gebhart/patrepeval huggingface dataset:
Gene Transfer into Hepatocytes and Human Liver Tissue by Baculovirus Vectors (1996)

Gene therapy of liver diseases requires the development of efficient vectors for gene transfer in vivo. Retroviral and adenoviral vectors have been shown to deliver genes efficiently into hepatocytes in vitro and in vivo. However, these vectors do not allow for exclusive infection of the liver which would be highly advantageous for in vivo gene therapy strategies. We have recently demonstrated that genetically modified baculoviruses (Autographa californica nuclear polyhedrosis virus) efficiently deliver genes into cultured cells and have a strong preference for hepatocytes of different origin. Baculoviral gene transduction efficiency into human hepatocytes was determined to approach 100% and expression levels are high, provided that gene expression is controlled by mammalian promoters. In this report, we present further properties of baculoviruses regarding their use for hepatocyte gene transfer. Baculovirus-mediated gene expression declines rapidly in the hepatocellular carcinoma cell line Huh7 and more slowly in primary cultures of mouse hepatocytes. Direct application of baculoviruses for gene delivery to the liver in vivo is hampered by serum components, presumably by complement. However, we demonstrate here that baculoviral gene transfer is feasible in ex vivo perfused human liver tissue. This result suggests the development of a strategy using baculoviral vectors for liver-directed gene therapy.
Technology evaluation: bevacizumab, Genentech/Roche. (2003)

Bevacizumab, an antivascular endothelial growth factor monoclonal antibody, is being developed by Genentech and Roche as an anti-angiogenesis therapy for the potential treatment of solid tumors. In June 2003, bevacizumab was granted Fast Track status by the FDA for the potential treatment of first-line colorectal cancer. The antibody is currently in phase III trials for non-small-cell lung, colorectal and breast cancers, and in phase II trials for various other solid tumor types.
Microvascular pressure and functional capillary density in extreme hemodilution with low- and high-viscosity dextran and a low-viscosity Hb-based O2 carrier (2004)

Blood losses are usually corrected initially by the restitution of volume with plasma expanders and subsequently by the restoration of oxygen-carrying capacity using either a blood transfusion or possibly, in the near future, oxygen-carrying plasma expanders. The present study was carried out to test the hypothesis that high-plasma viscosity hemodilution maintains perfused functional capillary density (FCD) by preserving capillary pressure. Microvascular pressure responses to extreme hemodilution with low- (LV) and high-viscosity (HV) plasma expanders and an exchange transfusion with a polymerized bovine cell-free Hb (PBH) solution were analyzed in the awake hamster window chamber model (n = 26). Systemic hematocrit was reduced from 50% to 11%. PBH produced a greater mean arterial blood pressure than the nonoxygen carriers. FCD was higher after a HV plasma expander (70 +/- 15%) vs. PBH (47 +/- 12%). Microvascular pressure spanning the capillary network was higher after a HV plasma expander (16-19 mmHg) compared with PBH (12-16 mmHg) and a LV plasma expander (11-14 mmHg) but lower than control (22-26 mmHg). FCD was found to be directly proportional to capillary pressure. The use of a HV plasma expander in extreme hemodilution maintained the number of perfused capillaries and tissue perfusion by comparison with a LV plasma expander due to increased mean arterial blood pressure and capillary pressure. The use of PBH increased mean arterial pressure but reduced capillary pressure due to vasoconstriction and did not maintain FCD.
The Effect of Acceptor Oligoribonucleotide Sequence on the T4 RNA Ligase Reaction (1982)

In order to make efficient use of T4 RNA ligase in a program involving chemical-enzymatic oligoribonucleotide synthesis, the sequence effects of the acceptor oligomer have been refined. The reaction of the donor molecules pCp and pUpUpUpCp with a series of trinucleoside diphosphates ApApN, CpNpA and NpCpA (where N = U, C, A or G) was examined. High-performance liquid chromatography was used for simultaneous analysis of all substrates, intermediates and products. For all trinucleoside bisphosphates tested a substantial amount of the intermediate A(5')pp(5')Cp or A(5')pp(5')UpUpUpCp was observed. This indicated that the extent of ligation was dependent upon sequence of the acceptor molecule and not upon adenylation of the donor. Conversely, examination of the four nucleoside 3',5'-bisphosphate donors pUp, pCp, pAp and pGp with a common acceptor ApApU indicated that in the case of poor ligation little of the intermediate adenylated donor was formed.
Adsorption Kinetics of Boron by Anion Exchange Resin in Packed Column Bed (2007)

In this paper, we present a novel application of Amberlite IRA 743 resin that has glucamine func- tional groups for specific boron exchange. The boron removal efficiency from seawater was examined through the packed column experiment. The efficiency of boron removal was investigated with respect to several key experimental parameters, including the pH of the solution, the initial concentration of boron, the bed volume of the resin, and the temperature. The performance of boron removal increased upon increasing the batch ratio of resin to boron and decreasing the initial concentration of boron in solution. Although the removal rate of boron increased at the initial state of increasing temperature, it was independent of temperature. Most of the boron in aqueous solution could be removed efficiently under the optimum operation conditions at pH 8.5. In addition, a kinetic study of boron removal under the optimum conditions fit Thomas's adsorption model well. The sim- ple method presented could be applied to the efficient removal of boron from wastewater.
Diversity–Multiplexing Tradeoff in Multiple-Access Channels (2004)

In a point-to-point wireless fading channel, multiple transmit and receive antennas can be used to improve the reliability of reception (diversity gain) or increase the rate of communication for a fixed reliability level (multiplexing gain). In a multiple-access situation, multiple receive antennas can also be used to spatially separate signals from different users (multiple-access gain). Recent work has characterized the fundamental tradeoff between diversity and multiplexing gains in the point-to-point scenario. In this paper, we extend the results to a multiple-access fading channel. Our results characterize the fundamental tradeoff between the three types of gain and provide insights on the capabilities of multiple antennas in a network context.
White LED phosphors: the next step (2010)

Application of white LEDs is extended toward high-output light sources, e.g. for automotive headlights, and better spectral matching with optical filters for LCD backlighting. To meet such new demands, phosphor materials have been investigated with focus on their luminescence spectra, temperature characteristics and reliability. The conventional yellow phosphor based on Y<sub>3</sub>Al<sub>5</sub>O<sub>12</sub>:Ce<sup>3+</sup> has excellent performance as a single phosphor combined with a blue LED. More recently developed nitrido- or oxonitrido-silicates activated with Eu<sup>2+</sup> are also promising materials showing green to red luminescence depending on a composition and high thermal and chemical stability. And yet, demands for specific application have been made clear and strong. This paper reviews the present status and challenging goals of phosphors in the next stage further to make progress in white LEDs.
Peptide priming of cytolytic activity to HER-2 epitope 369-377 in healthy individuals. (2000)

The presence of tumor-reactive CTLs in tumor infiltrates and in the peripheral blood of cancer patients demonstrates an immune response against tumors that apparently cannot control disease spread. This raises concerns as to whether amplification of this response may be useful during disease progression. Induction of tumor-reactive CTLs in healthy donors at risk, as well as in patients free of disease, may be therapeutically important, based on the hypothesis that CTLs that recognize tumors early may be more effective in containing their progression than CTLs that expand only when the disease progresses. To address the feasibility of priming cytolytic activity in healthy donors, we used the HER-2 peptide E75 (369-377) as an immunogen and autologous peripheral blood mononuclear cell-derived dendritic cells as antigen-presenting cells. We found that of 10 healthy donors tested, two responded at priming with E75 presented on autologous dendritic cells by induction of E75-specific CTL activity. Three other responders were identified after two additional restimulations. Of these five responders, three recognized E75 presented on the ovarian tumor line SKOV3.A2, as demonstrated by cold-target inhibition experiments. Induction of cytolytic activity at priming was enhanced in responders by tumor necrosis factor-alpha and interleukin 12 but not in the nonresponders. AlphaB7.1 monoclonal antibody added at priming enhanced induction of lytic activity in only one of the four nonresponding donors tested, suggesting that in the majority of donors, E75-precursor CTLs were not tolerized. Because of the possibility that disease may develop in nonresponders, strategies to improve the immunogenicity of tumor antigens for healthy donors may be required for development of cancer vaccines.
32P-postlabeling analysis of non-radioactive aromatic carcinogen — DNA adducts (1982)

A newly developed enzymatic 32P-postlabeling method was applied to the analysis of DNA's containing non-radioactive arylamine, arylamide, and polycyclic aromatic hydrocarbon adducts. DNA reacted in vitro with N-hydroxy-2-amino-fluorene, N-acetoxy-2-acetylaminofluorene, and 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, respectively, as well as DNA preparations from the liver of rats treated with N-hydroxy-2-acetylaminofluorene and benzo[a]pyrene, respectively, were enzymatically digested to deoxyribonucleoside 3'-monophosphates, which were then converted to [5'-32P]deoxyribonucleoside 3',5'-bisphosphates by T4 polynucleotide kinase-catalyzed [32P]phosphate transfer from [gamma-32P]ATP. The 32P-labeled nucleotides were resolved by anion-exchange t.l.c. on polyethyleneimine-cellulose and detected by autoradiography. Aromatic adduct nucleotides were found to be retained at the origin in aqueous electrolyte solutions, but to migrate as distinct spots in solvents containing 7-8.5 M urea. Advantage was taken of this observation to remove 32P-labeled normal DNA nucleotides from adduct nucleotides. This purification enabled the detection of a single adduct in 10(7)-10(8) normal nucleotides. The method appears applicable to the ultrasensitive detection of a large number of carcinogen--DNA adducts of diverse structure without requiring radioactive carcinogens or specific antibodies.
ACAT as a Drug Target for Alzheimer’s Disease (2008)

Accumulation of beta-amyloid peptide (Abeta) in the brain regions responsible for memory and cognitive functions is a neuropathological hallmark of Alzheimer's disease. Cholesterol may be involved in many aspects of Abeta metabolism. It affects generation, aggregation and clearance of Abeta in the brain. Not only the amount but also the distribution of cholesterol within cells appears to modulate Abeta biogenesis. ACAT is an enzyme that regulates subcellular cholesterol distribution by converting membrane cholesterol to cholesteryl esters for storage and transport. We have used various cell- and animal based models to show that inhibition of ACAT strongly reduces Abeta generation and protects from amyloid pathology. Here, we discuss data supporting ACAT inhibition as a strategy to treat Alzheimer's disease.
Enzymatic repair of oxidative damage to human apolipoprotein A‐I (1998)

Oxidative damage to apolipoprotein A-I that occurs in vivo commonly involves methionine oxidation, and is accompanied by alterations in structure, lipid association, and cholesterol efflux function. We have used the enzyme peptide methionine sulfoxide reductase (PMSR) to reverse this damage, and shown by a variety of criteria that enzyme treatment restores the primary, secondary, and tertiary structure and lipid association characteristic of the native unoxidized protein. Lipid-associated as well as lipid-free apolipoprotein A-I reacts with PMSR, suggesting that enzymatic reduction of oxidized apolipoprotein A-I in high density lipoproteins can result in restoration of biological activity and the ability to promote cholesterol efflux from cells.
Chemical vapor deposition of refractory metals and ceramics II (1992)

This symposium was held at the fall meeting of the Materials Research Society in Boston, Massachusetts on December 4--6, 1991. The purpose of this symposium was to provide a forum for exchange of state-of-the-art information on chemical vapor deposition of refractory metals and ceramics II. A number of papers discuss the fundamentals of CVD. They focus on the thermochemistry of CVD and the choice of halide gas species; CVD modeling for high-temperature materials; and kinetics and mass transport in CVD, with an emphasis on silicon carbide deposition. Papers are included which emphasize both the importance of in situ diagnostics and how this area is just now emerging. Papers on microstructure-process-property relationships reveal the ability to control the CVD coatings to a level not seen before. Chemical vapor infiltration to produce composite materials is the subject of a number of other papers and includes considerable discussion of the modeling of the infiltration process. Papers on organometallic CVD focus on a number of issues related to precursors and the mechanisms of deposition. Individual papers are processed separately for inclusion in the appropriate data bases.
The double‐strand RNA‐dependent protein kinase PKR plays a significant role in a sustained ER stress‐induced apoptosis (2007)

Sustained ER stress leads to apoptosis. However, the exact mechanism still remains to be elucidated. Here, we demonstrate that the double strand RNA-dependent protein kinase (PKR) is involved in the ER stress-mediated signaling pathway. ER stress rapidly activated PKR, inducing the phosphorylation of eIF2alpha, followed by the activation of the ATF4/CHOP pathway. ER-stress-mediated eIF2alpha/ATF4/CHOP signaling and associated cell death was markedly reduced by PKR knockdown. We also found that PKR activation was mediated by PACT, the expression of which was elevated by ER-stress. These results indicate that the ER-stress-mediated eIF2alpha/ATF4/CHOP/cell death pathway is, to some degree, dependent on PACT-mediated PKR activation apart from the PERK pathway.
Sketching mesh deformations (2005)

Techniques for interactive deformation of unstructured polygon meshes are of fundamental importance to a host of applications. Most traditional approaches to this problem have emphasized precise control over the deformation being made. However, they are often cumbersome and unintuitive for non-expert users.In this paper, we present an interactive system for deforming unstructured polygon meshes that is very easy to use. The user interacts with the system by sketching curves in the image plane. A single stroke can define a free-form skeleton and the region of the model to be deformed. By sketching the desired deformation of this reference curve, the user can implicitly and intuitively control the deformation of an entire region of the surface. At the same time, the reference curve also provides a basis for controlling additional parameters, such as twist and scaling. We demonstrate that our system can be used to interactively edit a variety of unstructured mesh models with very little effort. Furthermore, we can also use our formulation of the deformation to achieve a natural interpolation between character poses, thus producing simple key framed animations.
Copolymerization of Atactic Polypropene Macromonomer with Propene by an Isospecific Metallocene Catalyst (1999)

Atactic polypropene macromonomer (PPM) with a number-average polymerization degree of ca. 20 was synthesized by bis(pentamethylcyclopentadienyl)zirconium dichloride−methylaluminoxane and its structure was analyzed by 1H and 13C NMR spectroscopies. Copolymerization of propene and PPM was conducted with isospecific rac-dimethylsilylenebis(2-methylbenz[e]indenyl)zirconium dichloride using methylaluminoxane as a cocatalyst. The detailed analyses of resulting copolymers by GPC, DSC, and 13C NMR proved that PPM was copolymerized with propene to give poly(propene-co-PPM). PPM content in the copolymer was found to be controlled by the amount of PPM in feed.
Impaired Cytokine Signaling in Mice Lacking the IL-1 Receptor-Associated Kinase (1999)

Stimulation of the type 1 IL-1R (IL-1R1) and the IL-18R by their cognate ligands induces recruitment of the IL-1R-associated kinase (IRAK). Activation of IRAK leads in turn to nuclear translocation of NF-kappaB, which directs expression of innate and adaptive immune response genes. To study IRAK function in cytokine signaling, we generated cells and mice lacking the IRAK protein. IRAK-deficient fibroblasts show diminished activation of NF-kappaB when stimulated with IL-1. Immune effector cells without IRAK exhibit a defective IFN-gamma response to costimulation with IL-18. Furthermore, mice lacking the Irak gene demonstrate an attenuated response to injected IL-1. Deletion of Irak, however, does not affect the ability of mice to develop delayed-type hypersensitivity or clear infection with the intracellular parasite, Listeria monocytogenes. These results demonstrate that although IRAK participates in IL-1 and IL-18 signal transduction, residual cytokine responsiveness operates through an IRAK-independent pathway.
CD146 Expression in Human Breast Cancer Cell Lines Induces Phenotypic and Functional Changes Observed in Epithelial to Mesenchymal Transition (2012)

CD146 expression is associated with an EMT phenotype. Several molecules are affected by CD146 expression: direct or indirect signaling contributes to EMT by increasing Slug expression. CD146 may also interact with Erb signaling by modifying cell surface expression of ErbB3 and ErbB4 and increased resistance to chemotherapy. Antagonistic effects of JAM-A, a tight junction-associated protein, on CD146 promigratory effects underline the complexity of the adhesion molecules network in tumor cell migration and metastasis.
Temperature dependence of photoluminescence in noncrystalline silicon (2004)

Crystalline silicon being ubiquitous throughout the microelectronics industry has an indirect bandgap, and therefore is incapable of light emission. However, strong room temperature visible and near-IR luminescence from non-crystalline silicon, e.g., amorphous silicon, porous silicon, and black silicon, has been observed. These silicon based materials are morphologically similar to each other, and have similar luminescence properties. We have studied the temperature dependence of the photoluminescence from these non-crystalline silicons to fully characterize and optimize these materials in the pursuit of obtaining novel optoelectronic devices.
How Does Deep Brain Stimulation Work? Present Understanding and Future Questions (2004)

High-frequency deep brain stimulation (DBS) of the thalamus or basal ganglia represents an effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been vaulted forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address the present knowledge of the effects of high frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS. Four general hypotheses have been developed to explain the mechanism(s) of DBS: depolarization blockade, synaptic inhibition, synaptic depression, and stimulation-induced modulation of pathologic network activity. Using the results from microdialysis, neural recording, functional imaging, and neural modeling experiments, the authors address the main hypotheses and attempt to reconcile what have been considered conflicting results from different research modalities.
Strategies to Develop Inhibitors of Motif-Mediated Protein-Protein Interactions as Drug Leads (2016)

Protein-protein interactions are fundamental for virtually all functions of the cell. A large fraction of these interactions involve short peptide motifs, and there has been increased interest in targeting them using peptide-based therapeutics. Peptides benefit from being specific, relatively safe, and easy to produce. They are also easy to modify using chemical synthesis and molecular biology techniques. However, significant challenges remain regarding the use of peptides as therapeutic agents. Identification of peptide motifs is difficult, and peptides typically display low cell permeability and sensitivity to enzymatic degradation. In this review, we outline the principal high-throughput methodologies for motif discovery and describe current methods for overcoming pharmacokinetic and bioavailability limitations.
Ammonia-Lowering Strategies for the Treatment of Hepatic Encephalopathy (2012)

Hyperammonemia leads to neurotoxic levels of brain ammonia and is a major factor involved in the pathogenesis of hepatic encephalopathy (HE). Ammonia-lowering treatments primarily involve two strategies: inhibiting ammonia production and/or increasing ammonia removal. Targeting the gut has been the primary focus for many years, with the goal of inhibiting the generation of ammonia. However, in the context of liver failure, extrahepatic organs containing ammonia metabolic pathways have become new potential ammonia-lowering targets. Skeletal muscle has the capacity to remove ammonia by producing glutamine through the enzyme glutamine synthetase (amidation of glutamate) and, given its large mass, has the potential to be an important ammonia-removing organ. On the other hand, glutamine can be deaminated to glutamate by phosphate-activated glutaminase, thus releasing ammonia (ammonia rebound). Therefore, new treatment strategies are being focused on stimulating the removal of both ammonia and glutamine.
Site-Directed Neovessel Formation in Vivo (1988)

Angiogenesis is an important component of organogenesis and wound repair and occurs during the pathology of oncogenesis, atherogenesis, and other disease processes. Thus, it is important to understand the physiological mechanisms that control neovascularization, especially with methods that permit the molecular dissection of the phenomenon in vivo. Heparin-binding growth factor-1 was shown to bind to collagen type I and type IV. When complexed with gelatin, heparin-binding growth factor-1 can induce neovascularization at polypeptide concentrations that are consistent with the biological activity of the mitogen in vitro. The adsorption strategy induces rapid blood vessel formation at and between organ- and tissue-specific sites and permits recovery of the site-specific implant for examination and manipulation by molecular methods.