gebhart/patrepeval huggingface dataset:
Enhanced Long-Term Transduction and Multilineage Engraftment of Human Hematopoietic Stem Cells Transduced with Tyrosine-Modified Recombinant Adeno-Associated Virus Serotype 2 (2010)

The search for the ideal stem cell gene therapy vector continues as recognized problems persist. Although recombinant adeno-associated virus serotype 2 (rAAV2) mediates gene transfer into hematopoietic stem cells, identified restrictions to transgene expression reduce overall efficiency. Studies have shown that transduction efficiencies are significantly improved by preventing early proteasomal degradation after mutation of surface-exposed tyrosine residues on the capsid to phenylalanine. Here, we report that transduction of human cord blood CD34(+) stem cells by tyrosine-modified rAAV2 is significantly enhanced both in vitro and in vivo. Serial long-term in vivo bioluminescent imaging of immune-deficient recipients after xenotransplantation of CD34(+) cells transduced with tyrosine-modified rAAV2-luciferase revealed that modification of rAAV2 capsids led to a significant increase in the transduction of human CD34(+) cells, without adversely affecting engraftment capacity, or the ability to undergo multilineage differentiation and self-renewal. Together with observations of sustained high-level transgene expression in vivo and efficient persistence of rAAV genomes in human hematopoietic cells, these results suggest that, because of their ability to bypass restrictions to transduction, tyrosine-modified rAAV vectors, particularly Y500F, Y700F, Y444F, and Y704F, represent highly promising candidates for therapeutic evaluation for diseases of human hematopoietic stem cells.
Bioinformatics Research on Inter-racial Difference in Drug Metabolism I. Analysis on Frequencies of Mutant Alleles and Poor Metabolizers on CYP2D6 and CYP2C19 (2003)

The enzyme activities of CYP2D6 and CYP2C19 show a genetic polymorphism, and the frequency of poor metabolizers (PMs) on these enzymes depends on races. In the present study, the frequencies of mutant alleles and PMs in each race were analyzed based on information from published studies, considering the genetic polymorphisms of CYP2D6 and CYP2C19 as the causal factors of racial and inter-individual differences in pharmacokinetics. As a result, it was shown that there were racial differences in the frequencies of each mutant allele and PMs. The frequencies of PMs on CYP2D6 are 1.9% of Asians and 7.7% of Caucasians, and those of PMs on CYP2C19 are 15.8% of Asians and 2.2% of Caucasians. Based on the results, it was suggested that there would be racial differences in the frequencies of PM subjects whose blood concentrations might be higher for drugs metabolized by these enzymes. Additionally, it was suggested that enzyme activities would vary according to the number of functional alleles even in subjects judged to be extensive metabolizers (EMs). In the bridging study, genetic information regarding CYP2D6 and CYP2C19 of the subjects will help extrapolate foreign clinical data to a domestic population.
Comparative Pharmacokinetics and Pharmacodynamics of the New Propofol Prodrug GPI 15715 and Propofol Emulsion: Retracted (2004)

Compared with propofol emulsion, propofol from GPI 15715 showed different pharmacokinetics and pharmacodynamics, particularly a higher potency with respect to concentration. These differences may indicate an influence of the formulation.
Role of p53 in Hematopoietic Recovery After Cytotoxic Treatment (1998)

Prompt reconstitution of hematopoiesis after cytoreductive therapy is essential for patient recovery and may have a positive impact on long-term prognosis. We examined the role of the p53 tumor suppressor gene in hematopoietic recovery in vivo after treatment with the cytotoxic drug 5-fluorouracil (5-FU). We used p53 knock-out (p53-/-) and wild-type (p53+/+) mice injected with 5-FU as the experimental model. Analysis of the repopulation ability and clonogenic activity of hematopoietic stem cells (HSCs) and their lineage-committed descendants showed a greater number of HSCs responsible for reconstitution of lethally irradiated recipients in p53-/- bone marrow cells (BMCs) recovering after 5-FU treatment than in the corresponding p53+/+ BMCs. In post-5-FU recovering BMCs, the percentage of HSC-enriched Lin- Sca-1(+) c-Kit+ cells was about threefold higher in p53-/- than in p53+/+ cells. Although the percentage of the most primitive HSCs (Lin- Sca-1(+) c-Kit+ CD34(low/-)) did not depend on p53, the percentage of multipotential HSCs and committed progenitors (Lin- Sca-1(+) c-Kit+ CD34(high/+)) was almost fourfold higher in post-5-FU recovering p53-/- BMCs than in their p53+/+ counterparts. The pool of HSCs from 5-FU-treated p53-/- BMCs was exhausted more slowly than that from the p53+/+ population as shown in vivo using pre-spleen colony-forming unit (CFU-S) assay and in vitro using long-term culture-initiating cells (LTC-ICs) and methylcellulose replating assays. Clonogenic activity of various lineage-specific descendants was significantly higher in post-5-FU regenerating p53-/- BMCs than in p53+/+ BMCs, probably because of their increased sensitivity to growth factors. Despite all these changes and the dramatic difference in sensitivity of p53-/- and p53+/+ BMCs to 5-FU-induced apoptosis, lineage commitment and differentiation of hematopoietic progenitors appeared to be independent of p53 status. These studies suggest that suppression of p53 function facilitates hematopoietic reconstitution after cytoreductive therapy by: (1) delaying the exhaustion of the most primitive HSC pool, (2) stimulating the production of multipotential HSCs, (3) increasing the sensitivity of hematopoietic cells to growth factors, and (4) decreasing the sensitivity to apoptosis.
Coenzyme B12 riboswitches are widespread genetic control elements in prokaryotes (2004)

Recent studies have begun to reveal that numerous fundamental metabolic pathways in bacteria are regulated by riboswitches residing within certain messenger RNAs. These riboswitches selectively bind metabolites and modulate gene expression in response to changing ligand concentrations. Previously, we provided evidence that the btuB mRNAs of Escherichia coli and Salmonella typhimurium each carry a coenzyme B12-dependent riboswitch that causes repressed translation of the encoded cobalamin-transport protein at elevated coenzyme concentrations. Herein, we use a phylogenetic analysis to define a consensus sequence and secondary structure model for the ligand- binding domain of this riboswitch class. RNA structures that conform to this model are widespread in both Gram-positive and Gram-negative organisms. In addition, we find that the 5'-untranslated region (5'-UTR) of the cobalamin biosynthesis (cob) operon of S.typhimurium carries an RNA motif that matches this consensus sequence. Biochemical and genetic characterization of this motif confirms that the RNA directly binds coenzyme B12, and that it likely serves as a genetic control element for regulating expression of the 25-gene operon for cobalamin production in this pathogen.
Characterization and Quantification of Mouse Mannan‐Binding Lectins (MBL‐A and MBL‐C) and Study of Acute Phase Responses (2001)

Rat monoclonal antibodies (MoAbs) against mouse mannan-binding lectin (MBL)-A and MBL-C were generated and assays for MBL-A and MBL-C were constructed. This allowed for the quantitative analysis of both proteins for the first time. Previously only MBL-A has been quantified using less standardized methods. In a mouse serum pool the concentrations were now determined at 7.5 microg MBL-A and 45 microg MBL-C per ml. On gel permeation chromatography of mouse serum, MBL-A eluted corresponding to a M(r) of 850 kDa whereas the majority of MBL-C eluted corresponding to a Mr of 950 kDa. On sucrose density gradient centrifugation the sedimentation velocities of MBL-A and MBL-C were estimated at 7.3 S and 10.8 S, respectively. The MBL-A and MBL-C levels in 10 laboratory mice strains were compared and found to vary between 4 microg/ml to 12 microg/ml, and 16 microg/ml to 118 microg/ml, respectively. After the induction of acute phase responses by intraperitoneal injection of either casein or lipopolysaccharide (LPS), MBL-A was found to increase approximately two-fold, with a maximum after 32 h, while MBL-C did not increase significantly. In comparison, serum amyloid A component (SAA) peaked at 15 h with an approximate 100-fold increase.
Multidimensional Databases: Problems and Solutions (2003)

This book strives to be the point of reference for the most important issues in the field of multidimensional databases. This book provides a brief history of the field and distinguishes between what is new in recent research and what is merely a renaming of old concepts. The book reviews past papers and discusses current research projects in the hope of encouraging the search for new solutions to the many problems that are still unsolved. In addition, it outlines the incredible advances in technology and ever increasing demands from users in the most diverse applicative areas such as finance, medicine, statistics, business, and many more
Identification and analysis of domains in proteins (1995)

An automatic algorithm based on inter-residue contacts is presented to identify domains in proteins. The results of the algorithm are compared to an assignment performed by inspection that was guided by the authors' description in the literature. The authors' and the algorithm's assignments for a chain were considered to agree if the same number of domains were identified and if the assignments were the same for at least 95% of the residues. With this criterion, the algorithm agreed with the authors' assignment for 78% of the 284 non-redundant chains considered. When some of the authors' assignments were re-evaluated based on the results of the algorithm, an agreement of 84% was obtained. The algorithm is therefore a useful tool for data validation in domain assignment. The authors assignments of domains were analysed for structural principles of domains. The number of chains forming one, two, three, four and five domains are 197, 67, 13, 6 and 1 respectively. Most domains in multidomain proteins are formed from continuous segments and adopt the same structural class. Distributions of the number of residues and the ellipticity of domains and chains are presented. The relationship between accessible surface area and molecular weight for domains and chains is examined.
Chemical Characterization of 24 Strawberry Cultivars and Selections (1997)

Abstract Fruit quality of 24 selected strawberry cultivars and selections was evaluated. Early season genotypes were: ‘Earliglow,’ NJUS 8219-2, ‘Delmarvel,’ ‘Northeaster,’ MDUS4987, ‘Mohawk;’ mid-season genotypes: ‘Lester,’ ‘Chambly,’ MEUS 16, MEUS 12, MEUS 9, MEUS 8, MDUS 5016, ‘St. Williams,’ ‘Settler,’ ‘Prime-time’ (MDUS 5069), ‘Allstar’; and late season genotypes: ‘Scotland,’ ‘Governor Simcoe,’ ‘Selkirk,’ MDUS 5036, ‘Lateglow,’ ‘Jewel,’ and ‘Latestar’ (MDUS 5084). Soluble solids concentration (SSC), titratable acidity (TA), sugars, organic acids, and ascorbic acid varied greatly among the cultivars and selections, reflecting primarily genetic differences. Fructose, glucose, and sucrose were the three primary sugars, comprising > 65% of fruit total soluble solids. Fruit contained lower amounts of sucrose compared to fructose and glucose, whereas leaves contained similar amounts of fructose, glucose, and sucrose. Citric acid was the major organic acid in fruit and leaves, and showed high correlation to the titratable acid (r = 0.927). Strawberry fruit was also rich in ascorbic acid (70-112 mg/100g fresh weight). Ascorbic acid at the time of fruit harvest was much higher in leaves (233-478 mg/100 g fresh weight) than in fruit. Sugar and organic acid levels were not correlated between fruit and leaves. However, fruit and leaf ascorbic acid contents were correlated in early season genotypes (r = 0.891) and mid-season genotypes (r = 0.750), but not in late season genotypes (r = 0.237).
Amount variability of total and individual Ag-NOR proteins in cells stimulated to proliferate. (1995)

Ribosomal genes are associated with a subset of acidic proteins called Ag-NOR proteins. The amount of nucleolar Ag-NOR proteins varies, depending on nucleolar activity and/or cell proliferation. To understand the linkage between the amount of Ag-NOR proteins, ribosome biogenesis, and cell proliferation, we investigated the variability of Ag-NOR proteins in rRNA-stimulated cells maintained in G1 and in rRNA-stimulated cells entering the mitotic cycle. Rat hepatocytes were stimulated with cortisol for rRNA synthesis (1, 4, and 8 hr) and the cell cycle was induced by hepatectomy in regenerating hepatocytes (3-21 hr). In non-stimulated hepatocytes, nucleolin and protein B23 were the two major Ag-NOR proteins, corresponding to 70% of total Ag-NOR staining. In hepatocytes stimulated for rRNA synthesis in G1, the amount of Ag-NOR proteins was only slightly increased, whereas in cycle-stimulated cells it was increased 3.04-fold. This is the consequence of a differential increase of the major Ag-NOR proteins that appears earlier and is proportionally more important for nucleolin (3.5-fold) than for protein B23 (twofold) and also for the increase of several minor Ag-NOR proteins. We conclude that, in dividing cells, the mean value of the Ag-NOR proteins measured reflects the percentage of cells in the different phases. This could explain why the amount of Ag-NOR proteins can be used as a marker of cell proliferation.
Antigenic relationships among immunoglobulin A1 proteases from Haemophilus, Neisseria, and Streptococcus species (1994)

To investigate the antigenic variation and relationships of immunoglobulin A1 (IgA1) proteases among different species and genera, we examined a comprehensive collection of serine type and metallo-type IgA1 proteases and corresponding antisera in enzyme neutralization assays. Sharing of neutralizing epitopes of metallo-type IgA1 proteases from Streptococcus pneumoniae, Streptococcus sanguis, Streptococcus mitis, and Streptococcus oralis and of serine type IgA1 proteases from Haemophilus and pathogenic Neisseria species was extremely limited. A number of limited to strong cross-reactions in such epitopes were found among serine type IgA1 proteases released by members of the genera Haemophilus and Neisseria, reflecting the common origin of their iga gene. However, the relatively limited prevalence of shared "neutralizing" epitopes of IgA1 proteases from the two genera indicates that they rarely induce immunity to each other. In contrast, extensive sharing of neutralizing epitopes was found between N. meningitidis and N. gonorrhoeae IgA1 proteases, making them potentially attractive vaccine components. Among metallo-type IgA1 proteases, several pneumococcal proteases were found to induce neutralizing antibodies to IgA1 proteases of oral streptococci whereas the opposite was not the case.
In VivoStimulation of Endosteal Bone Formation by Basic Fibroblast Growth Factor in Rats (1993)

Intravenous administration of human basic fibroblast growth factor (bFGF) for 2 weeks stimulated osteoblast proliferation and new bone formation in various skeletal bones in young and aged rats at dosage levels of 0.1 mg/kg/day and greater. Morphometry of the soft X-ray radiograms of cross sections of the tibia indicated about a 20% increase in the calcified bone area of the diaphysis at 0.1 mg/kg/day. The Ca and hydroxyproline contents showed statistically significant increases at this dosage. The new bone formation was found only on the endosteal side, and no periosteal bone formation was found. Similar systemic osteogenic potential was seen after intravenous administration of other growth factors of the FGF family, human acidic FGF and human heparin-binding secretory transforming protein-1. The above results suggest a potential therapeutic role for these growth factors in bone-loss diseases such as osteoporosis.
VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding (2009)

Vitamin K hydroquinone is oxidised to the epoxide form (K>O) during vitamin K-dependent posttranslational gamma-glutamyl carboxylation resulting in biological active so called vitamin K-dependent proteins. In turn, K>O is reduced by the enzyme VKORC1 (vitamin K epoxide reductase complex component 1) to complete the vitamin K cycle. To investigate the biological role of VKORC1 in vivo, we generated VKORC1 knockout mice. Homozygous VKORC1-deficient mice developed normally until birth. Within 2-20 days after birth, the knockout mice died due to extensive, predominantly intracerebral haemorrhage. Bleeding resulted from a severe deficiency of gamma-carboxylated clotting factors. This lethal phenotype could be rescued by oral administration of vitamin K. Additionally, morphometric analysis of the limbs in VKORC1-deficient animals revealed reduced length of bone calcification relative to wild-type control mice. The observed phenotype of VKORC1 knockout mice excludes the existence of other enzymes with VKOR activity that can substitute to supply vitamin K hydroquinone required for maturation of blood clotting factors. Thus, our study underscores the essential role of VKORC1 in vitamin K-dependent gamma-glutamyl carboxylation.
Synchronization of passively mode-locked erbium-doped fiber lasers and its application to optical communication networks (1997)

We synchronized two passively mode-locked erbium-doped fiber lasers using a phase lock loop with a large dynamic range and bandwidth, which is realized by using a novel acoustooptic-modulator-grating scheme. Cross-correlation of the two lasers shows the interlaser jitter is under 2 ps (same as the laser pulse width) for period as long as hours. To prove the quality of phase locking, we apply synchronized lasers in two all-optical network applications, one of which requires the lasers to have the same wavelength and the second requires the lasers to be at different wavelengths. In the single wavelength application, the synchronized lasers drive a cascade of two low-birefringence, polarization maintaining, optical logic gates with switching timing window of 4 and 5 ps, respectively. We obtain nonlinear transmission of /spl sim/50% at a switching energy of 8 pJ and contrast ratio of 16 dB, which are comparable performance as that obtained using a single laser. In the different wavelength application, we use 0.8 ps pulses to switch 2 ps pulses in a two-wavelength nonlinear optical loop mirror demultiplexer with timing window of 5.5 ps. Stable switching is reached at a efficiency as high as 90% at switching energy of 0.8 pJ, and a contrast ratio of 20 dB. Excellent agreement is found between the experimental data and the simulated results, which exclude the timing jitter.
Reduction by coenzyme Q10 of the acute toxicity of adriamycin in mice. (1977)

Pretreatment for four days with coenzyme Q10 (COQ10) reduced the acute toxicity in mice treated with adriamycin. In two sequential protocols, adriamycin allowed only 36 and 42% survival, respectively. Pretreatment with COQ10 allowed 80 and 86% survival, respectively. The differences are significant, p less than 0.05. The mechanism for this reduction in the acute toxicity may be based upon the prevention by the supplementary COQ10 of the inhibition caused by adriamycin to COQ10-dependent enzymes in cardiac and and other tissues. The prospect of diminishing the toxicity of adriamycin in cancer patients remains promising and important.
Polarized entry of canine parvovirus in an epithelial cell line (1989)

The binding and uptake of canine parvovirus (CPV) in polarized epithelial cells were investigated by growing the cells on a permeable support and inoculating with the virus either from the apical or basolateral surface. Binding of radiolabeled CPV occurred preferentially on the basolateral surface. In contrast, when a similar experiment was carried out on nonpolarized A72 cells, virus binding occurred regardless of the direction of virus input. Binding appeared to be specific for CPV and could not be competitively inhibited by either bovine or porcine parvovirus. Analysis of the binding data revealed a high-affinity receptor (10(5) per cell) for CPV on the basolateral surfaces of MDCK cells (Kd, 29 pM). In indirect immunofluorescence studies, virus entered only from the basolateral surfaces of MDCK cells. These results provide evidence for a functional CPV-specific receptor that is expressed only on the basolateral surfaces of polarized epithelial cells, a result that has interesting consequences for viral pathogenesis.
Cholinesterase Inhibition by Potato Glycoalkaloids Slows Mivacurium Metabolism (2000)

These findings support the hypothesis that inhibition of endogenous enzyme systems by dietary factors can influence anesthetic drug metabolism and duration of action. Diet may contribute to the wide variation in recovery time from neuromuscular blockade seen in normal, healthy individuals.
Different attention bias patterns in anorexia nervosa restricting and binge/purge types (2018)

Patients with anorexia nervosa (AN) have been shown to display both elevated anxiety and attentional biases in threat processing. In this study, we compared threat-related attention patterns of patients with AN restricting type (AN-R; n = 32), AN binge/purge type (AN-B/P; n = 23), and healthy controls (n = 19). A dot-probe task with either eating disorder-related or general and social anxiety-related words was used to measure attention patterns. Severity of eating disorder symptoms, depression, anxiety, and stress were also assessed. Patients with AN-R showed vigilance to both types of threat words, whereas patients with AN-B/P showed avoidance of both threat types. Healthy control participants did not show any attention bias. Attention bias was not associated with any of the demographic, clinical, and psychometric parameters introduced. These findings suggest that there are differential patterns of attention allocation in patients with AN-R and AN-B/P. More research is needed to identify what causes/underlies these differential patterns.
Single-Crystal Nanowires of Platinum Can Be Synthesized by Controlling the Reaction Rate of a Polyol Process (2004)

Platinum nanowires of approximately 100 nm in length and approximately 5 nm in diameter have been synthesized by reducing H(2)PtCl(6) with ethylene glycol in the presence of poly(vinyl pyrrolidone) (PVP) and a trace amount of Fe(3+) or Fe(2+). The wires were generated at the final stage of the synthesis, which involved the formation of several intermediate species. The Fe(3+) or Fe(2+) ions had dual functions in the synthesis: they induced aggregation of Pt nanoparticles into larger structures that served as the nucleation sites, and they greatly reduced the reaction rate and supersaturation level to induce anisotropic growth. The reaction mechanism was studied by X-ray photoelectron spectroscopy (XPS) and UV-vis spectral analysis. The Pt nanowires could be readily separated from the surfaces of the agglomerates by sonication and obtained as pure samples by centrifugation.
Achieving Human Parity on Automatic Chinese to English News Translation (2018)

Machine translation has made rapid advances in recent years. Millions of people are using it today in online translation systems and mobile applications in order to communicate across language barriers. The question naturally arises whether such systems can approach or achieve parity with human translations. In this paper, we first address the problem of how to define and accurately measure human parity in translation. We then describe Microsoft's machine translation system and measure the quality of its translations on the widely used WMT 2017 news translation task from Chinese to English. We find that our latest neural machine translation system has reached a new state-of-the-art, and that the translation quality is at human parity when compared to professional human translations. We also find that it significantly exceeds the quality of crowd-sourced non-professional translations.