gebhart/patrepeval huggingface dataset:
Targeting of cytotoxic somatostatin analog AN-238 to somatostatin receptor subtypes 5 and/or 3 in experimental pancreatic cancers. (2001)

Growth of experimental human pancreatic cancers that express SSTRs can be inhibited by cytotoxic somatostatin analogue AN-238.
Numerical Model for Cavitational Flow in Hydraulic Poppet Valves (2012)

The paper presents a numerical simulation and analysis of the flow inside a poppet valve. First, the single-phase (liquid) flow is investigated, and an original model is introduced for quantitatively describing the vortex flow. Since an atmospheric outlet pressure produces large negative absolute pressure regions, a two-phase (cavitating) flow analysis is also performed. Both pressure and density distributions inside the cavity are presented, and a comparison with the liquid flow results is performed. It is found that if one defines the cavity radius such that up to this radius the pressure is no larger than the vaporization pressure, then both liquid and cavitating flow models predict the cavity extent. The current effort is based on the application of the recently developed full cavitation model that utilizes the modified Rayleigh-Plesset equations for bubble dynamics.
Joint coding for flash memory storage (2008)

Flash memory is an electronic non-volatile memory with wide applications. Due to the substantial impact of block erasure operations on the speed, reliability and longevity of flash memories, writing schemes that enable data to be modified numerous times without incurring the block erasure is desirable. This requirement is addressed by floating codes, a coding scheme that jointly stores and rewrites data and maximizes the rewriting capability of flash memories. In this paper, we present several new floating code constructions. They include both codes with specific parameters and general code constructions that are asymptotically optimal. We also present bounds to the performance of floating codes.
Generation of circular RNAs and trans-cleaving catalytic RNAs by rolling transcription of circular DNA oligonucleotides encoding hairpin ribozymes (1998)

A simple new strategy for the in vitro synthesis of circular RNAs and hairpin ribozymes is described. Circular single-strand DNA oligonucleotides 67-79 nt in length are constructed to encode both hairpin ribozyme sequences and ribozyme-cleavable sequences. In vitro transcription of these small circles by Escherichia coli RNA polymerase produces long repeating RNAs by a rolling circle mechanism. These repetitive RNAsundergo self-processing, eventually yielding unit length circular and linear RNAs as the chief products. The transcription is efficient despite the absence of promoter sequences, with RNA being produced in up to 400 times the amount of DNA circle used. It is shown that the linear monomeric hairpin ribozymes are active in cleaving RNA targets in trans , including one from HIV-1. Several new findings are established: (i) that rolling circle transcription can be extended to the synthesis of catalytic RNAs outside the hammerhead ribozyme motif; (ii) that rolling circle transcription is potentially a very simple and useful strategy for the generation of circular RNAs in preparative amounts; and (iii) that self-processed hairpin ribozymes can be catalytically active in trans despite the presence of self-binding domains.
Engineering DNA vaccines via co-delivery of co-stimulatory molecule genes (1998)

DNA immunization has been investigated as a potential immunization strategy against infectious diseases and cancer. To enhance a DNA vaccine's ability to induce CTL response in vivo, we co-administered CD80 and CD86 expression cassettes along with HIV-1 immunogens. This manipulation resulted in a dramatic increase in MHC class I-restricted and CD8+ T-cell-dependent CTL responses in both mice and chimpanzees. This strategy of engineering vaccine producing cells to be more efficient T-cell activators could be an important tool for optimizing antigen-specific T-cell-mediated immune responses in the pursuit of more rationally designed vaccines and immune therapies.
Activators Regenerated by Electron Transfer for Atom‐Transfer Radical Polymerization of (Meth)acrylates and Related Block Copolymers (2006)

Aktiv bleiben: Die im Titel genannte Methode ermöglicht eine kontinuierliche und kontrollierte Polymerisation mit deutlich weniger Cu-Katalysator als bei konventioneller Atomtransfer-Radikalpolymerisation (es genügen 10−3 Mol-% bezogen auf das Monomer). Der CuI-Aktivator wird mit einem Reduktionsmittel beständig regeneriert, was CuI-Verluste infolge von Radikalabbruchreaktionen kompensiert (siehe Schema).
Bacterial surface display of an anti‐pollutant antibody fragment (1999)

A peptidoglycan-associated lipoprotein (PAL) fused to an antibody fragment (scFv) specific to the herbicide and environmental pollutant atrazine, has been successfully targeted to the cell surface of Escherichia coli. Anti-atrazine binding could be observed via an atrazine-alkaline phosphatase conjugate. Cells containing the PAL fusion grew with little cellular toxicity when compared with the control. In contrast, expression of anti-atrazine antibody fragments alone caused the cells to lyse after 4 h. The surface display of anti-pollutant antibodies may have a future role in the bioremediation of contaminated water or the development of pollutant-specific, whole-cell biosensors.
Human Hepatocellular Carcinoma Cell Lines Secrete the Major Plasma Proteins and Hepatitis B Surface Antigen (1980)

Analysis of the cell culture fluid from two new human hepatoma-derived cell lines reveals that 17 of the major human plasma proteins are synthesized and secreted by these cells. One of these cell lines, Hep 3B, also produces the two major polypeptides of the hepatitis B virus surface antigen. When Hep 3B in injected into athymic mice, metastatic hepatocellular carcinomas appear. These cell lines provide experimental models for investigation of plasma protein biosynthesis and the relation of the hepatitis B viru genome to tumorigenicity.
Validation of cytochrome p450 1b1 as a target for the enzyme prodrug therapy of cancer (2005)

This study is comprised of three parts including: (1) clinical validation of cytochrome P450 CYP1B1 in clinical head and neck squamous cell carcinoma (HNSCC) and associated pre-malignant tissue, (2) the identification of a human tumour xenograft model which exhibits either constitutive or inducible expression of CYP1B1 for the evaluation of novel prodrug therapies in vivo, and (3) the identification of stable prodrugs targeted at CYPl-family enzymes designed to deliver nitric oxide to tumours.&#13;\n&#13;\nCYP1B1 protein was detected in HNSCC by immunohistochemistry (IHC) with a selective monoclonal antibody and was over-expressed to a high frequency in carcinoma (94 %, n = 70) and associated pre-malignant, hyperplastic (100 %, n = 14), and dysplastic tissues (100 %, n = 22). Quantitative analysis of CYP1B1 staining intensity by spectral imaging microscopy facilitated correlations with other clinico-pathological parameters including tumour grade, stage and anatomical site. CYP1B1 is mainly localised in the cancer tissue and is not present in adjacent stromal tissue, suggesting it may be a possible target for the enzyme prodrug therapy of cancer.&#13;\n&#13;\nA primary human tumour xenograft model was identified that constitutively expresses CYP1B1. Target enzyme protein expression was also inducible in a time- and dose-dependent manner in vivo as detected by western blotting, IHC and spectral imaging microscopy. Parallel studies also demonstrated CYPlA1 induction in the MCF-7 breast tumour xenograft model. This work has helped validate two potential human tumour xenograft models for the in vivo evaluation of both CYP1A1 - and CYP1B1 -activated prodrugs for cancer therapy.&#13;\n&#13;\nIn order to exploit the cytotoxic and hypoxic cell radiosensitising properties of nitric oxide (NO•), 10 novel benzo- or pyrido-fused indole oximes designed as prodrugs for NO• were screened for their selectivity for CYPl-family enzymes. GCI 510 was identified as a selective prodrug for CYP1Al, which generated NO• efficiently. This study has contributed to an understanding of the structural features of these prodrugs which confer selectivity for individual CYPl-family enzymes. Future work will seek to identify CYP1B1-selective prodrugs for NO• based on data from this study.
New low emission strategies and combustor designs for civil aeroengine applications (2004)

In the past, combustion computational fluid dynamics (CFD) in the framework of aeroengines mainly concentrated on high power conditions of combustors using diffusion type flames. In this paper, an overview of novel combustion concepts is given setting the scene for future CFD activities. The demand to lower emissions from jet engines powering passenger aircrafts has prompted a variety of research programmes devoted to this subject. In parallel to the optimisation of conventional combustors with respect to pollutant emissions, particularly nitrogen oxides, novel concepts have been invented, investigated and developed to different degrees of maturity. This presentation starts with a comprehensive overview on the requirements, discusses the NO formation mechanisms and presents concepts to overcome them. An assessment of the various concepts is made taking into account their specific advantages and drawbacks.
A role of GM-CSF in the accumulation of neutrophils in the airways caused by IL-17 and TNF‐α (2003)

The T-cell cytokine interleukin (IL)-17 selectively accumulates neutrophils in murine airways in vivo and may thus constitute a link between activation of T-lymphocytes and accumulation of neutrophils. In this study, the authors evaluated the role of granulocyte macrophage-colony stimulating factor (GM-CSF) in accumulation of neutrophils in the airways caused by IL-17 and tumour necrosis factor (TNF)-alpha. In vitro, human (h) IL-17 concentration-dependently stimulated the release of GM-CSF protein (enzyme-linked immunosorbent assay) in human bronchial epithelial cells (16HBE). IL-17 also time-dependently stimulated the release of GM-CSF protein in venous endothelial (human umbilical vein endothelial cells) cells in vitro. Co-stimulation with IL-17 plus the pro-inflammatory cytokine TNF-alpha potentiated the release of GM-CSF protein in 16HBE cells. hIL-17 also enhanced the expression of GM-CSF messenger ribonucleic acid in 16HBE cells (reverse transcriptase polymerase chain reaction), with a similar order of magnitude as TNF-alpha. Conditioned cell medium from bronchial epithelial cells co-stimulated with hIL-17 plus TNF-alpha prolonged survival (trypan blue exclusion) of human neutrophils in vitro and this effect was blocked by an anti-GM-CSF antibody. In vivo, local co-stimulation with mouse IL-17 plus TNF-alpha caused an additive potentiation of the accumulation of neutrophils in bronchoalveolar lavage fluid from mouse airways and this effect was blocked by an anti-GM-CSF antibody given systemically. In conclusion, granulocyte macrophage-colony stimulating factor is involved in the accumulation of neutrophils in the airways caused by interleukin-17 and tumour necrosis factor-alpha, probably via effects on both recruitment and survival of neutrophils.
Listeria monocytogenes Uses Listeria Adhesion Protein (LAP) To Promote Bacterial Transepithelial Translocation and Induces Expression of LAP Receptor Hsp60 (2010)

Listeria monocytogenes interaction with the intestinal epithelium is a key step in the infection process. We demonstrated that Listeria adhesion protein (LAP) promotes adhesion to intestinal epithelial cells and facilitates extraintestinal dissemination in vivo. The LAP receptor is a stress response protein, Hsp60, but the precise role for the LAP-Hsp60 interaction during Listeria infection is unknown. Here we investigated the influence of physiological stressors and Listeria infection on host Hsp60 expression and LAP-mediated bacterial adhesion, invasion, and transepithelial translocation in an enterocyte-like Caco-2 cell model. Stressors such as heat (41°C), tumor necrosis factor alpha (TNF-α) (100 U), and L. monocytogenes infection (10(4) to 10(6) CFU/ml) significantly (P < 0.05) increased plasma membrane and intracellular Hsp60 levels in Caco-2 cells and consequently enhanced LAP-mediated L. monocytogenes adhesion but not invasion of Caco-2 cells. In transepithelial translocation experiments, the wild type (WT) exhibited 2.7-fold more translocation through Caco-2 monolayers than a lap mutant, suggesting that LAP is involved in transepithelial translocation, potentially via a paracellular route. Short hairpin RNA (shRNA) suppression of Hsp60 in Caco-2 cells reduced WT adhesion and translocation 4.5- and 3-fold, respectively, while adhesion remained unchanged for the lap mutant. Conversely, overexpression of Hsp60 in Caco-2 cells enhanced WT adhesion and transepithelial translocation, but not those of the lap mutant. Furthermore, initial infection with a low dosage (10(6) CFU/ml) of L. monocytogenes increased plasma membrane and intracellular expression of Hsp60 significantly, which rendered Caco-2 cells more susceptible to subsequent LAP-mediated adhesion and translocation. These data provide insight into the role of LAP as a virulence factor during intestinal epithelial infection and pose new questions regarding the dynamics between the host stress response and pathogen infection.
The basis for the mechanistic bias for deletional over inversional V(D)J recombination. (1992)

V(D)J recombination between recognition sites in the genome is characterized by certain biases. At some loci, proximal sites undergo recombination substantially more frequently than distal ones. The joining of DH/JH is an example of this. Because the DH element bears signal sequences on each side, inversion would be expected as often as deletion in DH/JH recombination. However, the markedly favored outcome is deletion, entailing utilization of the closer recombination site. One model proposed to explain these biases is the tracking model in which the recombinase tracks from one site to the other. Here, we have directly tested for various types of tracking in V(D)J recombination and have found no indication that it occurs. In addition, we have created DH-JH minilocus substrates for analysis of the basis for the preference for deletion. We find that we can reproduce the deletional bias for the system. Moreover, by flipping the orientation of the D segment, we can reverse the bias such that the frequency of inversions can exceed the number of deletions. These results indicate (1) that there is no intrinsic topological preference in this reaction, and (2) that the sequence of the signal and coding ends determines the bias.
Photoluminescence of ZnO Nanoparticles Prepared by Laser Ablation in Different Surfactant Solutions (2004)

ZnO nanoparticles were prepared by laser ablation of a zinc metal plate in a liquid environment using different surfactant (cationic, anionic, amphoteric, and nonionic) solutions. The nanoparticles were obtained in deionized water and in all surfactant solutions except the anionic surfactant solution. The average particle size and the standard deviation of particle size decreased with increasing amphoteric and nonionic surfactant concentrations. With the increase of the amphoteric surfactant concentration, the intensity of the defect emission caused by oxygen vacancies of ZnO rapidly decreased, while the exciton emission intensity increased. This indicates that anionic oxygen in the amphoteric surfactant molecules effectively occupied the oxygen vacancy sites at the ZnO nanoparticle surface due to charge matching with the positively charged ZnO nanoparticles.
ICM—A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation (1994)

Abstract An efficient methodology, further referred to as ICM, for versatile modeling operations and global energy optimization on arbitrarily fixed multimolecular systems is described. It is aimed at protein structure prediction, homology modeling, molecular docking, nuclear magnetic resonance (NMR) structure determination, and protein design. The method uses and further develops a previously introduced approach to model biomolecular structures in which bond lengths, bond angles, and torsion angles are considered as independent variables, any subset of them being fixed. Here we simplify and generalize the basic description of the system, introduce the variable dihedral phase angle, and allow arbitrary connections of the molecules and conventional definition of the torsion angles. Algorithms for calculation of energy derivatives with respect to internal variables in the topological tree of the system and for rapid evaluation of accessible surface are presented. Multidimensional variable restraints are proposed to represent the statistical information about the torsion angle distributions in proteins. To incorporate complex energy terms as solvation energy and electrostatics into a structure prediction procedure, a “double‐energy” Monte Carlo minimization procedure in which these terms are omitted during the minimization stage of the random step and included for the comparison with the previous conformation in a Markov chain is proposed and justified. The ICM method is applied successfully to a molecular docking problem. The procedure finds the correct parallel arrangement of two rigid helixes from a leucine zipper domain as the lowest‐energy conformation (0.5 Å root mean square, rms, deviation from the native structure) starting from completely random configuration. Structures with antiparallel helixes or helixes staggered by one helix turn had energies higher by about 7 or 9 kcal/mol, respectively. Soft docking was also attempted. A docking procedure allowing side‐chain flexibility also converged to the parallel configuration starting from the helixes optimized individually. To justdy an internal coordinate approach to the structure prediction as opposed to a Cartesian one, energy hypersurfaces around the native structure of the squash seeds trypsin inhibitor were studied. Torsion angle minimization from the optimal conformation randomly distorted up to the rms deviation of 2.2 Å or angular rms deviation of l0° restored the native conformation in most cases. In contrast, Cartesian coordinate minimization did not reach the minimum from deviations as small as 0.3 Å or 2°. We conclude that the most promising detailed approach to the protein‐folding problem would consist of some coarse global sampling strategy combined with the local energy minimization in the torsion coordinate space. © 1994 by John Wiley &amp; Sons, Inc.
Carbon nanotube-modified microelectrodes for simultaneous detection of dopamine and serotonin in vivo (2007)

Dopamine and serotonin are important neurotransmitters that interact in the brain. While dopamine is easily detected with electrochemical sensors, the detection of serotonin is more difficult because reactive species formed after oxidation can adsorb to the electrode, reducing sensitivity. Carbon nanotube treatments of electrodes have been used to increase the sensitivity, promote electron transfer, and reduce fouling. Most methods have focused on nanotube coatings of large electrodes and slower electrochemical techniques that are not conducive to measurements in vivo. In this study, we investigated carbon-fiber microelectrodes modified with single-walled carbon nanotubes for the co-detection of dopamine and serotonin in vivo. Using fast-scan cyclic voltammetry, S/N ratios for the neurotransmitters increased after nanotube coating. Electrocatalytic effects of nanotubes were not apparent at fast scan rates but faster kinetics were observed with slower scanning. Nanotube-modified microelectrodes showed significantly less fouling after exposure to serotonin than bare electrodes. The nanotube-modified electrodes were used to monitor stimulated dopamine and serotonin changes simultaneously in the striatum of anesthetized rat after administration of a serotonin synthetic precursor. These studies show that nanotube-coated microelectrodes can be used with fast scanning techniques and are advantageous for in vivo measurements of neurotransmitters because of their greater sensitivity and resistance to fouling.
The design, expression, and characterization of human insulin-like growth factor II (IGF-II) mutants specific for either the IGF-II/cation-independent mannose 6-phosphate receptor or IGF-I receptor. (1991)

Five mutants of recombinant insulin-like growth factor-II (rIGF-II) that bound with high affinity to either the IGF-II/cation-independent mannose 6-phosphate (IGF-II/CIM6-P) or the IGF-I receptor were prepared by site-directed mutagenic procedures, expressed as fusion proteins in the larva of Bombyx mori or Escherichia coli, purified to homogeneity, renatured, and characterized in terms of their receptor binding affinities and specificities as well as their biological activities. Class I mutants in which Phe26, Tyr27, and Val43 were substituted with Ser, Leu, and Leu, respectively, bound to enriched preparations of rat placental IGF-II/CIM6-P receptors with apparent equilibrium dissociation constants (Kd(app)) that were only slightly greater, i.e. 0.10, 0.05, and 0.06 nM, than that of rIGF-II (0.04 nM) or hIGF-II (0.03 nM). In contrast, replacing Phe26 with Ser resulted in 5- and 20-fold decreases in the affinities of this mutant for highly purified human placental IGF-I and insulin receptors, respectively. The affinities of the two other Class I mutants, [Leu27]- and [Leu43]rIGF-IIs, for these two receptors were reduced 80- to 220-fold. The affinities of Class II mutants, i.e. [Thr48,Ser49,Ile50]- and [Arg54,Arg55] rIGF-IIs, for IGF-I receptors were as potent as rIGF-II; however, they bound very poorly or not at all to the IGF-II/CIM6-P receptor. In the binding study of those mutant rIGF-IIs, IGF-II was observed to have an unexpectedly high affinity for pure human placental insulin receptor preparations. For example, the affinities of hIGF-II, rIGF-II, and two Class II rIGF-II mutants for the insulin receptor were only 3-, 9-, and 5-fold less, respectively, than that of porcine insulin. In two biological assay systems, i.e. the stimulation of DNA synthesis in Balb/c 3T3 cells and glycogen synthesis in HepG2 cells, the Kd(app) of the rIGF-II mutants for the IGF-I receptor but not the IGF-II/CIM6-P receptor correlated with their abilities to produce biological responses.