conclusion paves the way for new strategies to prevent or treat osteoarthritis via inhibition and/or reversal of this process.
Antisense RNA-Induced Reduction in Murine TIMP Levels Confers Oncogenicity on Swiss 3T3 Cells (1989)

Mouse 3T3 cell lines capable of constitutively synthesizing an RNA complementary to the messenger RNA encoding TIMP, tissue inhibitor of metalloproteinases, were constructed by transfection with appropriate plasmid constructs. Many of the lines were down-modulated for TIMP messenger RNA levels and secreted less TIMP into the culture medium. In comparison to noninvasive, nontumorigenic controls, these cells not only were invasive in a human amnion invasion assay, but also were tumorigenic and metastatic in athymic mice. These results indicate that TIMP suppresses oncogenicity, at least in immortal murine 3T3 cells.
Diels-Alder reactions of trans-1-methoxy-3-trimethylsilyloxy-1,3-butadiene (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDiels-Alder reactions of trans-1-methoxy-3-trimethylsilyloxy-1,3-butadieneS. Danishefsky, T. Kitahara, C. F. Yan, and J. MorrisCite this: J. Am. Chem. Soc. 1979, 101, 23, 6996–7000Publication Date (Print):November 1, 1979Publication History Published online1 May 2002Published inissue 1 November 1979https://pubs.acs.org/doi/10.1021/ja00517a036https://doi.org/10.1021/ja00517a036research-articleACS PublicationsRequest reuse permissionsArticle Views2090Altmetric-Citations138LEARN 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