gebhart/patrepeval huggingface dataset:
Resistance to small molecule inhibitors of epidermal growth factor receptor in malignant gliomas. (2003)

Epidermal growth factor (EGF) receptor (EGFR) is commonly amplified and/or mutated in high-grade gliomas. Abnormal signaling from this receptor tyrosine kinase is believed to contribute to the malignant phenotypes seen in these tumors. Highly specific small molecule inhibitors of this receptor tyrosine kinase have been developed and may potentially improve the treatment of these highly aggressive brain tumors. A glioma cell line overexpressing EGFR was developed to mimic the situation of a malignant glioma with amplified EGFR, and this line was used to characterize the response to specific EGFR inhibitors. Treatment of our in vitro glioma model with the EGFR kinase inhibitors ZD1839 (Iressa) or PD153035, synthetic anilinoquinazolines with high specificity for EGFR, resulted in significant suppression of EGFR autophosphorylation even with very low levels of drug. However, significantly higher levels of drug were required to fully inhibit signaling through the phosphatidylinositol 3'-kinase/AKT and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) pathways. Interestingly, not all downstream signaling pathways displayed this resistance to inhibition. EGF-dependent activation of signal transducers and activators of transcription-3 occurred at low doses of EGFR inhibitors. The uncoupling of EGFR autophosphorylation and signaling through AKT and ERK was not dependent on EGFR overexpression. In addition, although this response was seen in other glioma and the SK-BR3 breast cancer cell lines, it was not universally present. The SQ20B head and neck squamous carcinoma cell line demonstrated loss of EGF-dependent AKT and ERK activation even at low doses of inhibitor. Despite significant loss of EGF-dependent autophosphorylation, the inability of low levels of EGFR inhibitor to suppress some downstream signaling pathways in our model glioma cell line permitted continued EGF-responsive decreases in the expression of the cyclin-dependent kinase inhibitor p27KIP and EGF-dependent proliferation/cell cycle progression. Although the mechanism responsible for the differential sensitivity of the various signal transduction pathways to EGFR inhibitors remains unclear, signaling through erbB2 does not appear to be involved. The ability of certain tumor cells to maintain signaling through AKT and ERK under EGFR inhibition may represent a potential mechanism of resistance by which a tumor cell may escape the antiproliferative activity of this new class of drugs.
Predicted efficiency of Si wire array solar cells (2009)

Solar cells based on arrays of CVD-grown Si nano- or micro-wires have attracted interest as potentially low-cost alternatives to conventional wafer-based Si photovoltaics [1-6], and single-wire solar cells have been reported with efficiencies of up to 3.4% [7]. We recently presented device physics simulations which predicted efficiencies exceeding 17%, based on experimentally observed diffusion lengths within our wires [8]. However, this model did not take into account the optical properties of a wire array device - in particular the inherently low packing fraction of wires within CVD-grown wire arrays, which might limit their ability to fully absorb incident sunlight. For this reason, we have combined a device physics model of Si wire solar cells with FDTD simulations of light absorption within wire arrays to investigate the potential photovoltaic efficiency of this cell geometry. We have found that even a sparsely packed array (14%) is expected to absorb moderate (66%) amounts of above-bandgap solar energy, yielding a simulated photovoltaic efficiency of 14.5%. Because the wire array comprises such a small volume of Si, the observed absorption represents an effective optical concentration, which enables greater operating voltages than previously predicted for Si wire array solar cells.
Synthetic Toll-Like Receptor 4 Agonist Enhances Vaccine Efficacy in an Experimental Model of Toxic Shock Syndrome (2007)

The development of new protein subunit vaccines has stimulated the search for improved adjuvants to replace traditional aluminum-containing products. We investigated the adjuvant effects of a synthetic Toll-like receptor 4 (TLR4) agonist on vaccine efficacy in an experimental model of toxic shock syndrome. The TLR4 agonist E6020 has a simplified structure consisting of a hexa-acylated acyclic backbone. The vaccine examined is a recombinantly attenuated form of staphylococcal enterotoxin B (STEBVax). Using cells stably transfected with TLRs, E6020 transduced signals only through TLR4, suggesting monospecificity, while Escherichia coli 055:B5 lipopolysaccharide activated both the TLR2/6 heterodimer and TLR4. Coadministration of E6020 with STEBVax, by the intramuscular or intranasal route, induced significant levels of immunoglobulin G (IgG) in BALB/c mice. Further, increased IgG production resulted from the combination of E6020 with aluminum hydroxide adjuvant (AH). The antibody response to the vaccine coadministered with E6020 was a mixed Th1/Th2 response, as opposed to the Th2-biased response obtained with AH. Mice vaccinated with STEBVax coadministered with AH, TLR4 agonists, or a combination of both adjuvants were protected from toxic shock. Our data demonstrate the effectiveness of the synthetic TLR4 agonist E6020 as an alternative adjuvant for protein subunit vaccines that may also be used in combination with traditional aluminum-containing adjuvants.
Nuclear Factor-κB–Related Serum Factors as Longitudinal Biomarkers of Response and Survival in Advanced Oropharyngeal Carcinoma (2007)

Pretreatment VEGF levels and longitudinal change in IL-6, IL-8, VEGF, HGF, and GRO-1 may be useful as biomarkers for response and survival in patients with locally advanced oropharyngeal and head and neck SCC treated with chemoradiation.
Novel therapeutic strategies for patients with triple-negative breast cancer (2016)

Triple-negative breast cancer (TNBC) represents a very heterogeneous group of breast diseases. Currently, the backbone of therapy for TNBC is mainly chemotherapy as there are no effective specific targeted agents approved to treat TNBC. Despite initial responses to chemotherapy, resistance frequently and rapidly develops and metastatic TNBC has a poor prognosis. Therefore, new targeted strategies are, accordingly, urgently needed. This article discusses the recent developments in targeted agents explored for TNBC, aiming to offer novel therapeutic strategies that can potentially assist in designing personalized therapeutics in the future as well as provide the basis for further research in an attempt to target TNBC.
Oligosaccharides and galactosyl cyclitols in seed desiccation tolerance (1997)

Abstract Soluble carbohydrates are one of multiple components required for the acquisition of desiccation tolerance during seed development and maturation. Sucrose and the raffinose series of oligosaccharides have been extensively studied in relation to seed desiccation tolerance. These galactosyl sucrose oligosaccharides are present in viable tissues of many edible seeds, especially the legumes, and contribute to flatulence after ingestion. A reduction in oligosaccharides of the raffinose series is desired by nutritionists but, if present at less than a threshold level, this this may result in reduced desiccation tolerance and storability of seeds. Some seeds that have very low amounts of raffinose and stachyose accumulate galactosyl cyclitols and small amounts of free cyclitols. Galactosyl cyclitols present in various seeds include galactosyl or methyl derivatives of myo -inositol, D-pinitol, D- chiro -inositol, D-ononitol, and scyllo -inositol. Castor bean seeds accumulate galactinol and buck-wheat seeds accumulate fagopyritol in addition to sucrose. Fagopyritol accumulation is associated with the acquisition of desiccation tolerance in buckwheat seeds. The galactosyl sucrose and galactosyl cyclitol soluble carbohydrates in maturing seeds have been proposed to have various roles in desiccation tolerance including non-toxic and non-reducing forms of seed storage products and intracellular osmotic agents contributing to the structural stability of organelles, membranes, enzymes and proteins, other macromolecules, and the glassy state. Ether derivatives of cyclitols may form liquid crystals. Methyl ether derivatives of cyclitols may have roles as cryoprotectants, desiccation protectants, and hydroxyl radical scavengers.
Serum sex hormone levels in pre- and postmenopausal breast cancer patients. (2009)

There were no statistically significant findings among the premenopausal cases. In postmenopausal women, serum progesterone and testosterone levels were significantly associated positively with the odds of having breast cancer.
Fractionized Milk Composition During Removal of Colostrum and Mature Milk (2003)

Experiments were designed to study compositional differences in colostrum and mature milk and during the course of milk removal. Fractionized milk samples during the course of machine milking were analyzed in single (right rear) quarters in the cisternal fraction, after 25, 50, 75, and 100% of spontaneously removed milk, in residual milk, and in composite samples from all quarters on d 2 (colostrum) and in wk 4 (mature milk) of lactation. Somatic cell counts; concentrations of dry matter, total protein, insulin-like growth factor-I, insulin, prolactin, tumor necrosis factor-alpha, Na, and Cl; gamma-glutamyltransferase activity; and electrical conductivity were higher, whereas lactose concentration was lower on d 2 than in wk 4. Concentrations of fat, potassium chloride, and osmolarity did not differ between lactational periods. During the course of milking, concentrations of dry matter, fat, lactose, and potassium, and osmolarity increased, whereas somatic cell counts, protein, insulin like-growth factor-I, insulin, prolactin, and sodium concentrations, electrical conductivity and gamma-glutamyltransferase activity decreased on d 2, and protein, sodium, and electrical conductivity decreased in wk 4. In conclusion, various milk constituents differed considerably between lactational periods (colostrum and mature milk). Milk isotonicity was only in part associated with lactose concentration. Electrical conductivity was associated with Na, K, and fat concentrations and was highest in the cisternal fraction. Changes in milk constituents during milking need to be considered if milk samples are taken for analytical purposes and to evaluate the health status of the udder.
Human lysosomal α-glucosidase: functional characterization of the glycosylation sites (1993)

N-linked glycosylation is one of the important events in the post-translational modification of human lysosomal alpha-glucosidase. Phosphorylation of mannose residues ensures efficient transport of the enzyme to the lysosomes via the mannose 6-phosphate receptor. The primary structure of lysosomal alpha-glucosidase, as deduced from the cDNA sequence, indicates that there are seven potential glycosylation sites. We have eliminated these sites individually by site-directed mutagenesis and thereby demonstrated that all seven sites are glycosylated. The sites at Asn-882 and Asn-925 were found to be located in a C-terminal propeptide which is cleaved off during maturation. Evidence is presented that at least two of the oligosaccharide side chains of human lysosomal alpha-glucosidase are phosphorylated. Elimination of six of the seven sites does not disturb enzyme synthesis or function. However, removal of the second glycosylation site at Asn-233 interferes dramatically with the formation of mature enzyme. The mutant precursor is synthesized normally and assembles in the endoplasmic reticulum, but immunoelectron microscopy reveals a deficiency of alpha-glucosidase in the Golgi complex and in the more distal compartments of the lysosomal transport pathway.
Equivalent Circuits for Discontinuities in Transmission Lines (1944)

Exact equivalent circuits for several types of discontinuities in parallel-plane transmission lines are obtained by Hahn's method of matching electromagnetic-wave solutions. Values of lumped elements to be used in these are given in curve form, with rules for using results in the corresponding coaxial-line problems. Experimental checks are reported, which verify results of the calculations and stress the importance of the discontinuity capacitances appearing in the equivalent circuits.
Protecting the Physician in HIV Misdiagnosis Cases (1996)

Tom Davis' physician informed him that his HIV test had come out positive, indicating he had the virus that causes Acquired Immune Deficiency Syndrome (AIDS). I was bawling my eyes out, Davis said. . . . gave me a death sentence and walked out.' After one month, Davis learned that the test had fact been a false positive: he did not actually have the disease. Davis brought a suit for negligent infliction of emotional distress against his physician and the hospital, asking for a written apology and symbolic compensation of $400. David Thompson, Davis' lawyer, said: An HIV test means so much more than just sticking a needle someone's arm. With a positive result you may not be able to get insurance, establish a mortgage or buy a car.2 In a more severe case, a man lived with the certainty that he had the HIV virus for nearly six years before learning that he had been misdiagnosed.3 During those years, Lon Blatteau had undergone treatment for AIDS, even taking Azidothymidine-the drug more commonly known as AZT. When he learned of the misdiagnosis, Blatteau filed suit against his physician for negligent infliction of emotional distress. According to attorney David Curtin, someone Blatteau's position is in no man's land. He is HIVnegative but for years he has taken drugs designed for people that are HIV-positive.4 Blatteau said that the misdiagnosis ruined [his] life.5 AIDS is well known to be fatal, and the reaction of those misdiagnosed with HIV is understandably one of anger and dis-
Transcreener™: screening enzymes involved in covalent regulation (2006)

Enzymes that catalyse group transfer reactions comprise a significant fraction of the human proteome and are a rich source of drug targets because of their role in covalent regulatory cycles. Phosphorylation, glycosylation, sulfonation, methylation and acetylation represent some of the key types of group transfer reactions that modulate the function of diverse biomolecules through covalent modification. Development of high-throughput screening methods for these enzymes has been problematic because of the diversity of acceptor substrates. Recently, the authors developed a novel assay platform called Transcreener that relies upon fluorescence detection of the invariant reaction product of a group transfer reaction, usually a nucleotide. This platform enables screening of any isoform in a family of group transfer enzymes, with any acceptor substrate, using the same assay reagents.
MYB: An old oncoprotein with new roles (1995)

Over the last decade, the c-myb gene and its protein product, Myb, have undergone extensive examination and manipulation in hemopoietic tissues. Although it is rarely disputed that, as a transcription factor, Myb regulates cell cycling, proliferation and differentiation, identification of genes directly controlled by Myb has been surprisingly difficult. More recently, genes with promoter regions that contain Myb recognition sequences have been identified, but a direct proliferative response to Myb via these 'target genes' has yet to be demonstrated. Mutagenesis studies have defined domains of the protein which influence its transcriptional activity and transforming potential; however how the molecule interacts with itself and with other cellular factors is only beginning to be understood. A broader examination of c-myb expression in normal and malignant tissues suggests an analogous role for Myb in proliferation, differentiation and transformation of non-hemopoietic tissues.
A Major External Source of Cholinergic Innervation of the Striatum and Nucleus Accumbens Originates in the Brainstem (2014)

Cholinergic transmission in the striatal complex is critical for the modulation of the activity of local microcircuits and dopamine release. Release of acetylcholine has been considered to originate exclusively from a subtype of striatal interneuron that provides widespread innervation of the striatum. Cholinergic neurons of the pedunculopontine (PPN) and laterodorsal tegmental (LDT) nuclei indirectly influence the activity of the dorsal striatum and nucleus accumbens through their innervation of dopamine and thalamic neurons, which in turn converge at the same striatal levels. Here we show that cholinergic neurons in the brainstem also provide a direct innervation of the striatal complex. By the expression of fluorescent proteins in choline acetyltransferase (ChAT)::Cre(+) transgenic rats, we selectively labeled cholinergic neurons in the rostral PPN, caudal PPN, and LDT. We show that cholinergic neurons topographically innervate wide areas of the striatal complex: rostral PPN preferentially innervates the dorsolateral striatum, and LDT preferentially innervates the medial striatum and nucleus accumbens core in which they principally form asymmetric synapses. Retrograde labeling combined with immunohistochemistry in wild-type rats confirmed the topography and cholinergic nature of the projection. Furthermore, transynaptic gene activation and conventional double retrograde labeling suggest that LDT neurons that innervate the nucleus accumbens also send collaterals to the thalamus and the dopaminergic midbrain, thus providing both direct and indirect projections, to the striatal complex. The differential activity of cholinergic interneurons and cholinergic neurons of the brainstem during reward-related paradigms suggest that the two systems play different but complementary roles in the processing of information in the striatum.
Oncogenic mutations in ras create HLA-A2.1 binding peptides but affect their extracellular antigen processing (1997)

Point mutations in oncogene products such as ras may create neoantigenic determinants recognizable by T lymphocytes as tumor antigens, that could be marshalled to eliminate a tumor by inducing specific cytotoxic T lymphocytes (CTL) with an appropriate vaccine. Peptide-pulsed dendritic cells are a promising new approach to cancer vaccines. For such an approach to work, the determinant must be appropriately processed to the right size fragment and be presented by an appropriate HLA molecule. We have investigated both of these issues for a series of ras codon 12 and 13 point mutations that contain sequences predicted to bind to HLA-A2.1, the most common class I HLA molecule. We find that not only do the different mutations affect binding to HLA-A2.1, but also they affect extracellular antigen processing in two ways: by influencing the trimming of flanking residues from the longer sequence and by influencing the susceptibility of the optimal decamer to further proteolytic degradation. The influence of internal residues on cleavage of flanking residues downstream demonstrates the importance of distant interactions between separated amino acid side chains and/or conformational effects in determining antigen processing. These results may be important in designing an effective vaccine to induce mutant ras-specific tumor immunity.
Construction of live vaccines using genetically engineered poxviruses: biological activity of vaccinia virus recombinants expressing the hepatitis B virus surface antigen and the herpes simplex virus glycoprotein D. (1984)

Potential live vaccines using recombinant vaccinia viruses have been constructed for both hepatitis B and herpes simplex. These recombinant vaccinia viruses express cloned genes of the hepatitis B virus surface antigen (HBsAg) or the glycoprotein D from herpes simplex virus (HSV-gD). The HBsAg synthesized in vitro under the regulation of vaccinia virus is secreted from infected cells as a particle of approximately equal to 22 nm diameter with a density of 1.2 g/ml as determined on CsCl gradients. Inoculation of rabbits with the recombinant vaccinia virus that expresses the HBsAg elicits the production of high-titered antibodies. Synthesis of the HSV-gD was detected in tissue culture by radioimmunoassay on unfixed cells, suggesting that the HSV-gD synthesized by the recombinant vaccinia virus is membrane associated. Inoculation of rabbits with the recombinant vaccinia virus expressing HSV-gD resulted in the production of antibodies that reacted with authentic HSV-gD as detected by radioimmunoassay. Furthermore, the anti-serum was shown by plaque-reduction assay to neutralize the infectivity of herpes simplex virus. Immunization of mice with the vaccinia recombinant expressing HSV-gD gave complete protection on subsequent challenge with lethal doses of live herpes simplex virus.
논문 : 2010상해엑스포의 친환경디자인에 관한 연구 -주요 국가관을 중심으로- (2010)

국제박람회는 1851년 런던에서 처음 개최되었고, 엑스포는 인류의 발전상을 보여주고 미래를 전망할 수 있는 세계 3대 국제행사로서 2010년 상해에서 개최되어 192개국에서 참가하였다. 2010상해엑스포의 테마인“도시”는 그 동안 보여주었던 산업화되고 문명화된 도시만을 보여준 것이 아니라 자연, 환경과 더불어 살아가는 의미를 주제관 및 여러 국가관을 통해 보여주었다. 이에 본 연구에서는 친환경디자인 요소가 잘 나타난 한국, 독일, 프랑스, 스페인, 덴마크, 스위스, 영국, 캐나다 등 총 8개 주요 국가관을 중심으로 친환경디자인 요소를 선정하여 분석을 실시하였다. 분석의 주요항목으로는 자연활용설계, 생태공간, 친환경건축자재, 그린에너지, 실내 공간, 유지관리 및 서비스였다. 사례가 된 주요 국가관을 통하여 친환경디자인이 엑스포전시장에 적극적으로 도입되고 있고 활용되고 있음을 잘 확인할 수 있었다. 또한 2012여수엑스포에서는 더욱 많은 친환경디자인이 엑스포전시관에서 새롭게 발전된 형태로 등장하리라 기대한다.
CNOT2 depletion disrupts and inhibits the CCR4-NOT deadenylase complex and induces apoptotic cell death (2011)

Eukaryotic mRNA decay is initiated by shortening of the poly (A) tail; however, neither the molecular mechanisms underlying deadenylation nor its regulation is well understood. The human CCR4-NOT complex is a major cytoplasmic deadenylase consisting of a combination of at least nine subunits, four of which have deadenylase activity. The roles of the other subunits remain obscure. Here, we show that CNOT2 depletion by siRNA induces apoptosis. We also show that CNOT2 depletion destabilizes the complex, resulting in the formation of a complex smaller than that formed in control siRNA-treated cells. The deadenylase activity of the CNOT6L subunit-containing complex prepared from CNOT2-depleted cells was less than that from control cells. Intriguingly, the formation of P-bodies, where mRNA degradation supposedly takes place, was largely suppressed in CNOT2-depleted cells. Furthermore, CNOT2 depletion enhanced CHOP mRNA levels, suggesting that endoplasmic reticulum (ER) stress was occurring, which causes apoptosis in a caspase-dependent manner. These results suggest that CNOT2 is important for controlling cell viability through the maintenance of the structural integrity and enzymatic activity of the CCR4-NOT complex.
MDCK (Madin-Darby Canine Kidney) Cells: A Tool for Membrane Permeability Screening (1999)

The goal of this work was to investigate the use of MDCK (Madin-Darby canine kidney) cells as a possible tool for assessing the membrane permeability properties of early drug discovery compounds. Apparent permeability (Papp) values of 55 compounds with known human absorption values were determined using MDCK cell monolayers. For comparison, Papp values of the same compounds were also determined using Caco-2 cells, a well-characterized in vitro model of intestinal drug absorption. Monolayers were grown on 0. 4-microm Transwell-COL membrane culture inserts. MDCK cells were seeded at high density and cultured for 3 days, and Caco-2 cells were cultured under standard conditions for 21 to 25 days. Compounds were tested using 100 microM donor solutions in transport medium (pH 7.4) containing 1% DMSO. The Papp values in MDCK cells correlated well with those in Caco-2 cells (r2 = 0.79). Spearman's rank correlation coefficient for MDCK Papp and human absorption was 0.58 compared with 0.54 for Caco-2 Papp and human absorption. These results indicate that MDCK cells may be a useful tool for rapid membrane permeability screening.