gebhart/patrepeval huggingface dataset:
New drugs for patients with pancreatic cancer (2002)

This past year has proved to be a relatively disappointing one for the development of agents that could improve the survival rates of patients with advanced pancreatic cancer. A well designed randomized trial of treatment of patients with gemcitabine with or without a farnesyl transferase inhibitor (tried because pancreatic cancers have a high incidence of K- abnormalities) showed no improvement in survival rates. A definitive randomized controlled trial with a histone deacetylase inhibitor also proved negative. There are some signs of hope in that in early nonrandomized studies there are some new agents that appear to have some activity against the disease. These agents include the thymidylate synthase inhibitor capecitabine (which is possibly activated at the tumor site), the antigastrin immunogen G17DT (which is an immunization designed to neutralize the pancreatic growth factor gastrin), and the topoisomerase I inhibitor 9-nitrocamptothecin. In addition, the combination of the new agent oxaliplatin to high-dose 5FU plus leucovorin, which gave a median survival rate of 12.5 months, is also worthy of further study. Supportive care findings of interest for the patient with advanced pancreatic cancer of note include: the study in which eicosapentaenoic acid (fish oil) caused a modest weight gain (median of 1 kg), and the finding that ofloxacin plus ursodeoxycholic acid was not superior to ursodeoxycholic acid alone for the prevention or occlusion of biliary stents.
Does an Outcome-based Education Curriculum Model Promote or Hinder Creativity? (2003)

Education systems in much of the industrialised world have undergone radical changes in the past decade. Changes to curriculum that have been occurring throughout the education systems in many countries have marked similarities, including the move towards an outcome-based model and the attempt to implement standardised assessment procedures as part of an accountability process. There has been criticism not only of the educational value of the changes but also of the problematic area of assessment this type of model demands. In a recent cross-national study educators indicated that they were not confident of the assessment requirements or with the appropriateness of some of the assessment proposals to meet the needs of music education. This paper outlines some of the concerns about outcomes-based education and its adequacy to promote and support the notion of creativity. It examines issues such as the right to assess another's creative efforts and the means by which we attempt to do so.
Purification of human urinary erythropoietin on controlled-pore glass and silicic acid. (1985)

Erythropoietin (Epo) has been isolated from raw human urine of anemic patients by controlled-pore glass and silicic acid chromatography. A purification factor of not less than 100-fold and recovery of about 80% of activity was routinely achieved. The resulting Epo preparation is active both in vivo and in vitro and can be neutralized by an antibody to human Epo indicating the native state and identity of the isolated Epo molecule. The preparation is stable at near neutral pH and is amenable to further purification.
The Thyrotrope-Restricted Isoform of the Retinoid-X Receptor-γ1 Mediates 9-cis-Retinoic Acid Suppression of Thyrotropin-β Promoter Activity (1997)

TSHbeta is a subunit of TSH that is uniquely expressed and regulated in the thyrotrope cells of the anterior pituitary gland. Thyroid hormone receptors (TR) are known to mediate T3 suppression of TSHbeta gene expression at the level of promoter activity. The role of other nuclear receptors in regulation of this gene is less clearly defined. Retinoid X receptors (RXR) are a family of nuclear transcription factors that function both as 9-cis-retinoic acid (RA) ligand-dependent receptors and heterodimeric partners with TR and other nuclear receptors. Recently, the RXR isoform, RXRgamma, has been identified in the anterior pituitary gland and found to be restricted to thyrotrope cells within the pitutiary. In this report, we have further characterized the distribution of RXRgamma1, the thyrotrope-restricted isoform of RXRgamma, in murine tissues and different cell types. We have found that RXRgamma1 mRNA and protein are expressed in the TtT-97 thyrotropic tumor, but not the thyrotrope-variant alphaTSH cells or somatotrope-derived GH3 cells. Furthermore, we have studied the effects of RXRgamma1 on TSHbeta promoter activity and hormone regulation in these pituitary-derived cell types. Both T3 and 9-cis-RA independently suppressed promoter activity in the TtT-97 thyrotropes. Interestingly, the combination of ligands suppressed promoter activity more than either alone, indicating that these hormones may act cooperatively to regulate TSHbeta gene expression in thyrotropes. The RXRgamma1 isoform was necessary for the 9-cis-RA-mediated suppression of TSHbeta promoter activity in alphaTSH and GH3 cells, both of which lack this isoform. RXRbeta, a more widely distributed isoform, did not mediate these effects. Finally, we showed that the murine TSHbeta promoter region between -200 and -149 mediated a majority of the 9-cis-RA suppression of promoter activity in thyrotropes. This region is distinct from the T3-mediated response region near the transcription start site. These data suggest that retinoids can mediate TSHbeta gene regulation in thyrotropes and the thyrotrope-restricted isoform, RXRgamma1, is required for this effect.
Real-Time In Vivo Loading in the Lumbar Spine (2000)

The study technique and technology are efficacious for measuring real-time in vivo loads in the spine. Measuring load on an intradiscal implant over the course of healing provides key information about the mechanics of this process. Loads may be used to indicate performance demands on the intervertebral disc and interbody implants for subsequent implant design.
Human cytotoxic T lymphocytes stimulated by endogenously processed human papillomavirus type 11 E7 recognize a peptide containing a HLA-A2 (A*0201) motif. (1994)

Cytotoxic T lymphocytes (CTL) may play an important role in the control of human papillomavirus (HPV)-induced anogenital neoplasias, but have been difficult to study owing to the difficulty in obtaining sufficient quantities of infectious virus. To address this we have stimulated human HPV-specific CTL in vitro using low-density cells (LDC) from peripheral blood mononuclear cells (PBMC). Low-density cells were used to present synthetic peptides, or endogenously processed peptides expressed from recombinant vaccinia viruses, to high-density PBMC (predominantly lymphocytes) for 6 days. Cytotoxic T lymphocytes stimulated with endogenously processed HPV 11 E7 recognized the synthetic HLA-A2 (A*0201) motif-containing nonamer, 4-12. In reciprocal experiments, CTL stimulated with this peptide in vitro recognized targets expressing endogenously processed E7. The responses in each case were A2 restricted and peptide specific. Two additional A2 motif-containing nonamers from HPV 6b E7 (21-30 and 47-55) also elicited peptide-specific, A2-restricted CTL. The data illustrate the potential that in vitro stimulation with LDC has in understanding CTL responses to experimentally problematic viral systems such as HPV, and may offer a route to specific immunotherapy of HPV-associated lesions.
Emotion detection in speech using deep networks (2014)

We propose a novel staged hybrid model for emotion detection in speech. Hybrid models exploit the strength of discriminative classifiers along with the representational power of generative models. Discriminative classifiers have been shown to achieve higher performances than the corresponding generative likelihood-based classifiers. On the other hand, generative models learn a rich informative representations. Our proposed hybrid model consists of a generative model, which is used for unsupervised representation learning of short term temporal phenomena and a discriminative model, which is used for event detection and classification of long range temporal dynamics. We evaluate our approach on multiple audio-visual datasets (AVEC, VAM, and SPD) and demonstrate its superiority compared to the state-of-the-art.
The Synthesis of Heptenic Derivatives of Aminoimidazoazaarene Cooked-food Mutagens (1987)

Synthese de derives N-[amino-3 propyl]-2 de mutagenes (IQ, MeIQx et PhIP) et d'amino-3' propylamide de l'acide amino-2 methyl-3 imidazo [4,5-f] quinoxalinepropionique-8 acide; ces composes peuvent etre utilises comme haptenes dans la production d'anticorps monoclonaux
Pharmacokinetics of Recombinant Activated Factor VII (rFVIIa) (2000)

Recombinant coagulation factor VIIa (NovoSeven, Novo Nordisk Pharmaceuticals, Inc., Princeton NJ, USA) is a new drug for treatment of bleeding in patients with hemophilia and inhibitors. The pharmacokinetic profiles of rFVIIa have been evaluated in healthy adult volunteers who were pretreated with acenocoumarol, in adult and pediatric patients with hemophilia A or B, and in adult patients with cirrhosis and a prolonged prothrombin time (PT). The clearance (CL) and half-life (t1/2) values of rFVIIa after bolus injection were in the same range in the adult populations studied: patients with hemophilia, patients with cirrhosis, and healthy volunteers. The volume of distribution at steady state (Vss), on the other hand, was slightly smaller in healthy adult volunteers than in patients with hemophilia. The pharmacokinetic profile of rFVIIa seems to be independent of bleeding or nonbleeding conditions in adult hemophilic patients; however, the patients in these studies did not suffer from major bleeding episodes. The values of CL and t1/2 were also dose independent in adult patients with hemophilia and in patients with cirrhosis. Pediatric patients with hemophilia had shorter t1/2 and higher CL values than the adults with hemophilia. The administration of rFVIIa by continuous infusion is still experimental and a number of practical issues remain to be resolved.
Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single‐guide RNA and carbohydrate selection (2014)

The CRISPR/Cas system allows targeting of multiple genes in a single reaction with the potential to create pigs of one genetic strain or multiple genetic modifications in a single pregnancy. The application of this phenotypic selection strategy with multiplexed sgRNA and the Cas9 nuclease has accelerated our ability to produce and evaluate pigs important to xenotransplantation.
Rho exchange factor ECT2 is induced by growth factors and regulates cytokinesis through the N‐terminal cell cycle regulator‐related domains (2003)

The ECT2 protooncogene plays a critical role in cytokinesis, and its C-terminal half encodes a Dbl homology-pleckstrin homology module, which catalyzes guanine nucleotide exchange on the Rho family of small GTPases. The N-terminal half of ECT2 (ECT2-N) contains domains related to the cell cycle regulator/checkpoint control proteins including human XRCC1, budding yeast CLB6, and fission yeast Cut5. The Cut5-related domain consists of two BRCT repeats, which are widespread to repair/checkpoint control proteins. ECT2 is ubiquitously expressed in various tissues and cell lines, but elevated levels of ECT2 expression were found in various tumor cell lines and rapidly developing tissues in mouse embryos. Consistent with these findings, induction of ECT2 expression was observed upon stimulation by serum or various growth factors. In contrast to other oncogenes whose expression is induced early in G1, ECT2 expression was induced later, coinciding with the initiation of DNA synthesis. To test the role of the cell cycle regulator/checkpoint control protein-related domains of ECT2 in cytokinesis, we expressed various ECT2 derivatives in U2OS cells, and analyzed their DNA content by flow cytometry. Expression of the N-terminal half of ECT2, which lacks the catalytic domain, generated cells with more than 4N DNA content, suggesting that cytokinesis was inhibited in these cells. Interestingly, ECT2-N lacking the nuclear localization signals inhibited cytokinesis more strongly than the derivatives containing these signals. Mutational analyses revealed that the XRCC1, CLB6, and BRCT domains in ECT2-N are all essential for the cytokinesis inhibition by ECT2-N. These results suggest that the XRCC1, CLB6, and BRCT domains of ECT2 play a critical role in regulating cytokinesis.
Identification of CDK4 Sequences Involved in Cyclin D1 and p16 Binding (1997)

Activation of CDK4 is regulated, in part, by its association with a D-type cyclin. Conversely, CDK4 activity is inhibited when it is bound to the cyclin-dependent kinase inhibitor, p16(INK4A). To investigate the molecular basis of the interactions between CDK4 and cyclin D1 or p16(INK4A) we performed site-directed mutagenesis of CDK4. The interaction was examined using in vitro translated wild type and mutant CDK4 proteins and bacterially expressed cyclin D1 and p16 fusion proteins. As mutational analysis of CDC2 suggests that its cyclin binding domain is primarily located near its amino terminus, the majority of the mutations constructed in CDK4 were located near its amino terminus. In addition, CDK4 residues homologous to CDC2 sites involved in Suc1 binding were also mutated. Our analysis indicates that cyclin D1 and p16 binding sites are overlapping and located primarily near the amino terminus. All CDK4 mutations that resulted in decreased p16 binding capability also diminished cyclin D1 binding. In contrast, amino-terminal sequences were identified, including the PSTAIRE region, that are important for cyclin D1 binding but are not involved in p16 binding.
Inhibition of the tetracycline efflux antiport protein by 13-thio-substituted 5-hydroxy-6-deoxytetracyclines (1993)

A series of 13-(alkylthio) and 13-(arylthio) derivatives of 5-hydroxy-6-deoxytetracycline (tetracycline, Tc) were synthesized and compared to the clinically used antibiotics tetracycline, methacycline, and minocycline for their ability to inhibit tetracycline efflux in an everted membrane vesicle assay of bacterial resistance to tetracyclines. The assay screened for the ability of tetracycline analogues to inhibit [3H]tetracycline uptake into everted membrane vesicles, thereby evaluating the molecular prerequisites for inhibition of an efflux-dependent resistant bacterial system. Thiol adducts attached at the exocyclic C13 carbon of methacycline led to an increase in inhibitor potency as compared to the reference antibiotics. The most potent inhibitors of [3H]tetracycline uptake into everted vesicles among these analogues, particularly members of the alkyl series, revealed important structure-activity relationships between inhibitor potency, steric parameters, and lipophilicity at the C13 sulfur position.
Diagnostic imaging and therapeutic application of nanoparticles targeting the liver (2014)

Liver diseases, particularly viral hepatitis, cirrhosis and hepatocellular carcinoma, are common in clinical practice with high morbidity and mortality worldwide. Many substances for diagnostic imaging and therapy of liver diseases may have either severe adverse effects or insufficient effectiveness in vivo because of their nonspecific uptake. Therefore, by targeting the delivery of drugs into the liver or specific liver cells, drug efficiency may be largely improved. This review summarizes the up-to-date research progress focusing on nanoparticles targeting the liver for both diagnostic and therapeutic purposes. Targeting strategies, mechanisms of enhanced effects, and clinical applications of nanoparticles are discussed specifically. We believe that new targeting nanotechnology such as nanoprobes for multi-modality imaging and multifunctional nanoparticles would facilitate significant advancements in this active research area in the near future.
Progress in Serodiagnosis of Mycobacterium tuberculosis Infection (2007)

One-third of the world population is estimated to have Mycobacterium tuberculosis infection. Accurate and timely identification of infected individuals is critical for treatment and control. The current diagnostic methods lack the desired sensitivity and specificity, require sophisticated equipment and skilled workforce or take weeks to yield results. Diagnosis of extrapulmonary TB, TB-HIV co-infection, childhood TB and sputum smear-negative pulmonary TB pose serious challenges. Interest in developing serodiagnostic methods is increasing because detection of antibody is rapid, simple and relatively inexpensive, and does not require a living cell for detection. Three types of tests, namely screening tests to overcome diagnostic delay, specific tests for diagnosis of extrapulmonary TB and other bacteriologically negative cases, and tests for vaccine-induced immunity need critical consideration. Several factors must be considered to develop serodiagnostic methods for TB. Antigen recognition by infected individuals is highly heterogeneous due to stage of disease, differences in HLA types, strain of the bacilli, health of the patient and bacillary load. With advances in molecular biological techniques, a number of novel antigens have been identified. Some of these antigens have proven valuable in detecting specific antibodies in some of the most challenging TB patients. The best example is a fusion protein containing several M. tuberculosis proteins (e.g. CFP-10, MTB8, MTB48, MTB81 and the 38-kDa protein) which showed encouraging results in detecting antibodies in sera of patients, including TB-HIV co-infection. This review presents progress made in the serodiagnosis of TB during the last decade.
Wet chemical routes to the assembly of organic monolayers on silicon surfaces via the formation of Si–C bonds: surface preparation, passivation and functionalization (2010)

Organic functionalization of non-oxidized silicon surfaces, while allowing for robust chemical passivation of the inorganic substrate, is intended and expected to broaden the chemical, physical and electronic properties of the currently most relevant technological material. Numerous protocols are now available for the preparation of Si-C, Si-O and Si-N bound layers. In particular, the covalent attachment of 1-alkenes and 1-alkynes onto hydride-terminated Si(100) and Si(111) has seen a wealth of research activity starting from the pioneering work of Linford and Chidsey (Alkyl monolayers covalently bonded to silicon surfaces, J. Am. Chem. Soc., 1993, 115(26), 12631-12632). This critical review aims to bring together the available wet-chemical routes toward the formation of silicon-organic monolayers under ambient conditions. Particular emphasis is placed on discussing the reasons behind the need for novel chemical approaches that are straightforward, modular and of wide scope so as to allow the application of silicon electrodes in aqueous electrolytes. A general introduction to biomolecular recognition events at functionalized silicon surfaces is also presented (281 references).
AccR Is a Master Regulator Involved in Carbon Catabolite Repression of the Anaerobic Catabolism of Aromatic Compounds in Azoarcus sp. CIB (2013)

Here we characterized the first known transcriptional regulator that accounts for carbon catabolite repression (CCR) control of the anaerobic catabolism of aromatic compounds in bacteria. The AccR response regulator of Azoarcus sp. CIB controls succinate-responsive CCR of the central pathways for the anaerobic catabolism of aromatics by this strain. Phosphorylation of AccR to AccR-P triggers a monomer-to-dimer transition as well as the ability to bind to the target promoter and causes repression both in vivo and in vitro. Substitution of the Asp(60) phosphorylation target residue of the N-terminal receiver motif of AccR to a phosphomimic Glu residue generates a constitutively active derivative that behaves as a superrepressor of the target genes. AccR-P binds in vitro to a conserved inverted repeat (ATGCA-N6-TGCAT) present at two different locations within the PN promoter of the bzd genes for anaerobic benzoate degradation. Because the DNA binding-proficient C-terminal domain of AccR is monomeric, we propose an activation mechanism in which phosphorylation of Asp(60) of AccR alleviates interdomain repression mediated by the N-terminal domain. The presence of AccR-like proteins encoded in the genomes of other β-proteobacteria of the Azoarcus/Thauera group further suggests that AccR constitutes a master regulator that controls anaerobic CCR in these bacteria.
Presence of the BCR-ABL mutation Glu255Lys prior to STI571 (imatinib) treatment in patients with Ph+ acute lymphoblastic leukemia (2003)

The tyrosine kinase inhibitor STI571 (imatinib) binds competitively to the adenosine triphosphate (ATP) binding site of the ABL kinase, thereby inhibiting auto- and substrate phosphorylation of the oncogenic protein BCR-ABL and preventing the activation of downstream signaling pathways. Comparative studies on leukemic cell samples obtained from chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) patients before and after treatment with STI571 reported point mutations in resistant samples after a short time of therapy. The aim of this study was to determine whether patients with Ph+ ALL in whom resistance developed as a consequence of the Glu255Lys mutation already harbored this subclone prior to STI571 treatment. First, the migration pattern of cDNAs from 30 bone marrow samples from patients with Ph+ ALL was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Thereafter, detailed mutational analysis using genomic DNA was performed on initial STI571-naive bone marrow samples of 4 individuals with Ph+ ALL, for whom the mutation Glu255Lys in association with STI571 treatment had been shown. A 166-bp PCR fragment spanning from nucleotide (nt) 862 to nt 1027 was cloned, and 108 clones per sample were analyzed by direct sequencing. This more sensitive technique revealed the presence of the Glu255Lys mutation in 2 initial samples, one clone each. We identified for the first time the mutation Glu255Lys in STI571-naive leukemic samples of Ph+ ALL patients. The findings suggest that the mutation exists in a very small subpopulation of leukemic cells at the beginning of STI571 therapy.