gebhart/patrepeval huggingface dataset:
Activity of Sulfonium Bisphosphonates on Tumor Cell Lines (2007)

We investigated three series of sulfonium bisphosphonates for their activity in inhibiting the growth of three human tumor cell lines. The first series consisted of 6 cyclic sulfonium bisphosphonates, the most active species having an (average) IC50 of 89 microM. The second consisted of 10 phenylalkyl and phenylalkoxy bisphosphonates, the most active species having an IC50 of 18 microM. The third series consisted of 17 n-alkyl sulfonium bisphosphonates, the most active species having an IC50 of approximately 240 nM. Three QSAR models showed that the experimental cell growth inhibition results could be well predicted. We also determined the structures of one sulfonium bisphosphonate bound to farnesyl diphosphate synthase, finding that it binds exclusively to the dimethylallyl diphosphate binding site. These results are of interest since they show that sulfonium bisphosphonates can have potent activity against a variety of tumor cell lines, the most active species having IC50 values much lower than conventional nitrogen-containing bisphosphonates.
Bimodal modulation of the botulinum neurotoxin protein-conducting channel (2009)

Clostridium botulinum neurotoxin (BoNT) is the causative agent of botulism, a neuroparalytic disease. We describe here a semisynthetic strategy to identify inhibitors based on toosendanin, a traditional Chinese medicine reported to protect from BoNT intoxication. Using a single molecule assay of BoNT serotypes A and E light chain (LC) translocation through the heavy chain (HC) channel in neurons, we discovered that toosendanin and its tetrahydrofuran analog selectively arrest the LC translocation step of intoxication with subnanomolar potency, and increase the unoccluded HC channel propensity to open with micromolar efficacy. The inhibitory profile on LC translocation is accurately recapitulated in 2 different BoNT intoxication assays, namely the mouse protection and the primary rat spinal cord cell assays. Toosendanin has an unprecedented dual mode of action on the protein-conducting channel acting as a cargo-dependent inhibitor of translocation and as cargo-free channel activator. These results imply that the bimodal modulation by toosendanin depends on the dynamic interactions between channel and cargo, highlighting their tight interplay during the progression of LC transit across endosomes.
Influence of Nuclear and Cytoplasmic Activity on the Development in Vivo of Sheep Embryos after Nuclear Transplantation (1989)

Reconstituted sheep embryos have been produced by electrofusion-mediated nuclear transplantation in which single cells derived from embryos at the 16-cell (Day 4) and the inner cell mass (ICM) of early blastocyst stage (Day 6) were fused to unfertilized enucleated secondary oocytes. Electrofusion rates were higher with 16-cell blastomeres (82%) than with ICM cells (47%) and when an alternating current (a.c.) preceded the direct current (d.c.) fusing pulse (88% vs. 47%). The addition of cytochalasin B (7.5% micrograms/ml) to the medium for 1 h after electrofusion significantly improved the development to morula-blastocyst stage of reconstituted embryos derived from both 16-cell blastomeres (11% vs. 35%) and ICM cells (0% vs. 56%), indicating that the cytoskeletal mechanisms operating at the time of oocyte activation may affect the developmental potential of exogenous nuclei. Transplantation of 22 reconstituted morulae and blastocysts from both groups into the uteri of recipient ewes led to the development of four lambs (18%) with the phenotype of the nuclear donor breed. These findings indicate that at least some nuclei derived from transcriptionally active embryos are totipotent and able to be reprogrammed to support full-term development when fused to enucleated secondary oocytes.
Structure of Steroidal Saponins from Underground Parts of Allium nutans L. (1999)

Four steroidal glycosides including deltoside and nolinofuroside D and two novel saponins were isolated from underground parts of Allium nutans L. On the basis of the spectral (LSIMS and NMR) analysis, the structures of the new compounds were established as 25R Δ5-spirostan 3β-ol-3-O-{α-L-rhamnopyranosyl(1→2)-[β-d-glucopyranosyl(1→4)]-O-β-d-galactopyranoside} and 25R Δ5-spirostan 1β,3β-diol 1-O-β-d-galactopyranoside. On the basis of the extraction efficiency, the concentration of saponins was established to be about 4% of dry matter, which makes this species a good source of steroidal saponins for commercial use. Keywords: Allium nutans; steroidal saponins; diosgenin; ruscogenin; glycosides
Production of Microspheres with Surface Amino Groups from Blends of Poly(Lactide-co-glycolide) and Poly(ε-CBZ-L-lysine) and Use for Encapsulation (1999)

Microspheres were formed from blends of the biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) together with poly(epsilon-CBZ-L-lysine) (PCBZL) by a double-emulsification/solvent evaporation technique. The size of the microspheres formed by this method was dependent both on the total concentration of the polymers and on the ratio of PLGA to PCBZL. The use of the microspheres for encapsulation was demonstrated by the inclusion of a solution of Texas Red fluorescent dye. Lysine epsilon-amino groups on the surface of the microspheres were deprotected by acid hydrolysis or lithium/liquid ammonia reduction. Acid hydrolysis damaged the surface of the microspheres as assessed by scanning electron microscopy, whereas deprotection by lithium/ammonia produced less damage and allowed the retention of encapsulated dye solution. The surface lysine groups made available on the surface of the microspheres could be used to covalently link a variety of biologically active molecules to alter their in vivo properties and allow targeting to specific cell types.
Directed Evolution of a Thermostable Phosphite Dehydrogenase for NAD(P)H Regeneration (2005)

NAD(P)H-dependent oxidoreductases are valuable tools for synthesis of chiral compounds. The expense of the cofactors, however, requires in situ cofactor regeneration for preparative applications. We have attempted to develop an enzymatic system based on phosphite dehydrogenase (PTDH) from Pseudomonas stutzeri to regenerate the reduced nicotinamide cofactors NADH and NADPH. Here we report the use of directed evolution to address one of the main limitations with the wild-type PTDH enzyme, its low stability. After three rounds of random mutagenesis and high-throughput screening, 12 thermostabilizing amino acid substitutions were identified. These 12 mutations were combined by site-directed mutagenesis, resulting in a mutant whose T50 is 20 degrees C higher and half-life of thermal inactivation at 45 degrees C is >7,000-fold greater than that of the parent PTDH. The engineered PTDH has a half-life at 50 degrees C that is 2.4-fold greater than the Candida boidinii formate dehydrogenase, an enzyme widely used for NADH regeneration. In addition, its catalytic efficiency is slightly higher than that of the parent PTDH. Various mechanisms of thermostabilization were identified using molecular modeling. The improved stability and effectiveness of the final mutant were shown using the industrially important bioconversion of trimethylpyruvate to l-tert-leucine. The engineered PTDH will be useful in NAD(P)H regeneration for industrial biocatalysis.
Extraction of Fetal ECG from Maternal ECG Early in Pregnancy (2008)

Abstract—The paper presents a method and results for extracting fetal ECG (fECG) from maternal ECG (mECG) early in the pregnancy. Extraction is based on a Blind-Adaptive-Filtering approach that overcomes the theoretical limitations in applying conventional Blind Signal Separation (BSS) methods based on ICA (independent component analysis) [1] or AMUSE [2,3] to this signal extraction problem and which greatly limited the extraction of fECG beyond the 30th gestation week (yielding very noisy separation even at these gestation weeks). We present separation results for actual maternal data down to 24th gestation week, which is the earliest for which we were able to obtain raw maternal ECG recordings. Our method has no foreseeable limitation to be successful at earlier gestation weeks. Keywords—Fetal ECG, fetal MCG, blind adaptive filtering, blind signal separation, neural networks, LAMSTAR, independent component analysis, AMUSE
Gellan gum biosynthesis in Sphingomonas paucimobilis ATCC 31461: Genes, enzymes and exopolysaccharide production engineering (2002)

The commercial gelling agent, gellan, is an extracellular polysaccharide (EPS) produced by Sphingomonas paucimobilis ATCC 31461. In recent years, significant progress in understanding the relationship between gellan structure and properties and elucidation of the biosynthesis and engineering of this recent product of biotechnology has been made. This review focuses on recent advances in this field. Emphasis is given to identification and characterization of genes and enzymes involved, or predicted to be involved, in the gellan biosynthetic pathway, at the level of synthesis of sugar-activated precursors, of the repeat unit assembly and of gellan polymerization and export. Identification of several genes, biochemical characterization of the encoded enzymes and elucidation of crucial steps of the gellan pathway indicate that possibilities now exist for exerting control over gellan production at any of the three levels of its biosynthesis. However, a better knowledge of the poorly understood steps and of the bottlenecks and regulation of the pathway, the characterization of the composition, structure and functional properties of gellan-like polymers produced either by the industrial strain under different culture conditions or by mutants are still required for eventual success of the metabolic engineering of gellan production. Journal of Industrial Microbiology & Biotechnology (2002) 29, 170–176 doi:10.1038/sj.jim.7000266
Interferon Action: RNA Cleavage Pattern of a (2′-5′)Oligoadenylate—Dependent Endonuclease (1981)

One of the mediators of interferon action is a latent endoribonuclease (ribonuclease L) that is activated by (2'-5')oligoadenylates. Among the homopolymers of the four common ribonucleotides, activated ribonuclease L degrades at an appreciable rate only polyuridylic acid. In two natural RNA's tested the most frequent ribonuclease L cleavages occur after UA, UG, and UU (A, adenine; U, uracil; and G, guanine) and much less frequent cleavages after CA and AC (C, cytosine).
Mixed oxides SiO2–ZrO2and SiO2–TiO2by a non-hydrolytic sol–gel route (1996)

SiO2–ZrO2 and SiO2–TiO2 mixed oxides with various metal contents have been prepared by a non-hydrolytic sol–gel route involving the condensation between chloride and isopropoxide functions at 110 °C. Well condensed, monolithic gels were obtained in one step, without the use of additives. The Si/M ratio of the oxide may be controlled easily by the composition of the starting mixture. The Si/Zr oxides remained amorphous after calcination for 5 h at 600 °C; IR and 29Si NMR spectroscopy showed a large amount of Si–O–Zr bonds, indicating a homogeneous distribution of the components on the atomic scale. The crystallization of tetragonal zirconia took place at higher temperature; the transformation of tetragonal to monoclinic zirconia was strongly retarded and did not take place after 2 h at 1300 °C. The crystallization of zircon (for a sample containing 50 mol% Zr) started at 1500°C and was completed after 20 h at 1500°C. IR spectroscopy indicated the presence of a limited number of Si–O–Ti bonds in all the Si/Ti oxides after calcination for 5 h at 500 °C. The sample within the stable glass region (5 mol% Ti) appeared perfectly homogeneous: it crystallized at 900 °C as single-phase cristobalite oxide, with Ti4+ ions substituting Si4+ ions at random. On the other hand, the precipitation of anatase was observed for the Si/Ti oxides with a high Ti content (20–50 mol% Ti), which are outside the stable glass region. The transformation of anatase to rutile was not observed even after 2 h at 1300 °C.
Improving the Performance of a Sol−Gel-Entrapped Metal-Binding Protein by Maximizing Protein Thermal Stability before Entrapment (1998)

We show that the performance of a sol−gel-entrapped protein can be improved substantially by maximizing the protein thermodynamic stability so that it can withstand the harsh conditions associated with entrapment. Two mutants of the calcium-binding protein oncomodulin were entrapped into optically clear tetraethyl orthosilicate-derived monoliths which were prepared by a two-step sol−gel processing method. The first mutant contained a single tryptophan residue at position 57 of the native CD binding loop in place of the native tryrosine (Y57W), while the second, more stable mutant contained a higher affinity engineered CD binding loop (CDOM33, with a single Trp residue at position 57). The thermodynamic stability of both proteins could be manipulated by adjusting the level of Ca2+ present during entrapment. Intrinsic tryptophan fluorescence and Tb3+ luminescence (resulting from energy transfer from the Trp residue) were monitored during binding of Tb3+ to examine terbium-binding capacity and response times for both entrapped proteins. Tryptophan fluorescence was also used to study the thermal stability of the entrapped proteins at different calcium levels. Improvements in binding ability, thermal stability, and response times were obtained when CDOM33 or Y57W was entrapped with increasing levels of Ca2+ present during entrapment.
Application of Thomeer Hyperbolas to decode the pore systems, facies and reservoir properties of the Upper Jurassic Arab D Limestone, Ghawar field, Saudi Arabia: A “Rosetta Stone” approach (2008)

ABSTRACT We investigated the basic geological and petrophysical properties of the multimodal pore systems in the Arab D limestone facies in Ghawar field, Saudi Arabia. The study used more than 500 mercury injection capillary pressure (MICP) data, which were type-curve matched using Thomeer Hyperbolas. The new MICP sample data were drawn from 10 cored wells that transect the Ghawar field from north to south and from a previous fieldwide study with 125 MICP samples. These 500 samples have a very rich statistical foundation in that they were selected using only random decimation within each of the facies from more than 3,500 core plugs all with assigned facies. In addition to MICP data and facies, a former, smaller sample set had both facies and Dunham texture codes. A new view of these pore systems emerged, that is built upon the intrinsic, fundamental and separate maximum pore-throat diameter modal elements named porositons. Porositons are stable, recurring and intrinsic modes in the maximum pore-throat diameter of the carbonate pore systems. Analytical results derived from the MICP data showed that the pore systems of the Arab D limestones can be classified based on porositons. The benefits of this new classification are demonstrated by considering in detail the relationships to geological facies, well-log responses, permeability modeling and simple nuclear magnetic resonance (NMR) well-log response. By analogy to the decoding of the Egyptian hieroglyphics using the Rosetta Stone, the use of porositons enables strong connections to be made between the geological facies, petrophysical and reservoir-flow properties of these complex carbonate rocks. The relationships between the new pore systems categories and the facies were thoroughly tested using north-south field trends.
Leukemia stem cells in a genetically defined murine model of blast-crisis CML (2007)

Myeloid leukemia arises from leukemia stem cells (LSCs), which are resistant to standard chemotherapy agents and likely to be a major cause of drug-resistant disease and relapse. To investigate the in vivo properties of LSCs, we developed a mouse model in which the biologic features of human LSCs are closely mimicked. Primitive normal hematopoietic cells were modified to express the BCR/ABL and Nup98/HoxA9 translocation products, and a distinct LSC population, with the aberrant immunophenotype of lineage(-), Kit(+/-), Flt3(+), Sca(+), CD34(+), and CD150(-), was identified. In vivo studies were then performed to assess the response of LSCs to therapeutic insult. Treatment of animals with the ABL kinase inhibitor imatinib mesylate induced specific modulation of blasts and progenitor cells but not stem- cell populations, thereby recapitulating events inferred to occur in human chronic myelogenous leukemia (CML) patients. In addition, challenge of leukemic mice with total body irradiation was selectively toxic to normal hematopoietic stem cells (HSCs), suggesting that LSCs are resistant to apoptosis and/or senescence in vivo. Taken together, the system provides a powerful means by which the in vivo behavior of LSCs versus HSCs can be characterized and candidate treatment regimens can be optimized for maximal specificity toward primitive leukemia cells.
Development of an imaging flow cytometer. (1987)

A cell analyzer that combines the characteristics of image cytometry and flow cytometry is being designed and constructed at the University of Sydney. This paper describes the image acquisition and processing components and some preliminary applications. Cells stained by a fluorescent dye and suspended in a liquid medium are conveyed by a hydraulic system to a flow channel assembly, where they are detected and illuminated by a laser beam. A two-dimensional charge-coupled device is used to acquire the cell images. Image processing and classification is to be carried out by a special-purpose computer comprising an array of four conventional microprocessors and a highly parallel processor consisting of an array of 32 X 32 processing elements. The analyzer will be capable of using morphologic, immunologic and biochemical information to classify and sort up to 500 cells per second. Because of its unique characteristics, the instrument will be of particular use in tumor heterogeneity studies.
Nucleosomes in Serum of Patients with Early Cerebral Stroke (2005)

Even if nucleosomes are nonspecific cell death markers, their release into serum after cerebral stroke correlates with the gross functional status as well as with the infarction volume and can be considered as biochemical correlative to the severity of stroke.
Lenalidomide downregulates the cell survival factor, interferon regulatory factor‐4, providing a potential mechanistic link for predicting response (2011)

Overexpression of the transcription factor interferon regulatory factor-4 (IRF4), which is common in multiple myeloma (MM), is associated with poor prognosis. Patients with higher IRF4 expression have significantly poorer overall survival than those with low IRF4 expression. Lenalidomide is an IMiD immunomodulatory compound that has both tumouricidal and immunomodulatory activity in MM. This study showed that lenalidomide downregulated IRF4 levels in MM cell lines and bone marrow samples within 8 h of drug exposure. This was associated with a decrease in MYC levels, as well as an initial G1 cell cycle arrest, decreased cell proliferation, and cell death by day 5 of treatment. In eight MM cell lines, high IRF4 levels correlated with increased lenalidomide sensitivity. The clinical significance of this observation was investigated in 154 patients with MM. Among MM patients with high levels of IRF4 expression, treatment with lenalidomide led to a significantly longer overall survival than other therapies in a retrospective analysis. These data confirm the central role of IRF4 in MM pathogenesis; indicate that this is an important mechanism by which lenalidomide exerts its antitumour effects; and may provide a mechanistic biomarker to predict response to lenalidomide.
Characterization of sidewall defects in selective epitaxial growth of silicon (1995)

The sidewall defects in high quality selective epitaxial growth (SEG) of silicon were characterized. Three different SEG diode structures were fabricated and the bulk and perimeter defects were characterized through electrical measurements and transmission electron microscopy (TEM). The structures investigated were SEG grown in a 1.2 μm thick wet-etched field oxide, SEG grown in 1.2 μm thick reactive-ion etched field oxide, and SEG grown in a 1.2 μm high and 0.3 μm wide sidewall oxide cavity. The thin sidewall oxide cavity SEG diode showed the best ideality factors and minimum saturation current densities for diodes intersecting the sidewall, indicating the least thermal stress generated at the SEG/oxide sidewall interface during the cool-down period. Cross-sectional TEM micrographs showed no defects in the bulk SEG or at the sidewall, indicating that the thermal stress in all the processes was not high enough to cause plastic deformation, dislocations, or stacking faults.
Transcranial Doppler Pulsatility Index (2010)

BACKGROUND Transcranial Doppler sonography (TCD) assessment of intracranial blood flow velocity has been suggested to accurately determine intracranial pressure (ICP). OBJECTIVE We attempted to validate this method in patients with communicating cerebrospinal fluid systems using predetermined pressure levels. METHODS Ten patients underwent a lumbar infusion test, applying 4 to 5 preset ICP levels. On each level, the pulsatility index (PI) in the middle cerebral artery was determined by measuring the blood flow velocity using TCD. ICP was simultaneously measured with an intraparenchymal sensor. ICP and PI were compared using correlation analysis. For further understanding of the ICP-PI relationship, a mathematical model of the intracranial dynamics was simulated using a computer. RESULTS The ICP-PI regression equation was based on data from 8 patients. For 2 patients, no audible Doppler signal was obtained. The equation was ICP = 23*PI + 14 (R2 = 0.22, P < .01, N = 35). The 95% confidence interval for a mean ICP of 20 mm Hg was −3.8 to 43.8 mm Hg. Individually, the regression coefficients varied from 42 to 90 and the offsets from −32 to +3. The mathematical simulations suggest that variations in vessel compliance, autoregulation, and arterial pressure have a serious effect on the ICP-PI relationship. CONCLUSIONS The in vivo results show that PI is not a reliable predictor of ICP. Mathematical simulations indicate that this is caused by variations in physiological parameters.
A History of New Zealand Literature (2016)

A History of New Zealand Literature traces the genealogy of New Zealand literature from its first imaginings by Europeans in the eighteenth century. Beginning with a comprehensive introduction that charts the growth of, and challenges to, a nationalist literary tradition, the essays in this History illuminate the cultural and political intricacies of New Zealand literature, surveying the multilayered verse, fiction and drama of such diverse writers as Katherine Mansfield, Allen Curnow, Frank Sargeson, Janet Frame, Keri Hulme, Witi Ihimaera and Patricia Grace. Written by a host of leading scholars, this History devotes special attention to the lasting significance of colonialism, biculturalism and multiculturalism in New Zealand literature. A History of New Zealand Literature is of pivotal importance to the development of New Zealand writing and will serve as an invaluable reference for specialists and students alike.