gebhart/patrepeval huggingface dataset:
Methioninase gene therapy of human cancer cells is synergistic with recombinant methioninase treatment. (2000)

Results obtained over the past 40 years have demonstrated that tumor cells of all types tested have an elevated growth requirement for methioninase compared with normal cells. Recombinant methioninase (rMETase) cloned from Pseudomonas putida has been found previously to be an effective antitumor agent attributable to deprivation of the extracellular methionine source of the tumor. To degrade intracellular methioninase, we have now developed an adenoviral vector inserted with the P. putida methioninase (MET) gene (rAd-MET). The in vitro efficacy of rAd-MET was tested on the OVCAR-8 human ovarian cancer cell line, the HT1080 human fibrosarcoma cell line, and human normal fibroblasts. rAd-MET transduction of OVACAR-8 and HT1080 resulted in high levels of methioninase expression up to 10% or more of the total protein of the cells, depending on the multiplicity of infection. The IC50 of rAd-MET for OVCAR-8 cells in 96-well plates was approximately 2 x 106 plaque-forming units (pfu)/well. The IC50 of control adenovirus (control-rAd) was 4 x 10(7) pfu/well, 20 times higher than rAd-MET. In the presence of the IC50 of 2 x 10(6) pfu/well of rAd-MET, the addition of 0.025 units/ml of rMETase, which is 25% of the IC50, resulted in a 90% inhibition of tumor cell number. This indicated that rAd-MET enhanced the efficacy of rMETase. In contrast, 2 x 10(6) pfu/well of control-rAd in combination with 0.025 units/ml of rMETase had an efficacy of only 10% inhibition of cell number. The synergistic effect of the combination of rMETase and rAd-MET was quantitated by calculating the combination index (CI). The CIs for all combinations of rAd-MET and rMETase tested on OVCAR-8 were <0.7 with a mean of 0.5, indicating synergy. Similar synergy of rAd-MET and rMETase was seen on HT1080 human fibrosarcoma cells with a mean of 0.74. In contrast, the CIs of all combinations of rMETase and control adenovirus concentrations tested on both cell lines had a mean CI of approximately 1, which indicated that this combination had only an additive effect. The normal fibroblasts, on the other hand, appeared relatively resistant to the MET gene because in the presence of rMETase, 2.5 x 10(7) pfu/well of rAd-MET or control rAd had almost an identical effect on cell survival. The selectively strong synergy of rAd-MET and rMETase on cancer cells allows reduced levels of each agent to be used, thus decreasing potential side effects.
Frequency and distribution of estrogen receptor-positive cells in normal, nonlactating human breast tissue. (1987)

We have analyzed the frequency and distribution of cells expressing estrogen receptor (ER) in cryosections of normal human breast tissue using quantitative microspectrophotometry and the estrogen receptor immunocytochemical assay. We found that the human mammary gland contained a small but distinct population of ER-positive cells, comprising approximately 7% of the total epithelial cell population from all biopsies. Stromal cells were found to be ER negative. The ER-positive cells were distributed as scattered single cells, with the highest frequency and intensity of measured staining in the lobules as compared to the interlobular ducts. Moreover, on the average, 87% of the ER-positive cells were luminal epithelial cells or occupied an intermediate position in the duct wall. The intermediate cells were found not to express basal cell phenotype as determined by combined immunocytochemistry to ER and "common acute lymphoblastic leukemia antigen" selectively decorating myoepithelial cells (B.A. Gusterson et al., J. Natl. Cancer Inst., 77: 343-349, 1986).
Serum levels of glial fibrillary acidic protein correlate to tumour volume of high-grade gliomas (2007)

Serum levels of GFAP demonstrated a linear correlation to tumour volume in patients with high-grade gliomas. GFAP seems to be a more reliable biomarker in patients with high-grade gliomas than the commercially available S-100B.
Mutations that alter the activity of the Rous sarcoma virus protease. (1992)

Mutations designed by analysis of the Rous sarcoma virus (RSV) and human immunodeficiency virus (HIV)-1 protease (PR) crystal structures were introduced into 1) the substrate binding pocket, 2) the substrate enclosing "flaps," and 3) surface loops of RSV PR. Each mutant PR was expressed in Escherichia coli. Changes in activity were detected by following cleavage of a truncated (NC-PR) precursor polypeptide in E. coli and cleavage of synthetic peptide substrates representing RSV and HIV-1 PR cleavage sites in vitro. Mutations in the substrate binding pocket exchanged amino acid residues located close to the substrate in the HIV-1 PR for structurally equivalent residues in the RSV PR. Changing histidine 65 to glycine (H65G) gave an inactive enzyme, while a double mutant R105P,G106V, as well as the triple mutant, H65G,R105P,G106V, produced enzymes which showed significant activity toward a substrate that represented a HIV-1 cleavage site. Mutating the catalytic aspartate (D37S) or an adjacent conserved alanine to threonine (A40T), produced inactive enzymes. In contrast, the substitution A40S was active, but showed a reduced rate of catalysis. Mutations in the flaps of conserved glycines (G69L, G70L) produced inactive PRs. Two extended RSV PR surface loops were shortened to the size found in HIV-1 PR and resulted in drastically reduced activity. These results have confirmed some of the basic predictions made from structural models but have also revealed unexpected roles and interactions in the protein.
In 2 O 3 nanowires as chemical sensors (2003)

We present an approach to use individual In2O3 nanowire transistors as chemical sensors working at room temperature. Upon exposure to a small amount of NO2 or NH3, the nanowire transistors showed a decrease in conductance up to six or five orders of magnitude and also substantial shifts in the threshold gate voltage. These devices exhibited significantly improved chemical sensing performance compared to existing solid-state sensors in many aspects, such as the sensitivity, the selectivity, the response time, and the lowest detectable concentrations. Furthermore, the recovery time of our devices can be shortened to just 30 s by illuminating the devices with UV light in vacuum.
Genomic alterations associated with malignancy in head and neck cancer (1998)

Our data indicate that the CGH patterns of chromosomal imbalances may help to define the malignant potential of head and neck squamous cell carcinomas.
IPCC, 2007: Climate Change 2007: Synthesis Report (2008)

This Synthesis Report is based on the assessment carried out by the three Working Groups (WGs) of the Intergovernmental Panel on Climate Change (IPCC). It provides an integrated view of climate change as the final part of the IPCC's Fourth Assessment Report (AR4).
III. Beobachtungen zur Collectio Corbeiensis und Collectio Bigotiana (Hs. Paris BN lat. 12097 und Hs. Paris BN lat. 2796) (2006)

Article III. Beobachtungen zur Collectio Corbeiensis und Collectio Bigotiana (Hs. Paris BN lat. 12097 und Hs. Paris BN lat. 2796) was published on August 1, 2006 in the journal Zeitschrift der Savigny-Stiftung für Rechtsgeschichte: Kanonistische Abteilung (volume 92, issue 1).
Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25− into CD25+ T regulatory cells (2006)

Indoleamine 2,3-dioxygenase (IDO) is a novel immunosuppressive agent expressed in some subsets of normal and neoplastic cells, including acute myeloid leukemia (AML) cells. Here, we show that IDO expression correlates with increased circulating CD4+CD25+FOXP3+ T cells in patients with AML at diagnosis. In vitro, IDO+ AML cells increase the number of CD4+ CD25+ T cells expressing surface CTLA-4 and FOXP3 mRNA, and this effect is completely abrogated by the IDO inhibitor, 1-methyl tryptophan (1-MT). Purified CD4+CD25+ T cells obtained from coculture with IDO+ AML cells act as T regulatory (T(reg)) cells because they do not proliferate, do not produce interleukin (IL)-2, and inhibit naive T-cell proliferation. Coculture with IDO+AML cells results in the conversion of CD4+CD25- into CD4+CD25+ T cells, which is completely abrogated by 1-MT. Moreover, in mice, intrasplenic injection of IDO+ leukemia/ lymphoma A20 cells induces the expansion of bona fide T(reg) cells by conversion of CD4+CD25- T cells; this effect is counteracted by 1-MT treatment. These data indicate that AML cells induce T-cell tolerance by directly converting CD4+CD25- T cells into CD4+CD25+ T(reg) cells through an IDO-dependent mechanism.
Short-Chain Fatty Acids and Human Colonic Function: Roles of Resistant Starch and Nonstarch Polysaccharides (2001)

Resistant starch (RS) is starch and products of its small intestinal digestion that enter the large bowel. It occurs for various reasons including chemical structure, cooking of food, chemical modification, and food mastication. Human colonic bacteria ferment RS and nonstarch polysaccharides (NSP; major components of dietary fiber) to short-chain fatty acids (SCFA), mainly acetate, propionate, and butyrate. SCFA stimulate colonic blood flow and fluid and electrolyte uptake. Butyrate is a preferred substrate for colonocytes and appears to promote a normal phenotype in these cells. Fermentation of some RS types favors butyrate production. Measurement of colonic fermentation in humans is difficult, and indirect measures (e.g., fecal samples) or animal models have been used. Of the latter, rodents appear to be of limited value, and pigs or dogs are preferable. RS is less effective than NSP in stool bulking, but epidemiological data suggest that it is more protective against colorectal cancer, possibly via butyrate. RS is a prebiotic, but knowledge of its other interactions with the microflora is limited. The contribution of RS to fermentation and colonic physiology seems to be greater than that of NSP. However, the lack of a generally accepted analytical procedure that accommodates the major influences on RS means this is yet to be established.
Strategies for Protein Purification and Characterization A Laboratory Course Manual (1996)

Part 1 Purification of calmodulin. Experiments: activity assays - assay of calmodulin fractions preparation of a tissue extract bulk fractionation ion-exchange chromatography hydrophobic interaction chromatography characterization of calmodulin - calculation of recovery characterization of calmodulin - electrophoresis proteolytic digestion reverse-phase HPLC physical analysis of calmodulin chemical analysis of calmodulin. Preparation of reagents. Part 2 Purification of transcription factor AP-1 from HeLa cells. Experiments: preparation of a nuclear extract from HeLa cells gel filtration chromatography with Sephacryl S-300 HR sequence-specific DNA affinity chromatography DNase 1 footprinting gel-mobility-shift assay preparation of heparin-sepharose CL-2B preparation of reagents. Part 3 Purification of recombinant protein overproduced in escherichia coli. Experiments: breakage of E. coli cells and preparation of inclusion bodies solubilization, refolding, and ion-exchange chromatography of the inclusion body pellet (o32) polyethyleneimine precipitation and immunoaffinity chromatography of the soluble extract (core RNA polymerase o32 complex) quantitation and summary of preparation protein characterization. Protocol development trials - purification of o32 from a bacterial overexpresser preparation of reagents. Part 4 Solubilization and purification of the rat liver insulin receptor. Experiments: isolation of plasma membranes from rat liver solubilization of insulin receptor from membranes lectin affinity chromatography of solubilized receptors insulin affinity chromatography of partially purified receptors cross-linking of insulin receptors with [125I] insulin insulin-stimulated insulin receptor autophosphorylation analysis of insulin receptor glycosylation. Preparation of reagents.
The rehabilitation of gamma (1998)

Gamma characterizes the reproduction of tone scale in an imaging system. Gamma summarizes, in a single numerical parameter, the nonlinear relationship between code value - in an 8-bit system, from 0 through 255 - and physical intensity. Nearly all image coding systems are nonlinear, and so involve values of gamma different from unity. Owing to poor understanding of tone scale reproduction, and to misconceptions about nonlinear coding, gamma has acquired a terrible reputation in computer graphics and image processing. In addition, the world-wide web suffers from poor reproduction of grayscale and color images, due to poor handling of nonlinear image coding. This paper aims to make gamma respectable again.
Hydrogenase of the hyperthermophile Pyrococcus furiosus is an elemental sulfur reductase or sulfhydrogenase: evidence for a sulfur-reducing hydrogenase ancestor. (1993)

Microorganisms growing near and above 100 degrees C have recently been discovered near shallow and deep sea hydrothermal vents. Most are obligately dependent upon the reduction of elemental sulfur (S0) to hydrogen sulfide (H2S) for optimal growth, even though S0 reduction readily occurs abiotically at their growth temperatures. The sulfur reductase activity of the anaerobic archaeon Pyrococcus furiosus, which grows optimally at 100 degrees C by a metabolism that produces H2S if S0 is present, was found in the cytoplasm. It was purified anaerobically and was shown to be identical to the hydrogenase that had been previously purified from this organism. Both S0 and polysulfide served as substrates for H2S production, and the S0 reduction activity but not the H2-oxidation activity was enhanced by the redox protein rubredoxin. The H2-oxidizing and S0-reduction activities of the enzyme also showed different responses to pH, temperature, and inhibitors. This bifunctional "sulfhydrogenase" enzyme can, therefore, dispose of the excess reductant generated during fermentation using either protons or polysulfides as the electron acceptor. In addition, purified hydrogenases from both hyperthermophilic and mesophilic representatives of the archaeal and bacterial domains were shown to reduce S0 to H2S. It is suggested that the function of some form of ancestral hydrogenase was S0 reduction rather than, or in addition to, the reduction of protons.
Comprehensive analysis of common mode EMI for three-phase UPS system (2004)

A comprehensive analysis of common mode (CM) EMI is conducted for three-phase UPS systems. The analysis is based on both the detailed circuit model and the common mode equivalent circuit model. The parasitic component parameters used in the models are extracted for a 20 kVA UPS, which is used in the experimental verification. The CM noise voltage source and coupling paths are identified. The contributions of the stray parameters CM choke, as well as, battery cable are discussed. Some mitigation methods are proposed. The conclusions are validated through experiment results.
A germanium NMOSFET process integrating metal gate and improved hi-κ dielectrics (2004)

A simple and novel self-aligned gate-last MOS process integrating metal gates and high-k dielectrics on Ge has been demonstrated. Improved surface passivation for excellent gate dielectric and field isolation, and n-type dopant incorporation with high surface concentration and shallow junctions has been developed. Conventional VLSI type Ge n-MOSFETs have been fabricated.
The gypsy moth here again (1982)

This pest of forest and shade trees has invaded California in the past and may become a periodic problem.
Bacterial Phosphorylcholine Decreases Susceptibility to the Antimicrobial Peptide LL-37/hCAP18 Expressed in the Upper Respiratory Tract (2000)

A number of pathogens of the upper respiratory tract express an unusual prokaryotic structure, phosphorylcholine (ChoP), on their cell surface. We tested the hypothesis that ChoP, also found on host membrane lipids in the form of phosphatidylcholine, acts so as to decrease killing by antimicrobial peptides that target differences between bacterial and host membranes. In Haemophilus influenzae, ChoP is a phase-variable structure on the oligosaccharide portion of the lipopolysaccharide (LPS). There was a bactericidal effect of the peptide LL-37/hCAP18 on a nontypeable H. influenzae strain, with an increasing selection for the ChoP(+) phase as the concentration of the peptide was raised from 0 to 10 microgram/ml. Moreover, constitutive ChoP-expressing mutants of unrelated strains showed up to 1,000-fold-greater survival compared to mutants without ChoP. The effect of ChoP on resistance to killing by LL-37/hCAP18 was dependent on the salt concentration and was observed only when bacteria were grown in the presence of environmental choline, a requirement for the expression of ChoP on the LPS. Further studies established that there is transcription of the LL-37/hCAP18 gene on the epithelial surface of the human nasopharynx in situ and inducible transcription in epithelial cells derived from the upper airway. The presence of highly variable amounts of LL-37/hCAP18 in normal nasal secretions (<1.2 to >80 microgram/ml) was demonstrated with an antibody against this peptide. It was concluded that ChoP alters the bacterial cell surface so as mimic host membrane lipids and decrease killing by LL-37/hCAP18, an antimicrobial peptide that may be expressed on the mucosal surface of the nasopharynx in bactericidal concentrations.
siRNA Delivery to the Glomerular Mesangium Using Polycationic Cyclodextrin Nanoparticles Containing siRNA (2015)

There is an urgent need for new therapies that can halt or reverse the course of chronic kidney disease with minimal side-effect burden on the patient. Small interfering RNA (siRNA) nanoparticles are new therapeutic entities in clinical development that could be useful for chronic kidney disease treatment because they combine the tissue-specific targeting properties of nanoparticles with the gene-specific silencing effects of siRNA. Recent reports have emerged demonstrating that the kidney, specifically the glomerulus, is a readily accessible site for nanoparticle targeting. Here, we explore the hypothesis that intravenously administered polycationic cyclodextrin nanoparticles containing siRNA (siRNA/CDP-NPs) can be used for delivery of siRNA to the glomerular mesangium. We demonstrate that siRNA/CDP-NPs localize to the glomerular mesangium with limited deposition in other areas of the kidney after intravenous injection. Additionally, we report that both mouse and human mesangial cells rapidly internalize siRNA/CDP-NPs in vitro and that nanoparticle uptake can be enhanced by attaching the targeting ligands mannose or transferrin to the nanoparticle surface. Lastly, we show knockdown of mesangial enhanced green fluorescent protein expression in a reporter mouse strain following iv treatment with siRNA/CDP-NPs. Altogether, these data demonstrate the feasibility of mesangial targeting using intravenously administered siRNA/CDP-NPs.
Treatment of hypoxia‐induced retinopathy with targeted proapoptotic peptidomimetic in a mouse model of disease (2007)

We have previously identified ligands from combinatorial peptide libraries that target tumor vasculature after in vivo selection. These ligands bind to differentially expressed receptors in angiogenic vasculature such as alpha(v)beta3/alpha(v)beta5 integrins, aminopeptidase N, and aminopeptidase A. We hypothesized that we can use these ligands to target angiogenic vasculature in retinopathies. Pathological retinal angiogenesis in conditions such as diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration is a major cause of blindness for which current treatments are inadequate. Here we tested whether known tumor vasculature targeting peptide ligands displayed on bacteriophage particles would home to the proliferating blood vessels of the retina in a standard mouse model of retinopathy of prematurity. We found that activated retinal blood vessels share many of the endothelial and periendothelial cell receptors expressed in tumor vasculature. Furthermore, these vascular receptors--alpha(v) integrins and aminopeptidases--are accessible through the circulation and mediate phage homing and internalization to endothelial and periendothelial cells. Treatment of mice with a peptide containing a alpha(v)beta3/alpha(v)beta5-integrin targeting domain fused to a proapoptotic domain significantly reduced oxygen-induced retinal angiogenesis by selectively inducing activated endothelial cell apoptosis. Targeted proapoptotic peptides may prove useful in the management of angiogenic retinal diseases.
On‐stage liquid‐phase lipid microextraction coupled to nanospray mass spectrometry for detailed, nano‐scale lipid analysis (2012)

The modified instrumentation of a multi-port, on-stage bioworkstation shows considerable versatility by combining nanomanipulation, microextraction and direct NMS for a variety of chemical, biological, industrial, and clinical applications.
Ethanol extract of Poria cocos reduces the production of inflammatory mediators by suppressing the NF-kappaB signaling pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages (2014)

Taken together, our data indicates that EEPC targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, IL-1β, and TNF-α through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of P. cocos as a traditional herbal medicine for treatment of inflammation and its associated disorders.
Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2 (2008)

Drug resistance during chemotherapy is the major obstacle to the successful treatment of many cancers. Here, we report that inhibition of NF-E2-related factor 2 (Nrf2) may be a promising strategy to combat chemoresistance. Nrf2 is a critical transcription factor regulating a cellular protective response that defends cells against toxic insults from a broad spectrum of chemicals. Under normal conditions, the low constitutive amount of Nrf2 protein is maintained by the Kelch-like ECH-associated protein1 (Keap1)-mediated ubiquitination and proteasomal degradation system. Upon activation, this Keap1-dependent Nrf2 degradation mechanism is quickly inactivated, resulting in accumulation and activation of the antioxidant response element (ARE)-dependent cytoprotective genes. Since its discovery, Nrf2 has been viewed as a 'good' transcription factor that protects us from many diseases. In this study, we demonstrate the dark side of Nrf2: stable overexpression of Nrf2 resulted in enhanced resistance of cancer cells to chemotherapeutic agents including cisplatin, doxorubicin and etoposide. Inversely, downregulation of the Nrf2-dependent response by overexpression of Keap1 or transient transfection of Nrf2-small interfering RNA (siRNA) rendered cancer cells more susceptible to these drugs. Upregulation of Nrf2 by the small chemical tert-butylhydroquinone (tBHQ) also enhanced the resistance of cancer cells, indicating the feasibility of using small chemical inhibitors of Nrf2 as adjuvants to chemotherapy to increase the efficacy of chemotherapeutic agents. Furthermore, we provide evidence that the strategy of using Nrf2 inhibitors to increase efficacy of chemotherapeutic agents is not limited to certain cancer types or anticancer drugs and thus can be applied during the course of chemotherapy to treat many cancer types.