gebhart/patrepeval huggingface dataset:
A General Introduction to Glucocorticoid Biology (2019)

Glucocorticoids (GCs) are steroid hormones widely used for the treatment of inflammation, autoimmune diseases, and cancer. To exert their broad physiological and therapeutic effects, GCs bind to the GC receptor (GR) which belongs to the nuclear receptor superfamily of transcription factors. Despite their success, GCs are hindered by the occurrence of side effects and glucocorticoid resistance (GCR). Increased knowledge on GC and GR biology together with a better understanding of the molecular mechanisms underlying the GC side effects and GCR are necessary for improved GC therapy development. We here provide a general overview on the current insights in GC biology with a focus on GC synthesis, regulation and physiology, role in inflammation inhibition, and on GR function and plasticity. Furthermore, novel and selective therapeutic strategies are proposed based on recently recognized distinct molecular mechanisms of the GR. We will explain the SEDIGRAM concept, which was launched based on our research results.
Mutational analysis and protein engineering of receptor-binding determinants in human placental lactogen (1991)

Human placental lactogen (hPL) shares 85% sequence identity to human growth hormone (hGH) yet has some very different receptor-binding properties. For example, hPL binds 2300-fold weaker than hGH to the hGH receptor, yet these two hormones have similar affinities for prolactin receptors. We have expressed hPL in Escherichia coli, and we show that, like hGH, hPL requires zinc for tight binding to the extracellular domain of the human prolactin receptor (hPRLbp). In fact, hPL contains virtually the same receptor-binding determinants and zinc ligands (His-18, His-21, and Glu-174) that hGH uses for coordinating zinc in the hGH.hPRLbp complex. As with hGH, mutation of Glu-174 to Ala in hPL reduces the affinity for the hPRLbp by 1400-fold. We can increase the affinity of hPL by over 200-fold for the hGHbp by installing four hGH receptor determinants that are not conserved in hPL. By simultaneously introducing E174A, we produced a pentamutant whose binding affinity for the hGHbp is only 1.6-fold weaker than hGH, but whose binding affinity for the hPRLbp is weaker by greater than 1000-fold relative to wild-type hPL. Thus, we have identified an hPRLbp epitope in hPL, "recruited" an hGHbp epitope into hPL, and produced receptor selective analogs of hPL that are designed to bind tightly to either, neither, or both receptors. Such variants should be important molecular probes to link specific receptor-binding, activation, and biological events.
A Maximum Likelihood Approach to Emission Image Reconstruction from Projections (1976)

The stochastic nature of the measurements used for image reconstruction from projections has largely been ignored in the past. If taken into account, the stochastic nature has been used to calculate the performance of algorithms which were developed independent of probabilistic considerations. This paper utilizes the knowledge of the probability density function of the measurements from the outset, and derives a reconstruction scheme which is optimal in the maximum likelihood sense. This algorithm is shown to yield an image which is unbiased -- that is, on the average it equals the object being reconstructed -- and which has the minimum variance of any estimator using the same measurements. As such, when operated in a stochastic environment, it will perform better than any current reconstruction technique, where the performance measures are the bias and viariance.
Fibrous from Globular Proteins (1945)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFibrous from Globular ProteinsF. R. Senti, M. J. Copley, and G. C. NuttingCite this: J. Phys. Chem. 1945, 49, 3, 192–211Publication Date (Print):March 1, 1945Publication History Published online1 May 2002Published inissue 1 March 1945https://doi.org/10.1021/j150441a002RIGHTS & PERMISSIONSArticle Views99Altmetric-Citations22LEARN 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 InReddit PDF (1 MB) Get e-Alerts
Photoisomerization of a Fullerene Dimer (2008)

A photo-switchable fullerene dimer and its analogous nitrogen endohedral species have been synthesized and characterized. Irradiation by ultraviolet and visible light has been used to switch between the trans and cis isomers of both the C60- and N@C60- based dimers. Environmental perturbations experienced by the encapsulated nitrogen atom upon switching between the two isomers in degassed carbon disulfide has been determined by pulse electron paramagnetic resonance. Both T1 and T2 electron spin relaxation times of the two isomers of the endohedral fullerene containing dimer revealed a biexponential decay. Although the zero field splitting parameter Deff for both isomers in solution was similar, around 13.0 MHz, the molecular rotation correlation time τc of the trans and cis isomers was calculated to be 37.2 ± 1.6 and 34.8 ± 2.7 ps, respectively.
The expression and the regulatory role of OX40 and 4-1BB heterodimer in activated human T cells (2005)

OX40 and 4-1BB are members of the tumor necrosis factor (TNF) family of costimulatory receptors whose signaling is important for differential immune responses mediated by CD4+ or CD8+ T cells. Although activated T cells may acquire OX40/4-1BB double-positive phenotype and signaling from each receptor is expected to influence cell functions, the relevance between OX40 and 4-1BB has never been investigated before. While we were investigating the expression of OX40 and 4-1BB on activated human T cells, we found that they colocalize. The study of receptor gene-transfected cells showed that both receptors coendocytose and the complex of OX40 and 4-1BB was detected by specific ligands or antibodies (Abs). The heterodimer of OX40 and 4-1BB was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreduced conditions and was associated with the tumor receptor-associated factor (TRAF) family proteins in a unique manner. Furthermore, the stimulation of OX40/4-1BB rendered cells sensitive to apoptosis induced by TNF-alpha that accompanied reduced activation of nuclear factor-kappaB (NF-kappaB). Finally, the OX40/4-1BB stimulation repressed the mitogen response in activated CD25+CD4+ T cells and preactivated CD8+ T cells. Thus, the OX40/4-1BB heterodimer appears to represent a unique regulatory receptor in activated T cells.
New approaches for imaging and therapy of solid cancer. (2015)

Radionuclide therapy is a systemic treatment that aims to deliver cytotoxic radiation to cancer cells. Due to their properties, antibodies have been considered as suitable agent for the delivery of therapeutic radioisotopes, radioimmunotherapy (RIT). This article gives an overview of new approaches for imaging and therapy of solid cancer with particular attention to strategies to enhance treatment success. Examples of increased antibody uptake by targeting stromal constituent of tumor microenvironment such as fibronectin (FN) an important tumor-associated angiogenesis targeting agent, with specifically designed antibody format will be provided. Strategies oriented to identify patients most likely to benefit from RIT including identification of radiosensitivity profiles, in vivo target identification by teragnostic approach and better prediction of dosimetric estimates would be presents. Combination regimens such as with chemo-radiotherapy and immunotherapy would be also discussed as an approach to enhance RIT success.
Mitogenic effects of platelet‐derived growth factor, fibroblast growth factor, transforming growth factor‐β, and heparin‐binding serum factor for adult mouse Schwann cells (1994)

Mitogenic effects of fetal calf serum (FCS), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), transforming growth factor-beta (TGF-beta), and forskolin to adult mouse Schwann cells were examined by bromodeoxyuridine (BrdU) incorporation and double immunofluorescence for S100 and BrdU. PDGF-BB, basic FGF, and TGF-beta 1 and beta 2 were all mitogenic for Schwann cells in media containing FCS. Forskolin suppressed the mitogenic activity of these factors. In serum-free media, PDGF-BB and bFGF were also mitogenic, but TGF-beta 1 and beta 2 were not. Heparin-binding fractions of FCS obtained by heparin-Sepharose chromatography synergized with TGF-beta 1 and beta 2 to produce a mitogenic response. Since PDGF-BB, acidic FGF, and basic FGF were not detected in these fractions by immunoabsorption and immunoblot assays, the presence of unidentified heparin-binding molecules in FCS bioactive for adult mouse Schwann cells is suggested.
Abstract P3-04-02: Multiple subtypes of triple negative breast cancer are dependent on androgen receptor (2015)

Abstract Triple negative breast cancer (TNBC) constitutes 10-20% of invasive breast carcinomas and has the lowest five-year survival rate. Currently, there are no targeted therapies for TNBC. Recent studies demonstrate that the androgen receptor (AR) is expressed in up to a third of TNBC. AR is highly expressed in the "luminal AR (LAR)" molecular TNBC subtype, but is also present in other TNBC subtypes and may present an opportunity for targeted therapy. We hypothesized that AR+ TNBC critically depend on AR and that AR inhibition will decrease tumor burden in preclinical models of breast cancer. To determine the extent to which AR+ TNBC depend on AR, we inhibited AR activity with the AR antagonist enzalutamide (ENZ) and shRNAs against AR in multiple TNBC subtypes. Treatment with ENZ prevented AR nuclear localization in response to DHT in multiple TNBC cell lines, reduced baseline proliferation in 2D culture (p&amp;lt;0.05), and decreased anchorage independent growth in soft agar (p&amp;lt;0.01). AR knockdown significantly reduced proliferation (p&amp;lt;0.001) and increased apoptosis (p&amp;lt;0.001) compared to cells transduced with a non-targeting control. In addition to reduced proliferation, AR knockdown or treatment with ENZ altered cellular morphology from stellate to round in Matrigel and significantly decreased migration (p&amp;lt;0.05) and invasion (p&amp;lt;0.001) of cell lines spanning multiple TNBC subtypes. Microarray profiling and ELISA of TNBC lines treated with DHT and ENZ suggested that AR regulation of the EGFR ligand amphiregulin (AREG, p&amp;lt;0.05) is a mechanism by which AR influences proliferation, migration and invasion in TNBC. Indeed, treatment with exogenous AREG rescued decreased proliferation, migration and invasion of AR knockdown cell lines (p&amp;lt;0.05). In vivo, ENZ significantly decreased tumor viability (p=0.008) and increased necrosis (p=0.009) in SUM159PT xenografts. Our findings suggest that AR influences both proliferation and invasion of AR+ TNBC cells representing multiple TNBC subtypes and provide promising preclinical data on the efficacy of ENZ in AR+ TNBC. Thus, inhibition of AR by anti-androgens such as ENZ may represent an effective targeted therapy for TNBC. Citation Format: Valerie N Barton, Nicholas C D'Amato, Michael A Gordon, Britta M Jacobsen, Jennifer K Richer. Multiple subtypes of triple negative breast cancer are dependent on androgen receptor [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-02.
Biochemical studies on the isolation and characterization of human spleen haemosiderin (1984)

Haemosiderin was isolated from thalassaemic human spleens by centrifugation through concentrated KI solutions. A method for solubilizing haemosiderin was developed which leaves the iron oxyhydroxide cores and constituent polypeptides intact, facilitating further purification and analysis. Purified haemosiderin contained no detectable haem, trace amounts of carbohydrate, and iron and phosphorus in a molar ration of 6:1; much of the phosphate may be present as core-adsorbed. Several lipids were present, but it is not certain whether these are contaminants or components of the haemosiderin granules. In all preparations examined, a characteristic group of six to seven peptides of apparent Mr 12 900-17 800 were found, with a major band at Mr 14 500 and, in addition, a minor component of Mr 42 000; these peptides co-chromatographed with the cores. Negatively stained electron micrographs suggest that these peptides form an incomplete shell about the cores, consistent with the view that haemosiderin is a proteolytic product of ferritin.
Polyprotein Gene Expression: Generation of Diversity of Neuroendocrine Peptides (1984)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Pseudomonas exotoxin: chimeric toxins (1989)

Pseudomonas exotoxin binds to and enters cells by receptor-mediated endocytosis. Within the cell it requires exposure to low pH to enable it to translocate to the cell cytoplasm where it inhibits protein synthesis by ADP-ribosylating elongation factor 2. The toxin has three main structural domains whose functions are: Ia, cell binding; II, translocation; and III, ADP-ribosylation. Key amino acids have been identified within each domain that are required for the function of the toxin. Chimeric toxins were made originally by using chemical cross-linking reagents to couple Pseudomonas exotoxin (or other toxins) to cell-binding proteins. More recently, a variety of Pseudomonas exotoxin-related chimeric toxins have been made by gene fusion technology. These chimeric toxins may be useful clinically for treating various diseases and experimentally for understanding receptor function.
Randomized, Double-Blind, Placebo-Controlled, Phase II Trial of Sorafenib and Erlotinib or Erlotinib Alone in Previously Treated Advanced Non–Small-Cell Lung Cancer (2011)

Although there was little difference in ORR or PFS, subset analyses in EGFR WT and EGFR FISH-negative patients suggest a benefit for the combination of erlotinib/sorafenib compared with single-agent erlotinib with respect to PFS and OS.
Immunocytochemical localization and functional determination of phytoene desaturase in photoautotrophic prokaryotes (1990)

The in situ location of phytoene desaturease, an enzyme in the carotenoid biosynthetic pathway, has been investigated in the photosynthetic organisms Rhodobacter capsulatus SB 1003, Synechocystis PCC 6714, and Anabaena variabilis ATCC 29413. A post-embedding immunogold electyron microscopy procedure using a polyclonal antibody against a phytoene desaturase fusion protein was employed. For all three species most of the gold particles (about 85% in the case of Anabaena and Synechocystis) were associated with the photosynthetic membreanes. Other parts of the were only randomly and not significanlty labelled. When the anti-phytoene desatuase antibody was omitted, or when pre-immune serum was used, no gold deposition was observed. In vitro phytoene desaturase reactions, especially with purified thylakoid membranes from Synechocystis, confirmed the nature of phytoene as an integral protein of the thylakoid membrane.
A flexible decoder buffer model for JVT video coding (2003)

Video coding standards require that a compliant bit stream be decodable by a hypothetical decoder that is conceptually connected to the output of an encoder and consists of a decoder buffer, a decoder, and a display unit. The encoder must create a bit stream so that the hypothetical decoder buffer does not overflow or underflow. Previous decoder models assume that a given bit stream will be transmitted through a channel of a given constant bit rate and will be decoded (after a given buffering delay) by a device of some given buffer size. Therefore, these models are quite rigid and do not address the requirements of many of today's important video applications such as broadcasting live video or streaming pre-encoded video on demand over network paths with various peak bit rates to devices with various buffer sizes. In this contribution, we present a new hypothetical reference decoder for JVT that is more general and flexible than those defined in prior standards and provides significant additional benefits.
The Role of Autophagy in Mitochondria Maintenance: Characterization of Mitochondrial Functions in Autophagy-Deficient S. cerevisiae Strains (2007)

Autophagy is a lysosome-dependent cellular degradation process. Organisms bearing deletions of the essential autophagy genes exhibit various pathological conditions, including cancer in mammals and shortened life span in C. elegans. The direct cause forthese phenotypes is not clear. Here we used yeast as a model system to characterize the cellular consequence of ATG (autophagy-related) gene deletions. We found that the atgmutant strains, atg1delta, atg6delta, atg8delta and atg12delta, showed defects related to mitochondrial biology. These strains were unable to degrade mitochondria in stationary culture. In non-fermentable medium, which requires mitochondrial oxidative phosphorylation for survival, these atg strains showed a growth defect with an increased cell population at the G(1) phase of the cell cycle. The cells had lower oxygen consumption rates and reduced mitochondrial electron transport chain activities. Under these growth conditions, the atg strains had lower mitochondrial membrane potential. In addition, these mutants generated higher levels of reactive oxygen species (ROS) and they were prone to accumulate dysfunctional mitochondria. This study clearly indicates that an autophagy defect has a functional impact on various aspects of mitochondrial functions and suggests a critical role of autophagy in mitochondria maintenance.
A strategy for mapping and neutralizing conformational immunogenic sites on protein therapeutics (2002)

Antibodies are highly specific recognition molecules which are increasingly being applied to target therapy in patients. One type of developmental antibody-based therapy is antibody directed enzyme prodrug therapy (ADEPT) for the treatment of cancer. In ADEPT, an antibody specific to a tumor marker protein delivers a drug-activating enzyme to the cancer. Subsequent intravenous administration of an inactive prodrug results in drug activation and cytotoxicity only within the locale of the tumor. Pilot clinical trials with chemical conjugates of the prodrug activating enzyme carboxypeptidase G2 (CPG2) chemically conjugated with an antibody to and carcinoembryonic antigen (CEA), have shown that CPG2-mediated ADEPT is effective but limited by formation of human antibodies to CPG2 (HACA). We have developed a recombinant fusion protein (termed MFE-CP) of CPG2 with an anti-CEA single chain Fv antibody fragment and we have developed methods to address the immunogenicity of this therapeutic. A HACA-reactive discontinuous epitope on MFE-CP was identified using the crystal structure of CPG2, filamentous phage technology and surface enhanced laser desorption/ionization affinity mass spectrometry. This information was used to create a functional mutant of MFE-CP with a significant reduction (range 19.2 to 62.5%, median 38.5%) in reactivity with the sera of 11 patients with post-therapy HACA. The techniques described here are valuable tools for identifying and adapting undesirable immunogenic sites on protein therapeutics.
Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016)

Biomedical devices are essential for patient diagnosis and treatment; however, when blood comes in contact with foreign surfaces or homeostasis is disrupted, complications including thrombus formation and bacterial infections can interrupt device functionality, causing false readings and/or shorten device lifetime. Here, we review some of the current approaches for developing antithrombotic and antibacterial materials for biomedical applications. Special emphasis is given to materials that release or generate low levels of nitric oxide (NO). Nitric oxide is an endogenous gas molecule that can inhibit platelet activation as well as bacterial proliferation and adhesion. Various NO delivery vehicles have been developed to improve NO's therapeutic potential. In this review, we provide a summary of the NO releasing and NO generating polymeric materials developed to date, with a focus on the chemistry of different NO donors, the polymer preparation processes, and in vitro and in vivo applications of the two most promising types of NO donors studied thus far, N-diazeniumdiolates (NONOates) and S-nitrosothiols (RSNOs).
Apotransferrin stimulation of thyroid hormone dependent rat pituitary tumor cell growth in serum‐free chemically defined medium: Role of FE(III) chelation (1993)

Triiodothyronine (T3) dependent growth of GH1 rat pituitary tumor cells in serum-free defined culture requires apotransferrin (apoTf) (Sirbasku et al.: Mol. Cell. Endocrinol., 77:C47-C55, 1991). Diferric transferrin (2Fe.Tf) also is necessary as an iron source (Eby et al.: Anal. Biochem., 203:317-325, 1992). Further, T3 dependence is prevented by soluble Fe(III) addition to the medium (Sato et al.: In Vitro Cell. Dev. Biol., 27A:599-602, 1991). While our data suggested that apoTf caused growth by chelation of Fe(III), direct evidence was required. We used urea polyacrylamide gel electrophoresis along with autoradiography and Western immunoblotting to measure the Fe(III) content of growing GH1 cell cultures and identify the apoTf, mono-metal transferrins and 2Fe.Tf present. We found that apoTf per se did not cause growth but instead chelated inhibitory levels of Fe(III). In fact, apoTf need not be present at all provided that Fe(III) is reduced to < or = 0.6 microM. In addition, other protein and non-protein Fe(III) chelators were shown to be as effective as apoTf. Here, we report that pituitary cells are completely inhibited by > or = 1.2 microM Fe(III), which are concentrations which might be expected in many culture media and usually are not thought to influence growth. The high sensitivity of pituitary cells to Fe(III) suggests further study to determine what cellular functions are affected and how they interfere with thyroid hormone dependence.