gebhart/patrepeval huggingface dataset:
A Novel Murine T-Cell Receptor Targeting NY-ESO-1 (2014)

Cancer testis antigens, such as NY-ESO-1, are expressed in a variety of prevalent tumors and represent potential targets for T-cell receptor (TCR) gene therapy. DNA encoding a murine anti-NY-ESO-1 TCR gene (mTCR) was isolated from immunized HLA-A*0201 transgenic mice and inserted into a γ-retroviral vector. Two mTCR vectors were produced and used to transduce human PBL. Transduced cells were cocultured with tumor target cell lines and T2 cells pulsed with the NY-ESO-1 peptide, and assayed for cytokine release and cell lysis activity. The most active TCR construct was selected for production of a master cell bank for clinical use. mTCR-transduced PBL maintained TCR expression in short-term and long-term culture, ranging from 50% to 90% efficiency 7-11 days after stimulation and 46%-82% 10-20 days after restimulation. High levels of interferon-γ secretion were observed (1000-12000 pg/mL), in tumor coculture assays and recognition of peptide-pulsed cells was observed at 0.1 ng/mL, suggesting that the new mTCR had high avidity for antigen recognition. mTCR-transduced T cells also specifically lysed human tumor targets. In all assays, the mTCR was equivalent or better than the comparable human TCR. As the functional activity of TCR-transduced cells may be affected by the formation of mixed dimers, mTCRs, which are less likely to form mixed dimers with endogenous hTCRs, may be more effective in vivo. This new mTCR targeted to NY-ESO-1 represents a novel potential therapeutic option for adoptive cell-transfer therapy for a variety of malignancies.
Formation of Initial Perturbation of Rayleigh‐Taylor Instability in Supernovae and Laser‐irradiated Targets—Is There Any Similarity? (2000)

It is suggested that the formation of initial hydrodynamic perturbation in the early phase of supernova explosions is analogous to the initial "imprint" process of laser nonuniformity on a target for inertial confinement fusion. If the radiation pressure in supernovae is spatially nonuniform due possible to nonuniform neutrino heating, the interface between the early bubble and the envelope will be deformed, resulting in a seed of the Rayleigh-Taylor instability and convection. When laser light is first applied on a target, nonuniformity in laser irradiation is "imprinted" on the surface, which then set the initial perturbation of the subsequent Rayleigh-Taylor instability. We will review a reasonably simple imprint model, test it in the laser experiments, and apply it on the supernova process. If this analogy is correct, the velocity perturbation may be significantly increased compared with a secular distortion due to the pressure nonuniformity.
Photochemistry of Colloidal Metal Sulfides. 7. Absorption and Fluorescence of Extremely Small ZnS Particles (The World of the Neglected Dimensions) (1984)

Abstract Extremely small colloidal ZnS particles (diameter ∼ 1.7 nm) were made by either photo‐degradation of 3 nm particles or rapid precipitation in phosphate containing solution at pH = 7‐−8. The absorption spectra of these particles are different from that of macrocrystalline ZnS, and the changes are regarded as an indication for the transition from semiconductor ZnS to polymolecular ZnS with decreasing particle size. – The dependence of the intensity of the fluorescence on particle size, temperature, photoanodic corrosion and the quenching of fluorescence were investigated for colloids on a silicon dioxide carrier, in phosphate solution, and without a stabilizer. Photo‐anodic corrosion strongly improves the fluorescence properties. – One adsorbed Cd 2+ ion per colloidal particle is sufficient for efficient quenching of the fluorescence. However, a new fluorescence band appears which is explained by the formation of a layer of 1:1 co‐colloid at the surface of the ZnS particles. – Methylviologen was also found to be a very efficient quencher. The decay of the fluorescence is wavelength dependent, i.e. the fraction of long‐lived fluorescence is greater at longer wavelengths. – A mechanism is discussed, where the fluorescence centers are anion vacancies, and fluorescence is emitted when electrons trapped in states of different energies and exhibiting different life‐times tunnel to the localized positive holes.
Bandwidth enhancement and broadband noise reduction in injection-locked semiconductor lasers (1995)

Injection locking of a semiconductor laser can significantly improve the broadband modulation characteristics. By adjusting the frequency offset between the master laser and the slave laser, improved modulation bandwidth or flatness of the modulation response can be emphasized. The improved modulation characteristics are accompanied by reduced broadband relative intensity noise. Our calculations predict that the parasitic-free modulation bandwidths can be enhanced above the theoretical limit for the free-running laser.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients (2004)

The burden of ADRs on the NHS is high, accounting for considerable morbidity, mortality, and extra costs. Although many of the implicated drugs have proved benefit, measures need to be put into place to reduce the burden of ADRs and thereby further improve the benefit:harm ratio of the drugs.
Resistive Pulse Analysis of Microgel Deformation During Nanopore Translocation (2011)

Deformation of 570-nm radius poly(N-isopropylacrylamide-co-acrylic acid) microgels passing through individual 375- to 915-nm radius nanopores in glass has been investigated by the resistive-pulse method. Particle translocation through nanopores of dimensions smaller than the microgel yields electrical signatures reflecting the dynamics of microgel deformation. Translocation rates, and event duration and peak shape, are functions of the conductivities of microgel and electrolyte. Our results demonstrate that nanopore resistive-pulse methods provide new fundamental insights into microgel permeation through porous membranes.
Gradient nanostructures for interfacing microfluidics and nanofluidics (2002)

It is difficult to introduce long genomic DNA molecules into nanometer scale fluidic channels directly from the macroscale world because of the steep entropic barrier caused by necessary stretching of the polymer. We present a very simple technique using optical lithography to fabricate continuous spatial gradient structures which smoothly narrow the cross section of a volume from the micron to the nanometer length scale, greatly reducing the local entropic barrier to nanochannel entry. This technique, diffraction gradient lithography, can be very valuable for the fabrication of micro/nano total analysis systems.
Metabolic flux analysis for succinic acid production by recombinant Escherichia coli with amplified malic enzyme activity (2001)

A pfl ldhA double mutant Escherichia coli strain NZN111 was used to produce succinic acid by overexpressing the E. coli malic enzyme. Escherichia coli strain NZN111 harboring pTrcML produced 6 and 8 g/L of succinic acid from 20 g/L of glucose in flask culture at 37 degrees C and 30 degrees C, respectively. When NZN111(pTrcML) was cultured at 30 degrees C with intermittent glucose feeding the final succinic acid concentration obtained was 9.5 g/L and the ratio of succinic acid to acetic acid was 13:1. This system could not be analyzed by conventional metabolic flux analysis techniques, since some pyruvate and succinic acid were accumulated intracellularly. Therefore, a new flux analysis method was proposed by introducing intracellular pyruvate and succinic acid pools. By this new method the concentrations of intracellular metabolites were successfully predicted and the differences between the measured and calculated reaction rates could be considerably reduced.
Low Energy Proton Beam Induces Efficient Cell Killing in A549 Lung Adenocarcinoma Cells (2010)

The aim of the current study was to determine the signaling differences between gamma- and proton beam-irradiations. A549 lung adenocarcinoma cells were irradiated with 2 Gy proton beam or gamma-radiation. Proton beam was found to be more cytotoxic than gamma-radiation. Proton beam-irradiated cells showed phosphorylation of H2AX, ATM, Chk2, and p53. The mechanism of excessive cell killing in proton beam-irradiated cells was found to be upregulation of Bax and downregulation of Bcl-2. The noteworthy finding of this study is the biphasic activation of the sensor proteins, ATM, and DNA-PK and no activation of ATR by proton irradiation.
Dramatic enhancement of enzymatic activity in organic solvents by lyoprotectants (1993)

When seven different hydrolytic enzymes (four proteases and three lipases) were lyophilized from aqueous solution containing a ligand, N-Ac-L-Phe-NH(2), their catalytic activity in anhydrous solvents was far greater (one to two orders of magnitude) than that of the enzymes lyophilized without the ligand. This ligand-induced activation was expressed regardless of whether the substrate employed in organic solvents structurally resembled the ligand. Furthermore, nonligand lyoprotectants [sorbitol, other sugars, and poly(ethylene glycol)] also dramatically enhanced enzymatic activity in anhydrous solvents when present in enzyme aqueous solution prior to lyophilization. The effects of the ligand and of the lyoprotectants were nonadditive, suggesting the same mechanism of action. Excipient activated and nonactivated enzymes exhibited identical activities in water. Also, addition of the excipients directly to suspensions of nonactivated enzymes in organic solvents had no appreciable effect on catalytic activity. These observations indicate that the mechanism of the excipient-induced activation is based on the ability of the excipients to alleviate reversible denaturation of enzymes upon lyophilization. Activity enhancement induced by the excipients is displayed even after their removal by washing enzymes with anhydrous solvents. Subtilisin Carlsberg, lyophilized with sorbitol, was found to be a much more efficient practical catalyst than its "regular" counterpart.
Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. (1977)

Methoxypolyethylene glycols of 1900 daltons (PEG-1900) or 5000 daltons (PEG-5000) were covalently attached to bovine liver catalase using 2,4,6-trichloro-s-triazine as the coupling agent. Rabbits were immunized by the intravenous and intramuscular routes with catalase modified by covalent attachment of PEG-1900 to 43% of the amino groups (PEG-1900-catalase). The intravenous antiserum did not yield detectable antibodies against PEG-1900-catalase or native catalase, as determined by Ouchterlony and complement fixation methods, whereas the intramuscular antiserum contained antibodies to both PEG-1900-catalase and catalase. PEG-1900 did not react with either antiserum. Catalase was prepared in which PEG-5000 was attached to 40% of the amino groups (PEG-5000-catalase). This catalase preparation did not react with either antiserum. PEG-1900-catalase retained 93% of its enzymatic activity; PEG-5000-catalase retained 95%. PEG-5000-catalase resisted digestion by trypsin, chymotrypsin, and a protease from Streptomyces griseus. PEG-1900-catalase and PEG-5000-catalase exhibited enhanced circulating lives in the blood of acatalasemic mice during repetitive intravenous injections. No evidence was seen of an immune response to injections of the modified enzymes. Mice injected repetitively with PEG-5000-catalase remained immune competent for unmodieied catalase, and no evidence of tissue or organ damage was seen.
HIBADH Plays an Important Role in the Course of Liver Cell Necrosis (2014)

Abstract Objective To observe the biological function of human 3-hydroxyisobutyrate dehydrogenase (HIBADH). Methods Human 3-hydroxyisobutyrate dehydrogenase (HIBADH, 3-hydroxy-2-methyl propanoate: NAD+ oxidoreductase) recombinant protein was expressed in E. coli BL21, and purified by Ni + column. The special antisera was obtained from rabbits immunized by this purified antigen. On the distribution of HIBADH, it was found that HIBADH over-expressed in the injured liver cells when serious hepatitis occurred. The phenomenon was confirmed in the animal models of SD rats with acute liver cell injury induced by CCl4, but this phenomenon did not exist in the models induced by endotoxin combined with galactosamine. Further more, HIBADH’s overexpression in liver cells will induce cell necrosis through the pathway of oxidative stress. Results When the liver cells injured by drug or other chemical materials, HIBADH will be compensationally over-expressed for the deficiency of energy, so liver cells can make enough ATP through brand-chain amino acid catabolism. However, the overexpression of HIBADH will be harmful for liver cells through the product of much more active oxygens which will induce the cell necrosis. Conclusions HIBADH over-expression is a signal of the liver cell metabolism injury, and it can aggravate the liver cell injury through oxidative stress.
Automatic and efficient evaluation of memory hierarchies for embedded systems (1999)

Automation is the key to the design of future embedded systems as it permits application-specific customization while keeping design costs low. A key problem faced by automatic design systems is evaluating the performance of the vast number of alternative designs in a timely manner. For this paper, we focus on an embedded system consisting of the following components: a VLIW processor, instruction cache, data cache, and second-level unified cache. A hierarchical approach of partitioning the system into its constituent components and evaluating each component individually is utilized. The performance of each processor is evaluated independent of its memory hierarchy, and each of the caches is simulated using the traces from a single reference processor. Since the changes in the processor architecture do indeed affect the address traces and thus the performance of the memory hierarchy, the overall performance is inaccurate. To overcome this error, the changes in the processor architecture are modeled as a dilation of the reference processor's address trace, where each instruction block in the trace is conceptually stretched out by the dilation coefficient. This approach provides a projected cache performance that more accurately accounts for changes in the processor architecture. In order to understand the accuracy of the dilation model, we separate the possible errors that the model introduces and quantify these errors on a set of benchmarks. The results show that the dilation model is effective for most of the design space and facilitates efficient automatic design.
Adoptively Transferred Tumor-Infiltrating Lymphocytes Can Cure Established Metastatic Tumor in Mice and Persist Long-Term In Vivo as Functional Memory T Lymphocytes (1991)

Tumor infiltrating lymphocytes (TILs) are derived from solid tumors by culturing single cell suspensions of the tumors in low dose interleukin-2 (IL-2) and intermittent tumor stimulation. We have investigated the survival of TILs after intravenous injection into tumor-bearing mice. Using several murine transplantable sarcomas, we examined the in vivo survival of TILs derived from B6.PL Thy 1a/CY mice (Thy-1.1), which were used to treat established experimental metastases in C57BL/6N (Thy-1.2) mice. Donor and host lymphoid cells could be clearly distinguished by fluorescence-activated cell sorting. We found that TILs or TILs + IL-2 could extend the survival of and, in some instances, cure established experimental hepatic and pulmonary metastases. Donor TILs could be recovered from treated animals at all time points tested; in mice cured of pulmonary metastases donor TILs could be detected as late as 119 days after intravenous injection even in the absence of exogenous IL-2. The administration of a relatively low dose of IL-2 in vivo to mice receiving TILs increased the number of donor TILs recovered from the lungs of cured animals 5-10-fold at all time points but did not change the period of time during which donor TILs could be detected in vivo. Additionally, TILs could be recovered from animals cured of established metastases and such cells retained their antitumor activity in vivo. Finally, when mice cured of pulmonary metastases by TILs or TILs + IL-2 were rechallenged with tumor, donor TILs specifically accumulated at the site of tumor rechallenge up to 4 months after adoptive transfer of TILs.(ABSTRACT TRUNCATED AT 250 WORDS)
Backpropagation-Based Cooperative Localization of Primary User for Avoiding Hidden-Node Problem in Cognitive Networks (2010)

Cognitive radio (CR) is a technology to implement opportunistic spectrum sharing to improve the spectrum utilization. However, there exists a hidden-node problem, which can be a big challenge to solve especially when the primary receiver is passive listening. We aim to provide a solution to the hidden-node problem for passive-listening receiver based on cooperation of multiple CRs. Specifically, we consider a cooperative GPS-enabled cognitive network. Once the existence of PU is detected, a localization algorithm will be employed to first estimate the path loss model for the environment based on backpropagation method and then to locate the position of PU. Finally, a disable region is identified taking into account the communication range of both the PU and the CR. The CRs within the disabled region are prohibited to transmit in order to avoid interfering with the primary receiver. Both analysis and simulation results are provided.
TRANSFAC: a database on transcription factors and their DNA binding sites (1996)

TRANSFAC is a database about eukaryotic transcription regulating DNA sequence elements and the transcription factors binding to and acting through them. This report summarizes the present status of this database and accompanying retrieval tools.
Immuno Gold Nanocages with Tailored Optical Properties for Targeted Photothermal Destruction of Cancer Cells (2007)

Gold nanocages with a relatively small size (e.g., approximately 45 nm in edge length) have been developed, and the structure of these nanocages was tailored to achieve strong absorption in the near-infrared (NIR) region for photothermal cancer treatment. Numerical calculations show that the nanocage has a large absorption cross section of 3.48 x 10(-14) m(2), facilitating conversion of NIR irradiation into heat. The gold nanocages were conjugated with monoclonal antibodies (anti-HER2) to target epidermal growth factor receptors (EGFR) that are overexpressed on the surface of breast cancer cells (SK-BR-3). Our preliminary photothermal results show that the nanocages strongly absorb light in the NIR region with an intensity threshold of 1.5 W/cm(2) to induce thermal destruction to the cancer cells. In the intensity range of 1.5-4.7 W/cm(2), the circular area of damaged cells increased linearly with the irradiation power density. These results suggest that this new class of bioconjugated gold nanostructures, immuno gold nanocages, can potentially serve as an effective photothermal therapeutic agent for cancer treatment.
Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12 (2005)

Human antibody 2G12 neutralizes a broad range of HIV-1 isolates. Hence, molecular characterization of its epitope, which corresponds to a conserved cluster of oligomannoses on the viral envelope glycoprotein gp120, is a high priority in HIV vaccine design. A prior crystal structure of 2G12 in complex with Man(9)GlcNAc(2) highlighted the central importance of the D1 arm in antibody binding. To characterize the specificity of 2G12 more precisely, we performed solution-phase ELISA, carbohydrate microarray analysis, and cocrystallized Fab 2G12 with four different oligomannose derivatives (Man(4), Man(5), Man(7), and Man(8)) that compete with gp120 for binding to 2G12. Our combined studies reveal that 2G12 is capable of binding both the D1 and D3 arms of the Man(9)GlcNAc(2) moiety, which would provide more flexibility to make the required multivalent interactions between the antibody and the gp120 oligomannose cluster than thought previously. These results have important consequences for the design of immunogens to elicit 2G12-like neutralizing antibodies as a component of an HIV vaccine.
Engineered Biosynthesis of Novel Polyketides (1993)

Polyketide synthases (PKSs) are multifunctional enzymes that catalyze the biosynthesis of a huge variety of carbon chains differing in their length and patterns of functionality and cyclization. Many polyketides are valuable therapeutic agents. A Streptomyces host-vector system has been developed for efficient construction and expression of recombinant PKSs. Using this expression system, several novel compounds have been synthesized in vivo in significant quantities. Characterization of these metabolites has provided new insights into key features of actinomycete aromatic PKS specificity. Thus, carbon chain length is dictated, at least in part, by a protein that appears to be distinctive to this family of PKSs, whereas the acyl carrier proteins of different PKSs can be interchanged without affecting product structure. A given ketoreductase can recognize and reduce polyketide chains of different length; this ketoreduction always occurs at the C-9 position. The regiospecificity of the first cyclization of the nascent polyketide chain is either determined by the ketoreductase, or the chain-extending enzymes themselves. However, the regiospecificity of the second cyclization is determined by a distinct cyclase, which can discriminate between substrates of different chain lengths.
Immunogenicity of a polyvalent melanoma antigen vaccine in humans (1988)

Fifty-five patients with Stage II (36 patients) or Stage III (19 patients) malignant melanoma confirmed histologically received adjuvant immunotherapy with a polyvalent melanoma antigen vaccine to evaluate toxicity and immunogenicity. There was no toxicity. Antibody and/or cellular immune responses to melanoma were induced more frequently in Stage II (36 patients [69%]) than Stage III (19 patients [53%]) disease. The ability of different immunization schedules, alum, or pretreatment with low-dose cyclophosphamide to potentiate immunogenicity was compared after 2 months of immunization. Immunization biweekly with a fixed intermediate dose of vaccine was more immunogenic than immunization weekly with escalating vaccine doses. Alum increased the intensity of cellular responses slightly, whereas pretreatment with cyclophosphamide augmented both the incidence and intensity of cellular immune responses slightly. However, these changes did not reach statistical significance. There was a reciprocal relationship between the induction of humoral and cellular immune responses. These results show that (1) active immunotherapy with a polyvalent melanoma vaccine is safe in patients with minimal disease, (2) the vaccine augments immunity to melanoma in many, but not all, patients, and (3) several immunization strategies failed to potentiate immunogenicity significantly.