gebhart/patrepeval huggingface dataset:
Vascular Endothelial Cell Growth Factor Promotes Tyrosine Phosphorylation of Mediators of Signal Transduction That Contain SH2 Domains (1995)

Vascular endothelial cell growth factor (VEGF), an endothelial cell-specific mitogen that plays an important role in angiogenesis, promotes the tyrosine phosphorylation of at least 11 proteins in bovine aortic endothelial cells (BAEC). Proteins immunoprecipitated from lysates of control- and VEGF-stimulated BAEC with antisera to phospholipase C-gamma (PLC-gamma) were fractionated by SDS-polyacrylamide gel electrophoresis and transferred to Immobilon-P. Evaluation of the Western blots with antisera to phosphotyrosine demonstrated that PLC-gamma and two proteins (100 and 85 kDa) that associate with PLC-gamma were phosphorylated in response to VEGF. By using antisera specific to other mediators of signal transduction that contain SH2 domains for immunoprecipitation, it was demonstrated that VEGF promotes phosphorylation of phosphatidylinositol 3-kinase, Ras GTPase activating protein (GAP), and the oncogenic adaptor protein NcK. Proteins of M(r) consistent with the VEGF receptors Flt-1 and Flk-1/KDR were also tyrosine phosphorylated in stimulated cells. Tyrosine-phosphorylated Nck, PLC-gamma, and two GAP-associated proteins, p190 and p62, were in GAP immunoprecipitates of VEGF-stimulated BAEC, and tyrosine-phosphorylated NcK was in phosphatidylinositol 3-kinase immunoprecipitates. These observations suggest that VEGF promotes formation of multimeric aggregates of VEGF receptors with proteins that contain SH2 domains and activate various signaling pathways. VEGF-promoted proliferation of endothelial cells and tyrosine phosphorylation of SH2 domain containing signaling molecules were inhibited by the tyrosine kinase inhibitor genistein.
Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation (2009)

Although 75% of endometrial cancers are treated at an early stage, 15% to 20% of these recur. We performed an integrated analysis of genome-wide expression and copy-number data for primary endometrial carcinomas with extensive clinical and histopathological data to detect features predictive of recurrent disease. Unsupervised analysis of the expression data distinguished 2 major clusters with strikingly different phenotypes, including significant differences in disease-free survival. To identify possible mechanisms for these differences, we performed a global genomic survey of amplifications, deletions, and loss of heterozygosity, which identified 11 significantly amplified and 13 significantly deleted regions. Amplifications of 3q26.32 harboring the oncogene PIK3CA were associated with poor prognosis and segregated with the aggressive transcriptional cluster. Moreover, samples with PIK3CA amplification carried signatures associated with in vitro activation of PI3 kinase (PI3K), a signature that was shared by aggressive tumors without PIK3CA amplification. Tumors with loss of PTEN expression or PIK3CA overexpression that did not have PIK3CA amplification also shared the PI3K activation signature, high protein expression of the PI3K pathway member STMN1, and an aggressive phenotype in test and validation datasets. However, mutations of PTEN or PIK3CA were not associated with the same expression profile or aggressive phenotype. STMN1 expression had independent prognostic value. The results affirm the utility of systematic characterization of the cancer genome in clinically annotated specimens and suggest the particular importance of the PI3K pathway in patients who have aggressive endometrial cancer.
Two‐Photon 3D Optical Data Storage via Fluorescence Modulation of an Efficient Fluorene Dye by a Photochromic Diarylethene (2006)

A two-photon 3D optical storage system based on a photochromic diarylethene (1,2-bis(2-methylbenzo[b]thiophen-3-yl)hexafluorocyclopentene) and a highly efficient two-photon absorbing fluorescent dye (2,7-bis[4-(9,9-didecylfluoren-2-yl)vinyl]phenylbenzothiazole) is demonstrated. The figure shows two-photon fluorescent readout of data recorded by single-photon excitation. The system is suitable for recording data in thick storage media and providing a non-destructive readout method.
High‐value oils from plants (2008)

The seed oils of domesticated oilseed crops are major agricultural commodities that are used primarily for nutritional applications, but in recent years there has been increasing use of these oils for production of biofuels and chemical feedstocks. This is being driven in part by the rapidly rising costs of petroleum, increased concern about the environmental impact of using fossil oil, and the need to develop renewable domestic sources of fuel and industrial raw materials. There is also a need to develop sustainable sources of nutritionally important fatty acids such as those that are typically derived from fish oil. Plant oils can provide renewable sources of high-value fatty acids for both the chemical and health-related industries. The value and application of an oil are determined largely by its fatty acid composition, and while most vegetable oils contain just five basic fatty acid structures, there is a rich diversity of fatty acids present in nature, many of which have potential usage in industry. In this review, we describe several areas where plant oils can have a significant impact on the emerging bioeconomy and the types of fatty acids that are required in these various applications. We also outline the current understanding of the underlying biochemical and molecular mechanisms of seed oil production, and the challenges and potential in translating this knowledge into the rational design and engineering of crop plants to produce high-value oils in plant seeds.
A New Regio-Defined Synthesis of PMEA (1998)

Abstract A new regio-defined synthesis of PMEA was developed suitable for gram-scale synthesis. Key to this synthesis was the early introduction of the phosphonomethoxy ethyl moiety and subsequent cyclization for the construction of the purine ring. This synthesis is regiospecific when compared to the commonly used adenine alkylation methods.
Microvascular Deposition of Complement Membrane Attack Complex in Dermatomyositis (1986)

We examined the role of the complement system in the pathogenesis of dermatomyositis. Using an antibody against the neoantigens of the terminal C5b-9 membrane attack complex, we performed immunocytochemical studies that localized this complex to the intramuscular microvasculature (arterioles and capillaries) of muscle biopsy specimens from 10 of 12 patients (83 percent) with childhood dermatomyositis and 5 of 19 patients (26 percent) with adult dermatomyositis. Fifty-two control specimens, including 14 from patients with polymyositis and 12 from patients with denervation atrophy (a condition known to be associated with necrotic capillaries), showed no deposition of membrane attack complex in the microvasculature. These findings indicate that the complement system is deposited, bound, and activated to completion within the intramuscular microvasculature of patients with dermatomyositis. In addition to providing further evidence for the presence of vasculopathy in dermatomyositis, these findings suggest a primary role for complement in mediating vessel injury in the disease, particularly in its childhood form.
Dissecting the Genetic Components of Adaptation of Escherichia coli to the Mouse Gut (2008)

While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments.
Wide-field-of-view narrow-band spectral filters based on photonic crystal nanocavities (2002)

We describe a novel approach to implementing wide-field-of-view narrow-band spectral filters, using an array of resonant nanocavities consisting of periodic defects in a two-dimensional three-material photonic-crystal nanostructure. We analyze the transmissivity of this type of filter for a range of wavelengths and in-plane incidence angles as a function of the defect's refractive index, the number of layers in the photonic-crystal reflectors, and the period of the defects and find that this structure diminishes the angular sensitivity of the resonance condition relative to that of a standard multilayer filter.
Barrier height estimation of asymmetric metal-insulator-metal tunneling diodes (2013)

A method is developed to estimate barrier heights of an asymmetric metal-insulator-metal (MIM) diode exhibiting Fowler-Nordheim tunneling. The method requires determination of slopes and intercepts of a log(|I(V+Δϕ)2|) versus 1V+Δϕ plot rather than a log(|I(V)2|) versus 1V plot (i.e., a conventional Fowler-Nordheim plot), where I, V, and Δϕ refer to tunneling current, applied voltage, and the difference in barrier heights, respectively. As the value of Δϕ directly impacts the applied electric field magnitude, it is a critical component in barrier height determination from a current-voltage measurement. Conventional Fowler-Nordheim plot analysis does not employ Δϕ, which compromises the accuracy of barrier height estimation when Δϕ≠0. Using the described method, the barrier heights of a ZrCuNiAl/Al2O3/Al MIM diode are estimated to be 1.75 V and 1.07 V, respectively, and the Al2O3 tunneling effective mass is estimated to be 0.47. Additional MIM diodes are analyzed to show that the accuracy of MIM diode barrier height and effective mass estimates is highly sensitive to contamination and/or energy imparted during the deposition of the upper electrode.
Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21‐year, multicentre study of acute hyperammonaemic episodes (2008)

Surprisingly, the majority (66%) of patients with heritable causes of hyperammonaemia present beyond the neonatal period (>30 days). Patients with late-onset presenting disorders exhibited prolonged survival compared to the neonatal-presenting group.
Purification of Erythropoietin (1971)

Erythropoietin, the hormone that is the primary regulator of erythrocyte production, has been purified from anemic-sheep plasma, with a purification factor of more than 1 million. Gel electrophoresis shows that the major contaminant is desialated erythropoietin.
Avicins, a family of triterpenoid saponins fromAcacia victoriae(Bentham), inhibit activation of nuclear factor-κB by inhibiting both its nuclear localization and ability to bind DNA (2001)

Triterpenoid saponins, which are present in leguminous plants and some marine animals, possess a broad range of biological actions. We have earlier reported the extraction of avicins, a family of triterpenoid saponins obtained from the Australian desert tree Acacia victoriae (Leguminosae: Mimosoideae) that inhibit tumor cell growth and induce apoptosis, in part, by perturbing mitochondrial function. These saponins have also been found to prevent chemical-induced carcinogenesis in mice. This study examines the effect of a triterpene mixture (F094) and a single molecular species (avicin G) isolated from the mixture on tumor necrosis factor (TNF)-induced activation of nuclear transcription factor-kappaB (NF-kappaB) in Jurkat cells (human T cell leukemia). Both F094 and avicin G were found to be potent inhibitors of TNF-induced NF-kappaB. Treatment of Jurkat cells with avicin G resulted in a much slower accumulation of the p65 subunit of NF-kappaB into the nucleus whereas the degradation of IkappaBalpha was unaffected. Avicin G also impaired the binding of NF-kappaB to DNA in in vitro binding assays. Treatment of cells with DTT totally reversed the avicin G-induced inhibition of NF-kappaB activity, suggesting that sulfhydryl groups critical for NF-kappaB activation were being affected. Avicin G treatment resulted in decreased expression of NF-kappaB-regulated proteins such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2). Thus, the avicins may prove important for reducing both oxidative and nitrosative cellular stress and thereby suppressing the development of malignancies and related diseases.
Pathological expression of tissue factor confers promising antitumor response to a novel therapeutic antibody SC1 in triple negative breast cancer and pancreatic adenocarcinoma (2017)

The pathological presence of tissue factor (TF) in cancer cells promotes tumor-initiated thrombosis and cancer metastasis. We found that TF is aberrantly present in large percentage of aggressive triple negative breast cancer (TNBC) and pancreatic adenocarcinoma (PaC), two most lethal forms of malignancy that urgently need effective treatment. TF expression in TNBC clustered with higher levels of vimentin, basal-type keratins KRT5/14 and caveolin-1 but lower levels of luminal-type biomarkers. We developed a novel and specific anti-TF therapeutic antibody SC1, which displayed an exceedingly high potency against TF extracellular domain (EC<sub>50</sub>: 0.019 nM), TF-positive TNBC- or PaC cells (EC<sub>50</sub>: 2.5 nM), intracellular protease activated receptor 2 (PAR2) signaling (IC<sub>50</sub>: 2-3 nM) and tumor-initiated coagulation (IC<sub>50</sub>: <10 nM). Depletion of TF or SC1-treatment in TNBC or PaC cells inhibited TF-induced cell migration, lung metastasis and tumor growth <i>in vivo</i>, accompanied by diminished levels of tumor angiogenesis and stromal fibrosis. We further propose TF as a promising target for antibody-drug conjugate (ADC) development based on its rapid and efficient internalization of SC1-drug conjugate. Both SC1-DM1 and SC1-MMAE elicited exquisite cytotoxicity in TF-positive TNBC and PaC cells (IC<sub>50</sub>: 0.02-0.1 nM) but not in TF-negative cells (>100 nM) achieving >5000 fold target selectivity. Following a weekly intravenous administration, SC1-MMAE and its humanized hSC1-MMAE inhibited TNBC- and PaC tumor growth achieving MED of 0.3-1 mg/kg and were both well tolerated. Thus, the prevalent TF expression in TNBC and PaC renders these challenging tumors highly susceptible to TF-targeted treatment and may offer new opportunity in cancer patients.
Ring closure reaction of 4‐(2‐hydroxyanilino)‐2‐phenyl‐5‐pyrimidinecarboxylic acid with acetic anhydride. Synthesis of pyrimido[5,4‐c] [1,5]benzoxazepin‐5(11H)ones (1972)

Abstract Syntheses of 11‐acety1‐2‐phenylpyrimido[5,4‐ c ][1,5]benzoxazepin‐5(11 H )one ( 16a ) and analogs ( 16b,c, 22 ) were described. The reaction of 4‐chloro‐2‐phenyl‐5‐pyrimidinecarboxylic acid ethyl ester ( 7 ) with 2‐aminophenol afforded 4‐(2‐hydroxyanilino)‐2‐phenyl‐5‐pyrimidine‐carboxylic acid ethyl ester ( 8a ). The latter was also prepared by catalytic reduction of 4‐(2‐nitrophenoxy)‐2‐phenyl‐5‐pyrimidinecarboxylic acid ethyl ester ( 9 ), which was obtained from 7 and 2‐nitrophenol. Involvement of 4‐(2‐aminophenoxy)‐2‐phenyl‐5‐pyrimidinecarboxylic acid ethyl ester ( 12a ) in this reduction as an intermediate was demonstrated by an independent synthesis of 12a and its subsequent rearrangement to 8a. Hydrolysis of 8a or 12a gave 4‐(2‐hydroxyanilino)‐2‐phenyl‐5‐pyrimidinecarboxylic acid ( 15a ). Reaction of 15a with acetic anhydride afforded 16a , the first member of a novel ring system, the pyrimido[5,4‐ c ][1,5]‐benzoxazepin. Additional examples ( 16b,c ) were prepared similarly. The corresponding 11‐ethyl derivative ( 22 ) was prepared in similar fashion, starting with 7 and 2‐ethylaminophenol. A possible reaction mechanism for the formation of 16a‐c from 15a‐c and acetic anhydride was discussed.
Strong, Tailored, Biocompatible Shape‐Memory Polymer Networks (2008)

Shape-memory polymers are a class of smart materials that have recently been used in intelligent biomedical devices and industrial applications for their ability to change shape under a predetermined stimulus. In this study, photopolymerized thermoset shape-memory networks with tailored thermomechanics are evaluated to link polymer structure to recovery behavior. Methyl methacrylate (MMA) and poly(ethylene glycol) dimethacrylate (PEGDMA) are copolymerized to create networks with independently adjusted glass transition temperatures (T(g)) and rubbery modulus values ranging from 56 to 92 °C and 9.3 to 23.0 MPa, respectively. Free-strain recovery under isothermal and transient temperature conditions is highly influenced by the T(g) of the networks, while the rubbery moduli of the networks has a negligible effect on this response. The magnitude of stress generation of fixed-strain recovery correlates with network rubbery moduli, while fixed-strain recovery under isothermal conditions shows a complex evolution for varying T(g). The results are intended to help aid in future shape-memory device design and the MMA-co-PEGDMA network is presented as a possible high strength shape-memory biomaterial.
Granulocyte-Macrophage Colony-Stimulating Factor-Armed Oncolytic Measles Virus Is an Effective Therapeutic Cancer Vaccine (2013)

Oncolytic measles viruses (MV) derived from the live attenuated vaccine strain have been engineered for increased antitumor activity, and are currently under investigation in clinical phase 1 trials. Approaches with other viral vectors have shown that insertion of immunomodulatory transgenes enhances the therapeutic potency. In this study, we engineered MV for expression of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). For the first time, therapeutic efficacy and adaptive immune response in the context of MV oncolysis could be evaluated in the previously established immunocompetent murine colon adenocarcinoma model MC38cea. MC38cea cells express the human carcinoembryonic antigen (CEA), allowing for infection with retargeted MV. Intratumoral application of MV-GMCSF significantly delayed tumor progression and prolonged median overall survival compared with control virus-treated mice. Importantly, more than one-third of mice treated with MV-GMCSF showed complete tumor remission and rejected successive tumor reengraftment, demonstrating robust long-term protection. An enhanced cell-mediated tumor-specific immune response could be detected by lactate dehydrogenase assay and interferon-γ enzyme-linked immunospot assay. Furthermore, MV-GMCSF treatment correlated with increased abundance of tumor-infiltrating CD3(+) lymphocytes analyzed by quantitative microscopy of tumor sections. These findings underline the potential of oncolytic, GM-CSF-expressing MV as an effective therapeutic cancer vaccine actively recruiting adaptive immune responses for enhanced therapeutic impact and tumor elimination. Thus, the treatment benefit of this combined immunovirotherapy approach has direct implications for future clinical trials.
Mild and Efficient Conjugation of Rabbit Fab' and Horseradish Peroxidase Using a Maleimide Compound and Its Use for Enzyme Immunoassay (1982)

A mild and efficient procedure for conjugating rabbit Fab' and horseradish peroxidase using a maleimide compound was developed. The enzyme was treated with N-hydroxysuccinimide ester of N-(4-carboxycyclohexylmethyl) maleimide to introduce maleimide groups. Then, the maleimide-enzyme was allowed to react with thiol groups of Fab', and the conjugate formed was separated from unreacted components by gel filtration with Ultrogel AcA 44. In the peak fraction of the separated conjugate, 98% of peroxidase was associated with Fab' and 90% of antibodies was associated with peroxidase. The recoveries in the conjugate of peroxidase and Fab' incubated for conjugation were 65-74%. The conjugate formed appeared to be largely monomeric. Both the enzyme activity and antigen-binding activity of Fab' were fairly well preserved in the conjugate. The cross-link formed was stable at 4 degrees C at least 6 months. Use of the conjugates obtained by this method gave greater sensitivity in sandwich enzyme immunoassay for human ferritin and human thyroid-stimulating hormone than conjugates prepared by the periodate method. The conjugation using N-hydroxysuccinimide ester of m-maleimidobenzoic acid provided a similar monomeric preparation but was less efficient.
Fluorescence Study of Inclusion Complexes between Star-Shaped Cholic Acid Derivatives and Polycyclic Aromatic Fluorescent Probes and the Size Effects of Host and Guest Molecules (2008)

Star-shaped host molecules containing two, three, and four cholic acid moieties have been used to form inclusion complexes with polycyclic aromatic hydrocarbon probes (guests) varying in size from four (pyrene) to five (benzo(e)pyrene) and seven aromatic rings (coronene) and investigated by steady-state fluorescence measurements and fluorescence lifetime techniques. The results indicated that these hydrophobic guest probes prefer to locate in the hydrophobic cavities formed by the host molecules in an aqueous solution. Further studies showed that the stoichiometric ratios of the complexes depended on the relative size of both the host and the guest. The complexes of 1:1 ratio (guest:host) were formed between pyrene and the host molecules of different sizes, while the complexes of 1:2 ratio (guest:host) were found for coronene in all cases. For benzo(e)pyrene with an intermediate size, the complexes with 1:1 and 1:2 ratios (guest:host) were formed depending on the relative sizes of the host molecules. The stability of the inclusion complexes was observed to change with the solvent polarity, indicative of an adaptation of the hydrophobicity of the host pockets to the polarity of the solvent. The formation of the complexes was driven by the solvophobic interactions.
Cutting edge: combined treatment of TNF-alpha and IFN-gamma causes redistribution of junctional adhesion molecule in human endothelial cells. (1999)

Proinflammatory cytokines such as TNF-alpha and IFN-gamma induce cell adhesion molecules in endothelial cells and promote transmigration of leukocytes across endothelial cells. However, when those two were administered together, leukocyte transmigration paradoxically decreased. We cloned a human and bovine homologue of the junctional adhesion molecule (JAM), a novel molecule at the tight junction, and examined the effects of proinflammatory cytokines on JAM in HUVECs. The combined treatment of TNF-alpha plus IFN-gamma caused a disappearance of JAM from intercellular junctions. However, flow cytometry, cell ELISA, and subcellular fractionation analysis demonstrated that the amount of JAM was not reduced. This suggested that JAM changed its distribution in response to proinflammatory cytokines. This redistribution of JAM might be involved in a decrease in transendothelial migration of leukocytes at inflammatory sites.
Evidence for phage-mediated gene transfer among Pseudomonas aeruginosa strains on the phylloplane (1994)

As the use of genetically engineered microorganisms for agricultural tasks becomes more frequent, the ability of bacteria to exchange genetic material in the agricultural setting must be assessed. Transduction (bacterial virus-mediated horizontal gene transfer) is a potentially important mechanism of gene transfer in natural environments. This study investigated the potential of plant leaves to act as surfaces on which transduction can take place among microorganisms. Pseudomonas aeruginosa and its generalized transducing bacteriophage F116 were used as a model system. The application of P. aeruginosa lysogens of F116 to plant leaves resulted in genetic exchange among donor and recipient organisms resident on the same plant. Transduction was also observed when these bacterial strains were inoculated onto adjacent plants and contact was made possible through high-density planting.