gebhart/patrepeval huggingface dataset:
Size-Dependent Melting of Silica-Encapsulated Gold Nanoparticles (2002)

We report on the size dependence of the melting temperature of silica-encapsulated gold nanoparticles. The melting point was determined using differential thermal analysis (DTA) coupled to thermal gravimetric analysis (TGA) techniques. The small gold particles, with sizes ranging from 1.5 to 20 nm, were synthesized using radiolytic and chemical reduction procedures and then coated with porous silica shells to isolate the particles from one another. The resulting silica-encapsulated gold particles show clear melting endotherms in the DTA scan with no accompanying weight loss of the material in the TGA examination. The silica shell acts as a nanocrucible for the melting gold with little effect on the melting temperature itself, even though the analytical procedure destroys the particles once they melt. Phenomenological thermodynamic predictions of the size dependence of the melting point of gold agree with the experimental observation. Implications of these observations to the self-diffusion coefficient of gold in the nanoparticles are discussed, especially as they relate to the spontaneous alloying of core-shell bimetallic particles.
Separation of Monocytes from Whole Human Blood (2002)

Human peripheral blood monocytes are isolated by flotation from whole blood through a single low-density barrier prepared from OptiPrep at 4 degrees C. The separation from lymphocytes depends on the more rapid rate of flotation of the monocytes because of their slightly lower density and larger size. The method works optimally only with fresh (within 2 h of drawing) EDTA-anticoagulated blood. Preliminary evidence suggests that this technique may be applicable to blood from rats.
Pretreatment Mitochondrial Priming Correlates with Clinical Response to Cytotoxic Chemotherapy (2011)

Cytotoxic chemotherapy targets elements common to all nucleated human cells, such as DNA and microtubules, yet it selectively kills tumor cells. Here we show that clinical response to these drugs correlates with, and may be partially governed by, the pretreatment proximity of tumor cell mitochondria to the apoptotic threshold, a property called mitochondrial priming. We used BH3 profiling to measure priming in tumor cells from patients with multiple myeloma, acute myelogenous and lymphoblastic leukemia, and ovarian cancer. This assay measures mitochondrial response to peptides derived from proapoptotic BH3 domains of proteins critical for death signaling to mitochondria. Patients with highly primed cancers exhibited superior clinical response to chemotherapy. In contrast, chemoresistant cancers and normal tissues were poorly primed. Manipulation of mitochondrial priming might enhance the efficacy of cytotoxic agents.
A mutated human homologue to yeast Upf1 protein has a dominant-negative effect on the decay of nonsensecontaining mRNAs in mammalian cells (1998)

All eukaryotic cells analyzed have developed mechanisms to eliminate the production of mRNAs that prematurely terminate translation. The mechanisms are thought to exist to protect cells from the deleterious effects of in-frame nonsense codons that are generated by routine inefficiencies and inaccuracies in RNA metabolism such as pre-mRNA splicing. Depending on the particular mRNA and how it is produced, nonsense codons can mediate a reduction in mRNA abundance either (i) before its release from an association with nuclei into the cytoplasm, presumably but not certainly while the mRNA is being exported to the cytoplasm and translated by cytoplasmic ribosomes, or (ii) in the cytoplasm. Here, we provide evidence for a factor that functions to eliminate the production of nonsense-containing RNAs in mammalian cells. The factor, variously referred to as Rent1 (regulator of nonsense transcripts) or HUPF1 (human Upf1 protein), was identified by isolating cDNA for a human homologue to Saccharomyces cerevisiae Upf1p, which is a group I RNA helicase that functions in the nonsense-mediated decay of mRNA in yeast. Using monkey COS cells and human HeLa cells, we demonstrate that expression of human Upf1 protein harboring an arginine-to-cysteine mutation at residue 844 within the RNA helicase domain acts in a dominant-negative fashion to abrogate the decay of nonsense-containing mRNA that takes place (i) in association with nuclei or (ii) in the cytoplasm. These findings provide evidence that nonsense-mediated mRNA decay is related mechanistically in yeast and in mammalian cells, regardless of the cellular site of decay.
Die Anforderungen der Bank (1993)

Die Mitarbeiter der Bank, die die Kundengespräche führen, machen sich selbstverständlich auch ein Bild von ihren Geschäftspartnern. Im allgemeinen sind das der Unternehmer oder auch sein Finanzmanager. Sehr schnell erkennbar werden dabei für den Firmenkundenbetreuer die Fachkompetenz seines Gesprächspartners sowie auch dessen persönliche Zuverlässigkeit (Werden Zusagen eingehalten? Stimmen früher gegebene Vorabinformationen?)
Insulin glargine (Aventis Pharma). (2000)

Insulin glargine is a biosynthetic human insulin analog which has been developed by Aventis Pharma (formerly Hoechst Marion Roussel, HMR), for the treatment of types I and II diabetes. In April 1999, HMR filed insulin glargine for approval in both Europe and the US [322507]. In April 2000, the FDA approved insulin glargine (as Lantus) for the treatment of adult patients with type II diabetes mellitus, who require basal insulin for the control of hyperglycemia, and for adult and pediatric patients with type I diabetes mellitus [363836]. Aventis expects to launch this product during 2000 [361988]. In June 2000, the EMEA approved insulin glargine for the treatment of both type I and II diabetes [370984]. In April 1999, the FDA recommended that HMR should initially submit 6-month efficacy and safety data, instead of the usual 12- month data, to hasten the FDA approval procedure. The rest of the phase III data would be added to the filing at a later date [279466]. Insulin glargine is in phase III trials in Japan as a substitute for basal insulin in the treatment of Type I diabetes [216445]. Two formulations of insulin glargine with zinc have also been tested in phase I trials. HOE-71/GT15 and GT80 contain 15 and 80 mu g/ml of zinc. These formulations appear to have longer duration of action with a reduced peak insulin effect [177507]. This insulin analog has a lower receptor binding affinity compared with human insulin, but shows equal potency in vivo [320724]. Insulin glargine was designated as a medium priority project by HMR, which means the project had been set tight deadlines which if not achieved, would have resulted in discontinuation [221118]. In April 2000, Novo Nordisk filed a complaint in Germany against Aventis claiming that the production and sale of insulin glargine infringes two German patents held by Novo Nordisk [364362]. In July 2000, Credit Lyonnais Securities Europe predicted that insulin glargine was likely to enjoy a strong competitive position for several years in Europe and the US, following launch in these territories during 2000, while it was predicted that a registration dossier would be submitted in Japn in 2002. Sales were predicted to reach Euro 600 million by 2005. In April 1999, ABN Amro predicted annual sales of DM 75 million in 2000, rising to DM 200 million in 2002 [328676].
Shaping Development of Autophagy Inhibitors with the Structure of the Lipid Kinase Vps34 (2010)

Phosphoinositide 3-kinases (PI3Ks) are lipid kinases with diverse roles in health and disease. The primordial PI3K, Vps34, is present in all eukaryotes and has essential roles in autophagy, membrane trafficking, and cell signaling. We solved the crystal structure of Vps34 at 2.9 angstrom resolution, which revealed a constricted adenine-binding pocket, suggesting the reason that specific inhibitors of this class of PI3K have proven elusive. Both the phosphoinositide-binding loop and the carboxyl-terminal helix of Vps34 mediate catalysis on membranes and suppress futile adenosine triphosphatase cycles. Vps34 appears to alternate between a closed cytosolic form and an open form on the membrane. Structures of Vps34 complexes with a series of inhibitors reveal the reason that an autophagy inhibitor preferentially inhibits Vps34 and underpin the development of new potent and specific Vps34 inhibitors.
Enhanced Expression of RAD51 Associating Protein-1 Is Involved in the Growth of Intrahepatic Cholangiocarcinoma Cells (2008)

Our findings may contribute to the better understanding of cholangiocarcinogenesis and open a new avenue to the development of novel therapeutic and/or diagnostic approach to this type of tumor.
Noninvasive continuous monitoring of solid-phase peptide synthesis by acid-base indicator (1988)

The course and the end point of the acylation of resin-bound amino groups in solid-phase peptide synthesis was monitored by a novel noninvasive qualitative and quantitative test based on the use of the acid-base indicator bromophenol blue.
Platelet-derived growth factor in human malignancy. (1992)

Platelet-derived growth factor (PDGF) was first implicated in the process of transformation when one of its peptide chains was found to be homologous to the viral sis oncogene (v-sis). Since that time, there have been multiple demonstrations of the transforming activity of v-sis in fibroblasts. Because of the near identity of the v-sis protein with the PDGF B chain, v-sis is thought to transform through an autocrine stimulatory mechanism of cell growth. Consistent with this view are studies which demonstrate inhibition of v-sis-mediated transformation by anti-PDGF antibodies. Expression of the cellular sis gene (c-sis) and its receptors, and secretion of PDGF-like factors have been demonstrated in many types of human malignant cells. Nevertheless, a causative role for c-sis in inducing or maintaining the transformed phenotype in human malignancies remains to be established. There are significant differences in structure between v-sis and c-sis. Studies of transforming ability have yielded conflicting results in transfection models, depending on the transfected vector and target cell type utilized. While there is compelling evidence for the involvement of PDGF in an autocrine growth mechanism in transformed fibroblasts, the evidence in human epithelial tumor types is less convincing because PDGF receptors are usually not detectable on the cell surface. The recent demonstration of intracellular co-localization of active PDGF precursors and PDGF receptors, however, supports the existence of an internal autocrine pathway independent of PDGF secretion. Further investigation of such a mechanism in de novo human malignancies is warranted to establish the role of PDGF in the development of these neoplasms.
Ueber Synthesen stickstoffhaltiger Verbindungen mit Hülfe des Stickoxyds (1898)

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Kinetics of chicken embryonic thymocyte development in ovo and in organ culture (1992)

Abstract Thymocyte development was monitored in an embryonic thymus organ culture system to establish a model in the chicken in which the functional nature of the thymic microenvironment could be assessed. Thymus lobes were removed from 10‐day‐old embryos and cultured for 2–10 days. Cell yield increased to a maximum in 4–8 days of culture with a corresponding decrease in average cell size. An initial thymocyte population of predominantly CD3 − CD4 − CD8 − cells gave rise to all CD3/CD4/CD8‐defined subpopulations in vitro , maintaining high levels of CD3 − CD4 − CD8 + and CD3 + CD4 − CD8 + cells and a low representation of CD3 − CD4 + CD8 − , CD3 + CD4 + CD8 − , CD3 − CD4 + CD8 − and CD3 + CD4 + CD8 + thymocytes. This is the first observation of a CD3 − CD4 + CD8 − population in the chicken. Developmental kinetics of CD3 + cells were similar to that in the embryo, suggesting that the in vitro environment is sufficient to promote and maintain thymocyte maturation. Thymocytes of both the γδ and αβ T cell receptor (TcR) lineages developed in that order, confirming in ovo data and the lineage potential of the first wave of thymocyte precursors. One unusual finding was a relative accumulation of γδ TcR + thymocytes in culture, incorporating all CD4/CD8 subsets, including a previously undetected population, CD4 + CD8 − . This may indicate a favorable developmental environment or simply a lack of normal cellular emigration. A detailed comparison with T cell development in the embryo demonstrated that the chicken thymus organ culture system reflects thymic events in ovo during a limited time period and thus should prove useful in the identification of functionally relevant thymic molecules.
RNA as a Boiling-Resistant Anionic Polymer Material To Build Robust Structures with Defined Shape and Stoichiometry (2014)

RNA is a polyribonucleic acid belonging to a special class of anionic polymers, holding a unique property of self-assembly that is controllable in the construction of structures with defined size, shape, and stoichiometry. We report here the use of RNA as polymers to fabricate boiling-resistant triangular nanoscaffolds, which were used to construct hexagons and patterned hexagonal arrays. The RNA triangular scaffolds demonstrated promising potential to construct fluorogenic probes and therapeutic agents as functionalization with siRNA, ribozyme, folate, and fluorogenic RNA aptamers revealed independent functional activity of each RNA moiety. The ribozyme was able to cleave hepatitis genomic RNA fragments, the siRNA silenced the target genes, and all fluorogenic RNA aptamers retained their fluorescence emission property. The creation of boiling-temperature-resistant RNA nanoparticles opens a new dimension of RNA as a special polymer, feasible in industrial and nanotechnological applications.
Topically Applied Testosterone and Phallic Growth (1980)

Topical application of 5% testosterone cream for 21 days resulted in enlargement of the penis to normal size for age in five boys with normal XY karyotype who had microphallus and hypopituitarism. In four patients, testosterone cream was applied locally to the penis and in one to an area of skin in the right axilla. Serum testosterone values rose from infantile levels before the start of therapy to normal adult male levels on the last day of treatment. All patients were receiving human growth hormone at the time of therapy with testosterone. No additional acceleration of linear growth and no advance in osseous maturation occurred during or after treatment. Application of testosterone locally for this brief period is a safe, effective, and simple means of stimulating phallic growth. Our findings suggest that topical testosterone causes penile growth predominantly through its systemic action.
Long non‐coding RNA modifies chromatin (2011)

Common themes are emerging in the molecular mechanisms of long non-coding RNA-mediated gene repression. Long non-coding RNAs (lncRNAs) participate in targeted gene silencing through chromatin remodelling, nuclear reorganisation, formation of a silencing domain and precise control over the entry of genes into silent compartments. The similarities suggest that these are fundamental processes of transcription regulation governed by lncRNAs. These findings have paved the way for analogous investigations on other lncRNAs and chromatin remodelling enzymes. Here we discuss these common mechanisms and provide our view on other molecules that warrant similar investigations. We also present our concepts on the possible mechanisms that may facilitate the exit of genes from the silencing domains and their potential therapeutic applications. Finally, we point to future areas of research and put forward our recommendations for improvements in resources and applications of existing technologies towards targeted outcomes in this active area of research.
Association Among an Ornithine Decarboxylase Polymorphism, Androgen Receptor Gene (CAG) Repeat Length and Prostate Cancer Risk (2004)

The ODC A allele was not associated with a statistically significant increased risk of prostate cancer. However, this association may vary according to the number of CAG repeats in the AR receptor and smoking status.
A Framework for Comparing IS Core Curriculum and IS Requirements for Accounting Majors (2004)

Core curriculum in information systems is of vital interest to the information systems community. Long scrutinized by the academic community and various stakeholders, the content of information systems core curriculum is once again a topic of debate. Accounting has undergone similar curriculum examination (including technology curriculum) amid criticisms for a variety of accounting failures in the 1990s. We map information systems core curriculum frameworks to accounting core curriculum frameworks for information systems courses and confirm the value of a core information systems curriculum for accounting majors. Using industry perspective as a focus, a pilot study in a graduate accounting information systems course identified information systems topics that are of distinct importance to managerial accountants as opposed to public accountants, suggesting different information systems curriculum needs within the major. This study resulted in the development of a three-dimensional modular information systems curriculum model mapping topical areas in information systems to specific major with Bloom's taxonomy represented on the third axis indicating how the learning takes place. Examination of information systems topics required by major within business may help confirm the identity of core concepts in information systems.
A Synthetic Optogenetic Transcription Device Enhances Blood-Glucose Homeostasis in Mice (2011)

Synthetic biology has advanced the design of genetic devices that can be used to reprogram metabolic activities in mammalian cells. By functionally linking the signal transduction of melanopsin to the control circuit of the nuclear factor of activated T cells, we have designed a synthetic signaling cascade enabling light-inducible transgene expression in different cell lines grown in culture or bioreactors or implanted into mice. In animals harboring intraperitoneal hollow-fiber or subcutaneous implants containing light-inducible transgenic cells, the serum levels of the human glycoprotein secreted alkaline phosphatase could be remote-controlled with fiber optics or transdermally regulated through direct illumination. Light-controlled expression of the glucagon-like peptide 1 was able to attenuate glycemic excursions in type II diabetic mice. Synthetic light-pulse-transcription converters may have applications in therapeutics and protein expression technology.
Mammalian Pax Genes (1994)

Orthologs and paralogs are two fundamentally different types of homologous genes that evolved, respectively, by vertical descent from a single ancestral gene and by duplication. Orthology and paralogy are key concepts of evolutionary genomics. A ...Read More
Expression of human pancreatic polypeptide precursors from a dicistronic mRNA in mammalian cells (1987)

The ability of eukaryotic ribosomes to reinitiate translation at downstream AUG codons on polycistronic mRNAs was used to select transfected CHO clones that secreted a precursor to the human pancreatic polypeptide (PP). In the in vitro constructed transcription unit, a viral promoter directed the synthesis of a dicistronic mRNA. The PP cDNA was placed in the 5'-part of this transcript, while a DHFR cDNA was placed 3' to the PP. This dicistronic expression unit was transfected into CHO cells, and methotrexate-resistant colonies were selected. RNA-blots verified that the PP precursor and DHFR were expressed from the same dicistronic mRNA. The CHO cells synthesized the hormone precursor and secreted it through the constitutive secretory pathway.
Disodium cromoglycate enhances ongoing immunoglobulin production in vitro in human B cells. (1991)

The effect of disodium cromoglycate (DSCG) upon human immunoglobulin (Ig) isotypes and IgG subclasses production by purified B cells was studied. DSCG enhanced IgM, IgG1, IgG2, IgG3, IgG4 and IgA production in a dose-dependent fashion, while DSCG failed to induce IgE production at any concentrations tested by purified B cells. When B cells were separated into small resting and large activated B cells, DSCG failed to induce Ig production from small resting B cells in the presence or absence of Staphylococcus aureus Cowan strain I (SAC). In contrast, in large activated B cells DSCG significantly enhanced all types of Ig production (two-to threefold), especially IgG4 production (seven-to 11-fold), except IgE, which large B cells did not produce. The enhancement of IgG subclass production was not subclass switching, since DSCG failed to enhance IgG1 production in B cells depleted of surface IgG1+ cells (sIgG1+ cells). Similarly, DSCG did not enhance IgG2, IgG3 or IgG4 production from sIgG2-, sIgG3- or sIgG4- B cells, respectively, Interleukin-4 (IL-4) or interleukin-6 (IL-6) also enhanced Ig production except IgG4 from large activated B cells. The enhancing effect of DSCG was not mediated by IL-4 or IL-6 since anti-IL-4 or anti-IL-6 antibody failed to block the DSCG-induced enhancement. DSCG also enhanced IgG2 and IgM production from human B-cell lines GM-1500 and CBL, respectively. These results suggest that DSCG directly and preferentially stimulates activated B cells which are producing Ig and, in addition, enhances their Ig production.
NCI experience using yeast-brachyury vaccine (GI-6301) in patients (pts) with advanced chordoma. (2014)

3081 Background: Saccharomyces cerevisiae has been genetically modified to express Brachyury (Br) protein and developed under a CRADA with GlobeImmune/NCI as a heat-killed immune-stimulating therapeutic cancer vaccine (GI-6301). Br is a member of the T-box family of transcription factors and is a key factor in embryonic (mesoderm) development. Chordoma, a rare tumor of the notochord (derived from mesoderm) is known to overexpress Br while expression in normal adult tissue is minimal or not present. Preclinical work has demonstrated Br specific T cells can lyse human Chordoma cells expressing Br in an MHC restricted fashion. Methods: We enrolled a cohort of 7 pts with advanced Chordoma on an expansion cohort of a phase I study (NCT01519817) and evaluated their clinical and immunologic outcomes. All pts had undergone previous radiation (median 470 days since radiation: range 111-1883). All received 40 yeast units of vaccine every 2 weeks x 7 with first restaging at day 85. If stable, pts went on to monthly dosing with restaging scans every 2 months. The primary endpoint was safety, but clinical outcomes were followed as well. Br-specific T cell responses were also analyzed by flow-cytometry intracellular staining (ICS) of CD4 and CD8 T lymphocytes for the cytokines IFN-g, TNF, and IL-2. Results: All 7 pts had undergone extensive previous treatment. Median age was 59 (41-66). Two pts had relatively stable disease for 6 and 12 months, respectively, coming on the study, and both remain stable at day 141 and 197 restaging, respectively. The remaining 5 had progressive disease at enrollment. Of those 5, 1 had a decrease in index lesions >30% at day 141 with a confirmed PR on repeat scan 4 weeks later. 1 has stable disease through day 141 restaging. The other 3 progressed at day 141 restaging. Adverse events were minimal with injection site reaction being the most common (13 events in 63 doses (21%), 6 of 7 pts (86%)). Two of 7 pts had a Br-specific T cell response by ICS. Conclusions: This cohort of pts with advanced Chordoma in the phase I study with GI-6301 vaccine demonstrated safety and enhanced immune response with a confirmed PR. These findings are encouraging and warrant further study using this vaccine in pts with Chordoma. Clinical trial information: NCT01519817.