gebhart/patrepeval huggingface dataset:
Involvement of Histone H3 Lysine 9 (H3K9) Methyltransferase G9a in the Maintenance of HIV-1 Latency and Its Reactivation by BIX01294 (2010)

Elucidating the mechanism of human immunodeficiency virus, type 1 (HIV-1) provirus transcriptional silencing in latently infected cells is crucial for understanding the pathophysiological process of HIV-1 infection. It is well established that hypoacetylation of histone proteins by histone deacetylases is involved in the maintenance of HIV-1 latency by repressing viral transcription. Although histone methylation is involved in the organization of chromatin domains and plays a central epigenetic role in gene expression, the role of histone methylation in the maintenance of HIV-1 latency has not been clarified. Here we present evidence that histone H3 Lys(9) (H3K9) methyltransferase G9a is responsible for transcriptional repression of HIV-1 by promoting repressive dimethylation at H3K9 and for the maintenance of viral latency. We observed that G9a significantly inhibited basal, as well as, the induced HIV-1 gene expression by tumor necrosis factor-alpha or Tat. Mutant G9a, however, lacking the SET domain responsible for the catalytic activity of histone methyltransferase, did not show such an effect. When G9a expression was knocked down by small interfering RNA, HIV-1 replication was augmented from cells transiently transfected with a full-length HIV-1 clone. Moreover, a specific inhibitor of G9a, BIX01294, could reactivate expression of HIV-1 from latently infected cells such as ACH-2 and OM10.1. Furthermore, chromatin immunoprecipitation assays revealed the presence of G9a and H3K9 dimethylation on nucleosome histones in the vicinity of the HIV-1 long terminal repeat promoter. These results suggest that G9a is responsible for the transcriptional quiescence of latent HIV-1 provirus and provide a molecular basis for understanding the mechanism by which HIV-1 latency is maintained.
Cognitive features of continuous antigenic determinants (1988)

We sought to identify the features controlling the specificity of antibody recognition and thus gain insights into molecular recognition between proteins in general. A total of 103 epitopes within 63 well-defined antigenic peptides homologous with the relevant antigen sequence were identified. The contribution of each amino acid residue to the antibody binding activity of each epitope was investigated by ELISA testing of complete sets of peptide analogs containing single amino acid replacements. The data are summarized in a replaceability matrix. Some of the high frequency replaceabilities were expected, such as aspartate for glutamate, serine for threonine, etc., but unexpected relationships were also found, such as a high degree of acceptability of methionine as a replacement. Replaceability with a residue of opposite charge was rare. Glycine and tyrosine were frequently of low acceptability, except for glycine as a replacement for alanine. It was found that on average only about four to five amino acid residues in epitopes were required to determine specificity and provide binding energy. Specificity and binding energy were attributed to amino acid side chains rather than main chain atoms. Propensity factors for occurrence of amino acids in antigenic determinants were calculated. The prominence of certain hydrophobic residues as residues critical to recognition by antibody suggests that the molecular surface of an antigen in its combined form with antibody is altered from that occurring in the absence of antibody. Thus, antigenicity is not a static surface phenomenon but depends on the ability of the antigen to undergo rearrangement, supporting the induced fit concept.
Melt Analysis of Process Cheese Spread or Product Using a Rapid Visco Analyzer (2005)

The objective of this study was to evaluate a rapid visco analyzer (RVA) method for measuring the melting characteristics of process cheese spread or product. The melt properties of 32 commercial process cheese spread and process cheese product samples from 4 manufacturers were analyzed with the RVA, tube melt test, texture profile analysis (TPA) hardness, and dynamic stress rheometry (DSR). For the RVA melt test, a 15-g disc of cheese was packed into the RVA canister and subjected to a heating, holding, and cooling profile during continuous mixing. During the test, the apparent viscosity was continuously measured and several data points (melt time, hot viscosity, time at 5000 cP during cooling, and solidification time) were collected from the viscosity vs. time curve. There was a high correlation (R2= 0.91) between the DSR melt temperature and the tube melt test. There was also a high correlation between the RVA melt time and the DSR melt temperature or the tube melt test (R2= 0.84 and 0.74, respectively). The RVA hot viscosity had a low correlation (R2< 0.44) with the DSR melt temperature and the tube melt test but had a high correlation (R2= 0.74) with DSR G'' at 85 degrees C. The results of this study indicate that RVA melt analysis of process cheese spread/product is correlated with the results from other melt tests and is capable of measuring the melt properties quantified by other methods. The RVA melt test may also provide additional information on the melt characteristics of process cheese spread/product not measured in other tests.
Extracellular expression of native human anti-lysozyme fragments in (1995)

Xylose-inducible vectors have been constructed for extracellular production of antibody fragments in Staphylococcus carnosus. The pre-pro sequence of S. hyicus lipase was taken as secretional signal sequence, and the S. xylosus Xyl repressor was used to confer xylose inducibility of transcription. Cleavage sites for the IgA protease were engineered between the pre-pro sequence and the antibody fragments to permit removal of the pro sequence. Extracellular expression of the light chain and the Fd fragment of a chimeric Fab fragment containing the variable regions of the anti-lysozyme antibody D1.3 was achieved with these vectors. The pro sequence could be removed from the expression product by IgA protease treatment. When the light chain and the Fd fragment were co-secreted as a protein fusion they accumulated in a structure capable of heterodimerization after IgA cleavage. This fusion contains the pre-pro sequence followed by the light chain, a second IgA site and the Fd fragment.
miR‐372 suppresses tumour proliferation and invasion by targeting IGF2BP1 in renal cell carcinoma (2015)

Our data indicated that miR-372 seemed to function as a tumour suppressor in renal cell carcinoma progression by inhibiting the IGF2BP1 expression.
Hsp90 (Heat Shock Protein 90) Inhibitor Occupancy Is a Direct Determinant of Client Protein Degradation and Tumor Growth Arrest in Vivo (2010)

Several Hsp90 (heat shock protein 90) inhibitors are currently under clinical evaluation as anticancer agents. However, the correlation between the duration and magnitude of Hsp90 inhibition and the downstream effects on client protein degradation and cancer cell growth inhibition has not been thoroughly investigated. To investigate the relationship between Hsp90 inhibition and cellular effects, we developed a method that measures drug occupancy on Hsp90 after treatment with the Hsp90 inhibitor IPI-504 in living cells and in tumor xenografts. In cells, we find the level of Hsp90 occupancy to be directly correlated with cell growth inhibition. At the molecular level, the relationship between Hsp90 occupancy and Hsp90 client protein degradation was examined for different client proteins. For sensitive Hsp90 clients (e.g. HER2 (human epidermal growth factor receptor 2), client protein levels directly mirror Hsp90 occupancy at all time points after IPI-504 administration. For insensitive client proteins, we find that protein abundance matches Hsp90 occupancy only after prolonged incubation with drug. Additionally, we investigate the correlation between plasma pharmacokinetics (PK), tumor PK, pharmacodynamics (PD) (client protein degradation), tumor growth inhibition, and Hsp90 occupancy in a xenograft model of human cancer. Our results indicate Hsp90 occupancy to be a better predictor of PD than either plasma PK or tumor PK. In the nonsmall cell lung cancer xenograft model studied, a linear correlation between Hsp90 occupancy and tumor growth inhibition was found. This novel binding assay was evaluated both in vitro and in vivo and could be used as a pharmacodynamic readout in the clinic.
Terahertz Imaging Applications in Agriculture and Food Engineering: A Review (2018)

Abstract. Terahertz technology, including terahertz spectroscopy and terahertz imaging, is gaining increasing attention and plays an important role in various fields. With the development of terahertz sources and detectors in recent decades, terahertz imaging has been applied in many fields, including security screening, material evaluation, biomedicine, agriculture, and food science. However, progress has been comparatively slow in applying terahertz imaging to agriculture and food engineering. In this article, some commonly used terahertz imaging systems are summarized, and various applications of terahertz imaging in agriculture and food engineering are reviewed, including food safety and quality inspection, seed inspection, water content evaluation of plant leaves, and others. Challenges and the future outlook of terahertz imaging are also discussed. Keywords: Agriculture, Food, Instrumentation, Seed, Terahertz imaging.
Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: A parasite adhesion trait implicated in cerebral malaria (2000)

Binding of infected erythrocytes to brain venules is a central pathogenic event in the lethal malaria disease complication, cerebral malaria. The only parasite adhesion trait linked to cerebral sequestration is binding to intercellular adhesion molecule-1 (ICAM-1). In this report, we show that Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) binds ICAM-1. We have cloned and expressed PfEMP1 recombinant proteins from the A4tres parasite. Using heterologous expression in mammalian cells, the minimal ICAM-1 binding domain was a complex domain consisting of the second Duffy binding-like (DBL) domain and the C2 domain. Constructs that contained either domain alone did not bind ICAM-1. Based on phylogenetic criteria, there are five distinct PfEMP1 DBL types designated alpha, beta, gamma, delta, and epsilon. The DBL domain from the A4tres that binds ICAM-1 is DBLbeta type. A PfEMP1 cloned from a distinct ICAM-1 binding variant, the A4 parasite, contains a DBLbeta domain and a C2 domain in tandem arrangement similar to the A4tres PfEMP1. Anti-PfEMP1 antisera implicate the DBLbeta domain from A4var PfEMP1 in ICAM-1 adhesion. The identification of a P. falciparum ICAM-1 binding domain may clarify mechanisms responsible for the pathogenesis of cerebral malaria and lead to interventions or vaccines that reduce malarial disease.
Regression of Human Prostate Cancer Xenografts in Mice by AMG 212/BAY2010112, a Novel PSMA/CD3-Bispecific BiTE Antibody Cross-Reactive with Non-Human Primate Antigens (2012)

For treatment of patients with prostate cancer (PCa), we developed a novel T cell-engaging (BiTE) antibody designated AMG 212 or BAY2010112 that is bispecific for prostate-specific membrane antigen (PSMA) and the CD3 epsilon subunit of the T cell receptor complex. AMG 212/BAY2010112 induced target cell-dependent activation and cytokine release of T cells, and efficiently redirected T cells for lysis of target cells. In addition to Chinese hamster ovary cells stably expressing human or cynomolgus monkey PSMA, T cells redirected by AMG 212/BAY2010112 also lysed human PCa cell lines VCaP, 22Rv1, MDA PCa 2b, C4-2, PC-3-huPSMA, and LnCaP at half maximal BiTE concentrations between 0.1 and 4 ng/mL (1.8-72 pmol/L). No lysis of PSMA-negative human PCa cell lines PC-3 and DU145 was observed. The subcutaneous (s.c.) formation of tumors from PC-3-huPSMA cells in NOD/SCID mice was significantly prevented by once daily intravenous (i.v.) injection of AMG 212/BAY2010112 at a dose level as low as 0.005 mg/kg/d. Rapid tumor shrinkage with complete remissions were observed in NOD/SCID mice bearing established s.c. 22Rv1 xenografts after repeated daily treatment with AMG 212/BAY2010112 by either the i.v. or s.c. route. Of note, 22Rv1 tumors were grown in the absence of human T cells followed by intraperitoneal injection of T cells 3 days before BiTE treatment. No effects on tumor growth were observed in the absence of human T cells or AMG 212/BAY2010112. On the basis of these preclinical results, AMG 212/BAY2010112 appears as a promising new BiTE antibody for the treatment of patients with PSMA-expressing PCa.
Effects of Smoking on the Pharmacokinetics of Erlotinib (2006)

This study confirms that the pharmacokinetics of erlotinib is different in current smokers and nonsmokers. The observation that AUC(0-infinity) and C(24h) were significantly decreased in smokers compared with nonsmokers, and a smaller decrease in C(max) was observed, is consistent with increased metabolic clearance of erlotinib in current smokers.
Chromosomal localization of the human gene for annexin V (placental anticoagulant protein I) to 4q26→q28 (1991)

Annexin V is a member of a new family of calcium-dependent phospholipid-binding proteins. It has been previously isolated as placental anticoagulant protein I, inhibitor of blood coagulation, vascular anticoagulant-alpha, endonexin II, lipocortin V, placental protein 4, and anchorin CII. The human gene encoding annexin V (ANX5) was localized to 4q26----q28 by in situ hybridization with a cDNA probe and polymerase chain-reaction (PCR) analysis of a human x hamster hybrid cell panel. The regional localization to 4q26----q28 was supported by Southern-blot analysis of a human cell line with a deletion in 4q23----q27. This localization overlaps but differs slightly from the previous assignment of ANX5 to 4q28----q32. Digestion with PvuII and TaqI identified polymorphisms at the ANX5 locus; the PvuII polymorphism could also be detected by PCR analysis.
Design and synthesis of digitally encoded polymers that can be decoded and erased (2015)

Biopolymers such as DNA store information in their chains using controlled sequences of monomers. Here we describe a non-natural information-containing macromolecule that can store and retrieve digital information. Monodisperse sequence-encoded poly(alkoxyamine amide)s were synthesized using an iterative strategy employing two chemoselective steps: the reaction of a primary amine with an acid anhydride and the radical coupling of a carbon-centred radical with a nitroxide. A binary code was implemented in the polymer chains using three monomers: one nitroxide spacer and two interchangeable anhydrides defined as 0-bit and 1-bit. This methodology allows encryption of any desired sequence in the chains. Moreover, the formed sequences are easy to decode using tandem mass spectrometry. Indeed, these polymers follow predictable fragmentation pathways that can be easily deciphered. Moreover, poly(alkoxyamine amide)s are thermolabile. Thus, the digital information encrypted in the chains can be erased by heating the polymers in the solid state or in solution.
Diversity and complexity of HIV-1 drug resistance: A bioinformatics approach to predicting phenotype from genotype (2002)

Drug resistance testing has been shown to be beneficial for clinical management of HIV type 1 infected patients. Whereas phenotypic assays directly measure drug resistance, the commonly used genotypic assays provide only indirect evidence of drug resistance, the major challenge being the interpretation of the sequence information. We analyzed the significance of sequence variations in the protease and reverse transcriptase genes for drug resistance and derived models that predict phenotypic resistance from genotypes. For 14 antiretroviral drugs, both genotypic and phenotypic resistance data from 471 clinical isolates were analyzed with a machine learning approach. Information profiles were obtained that quantify the statistical significance of each sequence position for drug resistance. For the different drugs, patterns of varying complexity were observed, including between one and nine sequence positions with substantial information content. Based on these information profiles, decision tree classifiers were generated to identify genotypic patterns characteristic of resistance or susceptibility to the different drugs. We obtained concise and easily interpretable models to predict drug resistance from sequence information. The prediction quality of the models was assessed in leave-one-out experiments in terms of the prediction error. We found prediction errors of 9.6-15.5% for all drugs except for zalcitabine, didanosine, and stavudine, with prediction errors between 25.4% and 32.0%. A prediction service is freely available at http://cartan.gmd.de/geno2pheno.html.
The Effect of Column Temperature on the Migration Time of Peptides in Free-Solution Capillary Electrophoresis (1993)

Abstract The effect of column temperature on the migration times of peptides in free - solution capillary electrophoresis (FSCE) is discussed. It has been found that there are parallel iinear relationships between the logarithm of the migration time and the reciprocal of column temperature. The changes in migration time with temperature for the peptides are predominantly due to the temperature - induced viscosity changes of water. The elec-trophoretic selectivity remains constant for a specific pair of peptides despite a considerable variation in the migration time for each of the peptides in FSCE.
Monitoring Renal Transplants: An Application of the Multiprocess Kalman Filter (1983)

The multiprocess Kalman filter offers a powerful general framework for the modelling and analysis of noisy time series which are subject to abrupt changes in pattern. It has considerable potential application to many forms of biological series used in clinical monitoring. In particular, the approach can be used to provide on-line probabilities of whether changes have occurred, as well as to identify the type of change that is involved. In this paper, we extend and illustrate the methodology within the context of a particular case study. The general features of the problem, and the approach adopted, will be seen to have wide application.
Differential increase of an alternatively polyadenylated mRNA species of murine CD40 upon B lymphocyte activation (1992)

CD40 is an integral membrane glycoprotein found on the surface of human B lymphocytes. Antibodies specific for CD40 have been shown to augment proliferation of activated B lymphocytes, prevent B lymphocyte apoptosis, and prolong the maintenance of normal B lymphocytes in culture. As a step toward developing an in vivo system to examine CD40 function, a molecular clone encoding the murine homologue of the human CD40 B lymphocyte surface Ag was isolated and characterized. Throughout their open reading frames, the murine and human proteins shared 62% predicted amino acid identity. Within the cytoplasmic domain, which includes a completely conserved region known to be important for signaling by human CD40, the CD40 homologues are 78% identical. The human and murine proteins are members of a new cytokine receptor family, which includes the receptors for nerve growth factor and TNF-alpha, that are homologous in their cysteine-rich extracellular domains. The murine CD40 gene is expressed in B lymphocytes as two mRNA species generated by alternative usage of polyadenylation signals in the 3' untranslated region. The activation of B lymphocytes differentially increases the relative levels of these two mRNA transcripts suggesting a posttranscriptional mechanism for the regulation of CD40 surface expression.
Fast embedding of sparse music similarity graphs (2003)

This paper applies fast sparse multidimensional scaling (MDS) to a large graph of music similarity, with 267K vertices that represent artists, albums, and tracks; and 3.22M edges that represent similarity between those entities. Once vertices are assigned locations in a Euclidean space, the locations can be used to browse music and to generate playlists.
Scanning Probe Evolution in Biology (2003)

Twenty years ago the first scanning probe instrument, the scanning tunneling microscope, opened up new realms for our perception of the world. Atoms that had been abstract entities were now real objects, clearly seen as distinguishable individuals at particular positions in space. A whole family of scanning probe instruments has been developed, extending our sense of touching to the scale of atoms and molecules. Such instruments are especially useful for imaging of biomolecular structures because they can produce topographic images with submolecular resolution in aqueous environments. Instruments with increased imaging rates, lower probe-specimen force interactions, and probe configurations not constrained to planar surfaces are being developed, with the goal of imaging processes at the single-molecule level-not only at surfaces but also within three-dimensional volumes-in real time.
A suite of objective biomechanical measurement tools for personal load carriage system assessment (2004)

For application to military and civilian needs, Defence Research and Development Canada--Toronto contracted Queen's University, Kingston to develop a suite of biomechanical assessment and analytical tools to supplement human-based load carriage system assessment methods. This suite of tools permitted efficient objective evaluation of biomechanical aspects of load-bearing webbing, vests, packs and their components, and therefore contributed to early system assessment and a rapid iterative design process. This paper is a summary of five assessment and analytical tools. A dynamic load carriage simulator was developed to simulate cadence of walking, jogging and running. The simulator comprised a computer-controlled pneumatic platform that oscillated anthropometrically weighted mannequins of varying dimensions from which measures of skin contact pressure, hip reaction forces and moments and relative pack-person displacements were taken. A stiffness tester for range of motion provided force-displacement data on pack suspension systems. A biomechanical model was used to determine forces and moments on the shoulders and hips, and validated using a static load distribution mannequin. Subjective perceptual rating systems were used gather soldier feedback during a standardized mobility circuit. Objective outcome measures were validated by means of other objective measures (e.g., Optotrak, video, Instron, etc.) and then compared to subjective ratings. This approach led to development of objective performance criteria for load carriage systems and to improvements in load carriage designs that could be used both in the military and in general.