gebhart/patrepeval huggingface dataset:
Altered epidermal growth factor (EGF)-stimulated protein kinase activity in variant A431 cells with altered growth responses to EGF (1982)

To determine the role of epidermal growth factor (EGF)-stimulated protein kinase in the biological effects caused by EGF, tyrosine-specific kinase activity has been quantitated in A431 human epidermoid carcinoma cells and six variant cell lines. Because EGF inhibited proliferation of A431 cells, variants resistant to this inhibition were selected by treatment with mutagen and maintenance for 1 month in 0.1 muM EGF. After cloning and growth for 6-20 generations without EGF, the resistance of the variants to the growth-inhibitory effect of EGF was confirmed. Whereas EGF increased cellular phosphotyrosine content approximately 10-fold in parental A431 cells, EGF caused smaller or undetectable increases in the six variant cell lines. Solubilized membranes from the six variants displayed diminished EGF-stimulated phosphorylation of the EGF receptor and of antibodies to p60(src) (the product of the Rous sarcoma virus transforming gene), which act as an exogenous substrate. The decrease in EGF-stimulated tyrosine-specific protein kinase activity varied from approximately 40% (clone 16) to approximately 8% (clone 18) of parental A431 activity. Phosphorylated EGF receptors from parental and variant cells migrated identically on sodium dodecyl sulfate/polyacrylamide gels. The number of EGF receptors in variant cells decreased in parallel with EGF-stimulated protein kinase activity, so that the specific activity of EGF-stimulated protein kinase per EGF receptor remained constant in the six variant cell lines with reductions in both activities to as low as 10%. These results suggest that this tyrosine-specific protein kinase activity mediates the growth-inhibitory effect of EGF on A431 cells and that both EGF binding and kinase activities reside in the same or tightly associated molecules.
Allele-Specific Amplification in Cancer Revealed by SNP Array Analysis (2005)

Amplification, deletion, and loss of heterozygosity of genomic DNA are hallmarks of cancer. In recent years a variety of studies have emerged measuring total chromosomal copy number at increasingly high resolution. Similarly, loss-ofheterozygosity events have been finely mapped using high-throughput genotyping technologies. We have developed a probe-level allele-specific quantitation procedure that extracts both copy number and allelotype information from single nucleotide polymorphism (SNP) array data to arrive at allele-specific copy number across the genome. Our approach applies an expectation-maximization algorithm to a model derived from a novel classification of SNP array probes. This method is the first to our knowledge that is able to (a) determine the generalized genotype of aberrant samples at each SNP site (e.g., CCCCT at an amplified site), and (b) infer the copy number of each parental chromosome across the genome. With this method, we are able to determine not just where amplifications and deletions occur, but also the haplotype of the region being amplified or deleted. The merit of our model and general approach is demonstrated by very precise genotyping of normal samples, and our allele-specific copy number inferences are validated using PCR experiments. Applying our method to a collection of lung cancer samples, we are able to conclude that amplification is essentially monoallelic, as would be expected under the mechanisms currently believed responsible for gene amplification. This suggests that a specific parental chromosome may be targeted for amplification, whether because of germ line or somatic variation.
Inhibition of the K+channel KCa3.1 ameliorates T cell–mediated colitis (2010)

The calcium-activated K(+) channel KCa3.1 plays an important role in T lymphocyte Ca(2+) signaling by helping to maintain a negative membrane potential, which provides an electrochemical gradient to drive Ca(2+) influx. To assess the role of KCa3.1 channels in lymphocyte activation in vivo, we studied T cell function in KCa3.1(-/-) mice. CD4 T helper (i.e., Th0) cells isolated from KCa3.1(-/-) mice lacked KCa3.1 channel activity, which resulted in decreased T cell receptor-stimulated Ca(2+) influx and IL-2 production. Although loss of KCa3.1 did not interfere with CD4 T cell differentiation, both Ca(2+) influx and cytokine production were impaired in KCa3.1(-/-) Th1 and Th2 CD4 T cells, whereas T-regulatory and Th17 function were normal. We found that inhibition of KCa3.1(-/-) protected mice from developing severe colitis in two mouse models of inflammatory bowel disease, which were induced by (i) the adoptive transfer of mouse naïve CD4 T cells into rag2(-/-) recipients and (ii) trinitrobenzene sulfonic acid. Pharmacologic inhibitors of KCa3.1 have already been shown to be safe in humans. Thus, if these preclinical studies continue to show efficacy, it may be possible to rapidly test whether KCa3.1 inhibitors are efficacious in patients with inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.
Proteomics for discovery of candidate colorectal cancer biomarkers (2014)

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in Europe and other Western countries, mainly due to the lack of well-validated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early stages. Although it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes, much less is known at the proteome level. Therefore, in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis, prognosis and as therapeutic targets for this malignancy, as well as to elucidate the molecular mechanisms of colorectal carcinogenesis. An important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single study. This review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods, quantitative mass spectrometry-based techniques or protein microarrays. Additionally, we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue, serum and faeces, besides cell lines and murine models, discussing their advantages and disadvantages, and summarize the most frequently identified candidate CRC markers.
Conjugated and Fullerene-Containing Polymers for Electronic and Photonic Applications: Advanced Syntheses and Microlithographic Fabrications (1999)

(1999). Conjugated and Fullerene-Containing Polymers for Electronic and Photonic Applications: Advanced Syntheses and Microlithographic Fabrications. Journal of Macromolecular Science, Part C: Vol. 39, No. 2, pp. 273-387.
Direct Injection of Protamine-protected mRNA: Results of a Phase 1/2 Vaccination Trial in Metastatic Melanoma Patients (2009)

In mice, injection of messenger RNA (mRNA) coding for tumor-associated antigens can induce antitumor immune responses and therefore offers a broadly applicable immunotherapy approach. We injected intradermally protamine-stabilized mRNAs coding for Melan-A, Tyrosinase, gp100, Mage-A1, Mage-A3, and Survivin in 21 metastatic melanoma patients. In 10 patients keyhole limpet hemocyanin (KLH) was added to the vaccine. Granulocyte macrophage colony-stimulating factor was applied as an adjuvant. Endpoints were toxicity and immune responses. No adverse events more than grade II have been observed. During treatment the frequency of Foxp3+/CD4+ regulatory T cells was significantly decreased upon mRNA vaccination in peripheral blood of the patients in the KLH arm, whereas myeloid suppressor cells (CD11b+HLA-DR lo monocytes) were reduced in the patients not receiving KLH. A reproducible increase of vaccine-directed T cells was observed in 2 of 4 immunologically evaluable patients. One of 7 patients with measurable disease showed a complete response. In conclusion, we show here that direct injection of protamine-protected mRNA is feasible and safe. The significant influence of the treatment on the frequency of immunosuppressive cells, the increase of vaccine-directed T cells upon treatment in a subset of patients together with the demonstration of a complete clinical response encourage further clinical investigation of the protamine-mRNA vaccine.
Physiological effects of free fatty acid production in genetically engineered Synechococcus elongatus PCC 7942 (2012)

The direct conversion of carbon dioxide into biofuels by photosynthetic microorganisms is a promising alternative energy solution. In this study, a model cyanobacterium, Synechococcus elongatus PCC 7942, is engineered to produce free fatty acids (FFA), potential biodiesel precursors, via gene knockout of the FFA-recycling acyl-ACP synthetase and expression of a thioesterase for release of the FFA. Similar to previous efforts, the engineered strains produce and excrete FFA, but the yields are too low for large-scale production. While other efforts have applied additional metabolic engineering strategies in an attempt to boost FFA production, we focus on characterizing the engineered strains to identify the physiological effects that limit cell growth and FFA synthesis. The strains engineered for FFA-production show reduced photosynthetic yields, chlorophyll-a degradation, and changes in the cellular localization of the light-harvesting pigments, phycocyanin and allophycocyanin. Possible causes of these physiological effects are also identified. The addition of exogenous linolenic acid, a polyunsaturated FFA, to cultures of S. elongatus 7942 yielded a physiological response similar to that observed in the FFA-producing strains with only one notable difference. In addition, the lipid constituents of the cell and thylakoid membranes in the FFA-producing strains show changes in both the relative amounts of lipid components and the degree of saturation of the fatty acid side chains. These changes in lipid composition may affect membrane integrity and structure, the binding and diffusion of phycobilisomes, and the activity of membrane-bound enzymes including those involved in photosynthesis. Thus, the toxicity of unsaturated FFA and changes in membrane composition may be responsible for the physiological effects observed in FFA-producing S. elongatus 7942. These issues must be addressed to enable the high yields of FFA synthesis necessary for large-scale biofuel production.
Secure RPC authentication (SRA) for TELNET and FTP (1993)

TELNET and FTP currently exchange user authentication (passwords) in plain text, which is easily eavesdropped. Several techniques, such as Kerberos and SPX, have been proposed in draft RFCs to implement secure authentication. These techniques, however, have several drawbacks, including technical complexity, poor vendor support, and organizational problems. This paper presents SRA, a very simple and tested technique based on Secure RPC which, while certainly not as strong as RSA, is reasonably strong, fast, and trivial to implement immediately for both inter and intradomain communication. 2. Background TELNET and FTP currently pass the user authentication across the network in the form of plaintext passwords. These passwords can trivially be eavesdropped with such simple tools as etherfind and tcpdump. During intrusions at Texas A&amp;amp;M University in August 1992, significant amounts of the tools used by the crackers were captured. They had much better tools than simple ones such as these,...
Soluble macromolecular complexes involving bacterial teichoic acids (1975)

Cell wall and membrane teichoic acids from several bacteria formed soluble complexes with polysaccharides and bovine plasma in alkyl alcohol solutions. Polysaccharides which contain different monomeric units and anomeric configurations complexed with the teichoic acids, suggesting that the interaction is relatively nonspecific. Teichoic acids complexed glycogen or bovine plasma albumin in 50 to 97% ethanol solutions. The macromolecular association between teichoic acids and polysaccharides or proteins was independent of teichoic acid size over a threefold molecular weight range. Glycerol phosphates or an acid hydrolysate of teichoic acid would not complex to either glycogen or bovine plasma albumin in ethanol. The optimal interaction between glycogen and the Bacillus subtilis lipoteichoic acid occurred between pH 4.5 and 8.2. The ability of teichoic acids to bind polysaccharides and proteins in moderate dielectric constant solvents suggests that these polymers may serve as complexing agents for hydrophilic molecules found in membranes.
Enhancement of adriamycin delivery to liver metastatic cells with increased tumoricidal effect using liposomes as drug carriers. (1983)

We have investigated the tissue distribution of liposome-entrapped Adriamycin (ADM) in mice with metastatic spread to the liver and spleen after inoculation of J-6456 lymphoma cells. Sonicated phosphatidylserine:phosphatidylcholine:cholesterol liposomes were used as carriers of ADM, based on previous studies on the drug entrapment, stability, and tissue distribution of ADM-containing liposomes of various compositions (A. Gabizon, A. Dagan, D. Goren, Y. Barenholz, and Z. Fuks. Cancer Res., 42: 4734-4739, 1982). Increased hepatic and splenic levels of ADM were found in tumor-bearing mice when the drug was injected in the liposome-entrapped form. Concomitantly, decreased cardiac uptake of ADM was observed in tumor-bearing mice treated with liposome-entrapped ADM. In order to measure the concentration of ADM directly in metastatic cells, J-6456 lymphoma cells were isolated from the liver by Percoll density gradients. It was found that the ADM levels were significantly augmented in tumor cells from mice given injections of liposome-entrapped ADM as compared to those given injections of free ADM at all time intervals checked after drug injection. In addition, the in vitro and in vivo growth ability of these isolated metastatic cells was significantly more impaired when they were obtained from mice receiving liposome-entrapped ADM as compared to mice which received free ADM. The histopathological damage to the normal liver parenchyma of mice treated with liposome-entrapped ADM was mild and confined to discrete foci and was not significantly different from that observed in mice treated with free ADM. These results indicate that liposome delivery may provide an efficient means of improving the therapeutic efficiency of ADM in certain forms of metastatic liver disease, while diminishing the potential hazard of cardiotoxicity.
Large-scale preparation and biochemical characterization of a new high purity factor IX concentrate prepared by metal chelate affinity chromatography (1994)

Metal chelate affinity chromatography on copper-charged Chelating Sepharose has been used to purify a factor IX concentrate from 4,000- to 5,000-kg pools of human plasma, with an overall yield of 194 IU/kg. Unwanted proteins and solvent-detergent reagents added to inactivate lipid-enveloped viruses were removed during the chromatographic step. The freeze-dried product was > 80% pure factor IX with a mean specific activity of > 160 IU/mg protein. The concentrate showed no evidence of clotting factor activation by in vitro tests for potential thrombogenicity or by direct assay for activated factor IX. The concentrate did not exhibit proteolytic activity against a range of synthetic peptide chromogenic substrates. Full functional factor IX activity was retained and there was no evidence of protein degradation. Metal chelate affinity chromatography therefore appears to present less physicochemical challenge to the protein than other factor IX purification methods, while allowing the preparation of a clinical factor IX concentrate at a large scale.
Regulation of Cardiomyocyte Mechanotransduction by the Cardiac Cycle (2001)

Mechanical activation of p44/42 MAPK and MEK1/2, gene expression, and protein synthesis is regulated by the cardiac cycle, suggesting that mechanotransduction at the cellular level may underlie differences between pressure and volume overload of the heart.
Agrobacterium‐mediated transformation of cereals: a promising approach crossing barriers (2006)

Cereal crops have been the primary targets for improvement by genetic transformation because of their worldwide importance for human consumption. For a long time, many of these important cereals were difficult to genetically engineer, mainly as a result of their inherent limitations associated with the resistance to Agrobacterium infection and their recalcitrance to in vitro regeneration. The delivery of foreign genes to rice plants via Agrobacterium tumefaciens has now become a routine technique. However, there are still serious handicaps with Agrobacterium-mediated transformation of other major cereals. In this paper, we review the pioneering efforts, existing problems and future prospects of Agrobacterium-mediated genetic transformation of major cereal crops, such as rice, maize, wheat, barley, sorghum and sugarcane.
Gold Nanoparticle Formation during Bromoaurate Reduction by Amino Acids (2005)

The synthesis and characterization of water-soluble dispersions of gold nanoparticles by the reduction of a potassium tetrabromoaurate precursor solution using the amino acids L-tyrosine, glycyl-L-tyrosine, and L-arginine using alkaline synthesis conditions are reported. The particle sizes determined by small-angle X-ray scattering (SAXS) and high-resolution transmission electron microscopy (HRTEM) measurements are found to be inversely proportional to the rate of particle formation, which was determined by time-resolved UV-visible spectrophotometry measurements, and vary very slowly at intermediate gold concentrations and rapidly at the extremes. Dispersions produced with a mixture of the two amino acids glycyl-L-tyrosine and L-tyrosine showed particle sizes and particle size distributions which were directly proportional to the ratio of the two L-amino acids, thus offering the possibility for control over the properties of the gold nanoparticle dispersions.
Patterning of x-ray masks using the negative-acting resist P(SI-CMS) (1993)

The copolymer of trimethylsilylmethyl methacrylate with chloromethylstyrene [P(SI-CMS)] is a negative electron-beam and deep-UV resist which can withstand erosion in O2-containing plasma environments [J. R. Maldonado, J. Electron. Mater. 19, 6699 (1990)]. Manipulation of its composition and molecular weight allows control of the etch resistance and radiation sensitivity properties. Methods have been developed to provide reproducible synthesis of P(SI-CMS) with molecular weight and composition tailored to specific lithographic demands. For x-ray mask patterning, the copolymer having a 90:10 mole ratio of SI:CMS [P(SI90-CMS10)] and M̄w between 30 000 and 41 000 g/mol has been found to provide an optimal combination of resist sensitivity, dry-etching resistance, and pattern resolution. P(SI90-CMS10) is used to image the Cr–W–Cr metallization layer of a monolithic x-ray mask structure, by subtractive etching techniques [G. K. Celler et al., Appl. Phys. Lett. 59, 3105 (1991); G. K. Cellar et al., J. Vac. Sci. Technol. B 10, 3186 (1992); C. W. Jurgensen et al., J. Vac. Sci. Technol. B 9, 3280 (1991)]. The resist pattern is transferred into chromium with a O2–Cl2 plasma, and then into tungsten with a fluorine-based plasma. Resolution of 0.15 μm (line–space) in the resist has been achieved with 50 keV electron-beam exposure, and 0.20 μm patterns (line–space) have been successfully transferred into the tungsten of the x-ray mask.
Interferons and Inflammation (1987)

The local inflammatory response to exogenous or endogenous agents is regulated by various humoral factors. Amongst these, the cytokines represent a prominent group to which belong not only cytotoxins, chemotactic factors, and cellular growth factors, but also the interferons. Evidence is reviewed indicating that, at the local level, interferon-gamma (IFN-gamma) constitutes a positive factor triggering or promoting the inflammatory response. Studies employing monoclonal antibodies against IFN-gamma indicate that inflammatory agents, such as bacterial endotoxin, induce local production of IFN-gamma, which acts as an up-regulator of the primary phase of the inflammatory response. Antibodies against IFN-alpha/beta, on the contrary, have so far not been found to affect inflammation. Systemic interferons, on the other hand, seem to fulfil a down-regulating role, as evidenced by the observation that exogenously administered IFN-alpha, -beta, and -gamma inhibit local inflammation.
Dislocation Scattering in GaN (1999)

A theory of charged-dislocation-line scattering is developed within the framework of the Boltzmann transport equation. A fit of the theory to temperature-dependent Hall-effect data in GaN gives dislocation densities which are in excellent agreement with those measured by transmission electron microscopy. This work shows that threading edge dislocations in GaN indeed are electrically active, in agreement with recent theoretical predictions.
Pathways for oxidation of high-density lipoprotein in human cardiovascular disease. (2006)

The cardioprotective effect of high-density lipoprotein (HDL) is thought to involve, in part, the membrane-associated ATP-binding cassette transporter ABCA1, which clears cholesterol from lipid-laden macrophages in the artery wall. If HDL is unable to interact with this transporter because of oxidative damage, cholesterol clearance is impaired. Important insights into the mechanisms that oxidize proteins in the human artery wall have come from the mass spectrometric (MS) detection of oxidized amino acids that result from specific reaction pathways. Recent MS studies indicate that HDL isolated from patients with cardiovascular disease contains elevated levels of 3-chlorotyrosine and 3-nitrotyrosine, which are two characteristic products of myeloperoxidase (MPO), a heme enzyme secreted by macrophages. MPO-dependent chlorination of apolipoprotein A-I (apoA-I), the major HDL protein, impairs its ability to remove excess cellular cholesterol by the ABCA1 pathway. Tandem MS analysis of apoA-I has demonstrated that this loss of activity is associated with methionine oxidation and chlorination of a single tyrosine residue. Analysis of mutated forms of apoA-I has implicated lysine residues in the regiospecific chlorination of tyrosine. It is further suggested that the tyrosine chlorination and methionine oxidation of apoA-I impairs ABCA1 transport activity. The crystal structure of lipid-free apoA-I suggests a potential mechanism for rendering this protein dysfunctional. Collectively, these observations indicate that MPO oxidatively damages HDL in humans and suggest that oxidation of specific amino acid residues in apoA-I may contribute to atherogenesis by impairing cholesterol efflux from macrophages.