gebhart/patrepeval huggingface dataset:
Hydroformylation Reactions with Recyclable Rhodium-Complexed Dendrimers on a Resin (2003)

Rhodium-complexed dendrimers supported on a resin were evaluated as catalysts for the hydroformylation of aryl olefins and vinyl esters. The results showed the reactions proceeded very efficiently at room temperature with excellent yields. Outstanding selectivity for the branched aldehydes was also observed in all cases. The dendritic catalysts can be recycled by simple filtration and reused even up to the tenth cycle without loss of activity and selectivity. These results represent a dramatic improvement over those previously described for rhodium-catalyzed (dendrimer and nondendrimer based) hydroformylation reactions.
A Nanoparticle-Based Model Delivery System To Guide the Rational Design of Gene Delivery to the Liver. 2. In Vitro and In Vivo Uptake Results (2005)

In Part 1 of our work (1), four nanoparticles were synthesized specifically for the purpose of identifying design constraints to guide next generation gene delivery to the liver. The four nanoparticles are Gal-50 and Gal-140 (galactosylated 50 and 140 nm nanoparticles) and MeO-50 and MeO-140 (methoxy-terminated 50 and 140 nm nanoparticles). All four particles have the same surface charge, and Gal-50 and Gal-140 have the same surface galactose density (ca. 25-30 pmol/cm2). Here, the hepatocyte uptake in vitro and hepatic distribution in vivo of these four nanoparticles is investigated. With freshly isolated hepatocytes, Gal-50 nanoparticles are taken up to a greater extent than are MeO-50, and both 50 nm beads are taken up to a much greater extent than either of the 140 nm nanoparticles. In mice, about 90% of the in vivo dose of Gal-140 nanoparticles is found within the liver 20 min after tail-vein injection. TEM and immunohistochemistry images confirm that Gal-140 nanoparticles are primarily internalized by Kupffer cells, though isolated examples of a few Gal-140 in hepatocytes are also observed. Gal-50 nanoparticles are overwhelmingly found in vesicles throughout the cytoplasm of hepatocytes, with only isolated examples of Kupffer cell uptake 20 min after tail vein injections in mice. Despite similar surface charge and ligand density, 50 nm nanoparticles are primarily found in hepatocytes while 140 nm nanoparticles are primarily observed in Kupffer cells. These results clearly show that slightly anionic, galactose-PEGylated nanoparticles with 25-30 pmol/cm2 galactose should be about 50 nm in diameter to preferentially target hepatocytes while they should be about 140 nm in diameter to selectively target Kupffer cells.
Irrigation Differentially Impacts Populations of Indigenous Antibiotic-Producing Pseudomonas spp. in the Rhizosphere of Wheat (2012)

This work determined the impact of irrigation on the seasonal dynamics of populations of Pseudomonas spp. producing the antibiotics phenazine-1-carboxylic acid (Phz(+)) and 2,4-diacetylphloroglucinol (Phl(+)) in the rhizosphere of wheat grown in the low-precipitation zone (150 to 300 mm annually) of the Columbia Plateau of the Inland Pacific Northwest. Population sizes and plant colonization frequencies of Phz(+) and Phl(+) Pseudomonas spp. were determined in winter and spring wheat collected during the growing seasons from 2008 to 2009 from selected commercial dryland and irrigated fields in central Washington State. Only Phz(+) bacteria were detected on dryland winter wheat, with populations ranging from 4.8 to 6.3 log CFU g(-1) of root and rhizosphere colonization frequencies of 67 to 100%. The ranges of population densities of Phl(+) and Phz(+) Pseudomonas spp. recovered from wheat grown under irrigation were similar, but 58 to 100% of root systems were colonized by Phl(+) bacteria whereas only 8 to 50% of plants harbored Phz(+) bacteria. In addition, Phz(+) Pseudomonas spp. were abundant in the rhizosphere of native plant species growing in nonirrigated areas adjacent to the sampled dryland wheat fields. This is the first report that documents the impact of irrigation on indigenous populations of two closely related groups of antibiotic-producing pseudomonads that coinhabit the rhizosphere of an economically important cereal crop. These results demonstrate how crop management practices can influence indigenous populations of antibiotic-producing pseudomonads with the capacity to suppress soilborne diseases of wheat.
Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice (2020)

The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.
Defining GM-CSF– and Macrophage-CSF–Dependent Macrophage Responses by In Vitro Models (2012)

GM-CSF and M-CSF (CSF-1) induce different phenotypic changes in macrophage lineage populations. The nature, extent, and generality of these differences were assessed by comparing the responses to these CSFs, either alone or in combination, in various human and murine macrophage lineage populations. The differences between the respective global gene expression profiles of macrophages, derived from human monocytes by GM-CSF or M-CSF, were compared with the differences between the respective profiles for macrophages, derived from murine bone marrow cells by each CSF. Only 17% of genes regulated differently by these CSFs were common across the species. Whether a particular change in relative gene expression is by direct action of a CSF can be confounded by endogenous mediators, such as type I IFN, IL-10, and activin A. Time-dependent differences in cytokine gene expression were noted in human monocytes treated with the CSFs; in this system, GM-CSF induced a more dramatic expression of IFN-regulated factor 4 (IRF4) than of IRF5, whereas M-CSF induced IRF5 but not IRF4. In the presence of both CSFs, some evidence of "competition" at the level of gene expression was observed. Care needs to be exercised when drawing definitive conclusions from a particular in vitro system about the roles of GM-CSF and M-CSF in macrophage lineage biology.
Abstracting Vector Architectures in Library Generators (2014)

We present FGen, a program generator for high performance convolution operations (finite-impulse-response filters). The generator uses an internal mathematical DSL to enable structural optimization at a high level of abstraction. We use FGen as a testbed to demonstrate how to provide modular and extensible support for modern SIMD vector architectures in a DSL-based generator. Specifically, we show how to combine staging and generic programming with type classes to abstract over both the data type (real or complex) and the target architecture (e.g., SSE or AVX) when mapping DSL expressions to C code with explicit vector intrinsics. Benchmarks shows that the generated code is highly competitive with commercial libraries.
Mucoadhesive poly(vinyl alcohol) hydrogels produced by freezing/thawing processes: Applications in the development of wound healing systems (1996)

Ultrapure poly(vinyl alcohol) (PVA) hydrogels were prepared by exposing an aqueous solution of 15 or 20 wt% PVA to repeated cycles of freezing for 6 or 12 h at -20 degrees C and thawing for 2 hours at 25 degrees C. The adhesive characteristics of the PVA gels in contact with a reconstituted mucus surface were quantified using a tensile technique. As the number of freezing/thawing cycles increased, the work of fracture (adhesion) decreased due to the increase in the PVA degree of crystallinity. Crystallinity was determined using differential scanning calorimetry. PVA gels prepared from the 20 wt% solution and exposed to two cycles of freezing/thawing exhibited the largest work of adhesion. Drug delivery studies were conducted with ketanserin, a wound healing enhancer. Release studies were conducted using PVA samples prepared from a 20-wt% solution that were exposed to two or three freezing cycles for 12 h followed by thawing for 2 h. Results from the release of the drug from the PVA sample exposed to two cycles showed that approximately 80% of the ketanserin was released within 4 h.
TNF-α in Cancer Treatment: Molecular Insights, Antitumor Effects, and Clinical Utility (2006)

Tumor necrosis factor alpha (TNF-alpha), isolated 30 years ago, is a multifunctional cytokine playing a key role in apoptosis and cell survival as well as in inflammation and immunity. Although named for its antitumor properties, TNF has been implicated in a wide spectrum of other diseases. The current use of TNF in cancer is in the regional treatment of locally advanced soft tissue sarcomas and metastatic melanomas and other irresectable tumors of any histology to avoid amputation of the limb. It has been demonstrated in the isolated limb perfusion setting that TNF-alpha acts synergistically with cytostatic drugs. The interaction of TNF-alpha with TNF receptor 1 and receptor 2 (TNFR-1, TNFR-2) activates several signal transduction pathways, leading to the diverse functions of TNF-alpha. The signaling molecules of TNFR-1 have been elucidated quite well, but regulation of the signaling remains unclear. Besides these molecular insights, laboratory experiments in the past decade have shed light upon TNF-alpha action during tumor treatment. Besides extravasation of erythrocytes and lymphocytes, leading to hemorrhagic necrosis, TNF-alpha targets the tumor-associated vasculature (TAV) by inducing hyperpermeability and destruction of the vascular lining. This results in an immediate effect of selective accumulation of cytostatic drugs inside the tumor and a late effect of destruction of the tumor vasculature. In this review, covering TNF-alpha from the molecule to the clinic, we provide an overview of the use of TNF-alpha in cancer starting with molecular insights into TNFR-1 signaling and cellular mechanisms of the antitumor activities of TNF-alpha and ending with clinical response. In addition, possible factors modulating TNF-alpha actions are discussed.
Mechanistic Role of Calpains in Postischemic Neurodegeneration (2007)

The calpain family of proteases is causally linked to postischemic neurodegeneration. However, the precise mechanisms by which calpains contribute to postischemic neuronal death have not been fully elucidated. This review outlines the key features of the calpain system, and the evidence for its causal role in postischemic neuronal pathology. Furthermore, the consequences of specific calpain substrate cleavage at various subcellular locations are explored. Calpain substrates within synapses, plasma membrane, endoplasmic reticulum, lysosomes, mitochondria, and the nucleus, as well as the overall effect of postischemic calpain activity on calcium regulation and cell death signaling are considered. Finally, potential pathways for calpain-mediated neurodegeneration are outlined in an effort to guide future studies aimed at understanding the downstream pathology of postischemic calpain activity and identifying optimal therapeutic strategies.
Oral Contraceptives in the United States: Trends in Content and Potency (1987)

Data from the National Prescription Audit, a nationwide pharmaceutical marketing research data base, were reviewed to study changes in the type of oral contraceptives marketed in the US, their content and their relative oestrogen and progestin potency over the 21-year time period of 1964-84. Three major types and 42 brands of oral contraceptives were marketed in the US during this time period. All oral contraceptives dispensed in the US have contained one of nine different progestins and one of two oestrogens or, in the case of the progestin-only pills, no oestrogen at all. A comprehensive classification listing all 42 brands of oral contraceptives by content and strength is presented. Secular changes in oral contraceptive potency are described in terms of a categorization scheme which simultaneously ranks both the oestrogen and progestin potencies of each oral contraceptive. Over the time period studied, oral contraceptives have evolved from high strength, high potency drugs to much lower strength, lower potency drugs. The epidemiological implications of these shifts in oral contraceptive content and potency are discussed.
Discovery of Novel Benzimidazoles as Potent Inhibitors of TIE-2 and VEGFR-2 Tyrosine Kinase Receptors (2007)

We herein disclose a novel chemical series of benzimidazole-ureas as inhibitors of VEGFR-2 and TIE-2 kinase receptors, both of which are implicated in angiogenesis. Structure-activity relationship (SAR) studies elucidated a critical role for the N1 nitrogen of both the benzimidazole (segment E) and urea (segment B) moieties. The SAR results were also supported by the X-ray crystallographic elucidation of the role of the N1 nitrogen and the urea moiety when the benzimidazole-urea compounds were bound to the VEGFR-2 enzyme. The left side phenyl ring (segment A) occupies the backpocket where a 3-hydrophobic substituent was favored for TIE-2 activity.
Total synthesis of parabactin, a spermidine siderophore (1984)

Y. Nagao, T. Miyasaka, Y. Hagiwara and E. Fujita, J. Chem. Soc., Perkin Trans. 1, 1984, 183 DOI: 10.1039/P19840000183
Cloning of an M. tuberculosis DNA fragment associated with entry and survival inside cells (1993)

Mycobacterium tuberculosis infects one-third of the world's human population. This widespread infection depends on the organism's ability to escape host defenses by gaining entry and surviving inside the macrophage. DNA sequences of M. tuberculosis have been cloned; these confer on a nonpathogenic Escherichia coli strain an ability to invade HeLa cells, augment macrophage phagocytosis, and survive for at least 24 hours inside the human macrophage. This capacity to gain entry into mammalian cells and survive inside the macrophage was localized to two distinct loci on the cloned M. tuberculosis DNA fragment.
Electrospun PHBV/collagen composite nanofibrous scaffolds for tissue engineering (2006)

Electrospinning has recently emerged as a leading technique for the formation of nanofibrous structures made of synthetic and natural extracellular matrix components. In this study, nanofibrous scaffolds were obtained by electrospinning a combination of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and type-I collagen in 1,1,1,3,3,3-hexafluoro-2-isopropanol (HIFP). The resulting fibers ranged from 300 to 600 nm in diameter. Their surfaces were characterized by attenuated total reflection Fourier transform infrared spectroscopy, electron spectroscopy for chemical analysis and atomic force microscopy. The PHBV and collagen components of the PHBV/collagen nanofibrous scaffold were biodegraded by PHB depolymerase and a type-I collagenase aqueous solution, respectively. The cell culture experiments indicated that the PHBV/collagen nanofibrous scaffold accelerated the adhesion and growth of NIH3T3 cells more effectively than the PHBV nanofibrous scaffold, thus making the former a good scaffold for tissue engineering.
Folinic acid augmentation of the effects of fluoropyrimidines on murine and human leukemic cells. (1986)

The effects of the fluoropyrimidines on leukemic cells of mouse and human origin have been studied in the presence of folinic acid. This reduced folate enhanced the cytotoxicity and the growth inhibitory potency of 5-fluorouracil (5-FUra) and of 5-fluoro-2'-deoxyuridine (FUdR) against all cell lines examined. The human leukemic cell lines used (two T- and two B-cells) were affected by these fluoropyrimidines only at substantially higher concentrations than were found to be inhibitory to mouse L1210 cells; however, the enhancement of the activity of the fluoropyrimidines occurred over the same range of folinic acid concentrations in mouse and human cells. Whereas the total intracellular folate pool increased continuously with every increment of folinic acid added to the medium, the enhancement of the potency of the fluoropyrimidines was limited. Augmentation of the effects of FUdR exceeded that of 5-fluorouracil in the human leukemic cells studied. The cytotoxicity of the fluoropyrimidines (as defined by cloning efficiency) was enhanced to a greater extent than was growth inhibition so that an impressive lethal synergism was noted; for instance, exposure of L1210 cells to nontoxic concentrations of 5-fluorouracil or FUdR in the presence of folinic acid resulted in a 98 or 99.9% cell kill, respectively. In contrast to previous predictions, the fluoropyrimidines were more inhibitory to mouse leukemic cells containing folate pools that were suboptimal for growth than for folate-replete cells. Growth rate experiments showed that cells exposed to moderate concentrations of FUdR were initially inhibited but recovered with time, whereas in cells exposed to both FUdR and folinic acid, the initial growth inhibitory effects were sustained. We conclude that folinic acid stabilizes the effects of the fluoropyrimidines on thymidylate synthase of both mouse and human leukemic cell populations and that this enhancement is reflected in both inhibition of the growth of and the lethality to these cells. We suggest that only doses of the fluoropyrimidines that are capable of initially inhibiting thymidylate synthase to a high degree will be synergistic with excess reduced folates.
Liuhua 11-1 Field Development: An Innovative Application of Technology (1992)

ABSTRACT Amoco Orient Petroleum Company (Amoco) and Nanhai East Oil Corporation (NHEOC) are currently evaluating the development of the Liuhua 11–1 Field, situated in the South China Sea. The development poses a number of challenges including deep water, harsh environment and a complex reservoir containing a heavy, viscous crude overlying an active aquifer. An imaginative solution to these problems has been identified through the application of existing and new technologies, involving a floating production system, subsea trees with Electric Submersible Pumps (ESPS), wet-mateable electrical power connectors and horizontal well completions. This paper provides an overview of this technology and demonstrates how an innovative design developed to address the unique set of Liuhua 11–1 Field Development. INTRODUCTION The Liuhua 11–1 Field is located in the South China Sea approximately 120 miles (193 km) southeast of Hong Kong. Water depth over the field site averages 1000 feet (305 m). A location map is shown in Figure 1. Following the discovery of the Liuhua 11–1 Field in 1987, Amoco and NHEOC undertook an extensive delineation and appraisal drilling program which concluded in 1989. After further review of the appraisal results, pre-development operations engineering studies commenced in 1991 with the objective of identifying and evaluating the most economic and technically feasible methods of developing the field. It became clear that the Liuhua 11–1 Development posed a particularly complex series of problems that would require the adaptation of existing technology and the application of technology new to the industry. Reservoir evaluations showed that artificial lift in the form of ESPS would be required to lift the heavy (20-22aAPI) crude and that all wells should be horizontal to minimize formation water ingress and optimize recovery rates. Environmental data showed the development site to be in a region of severe typhoon and monsoon activity and, more unexpectedly, subject to internal waves or "solitons" in the1000 feet (305 m) water column, giving rise to subsea currents up to 6 knots down to the seabed. Amoco and NHEOC are currently nearing completion of the pre-development operations engineering studies with the objective of preparing for the submission of an Overall Development Program (ODP) in mid-1992. The prime focus of work has been technology resolution, component feasibility testing and development of cost estimates in order determine field commerciality. The success of the Liuhua 11–1 Field Development is dependent upon the use and application of technology new to the industry. In particular, the development would be the first industry application of ESPS with subsea trees. This has led to the development of a novel tree design to facilitate ESP workover operations and the design and development of an underwater mate able electric power connector for use at the subsea tubing hanger/tree cap interface. This paper gives a brief overview of the background, current status and assessment of the key technological components involved in the development.
Reduction of quinones and phenoxy radicals by extracellular glucose dehydrogenase from Glomerella cingulata suggests a role in plant pathogenicity (2011)

The plant-pathogenic fungus Glomerella cingulata (anamorph Colletotrichum gloeosporoides) secretes high levels of an FAD-dependent glucose dehydrogenase (GDH) when grown on tomato juice-supplemented media. To elucidate its molecular and catalytic properties, GDH was produced in submerged culture. The highest volumetric activity was obtained in shaking flasks after 6 days of cultivation (3400 U l⁻¹, 4.2 % of total extracellular protein). GDH is a monomeric protein with an isoelectric point of 5.6. The molecular masses of the glycoforms ranged from 95 to 135 kDa, but after deglycosylation, a single 68 kDa band was obtained. The absorption spectrum is typical for an FAD-containing enzyme with maxima at 370 and 458 nm and the cofactor is non-covalently bound. The preferred substrates are glucose and xylose. Suitable electron acceptors are quinones, phenoxy radicals, 2,6-dichloroindophenol, ferricyanide and ferrocenium hexafluorophosphate. In contrast, oxygen turnover is very low. The GDH-encoding gene was cloned and phylogenetic analysis of the translated protein reveals its affiliation to the GMC family of oxidoreductases. The proposed function of this quinone and phenoxy radical reducing enzyme is to neutralize the action of plant laccase, phenoloxidase or peroxidase activities, which are increased in infected plants to evade fungal attack.
Homocamptothecins:  Synthesis and Antitumor Activity of Novel E-Ring-Modified Camptothecin Analogues (1998)

Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c, d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.