gebhart/patrepeval huggingface dataset:
Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells. (1999)

The human carcinoembryonic antigen (CEA) and HER-2/neu are potential target antigens for CTL specific immunotherapy for common malignancies such as breast, lung, colon, and gastric carcinomas. Several CTL epitopes restricted by HLA-A2, the most common human histocompatibility molecule, have been previously reported. However, to develop CTL-based immunotherapies for the general population, it is necessary to identify epitopes restricted by other common histocompatibility alleles. Here, we describe two HLA-A3-restricted CTL epitopes from the CEA and HER-2/neu antigens. HLA-A3 binding synthetic peptides from CEA and HER-2/neu were tested for immunogenicity by in vitro primary CTL induction protocol using peripheral blood mononuclear cells from normal healthy volunteers. One peptide from CEA (CEA[9(61)]: HLFGYSWYK) and one peptide from HER-2/neu (HER2[9(754)]: VLRENTSPK) were shown to induce CTL that was capable of killing a tumor cell line expressing HLA-A3 and the corresponding tumor-associated antigen. Additional MHC binding studies with the most common HLA molecules belonging to the HLA-A3 superfamily (HLA-A*1101, -A*3101, -A*3301, and -A*6801), demonstrated that CEA[9(61)] binds five of five A3 supertype molecules with high affinity, and the HER2[9(754)] epitope was able to bind to four of the same five alleles. These results indicate that these two new CTL epitopes should be immunogenic in individuals expressing either HLA-A3, or other members of the HLA-A3 superfamily.
Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome (2013)

Studies of the genetics underlying inflammatory bowel diseases have increased our understanding of the pathways involved in both ulcerative colitis and Crohn's disease and focused attention on the role of the microbiome in these diseases. Full understanding of pathogenesis will require a comprehensive grasp of the delicate homeostasis between gut bacteria and the human host. In this review, we present current evidence of microbiome-gene interactions in the context of other known risk factors and mechanisms, and describe the next steps necessary to pair genetic variant and microbiome sequencing data from patient cohorts. We discuss the concept of dysbiosis, proposing that the functional composition of the gut microbiome may provide a more consistent definition of dysbiosis and may more readily provide evidence of genome-microbiome interactions in future exploratory studies.
Induction of Vascular Endothelial Growth Factor by Insulin-like Growth Factor 1 in Colorectal Carcinoma (1996)

Vascular endothelial growth factor (VEGF) is an angiogenic hormone that is produced by and supports the growth of many types of malignancies. The present study shows that insulin-like growth factor 1 (IGF-I), a mitogen that promotes the propagation of cancers through autocrine and paracrine mechanisms, increases the expression of mRNA for VEGF and production of VEGF protein by COLO 205 colon carcinoma cells. IGF-I also induces expression of VEGF mRNA in SW620, LSLiM6, and HCT15 colon carcinoma cells showing that this is a common response to IGF-I. Whereas IGF-I induced VEGF mRNA in each cell line examined (2.3-12-fold), it induced proliferation only in COLO 205 and LSLiM6 cells. Thus, the proliferative response induced by IGF-I and its ability to induce VEGF occur through distinguishable mechanisms. IGF-I increases the cellular content of VEGF mRNA by increasing the rate of transcription (5-fold after 4 h) and also by increasing the half-life of VEGF mRNA (0.6 +/- 0.07 h in control cells to 2.0 +/- 0.37 h in IGF-I-treated cells). Monoclonal antibody (alphaIR3) directed against the type 1 IGF receptor significantly attenuated the ability of IGF-I to promote expression of VEGF mRNA. Interestingly, by itself alphaIR3 acted as a weak agonist and induced a modest increase in the cellular content of VEGF mRNA. alphaIR3 also promoted tyrosine phosphorylation of the beta subunit of the IGF-I receptor, and the magnitude of this response was comparable with that induced by IGF-I. These observations point to a nonlinear relationship between activation of the IGF-I receptor and induction of VEGF mRNA. Thus, in addition to its direct, growth stimulatory effect on transformed cells, IGF-I induces the expression of VEGF which can promote the progression of cancer by regulating the development of new blood vessels.
Surfactant-Stabilized Protein Formulations: A Review of Protein-Surfactant Interactions and Novel Analytical Methodologies (1997)

Nonionic surfactants play an important role in the pharmaceutics industry. They are found in purification steps as well final product formulations. Despite the extensive use of nonionic surfactants, their properties, roles and mechanisms by which they yield desired effects are not well understood. This paper discusses the characterization of nonionic surfactants used in pharmaceutics. A review of the binary surfactant - water system provides an introduction to the difficulties encountered when studying more complex systems. Surfactant behavior under formulation conditions, surfactant binding to pharmaceutical products, the role of surfactants in protein refolding, and the effects of surfactants on accelerated testing of formulations is the focus of this review.
Identification of Aptamers Against the DNA Template for In Vitro Transcription of the HIV-1 TAR Element (1997)

We have extracted from a random population of about 109 oligodeoxynucleotides a series of 21-mers that are able to bind to a folded DNA 76-mer used as a template for in vitro transcription of the TAR element of the retrovirus HIV-1, by the T7 RNA polymerase. Five aptastrucs, that is, aptamers able to bind to the structure, out of 15 analyzed sequences, share the consensus motif 5‵-PyGGG(TG)PyC, complementary in part to a weak double-stranded region of the target. (The parentheses indicate that either T or G is missing in one of these aptastrucs.) A dissociation constant of about 3 μM was evaluated by electrophoretic mobility shift assay for the winner sequence. Interactions between the aptastruc and the target sequences involve more than Watson-Crick base pairing of the consensus octamer. The binding is chemistry dependent. Phosphorothioate oligodeoxyribonucleotides and 2‵-O-methyl oligoribonucleotides derived from the selected aptastrucs exhibit a weak if any affinity for the target.
Enantiopure Pyridine Bis(oxazoline) “Pybox” and Bis(oxazoline) “Box” Iron Dialkyl Complexes: Comparison to Bis(imino)pyridine Compounds and Application to Catalytic Hydrosilylation of Ketones (2009)

The chemistry of enantiopure pyridine bis(oxazoline) iron compounds has been explored. The electronic properties of this ligand class have been evaluated relative to aryl- and alkyl-substituted bis(imino)pyridines using cyclic voltammetry and CO stretching frequencies of iron dicarbonyl compounds. Attempts to prepare a pyridine bis(oxazoline) iron dinitrogen complex by sodium amalgam reduction of the corresponding dichloride precursor yielded a catalytically inactive S = 1 bis(chelate) iron complex. Dialkyl derivatives of the general formula (RPybox)Fe(CH2SiMe3)2 were prepared either by pyridine displacement from (py)2Fe(CH2SiMe3)2 or by direct dialkylation of the appropriate iron dichloride. Two examples of the S = 2 complexes were characterized by single-crystal X-ray diffraction. Each enantiopure Pybox iron dialkyl was evaluated in the catalytic hydrosilylation of various ketones. Efficient turnover was observed at 23 °C with 0.3% of the iron precatalyst using PhSiH3 as the stoichiometric reductant. For comparison, related bis(oxazoline) iron dialkyl compounds were also evaluated and found to be equally effective at 1.0 mol % iron loadings. While low to modest enantioselectivities were observed with both classes of neutral iron dialkyl compounds, high levels of asymmetric induction were obtained for a hindered acetophenone and α-tetralone upon activation of the iron derivative with B(C6F5)3.
Optimal feature extraction for partial discharge recognition (2002)

Pattern recognition of partial discharge (PD) is significant for condition judgment of power equipment. To select the optimal features out of the original PD features, this paper introduces a novel feature extraction algorithm, which is based directly upon the decision boundary between the classes, and determines the feature transformation according to the separability as opposed to the more common approach of fitting, such as principal component transformation. Experiment calculations are conducted on PD data obtained through measurements on industrial models of generator stator winding bars. Statistical and moment features, drawn respectively from each PD sample, are used in the experiments. Results show that when used together, the two sets of features are more powerful in discrimination. It is also shown that most discriminant information is concentrated in a subset of features, which can be determined and extracted successfully using the proposed algorithm. With the few selected features, approximate recognition accuracy could be achieved while substantial increases in computation complexity are refrained.
Proliferation and immunoglobulin secretion of lymphoblastoid cell lines are differently affected by soluble cytokines (1994)

The aim of our study was to investigate whether supernatant from lipopolysaccharide-activated monocytes (monocyte-factor) and/or cytokines could enhance secretion of human monoclonal antibodies specific to HLA antigens produced by Epstein-Barr virus lymphoblastoid cell lines (EBV-LCLs). In a low cell density culture system, the monocyte-factor significantly stimulated cell growth of three monoclonal and two polyclonal EBV-LCLs while no enhancement of immunoglobulin production was observed. The enhancement of proliferation was completely neutralized by an antiserum to human IL-6 suggesting that IL-6 was required for the stimulation of growth of LCLs. The effect of cytokines on proliferation showed large variations among the cell lines, with IL-1beta generally inducing the highest response. Of the cytokines tested, only IL-2 was able to enhance total immunoglobulin secretion due to the induction of a higher production of light chains. The specific anti-HLA activity was slightly increased by IL-10 although this cytokine had no effect on total immunoglobulin concentration or proliferation.
N -Acetylglucosamine Prevents IL-1β-Mediated Activation of Human Chondrocytes (2001)

Glucosamine represents one of the most commonly used drugs to treat osteoarthritis. However, mechanisms of its antiarthritic activities are still poorly understood. The present study identifies a novel mechanism of glucosamine-mediated anti-inflammatory activity. It is shown that both glucosamine and N-acetylglucosamine inhibit IL-1beta- and TNF-alpha-induced NO production in normal human articular chondrocytes. The effect of the sugars on NO production is specific, since several other monosaccharides, including glucose, glucuronic acid, and N-acetylmannosamine, do not express this activity. Furthermore, N-acetylglucosamine polymers, including the dimer and the trimer, also do not affect NO production. The observed suppression of IL-1beta-induced NO production is associated with inhibition of inducible NO synthase mRNA and protein expression. In addition, N-acetylglucosamine also suppresses the production of IL-1beta-induced cyclooxygenase-2 and IL-6. The constitutively expressed cyclooxygenase-1, however, was not affected by the sugar. N-acetylglucosamine-mediated inhibition of the IL-1beta response of human chondrocytes was not associated with the decreased inhibition of the mitogen-activated protein kinases c-Jun N-terminal kinase, extracellular signal-related kinase, and p38, nor with activation of the transcription factor NF-kappaB. In conclusion, these results demonstrate that N-acetylglucosamine expresses a unique range of activities and identifies a novel mechanism for the inhibition of inflammatory processes.
Field emitter arrays for a free electron laser application (2005)

In this paper, the results on current performance of some field emitter materials showed high and stable current pulses at low frequency can be emitted with less contamination problems. For a free electron laser application, peak current values are still too small but by using shorter pulses and small internal field emitter array resistance, a required current was expected to be reached.
Comparative effects of two antimycotic agents, ketoconazole and terbinafine on the metabolism of tolbutamide, ethinyloestradiol, cyclosporin and ethoxycoumarin by human liver microsomes in vitro. (1989)

Two antimycotic agents, the azole ketoconazole and the allylamine terbinafine, have been examined for their effects on the metabolism of tolbutamide, ethinyloestradiol, cyclosporin and ethoxycoumarin by human liver microsomes (n = 4) in vitro. Ketoconazole caused marked inhibition of all enzyme activities with mean IC50 values (concentration producing 50% inhibition) of 17.9 microM (tolbutamide hydroxylase), 1.9 microM (ethinyloestradiol 2-hydroxylase), 2.0 microM (cyclosporin N-demethylase), 2.1 microM (cyclosporin hydroxylase) and 25 microM (ethoxycoumarin O-deethylase). At 50 microM terbinafine concentration, inhibition was less than 5% for tolbutamide and ethoxycoumarin, approximately 12% for both cyclosporin pathways and 35% for ethinyloestradiol. Terbinafine does not have the same inhibitory potential for cytochrome P-450 isozymes as ketoconazole.
A Linearization Technique for RF Receiver Front-End Using Second-Order-Intermodulation Injection (2008)

A linearization technique is proposed in which low-frequency second-order-intermodulation (IM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) is generated and injected to suppress the third-order intermodulation (IM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> ). The proposed linearization technique is applied to both a low-noise amplifier (LNA) and a down-conversion mixer in an RF receiver front-end (RFE) working at 900 MHz. Fabricated in a 0.18 mum CMOS process and operated at 1.5 V supply with a total current of 13.1 mA, the RFE delivers 22 dB gain with 5.3 dB noise figure (NF). The linearization technique achieves around 20 dB IM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> suppression and improves the RFE's IIP <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> from -10.4 dBm to 0.2 dBm without gain reduction and noise penalty while requiring only an extra current of 0.1 mA.
Adipose stromal vascular fraction cell construct sustains coronary microvascular function after acute myocardial infarction (2011)

A three-dimensional tissue construct was created using adipose-derived stromal vascular fraction (SVF) cells and evaluated as a microvascular protection treatment in a myocardial infarction (MI) model. This study evaluated coronary blood flow (BF) and global left ventricular function after MI with and without the SVF construct. Fischer-344 rats were separated into four groups: sham operation (sham), MI, MI Vicryl patch (no cells), and MI SVF construct (MI SVF). SVF cells were labeled with green fluorescent protein (GFP). Immediately postinfarct, constructs were implanted onto the epicardium at the site of ischemia. Four weeks postsurgery, the coronary BF reserve was significantly decreased by 67% in the MI group and 75% in the MI Vicryl group compared with the sham group. The coronary BF reserve of the sham and MI SVF groups in the area at risk was not significantly different (sham group: 83 ± 22% and MI SVF group: 57 ± 22%). Griffonia simplicifolia I and GFP-positive SVF immunostaining revealed engrafted SVF cells around microvessels in the infarct region 4 wk postimplant. Overall heart function, specifically ejection fraction, was significantly greater in MI SVF hearts compared with MI and MI Vicryl hearts (MI SVF: 66 ± 4%, MI: 37 ± 8%, and MI Vicryl: 29 ± 6%). In conclusion, adipose-derived SVF cells can be used to construct a novel therapeutic modality for treating microvascular instability and ischemia through implantation on the epicardial surface of the heart. The SVF construct implanted immediately after MI not only maintains heart function but also sustains microvascular perfusion and function in the infarct area by sustaining the coronary BF reserve.
Probiotics in human medicine. (1991)

Probotics have been with us for as long as people have eaten fermented milks, but their association with health benefits dates only from the turn of the century when Metchnikoff drew attention to the adverse effects of the gut microflora on the host and suggested that ingestion of fermented milks ameliorated this so called autointoxication. Later work, based on the assumption that colonisation of the gut was essential for the maximum effect, used intestinal strains ofLacto- bacillus acidophilus for treatment ofconstipation. 1 The use of the term 'probiotic' to describe food supplements specifically designed to improve health, however, dates from 1974 when Parker used it to describe growth promoting animal feed supplements. He defined the term as 'organisms and substances which contribute to intestinal microbial balance'. I have recently2 revised this definition to read, 'A live microbial feed supplement which beneficially affects the host animal by improving its microbial balance'. This definition stresses the importance of viability and avoids the use of the too broad term 'substances' which could even include antibiotics.
Random Forest:  A Classification and Regression Tool for Compound Classification and QSAR Modeling (2003)

A new classification and regression tool, Random Forest, is introduced and investigated for predicting a compound's quantitative or categorical biological activity based on a quantitative description of the compound's molecular structure. Random Forest is an ensemble of unpruned classification or regression trees created by using bootstrap samples of the training data and random feature selection in tree induction. Prediction is made by aggregating (majority vote or averaging) the predictions of the ensemble. We built predictive models for six cheminformatics data sets. Our analysis demonstrates that Random Forest is a powerful tool capable of delivering performance that is among the most accurate methods to date. We also present three additional features of Random Forest: built-in performance assessment, a measure of relative importance of descriptors, and a measure of compound similarity that is weighted by the relative importance of descriptors. It is the combination of relatively high prediction accuracy and its collection of desired features that makes Random Forest uniquely suited for modeling in cheminformatics.
Energy Transfer in Dendritic Macromolecules:  Molecular Size Effects and the Role of an Energy Gradient (1996)

Perylene-terminated monodendrons 1−7 and phenyl-terminated reference monodendrons 8−14 have been synthesized, and the intramolecular energy transfer has been studied using steady-state as well as time-resolved fluorescence spectroscopy. In the series 2−7, the light-harvesting ability of these compounds increases with increasing generation due to the increase in molar extinction coefficient. However, the efficiency of the energy transfer decreases with increasing generation in this series. With increasing generation, the photoluminescence intensity from the perylene core still increases and the expected level-off in the photoluminescence intensity has not been reached in this series of compounds. Dendrimer 1 is unique in that the energy transfer in this molecule occurs at a very fast rate. The rate constant for energy transfer in 1 is at least 2 orders of magnitude larger than in 2−7. In contrast to monodendrons 2−7, 1 possesses a variable monomer type at each generation that creates an energy funnel. The ultrafast energy transfer in this system is best explained by the presence of this energy gradient.
Incorporation of Transmembrane Hydrophobic Mutations in the TCR Enhance Its Surface Expression and T Cell Functional Avidity (2012)

TCR-gene transfer represents an effective way to redirect the specificity of T lymphocytes for therapeutic purposes. Recent successful clinical trials have underscored the potential of this approach in which efficient expression of the exogenous TCR has been directly linked to the efficacy of T cell activity. It has been also demonstrated that the TCR exhibits a lack of stability associated with the presence of positively charged residues in its transmembrane (TM) region. In this study, we designed an original approach selectively to improve exogenous TCR stability by increasing the hydrophobic nature of the TCRα TM region. Incorporation of hydrophobic residues at evolutionarily permissive positions resulted in an enhanced surface expression of the TCR chains, leading to an improved cellular avidity and anti-tumor TCR activity. Furthermore, this strategy was successfully applied to different TCRs, enabling the targeting of human tumors from different histologies. We also show that the combination of these hydrophobic mutations with another TCR-enhancing approach further improved TCR expression and function. Overall, these findings provide information regarding TCR TM composition that can be applied for the improvement of TCR-gene transfer-based treatments.
Angiotensin inhibition potentiates the renal responses to neutral endopeptidase inhibition in dogs with congestive heart failure. (1991)

The renal natriuretic actions of endogenous atrial natriuretic factor are enhanced by neutral endopeptidase inhibition (NEP-I). Recognizing that activation of the renin-angiotensin-aldosterone system in congestive heart failure (CHF) antagonizes the renal actions of atrial natriuretic factor, we hypothesized that angiotensin II antagonism with converting enzyme inhibition would potentiate the renal actions of NEP-I in CHF. To test this hypothesis, the renal responses to a specific NEP-I (SQ 28,603) were assessed in dogs with eight days of experimental CHF produced by rapid ventricular pacing. The renal natriuretic responses to NEP-I in experimental CHF were significant. In the same model of CHF, chronic angiotensin antagonism with converting enzyme inhibition potentiated both renal hemodynamic and excretory responses to NEP-I. The potentiated renal hemodynamic response included significant increases in glomerular filtration rate and filtration fraction. In the CHF group with angiotensin antagonism, an intrarenal infusion of low-dose angiotensin abolished the potentiated renal responses to NEP-I, supporting the concept that intrarenal angiotensin antagonism, rather than improved systemic hemodynamics or potentiation of other peptide systems, mediated the enhanced renal responses to NEP-I in the presence of converting enzyme inhibition.