gebhart/patrepeval huggingface dataset:
Vascular endothelial growth factor and its soluble receptors VEGFR‐1 and VEGFR‐2 in the serum of patients with systemic lupus erythematosus (2003)

We investigated the serum concentration of vascular endothelial growth factor (VEGF) and its two soluble receptors, sVEGFR-1 and sVEGFR-2, in a group of 60 patients with systemic lupus erythematosus (SLE), and 20 healthy controls, using an enzyme-linked immunosorbent assay. We examined a possible association between serum levels of these proteins and certain clinical and laboratory parameters as well as SLE activity. VEGF, sVEGFR-1 and sVEGFR-2 were detectable in all patients with SLE and in all normal individuals. The VEGF level was higher in active SLE (mean, 300.8 pg/ml) than in inactive SLE (mean, 165.9 pg/ml) (p < 0.05) or in the control group (mean, 124.7 pg/ml) (p < 0.04). The highest sVEGFR-1 concentrations were also detected in active SLE patients (mean, 42.2 pg/ml) and the lowest in inactive disease (mean, 32.0 pg/ml) (p < 0.01). In contrast, the levels of sVEGFR-2 were lower in SLE (mean, 12557.6 pg/ml) than in the control group (mean, 15025.3 pg/ml) (p < 0.05). We found a positive correlation between sVEGFR-1 concentration and the SLE activity score p = 0.375 (p < 0.004) and a negative, but statistically insignificant correlation between sVEGFR-2 and SLE activity (p = -0.190, p > 0.05). Treatment with steroids and cytotoxic agents did not influence VEGF or its soluble receptors levels. In conclusion, in SLE patients the levels of VEGF and sVEGFR-1 are higher in patients with active SLE than in inactive disease or healthy persons. In contrast, the level of sVEGFR-2 is lower in active SLE than in inactive disease. The imbalance between VEGF and its soluble receptors may be important in SLE pathogenesis.
Silica‐ and Silsesquioxane‐Containing Polymer Nanohybrids (2005)

The synthesis and characterization of silica and silsesquioxane-containing nanohybrids is described. The use of the sol-gel technique for synthesis is reviewed. The use of other metal oxides to produce similar materials is described. An emphasis on polyimide-containing materials is given. Importance and determination of pore size is discussed.
Review Article Multiparticulates Drug Delivery Systems: A Review (2013)

Pharmaceutical research and development are increasingly focusing on delivery systems which enhance desirable therapeutic objectives while minimising side effects. Recent trends indicate that multiparticulate drug delivery systems are especially suitable for achieving controlled and delayed release oral formulations with low risk of dose dumping. These oral multiparticulate drug delivery systems offer biopharmaceutical advantages with respect to predictable and even distribution and transportation in the gastro-intestinal tract. Pelletization is novel drug delivery system that converts fine powder particles into pellets and it is usefull in order to develop a site-specific drug delivery system. There are different techniques in the preparation of pellets. Consequently, multiparticulate drug delivery systems provide tremendous opportunities for designing new controlled and delayed release oral formulations, thus extending the frontier of future pharmaceutical development.
Investigation of reaction mechanisms by electrospray ionization mass spectrometry: characterization of intermediates in the degradation of phenol by a novel iron/magnetite/hydrogen peroxide heterogeneous oxidation system (2006)

Electrospray ionization (ESI) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) were used to monitor the oxidation of phenol by a novel heterogeneous Fenton system based on a Fe(0)/Fe(3)O(4) composite and H(2)O(2). On-line ESI-MS(/MS) shows that this heterogeneous system promotes prompt oxidation of phenol to hydroquinone, which is subsequently oxidized to quinone, other cyclic poly-hydroxylated intermediates and an acyclic carboxylic acid. A peroxide-type intermediate, probably formed via an electrophilic attack of HOO(.) on the phenol ring, was also intercepted and characterized. ESI-MS(/MS) monitoring of the oxidation of two other model aromatic compounds, benzene and chlorobenzene, indicates the participation of analogous intermediates. These results suggest that oxidation by the heterogeneous system is promoted by highly reactive HO(.) and HOO(.) radicals generated from H(2)O(2) on the surface of the Fe(0)/Fe(3)O(4) composite via a classical Fenton-like mechanism.
Expressed sequence tags of full-length cDNA clones from the miniature tomato (Lycopersicon esculentum) cultivar Micro-Tom (2005)

Tomato genome sequencing projects have started to become an internationally coordinated program. To accelerate tomato functional genomics studies in coordination with the complete sequencing of the tomato genome, we prepared a full-length cDNA library from the miniature tomato (Lycopersicon esculentum) cultivar Micro-Tom, which has attracted attention as a laboratory-grown model plant. Total RNA from maturing fruits was subjected to a vector-capping protocol for full-length cDNA synthesis. We generated 8,046 expressed sequence tags (ESTs), which comprised 3,484 contigs. We calculated that 80.7% of the cDNA clones in the library met the criteria for full-length clones, and 1,920 non-redundant full-length clones were identified. As a pilot experiment, we chose seven clones, whose encoded proteins shared low homology with Arabidopsis proteins, for full sequencing. Of these, three genes had no or very low homology with Arabidopsis genes, indicating the usefulness of the library for analyses of “not-found-in-Arabidopsis” genes.
Referral for Colposcopy: Do Our Present Criteria Need Reviewing? (1987)

Three hundred and seven women referred to a colposcopy clinic over an 11-year period with mildly atypical cervical cytology had a histological diagnosis established by colposcopically directed biopsy. Of the 256 women who had dyskaryosis on the referral smear, 176 (68.8%) had cervical intraepithelial neoplasia (CIN) grade II or III on histology. One woman had microinvasive carcinoma. Fourteen (27.5%) of the 51 women without dyskaryosis had CIN II or III. Of smears taken at the time of colposcopy, 28.9% had normal cytology, although over one third of these women had CIN II or III diagnosed on histology at that time. This poor correlation of mildly atypical cervical cytology and histology suggests that the common practice of relying on cytology alone for the surveillance of women who have already had an atypical smear should be discouraged.
New Strategies for Cyclization and Bicyclization of Oligonucleotides by Click Chemistry Assisted by Microwaves (2007)

The synthesis of cyclic, branched, and bicyclic oligonucleotides was performed by copper-catalyzed azide-alkyne cycloaddition assisted by microwaves in solution and on solid support. For that purpose, new phosphoramidite building blocks and new solid supports were designed to introduce alkyne and bromo functions into the same oligonucleotide by solid-phase synthesis on a DNA synthesizer. The bromine atom was then substituted by sodium azide to yield azide oligonucleotides. Cyclizations were found to be more efficient in solution than on solid support. This method allowed the efficient preparation of cyclic (6- to 20-mers), branched (with one or two dangling sequences), and bicyclic (2 x 10-mers) oligonucleotides.
Effect of tsl mutations in decreasing radiation sensitivity of a recA- strain of Escherichia coli K-12 (1975)

It has been shown previously that the radiation sensitivity of lexA- strains of Escherichia coli K-12 can be suppressed by thermosensitive mutations (designated tsl) that are closely linked to the lexA locus and are thought to be intragenic suppressors of lexA mutations (Mount et al., 1973). When a recA mutation is crossed into a suppressed tsl- strain, the extreme radiation sensitivity usually conferred by a recA mutation is decreased, but there is no detectable change in genetic recombination deficiency. Increased resistance to UV in the tsl-reA-strains depends upon ability to synthesize active uvrA+ product.
Interleukin 7 enhances cytolytic T lymphocyte generation and induces lymphokine-activated killer cells from human peripheral blood. (1990)

The effects of purified recombinant interleukin 7 (IL-7) on the generation of cytolytic T lymphocytes (CTL) in mixed lymphocyte culture (MLC) and on the induction of lymphokine-activated killer (LAK) cells in autologous cultures of human peripheral blood mononuclear cells were investigated. IL-7 was found to induce the generation of both CTL and LAK cells in bulk cultures. The appearance of peak CTL activity in MLC established with exogenous IL-7 was delayed in comparison with replicate cultures containing exogenous IL-2, but both cytokines stimulated quantitatively similar levels of antigen-specific lytic activity. An IL-2-neutralizing antiserum inhibited substantially, but not completely, the effect of IL-7 on CTL generation, implying the existence of both an indirect component of IL-7 activity via IL-2 utilization, as well as an IL-2-independent component. Cell surface phenotypic analysis of IL-2- or IL-7-generated CTL effector cells revealed that CD8+ cells were responsible for the vast majority of lytic activity. Limiting dilution analysis (LDA) revealed that essentially identical frequencies of CTL precursors (CTL-P) were capable of clonal expansion and/or differentiation in the presence of exogenous IL-2, IL-4, or IL-7, supporting the concept that all three of these cytokines are capable of exerting a major influence on T cell growth and differentiation. Approximately half of the CTL-P that responded in IL-7-supplemented LDA cultures did so in an IL-2-independent manner. IL-7 stimulated the development of LAK cells in autologous bulk cultures, but only weakly in comparison with IL-2. In contrast to its effects on CTL generation, the induction of LAK cells by IL-7 was virtually independent of IL-2. LAK cells induced by IL-7, like those induced by IL-2, were phenotypically heterogeneous and included CD8+, CD56+, and gamma/delta+ cells. Limiting dilution analysis indicated that IL-2 stimulated fivefold more LAK-P than IL-7 and 220-fold more than IL-4. Collectively, these data suggest that IL-7 has potent regulatory effects on human cytolytic cell populations and, either alone or in combination with other cytokines, could be important for the in vitro expansion of cells for adoptive immunotherapy.
Differential Prevalence of Antibodies Against Adeno-Associated Virus in Healthy Children and Patients with Mucopolysaccharidosis III: Perspective for AAV-Mediated Gene Therapy (2017)

Recombinant adeno-associated virus (AAV) vectors are promising gene therapy tools. However, pre-existing antibodies (Abs) to many useful AAV serotypes pose a critical challenge for the translation of gene therapies. As part of AAV gene therapy program for treating mucopolysaccharidosis (MPS) III patients, the seroprevalence profiles of AAV1-9 and rh74 were investigated in MPS IIIA/IIIB patients and in healthy children. Using enzyme-linked immunosorbent assay for αAAV-IgG, significantly higher seroprevalence was observed for AAV1 and AAVrh74 in 2- to 7-year-old MPS III patients than in healthy controls. Seroprevalence for the majority of tested AAV serotypes appears to peak before 8 years of age in MPS III subjects, with the exception of increases in αAAV8 and αAAV9 Abs in 8- to 19-year-old MPS IIIA patients. In contrast, significant increases in seroprevalence were observed for virtually all tested AAV serotypes in 8- to 15-year-old healthy children compared to 2- to 7-year-olds. Co-prevalence and Ab level correlation results followed the previously established divergence-based clade positions of AAV1-9. Interestingly, the individuals positive for αAAVrh74-Abs showed the lowest co-prevalence with Abs for AAV1-9 (22-40%). However, all or nearly all (77-100%) of subjects who were seropositive for any of serotypes 1-9 were also positive for αAAVrh74-IgG. Notably, the majority (78%) of αAAV seropositive individuals were also Ab-positive for one to five of the tested AAV serotypes, mostly with low levels of αAAV-Abs (1:50-100), while a minority (22%) were seropositive for six or more AAV serotypes, mostly with high levels of αAAV-IgG for multiple serotypes. In general, the highest IgG levels were reactive to AAV2, AAV3, and AAVrh74. The data illustrate the complex seroprevalence profiles of AAV1-9 and rh74 in MPS patients and healthy children, indicating the potential association of AAV seroprevalence with age and disease conditions. The broad co-prevalence of Abs for different AAV serotypes reinforces the challenge of pre-existing αAAV-Abs for translating AAV gene therapy to clinical applications, regardless of the vector serotype.
Busulfan Produces Efficient Human Cell Engraftment in NOD/LtSz-Scid IL2Rγ Null Mice (2008)

Xenografting immunodeficient mice after low-dose irradiation has been used as a surrogate human hematopoietic stem cell (HSC) assay; however, irradiation requires strict and meticulous animal support and can produce significant mortality rates, limiting the usefulness of this model. In this work, we examined the use of parenteral busulfan as an alternative conditioning agent. Busulfan led to dose-dependent human HSC engraftment in NOD/LtSz-scid/IL2Rgamma(null) mice, with marked improvement in survival rates. Terminally differentiated B and T lymphocytes made up most of the human CD45+ cells observed during the initial 5 weeks post-transplant when unselected cord blood (CB) products were infused, suggesting derivation from existing mature elements rather than HSCs. Beyond 5 weeks, CD34+-enriched products produced and sustained superior engraftment rates compared with unselected grafts (CB CD34+, 65.8% +/- 5.35%, vs. whole CB, 4.27% +/- 0.67%, at 24 weeks). CB CD34+ group achieved significantly higher levels of engraftment than mobilized CD34+-enriched peripheral blood (PB CD34+). At 8 weeks, all leukocyte subsets were detected, yet human red blood cells (RBCs) were not observed. Transfused human red cells persisted in the chimeric mice for up to 3 days; an accompanying rise in total bilirubin suggested hemolysis as a contributing factor to their clearance. Recipient mouse-derived human HSCs had the capacity to form erythroid colonies in vitro at various time points post-transplant in the presence of human transferrin (Tf). When human Tf was administered singly or in combination with anti-CD122 antibody and human cytokines, up to 0.1% human RBCs were detectable in the peripheral blood. This long evasive model should prove valuable for the study of human erythroid cells.
Precise pointer reasoning for dynamic test generation (2009)

Dynamic test generation consists of executing a program while gathering symbolic constraints on inputs from predicates encountered in branch statements, and of using a constraint solver to infer new program inputs from previous constraints in order to steer next executions towards new program paths. Variants of this technique have recently been adopted in several bug detection tools, including our whitebox fuzzer SAGE, which has found dozens of new expensive security-related bugs in many Windows applications and is now routinely used in various Microsoft groups.
Interacting at a distance (2002)

It is difficult to interact with computer displays that are across the room. A popular approach is to use laser pointers tracked by a camera, but interaction techniques using laser pointers tend to be imprecise, error-prone, and slow. Although many previous papers discuss laser pointer interaction techniques, none seem to have performed user studies to help inform the design. This paper reports on two studies of laser pointer interactions that answer some of the questions related to interacting with objects using a laser pointer. The first experiment evaluates various parameters of laser pointers. For example, the time to acquire a target is about 1 second, and the jitter due to hand unsteadiness is about ±8 pixels, which can be reduced to about ±2 to ±4 pixels by filtering. We compared 7 different ways to hold various kinds of laser pointers, and found that a laser pointer built into a PalmOS device was the most stable. The second experiment compared 4 different ways to select objects on a large projected display. We found that tapping directly on a wall-size SmartBoard was the fastest and most accurate method, followed by a new interaction technique that copies the area of interest from the big screen to a handheld. Third in speed was the conventional mouse, and the laser pointer came in last, with a time almost twice as long as tapping on the SmartBoard
Upregulated Transcription of Plasmid and Chromosomal Ribulose Monophosphate Pathway Genes Is Critical for Methanol Assimilation Rate and Methanol Tolerance in the Methylotrophic Bacterium Bacillus methanolicus (2006)

The natural plasmid pBM19 carries the key mdh gene needed for the oxidation of methanol into formaldehyde by Bacillus methanolicus. Five more genes, glpX, fba, tkt, pfk, and rpe, with deduced roles in the cell primary metabolism, are also located on this plasmid. By using real-time PCR, we show that they are transcriptionally upregulated (6- to 40-fold) in cells utilizing methanol; a similar induction was shown for two chromosomal genes, hps and phi. These seven genes are involved in the fructose bisphosphate aldolase/sedoheptulose bisphosphatase variant of the ribulose monophosphate (RuMP) pathway for formaldehyde assimilation. Curing of pBM19 causes higher methanol tolerance and reduced formaldehyde tolerance, and the methanol tolerance is reversed to wild-type levels by reintroducing mdh. Thus, the RuMP pathway is needed to detoxify the formaldehyde produced by the methanol dehydrogenase-mediated conversion of methanol, and the in vivo transcription levels of mdh and the RuMP pathway genes reflect the methanol tolerance level of the cells. The transcriptional inducer of hps and phi genes is formaldehyde, and not methanol, and introduction of multiple copies of these two genes into B. methanolicus made the cells more tolerant of growth on high methanol concentrations. The recombinant strain also had a significantly higher specific growth rate on methanol than the wild type. While pBM19 is critical for growth on methanol and important for formaldehyde detoxification, the maintenance of this plasmid represents a burden for B. methanolicus when growing on mannitol. Our data contribute to a new and fundamental understanding of the regulation of B. methanolicus methylotrophy.
6‐Acylamino‐penam Derivatives: Synthesis and Inhibition of Cathepsins B, L, K, and S. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Forced Unfolding of Proteins Within Cells (2007)

To identify cytoskeletal proteins that change conformation or assembly within stressed cells, in situ labeling of sterically shielded cysteines with fluorophores was analyzed by fluorescence imaging, quantitative mass spectrometry, and sequential two-dye labeling. Within red blood cells, shotgun labeling showed that shielded cysteines in the two isoforms of the cytoskeletal protein spectrin were increasingly labeled as a function of shear stress and time, indicative of forced unfolding of specific domains. Within mesenchymal stem cells-as a prototypical adherent cell-nonmuscle myosin IIA and vimentin are just two of the cytoskeletal proteins identified that show differential labeling in tensed versus drug-relaxed cells. Cysteine labeling of proteins within live cells can thus be used to fluorescently map out sites of molecular-scale deformation, and the results also suggest means to colocalize signaling events such as phosphorylation with forced unfolding.
Nonsteroidal anti‐inflammatory drugs prevent early diabetic retinopathy via TNF‐α suppression (2002)

Leukocyte adhesion to the diabetic retinal vasculature results in blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Intercellular adhesion molecule-1 (ICAM-1) and the leukocyte integrin CD18 are required for these processes. Diabetes was induced in Long Evans rats, resulting in a two- to threefold increase in retinal leukocyte adhesion. Following one week of diabetes, neutrophil CD11a, CD11b, and CD18 expression was increased significantly, as were retinal ICAM-1 levels. Animals were treated with aspirin, a cyclooxygenase 2 (COX-2) inhibitor (meloxicam), or a soluble tumor necrosis factor alpha (TNF-alpha) receptor/Fc construct (TNFR-Fc, etanercept). High-dose aspirin, etanercept, and high-dose meloxicam each reduced leukocyte adhesion and suppressed blood-retinal barrier breakdown. High-dose aspirin also reduced the expression of CD11a, CD11b, and CD18, whereas meloxicam and etanercept did not. High-dose aspirin, etanercept, and high-dose meloxicam each reduced retinal ICAM-1 expression. Aspirin and meloxicam both lowered retinal TNF-alpha levels. Notably, aspirin, meloxicam, and etanercept did not change retinal vascular endothelial growth factor levels. High-dose aspirin, etanercept and high-dose meloxicam, each suppressed the retinal expression of eNOS and the DNA-binding capacity of retinal nuclear factor-kappaB. High-dose aspirin also suppressed Erk kinase activity, which is involved in CD18 up-regulation. Taken together, these data identify COX-2 and TNF-alpha as operative in the early signature pathologies of diabetic retinopathy, a newly recognized inflammatory disease.
Neural networks for sensor validation and plant monitoring (1990)

Sensor and process monitoring in power plants require the estimation of one or more process variables. Neural network paradigms are suitable for establishing general nonlinear relationships among a set of plant variables. Multiple-input multiple-output autoassociative networks can follow changes in plant-wide behavior. The backpropagation algorithm has been applied for training feedforward networks. A new and enhanced algorithm for training neural networks (BPN) has been developed and implemented in a VAX workstation. Operational data from the Experimental Breeder Reactor-II (EBR-II) have been used to study the performance of BPN. Several results of application to the EBR-II are presented.
Characterization of the human homologue of the mouse Tg737 candidate polycystic kidney disease gene (1995)

We previously identified a gene from the mutant locus in a new mouse mutation that causes recessive polycystic kidney disease. Here we describe the cloning, characterization and mapping of the homologous human gene. The human and mouse genes are 95% identical at the predicted amino acid sequence level, and both genes encode a putative protein that contains a tetratricopeptide repeat motif. The human gene, called hTg737, is expressed with a broad tissue distribution that includes the the kidney and liver, and gives rise to a 2.9 kb mRNA. The gene contains 26 exons and spans a genomic region greater than 100 kb. Chromosome mapping experiments revealed that the hTg737 gene maps near the centromere on the long arm of human chromosome 13, at position 13q12.1. While this gene does not map to the primary locus that has been identified for ARPKD in humans, it may represent a candidate gene for other recessive renal disorders that have yet to be mapped.