gebhart/patrepeval huggingface dataset:
Postnatally Induced Formation of the Corpus Callosum in Acallosal Mice on Glia-Coated Cellulose Bridges (1983)

Developing axons of the corpus callosum of mice are guided across the cerebral midline by a slinglike glial structure that forms transiently between the hemispheres. If the "sling" is cut at precallosal stages, the would-be callosal fibers whirl into paired neuromas adjacent to the longitudinal cerebral fissure. In experiments on such surgically acallosal animals, the aberrant commissural axons maintained a potential to regrow across the hemispheres at prenatal and early postnatal stages if they were presented with a properly aligned, glia-covered scaffold spanning the hemispheres.
Synaptic evidence for the efficacy of spaced learning (2012)

The superiority of spaced vs. massed training is a fundamental feature of learning. Here, we describe unanticipated timing rules for the production of long-term potentiation (LTP) in adult rat hippocampal slices that can account for one temporal segment of the spaced trials phenomenon. Successive bouts of naturalistic theta burst stimulation of field CA1 afferents markedly enhanced previously saturated LTP if spaced apart by 1 h or longer, but were without effect when shorter intervals were used. Analyses of F-actin-enriched spines to identify potentiated synapses indicated that the added LTP obtained with delayed theta trains involved recruitment of synapses that were "missed" by the first stimulation bout. Single spine glutamate-uncaging experiments confirmed that less than half of the spines in adult hippocampus are primed to undergo plasticity under baseline conditions, suggesting that intrinsic variability among individual synapses imposes a repetitive presentation requirement for maximizing the percentage of potentiated connections. We propose that a combination of local diffusion from initially modified spines coupled with much later membrane insertion events dictate that the repetitions be widely spaced. Thus, the synaptic mechanisms described here provide a neurobiological explanation for one component of a poorly understood, ubiquitous aspect of learning.
Synergistic Effect of Human Chorionic Gonadotropin and Extracellular Matrix on in Vitro Differentiation of Human Granulosa Cells: Progesterone Production and Gap Junction Formation* (1989)

The effects of extracellular matrix (ECM) in the form of a native basement membrane and of hCG on progesterone production, cellular morphology, and gap junction formation in cultured human granulosa cells (GCs) were examined. GCs were harvested from human preovulatory follicles in the course of oocyte retrieval for in vitro fertilization. Cells grown on ECM secreted by bovine corneal endothelial cells (BCE) produced significantly higher amounts of progesterone (up to 3-fold) than cells on uncoated dishes. Culturing of cells on BCE-ECM in the presence of hCG resulted in a further increase in progesterone production; in the first 2 days an additive effect was noted, and on days 3, 4, and 5 a synergistic effect became evident (1.2- to 1.8-fold above the sum of the individual treatments). LH/hCG receptor content on day 3 of culture was 4-fold higher in GCs grown on BCE-ECM compared to that in uncoated dishes. A similar elevation was found when cells were grown on ECM secreted by PFHR-9 mouse endodermal cells. Cells grown on both types of ECM maintained their epithelioid shape but, in addition, formed cytoplasmic processes interconnected with neighboring cells by gap junctions. Morphometric analysis revealed that the area of cell membrane occupied by gap junctions increased by 3- to 4-fold on ECM compared to that in cells grown on plastic. Enlargement of endoplasmic reticulum was evident on ECM along with clustering of numerous mitochondria, lipid droplets, and lysosomes characteristic of highly luteinized cells. Cells grown in the presence of hCG on ECM showed morphological modulation similar to that of cells cultured on ECM alone. These observations suggest that growing of human GCs on a ECM similar to a naturally produced basement membrane enhances morphological and biochemical differentiation, and that ECM and gonadotropin affect synergistically the extent of luteinization in these cells.
Studies on Antiallergy Agent. I. Synthesis of 1, 4-Dihydro-4-oxo-3-quinolinecarboxylic Acids (1987)

A series of 1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids with a variety of substituents was prepared and evaluated in the rat passive cutaneous anaphylaxis test for antiallergic activity. The introduction of alkoxy group into 8 position of quinoline nucleus provided significantly active compounds. However, the conversion to 3-quinolinecarboxylic acids with alkoxy group at 6 or 7 position and the replacement of alkoxy group with alkylthio, alkylsulfonyl and other groups resulted in substantial reduction or loss of activity. Among the analogues, 8-butoxy-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acid (69) was found to possess remarkably potent activity by oral administration. Structure-activity relationships are discussed.
Malacca 3-D -- A Comprehensive Approach to Seismic Data Acquisition in Transition Zones (1999)

ABSTRACT A 3-D seismic survey utilizing innovative techniques and technology has been performed in an extremely challenging transition zone program acquired in the Malacca Strait region of Sumatra, Indonesia. Although this project was nearly antipodal to the Gulf Coast, it is an excellent example of salt water transition zone and marsh 3-D seismic data acquisition. In addition to heavy jungle, the project crossed water with depths of up to 50 meters and tidal currents of five to seven knots. These conditions would normally have dictated the use of two different acquisition systems for the project; a land/marsh system and a bay-bottom system. Utilizing two systems introduces several problems to the acquisition contractor. Capital equipment expenditures increase, because the contractor must either rent or purchase two systems. The contractor also faces increased logistics in supporting two systems and training personnel in the use and deployment of two systems. The end user may also face compromises, because he must merge data sets from what are essentially discrete surveys recorded by two different systems. This may introduce geometry errors, inconsistent data quality, and increased data processing costs. Geo-X System Ltd.'s ARAM24 system offered technology developed in the Gulf Coast of Texas and Louisiana that enabled the contractor to use a single system on the entire project, thereby eliminating the logistical and economic difficulties associated with the two system approach. The solutions adopted in response to this very difficult acquisition problem offer a comprehensive approach to seismic data acquisition in the transition zone environment.
Activity of synthetic peptides from the Tat protein of human immunodeficiency virus type 1. (1989)

To determine which of the 86 amino acids in the Tat protein of human immunodeficiency virus type 1 (HIV-1) are important for transactivation, peptides from Tat were synthesized and their activity was measured in cells containing a chloramphenicol acetyltransferase reporter gene under control of the HIV long terminal repeat promoter. Although the Tat sequence contains arginine- and cysteine-rich stretches that are difficult to synthesize, it was possible to prepare pure peptides in good yield by using fluoren-9-ylmethoxycarbonyl (Fmoc) chemistry. A peptide containing residues 1-58 had 5-10% the activity of full-length Tat. Deleting 4 amino acids from the N terminus of this peptide further reduced activity, while peptides with more extensive N-terminal deletions and peptides missing the basic region at the C terminus had no detectable activity. A peptide previously reported to transactivate, Tat-(37-62), was completely inactive in our assays. Inactive peptides were also tested as possible inhibitors of transactivation. Tat-(21-38), which contains the cysteine-rich region and can form heterodimers with intact Tat in vitro, showed inhibition at high peptide concentrations. However, this effect was not specific for Tat or for the HIV promoter, since the peptide also inhibited expression from the simian virus 40 early promoter.
Inflammatory bowel disease and anemia: intravenous iron treatment (2018)

Ferric carboxymaltose was found to be an effective and well tolerated treatment for iron deficiency anemia in patients with IBD. The results of our study further strengthen the current knowledge of the effectiveness and safety of the treatment.
Original 2-(3-Alkoxy-1H-pyrazol-1-yl)pyrimidine Derivatives as Inhibitors of Human Dihydroorotate Dehydrogenase (DHODH) (2015)

From a research program aimed at the design of new chemical entities followed by extensive screening on various models of infectious diseases, an original series of 2-(3-alkoxy-1H-pyrazol-1-yl)pyrimidines endowed with notable antiviral properties were found. Using a whole cell measles virus replication assay, we describe here some aspects of the iterative process that, from 2-(4-benzyl-3-ethoxy-5-methyl-1H-pyrazol-1-yl)pyrimidine, led to 2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1H-pyrazol-1-yl)-5-ethylpyrimidine and a 4000-fold improvement of antiviral activity with a subnanomolar level of inhibition. Moreover, recent precedents in the literature describing antiviral derivatives acting at the level of the de novo pyrimidine biosynthetic pathway led us to determine that the mode of action of this series is based on the inhibition of the cellular dihydroorotate dehydrogenase (DHODH), the fourth enzyme of this pathway. Biochemical studies with recombinant human DHODH led us to measure IC50 as low as 13 nM for the best example of this original series when using 2,3-dimethoxy-5-methyl-6-(3-methyl-2-butenyl)-1,4-benzoquinone (coenzyme Q1) as a surrogate for coenzyme Q10, the cofactor of this enzyme.
Comparative genomics and evolution of transcriptional regulons in Proteobacteria (2016)

Comparative genomics approaches are broadly used for analysis of transcriptional regulation in bacterial genomes. In this work, we identified binding sites and reconstructed regulons for 33 orthologous groups of transcription factors (TFs) in 196 reference genomes from 21 taxonomic groups of <i>Proteobacteria</i>. Overall, we predict over 10 600 TF binding sites and identified more than 15 600 target genes for 1896 TFs constituting the studied orthologous groups of regulators. These include a set of orthologues for 21 metabolism-associated TFs from <i>Escherichia coli</i> and/or <i>Shewanella</i> that are conserved in five or more taxonomic groups and several additional TFs that represent non-orthologous substitutions of the metabolic regulators in some lineages of <i>Proteobacteria</i>. By comparing gene contents of the reconstructed regulons, we identified the core, taxonomy-specific and genome-specific TF regulon members and classified them by their metabolic functions. Detailed analysis of ArgR, TyrR, TrpR, HutC, HypR and other amino-acid-specific regulons demonstrated remarkable differences in regulatory strategies used by various lineages of <i>Proteobacteria</i>. The obtained genomic collection of <i>in silico</i> reconstructed TF regulons contains a large number of new regulatory interactions that await future experimental validation. The collection provides a framework for future evolutionary studies of transcriptional regulatory networks in <i>Bacteria</i>. It can be also used for functional annotation of putative metabolic transporters and enzymes that are abundant in the reconstructed regulons.
mRNA-transfected dendritic cell vaccine in combination with metronomic cyclophosphamide as treatment for patients with advanced malignant melanoma (2016)

Treatment with autologous DCs transfected with mRNA in combination with mCy was feasible and safe. Importantly, mCy did not alter the percentage of Tregs in our patient cohort. There was an indication of clinical benefit; however, more knowledge is needed in order for DCs to be exploited as a therapeutic option.
Predicting remission in juvenile rheumatoid arthritis with methotrexate treatment. (1993)

Forty-nine children with a polyarticular course of juvenile rheumatoid arthritis treated with methotrexate (MTX) for at least one year were analyzed to identify clinical characteristics that would predict remission of arthritis after MTX treatment. Twenty-two children (45%) had remission of arthritis after a mean of 13.6 months of treatment and did not differ from the 27 with persistently active arthritis regarding years of disease before starting MTX, age starting MTX, maximum MTX dose, disease onset type, presence of radiographic joint destruction, concomitant treatment with hydroxychloroquine, sulfasalazine or prednisone, or presence of rheumatoid factor or antinuclear antibodies. Higher dose MTX, earlier treatment, genetic markers, and a standardized route of therapy may yield important information in future studies.
Repair of critical-sized bone defects with anti-miR-31-expressing bone marrow stromal stem cells and poly(glycerol sebacate) scaffolds (2014)

The repair of critical-sized defects (CSDs) is a significant challenge in bone tissue engineering. Combining the use of progenitor cells with gene therapy represents a promising approach for bone regeneration. MicroRNAs play important roles in most gene regulatory networks, regulate the endogenous expression of multiple growth factors and simultaneously modulate stem cell differentiation. Our previous study showed that knocking down miR-31 promotes the osteogenesis of bone marrow stromal stem cells (BMSCs). To investigate the therapeutic potential of cells engineered to express anti-miR-31 for CSD repair, lentiviral vectors encoding negative control, miR-31 precursor and anti-sense sequences were constructed and transduced into osteo-inductive BMSCs. The expression of osteogenic-specific genes, alkaline phosphatase activity and Alizarin Red S staining were investigated to evaluate the effects of miR-31 on the cell fate of BMSCs over a 3-week period. In addition, miR-31-modified BMSCs seeded on poly(glycerol sebacate) (PGS) scaffolds were used to repair 8 mm critical-sized calvarial defects in rats. The results showed that miR-31 suppression significantly increased the expression of osteogenic-specific genes in vitro at the mRNA and protein levels, and that robust new bone formation with high local bone mineral density was observed in the anti-miR groups in vivo. Moreover, the PGS scaffolds carrying anti-miR-31-expressing BMSCs exhibited good biocompatibility and a high regeneration rate (~60%) within in vivo bone defects. Our results suggest that miR-31 gene delivery affects the potential of BMSCs for osteogenic differentiation and bone regeneration and that PGS is a potential substrate for genetically modified, tissue-engineered bone in the repair of large bone defects.
Age-associated memory impairment: diagnostic criteria and treatment strategies. (1988)

In general, then, the term Age-Associated Memory Impairment (AAMI) has been adopted to describe healthy persons over 50 years of age who have experienced memory loss since early life, but who are not demented. Specific diagnostic criteria have been proposed for AAMI and these criteria are now being applied in clinical studies, including a number of pharmacologic treatment studies. Many of these latter studies are supported by evidence from preclinical studies suggesting that age-related memory deficits in animals can be pharmacologically altered. This evidence gives reason to hope that an important behavioral deficit associated with aging may be controlled or corrected through drug treatment. The development of such a treatment would be an accomplishment of immense clinical and scientific significance.
Effects of Guanine Nucleotide Depletion on Cell Cycle Progression in Human T Lymphocytes (1998)

Depletion of guanine nucleotide pools after inhibition of inosine monophosphate dehydrogenase (IMPDH) potently inhibits DNA synthesis by arresting cells in G1 and has been shown to induce the differentiation of cultured myeloid and erythroid cell lines, as well as chronic granulocytic leukemic cells after blast transformation. Inhibitors of IMPDH are also highly effective as immunosuppressive agents. The mechanism underlying these pleiotropic effects of depletion of guanine nucleotides is unknown. We have examined the effects of mycophenolic acid (MPA), a potent IMPDH inhibitor, on the cell cycle progression of activated normal human T lymphocytes. MPA treatment resulted in the inhibition of pRb phosphorylation and cell entry into S phase. The expression of cyclin D3, a major component of the cyclin-dependent kinase (CDK) activity required for pRb phosphorylation, was completely abrogated by MPA treatment of T cells activated by interleukin-2 (IL-2) and leucoagglutinin (PHA-L), whereas the expression of cyclin D2, CDK6, and CDK4 was more mildly attenuated. The direct kinase activity of a complex immunoprecipitated with anti-CDK6 antibody was also inhibited. In addition, MPA prevented the IL-2-induced elimination of p27(Kip1), a CDK inhibitor, and resulted in the retention of high levels of p27(Kip1) in IL-2/PHA-L-treated T cells bound to CDK2. These results indicate that inhibition of the de novo synthesis of guanine nucleotides blocks the transition of normal peripheral blood T lymphocytes from G0 to S phase in early- to mid-G1 and that this cell cycle arrest results from inhibition of the induction of cyclin D/CDK6 kinase and the elimination of p27(Kip1) inhibitory activity.
Flexible OS support and applications for trusted computing (2003)

Trusted computing (e.g. TCPA and Microsoft&amp;apos;s Next-Generation Secure Computing Base) has been one of the most talked about and least understood technologies in the computing community over the past year. The capabilities trusted computing provides have the potential to radically improve the security and robustness of distributed systems. Unfortunately, the debate over its application to digital rights management has caused its significant other applications to be largely overlooked. In this paper we present a broader vision for trusted computing. We give an intuitive model for understanding the capabilities and limitations of the mechanisms provided by trusted computing. We describe a flexible OS architecture to support trusted computing. We present a range of practical applications that illustrate how trusted computing can be used to improve security and robustness in distributed systems.
Temperature dependence of the etch rate and selectivity of silicon nitride over silicon dioxide in remote plasma NF3/Cl2 (1995)

The etch rates and selectivity of Si3N4 over SiO2 have been investigated by microwave discharging a mixture of NF3 and Cl2 and flowing the resultant fluorine and chlorine atoms and interhalogenous molecules simultaneously over a silicon wafer covered with low pressure chemical vapor deposition (LPCVD) Si3N4, and a wafer covered with thermally grown SiO2. The temperature dependence of the etch rates of Si3N4 and SiO2 in the NF3/Cl2 mixture was examined in the range from 25 to 500 °C, and the selectivity of the nitride etch over the oxide etch as well as nitride etch rate was found to increase with increasing temperature. It was also found that both etch rates and selectivities increase with NF3 flow rates within the range used in this study.
Analysis of lipopolysaccharide binding by CD14. (1993)

The cell surface protein CD14 binds bacterial lipopolysaccharide (LPS) in the presence of the serum protein, LPS-binding protein (LBP). This interaction is important for LPS-induced activation of mammalian myeloid cells. We performed quantitative studies of 3H-labeled LPS binding to human CD14 expressed on Chinese hamster ovary cells and on a human macrophage cell line (THP-1). At the concentrations studied (20-100 nM) LPS binding required the expression of CD14 and could be inhibited by a subset of anti-CD14 monoclonal antibodies. LBP was required for LPS binding to CD14. The binding occurred within 10 min and was relatively unaffected by temperature over the range of 4-37 degrees C. Quantitative binding assays were performed at 10 degrees C, or at 37 degrees C, using Chinese hamster ovary cells depleted of ATP. In both cases, 75-90% of the LPS could be released by treatment with phosphatidylinositol-specific phospholipase C, suggesting that it remains associated with the glycosyl phosphatidylinositol-anchored CD14. The apparent dissociation constant of recombinant human CD14 expressed on Chinese hamster ovary cells for LPS at 10 degrees C was 2.74 (+/- 0.99) x 10(-8) M; the apparent dissociation constant of CD14 expressed on THP-1 cells at 10 degrees C was 4.89 (+/- 1.42) x 10(-8) M. In both cell lines, at saturating LPS concentrations, the molar ratio of LPS bound per surface CD14 was approximately 20:1. At 37 degrees C the apparent dissociation constant of recombinant human CD14 for LPS at 37 degrees C was 2.7 (+/- 1.2) x 10(-8) M, and the molar ratio of LPS bound per surface CD14 was approximately 8:1. Although the difference in molar ratio of LPS bound per surface CD14 at the two temperatures is difficult to interpret, it is clear that at both temperatures the molar ratio is not 1:1. The basis of this phenomenon is unclear, but may involve the repeated leucine-rich motifs, which are found within CD14.
Genetic analysis of sequences in maltoporin that contribute to binding domains and pore structure (1988)

Maltoporin (LamB protein) is a maltodextrin transport protein in the outer membrane of Escherichia coli with binding sites for bacteriophage lambda and maltosaccharides. Binding of starch by bacteria was found to inhibit swarming of Escherichia coli in soft agar plates; the inhibition was dependent on the maltodextrin affinity of maltoporin. On the basis of this observation, chemotactic cell-sorting techniques were developed for the isolation and analysis of mutants with an altered starch-binding phenotype. Fifteen lamB mutations generated by hydroxylamine and linker mutagenesis, as well as spontaneous mutations, were analyzed. The effects of the mutations on starch and lambda-binding, as well as transport specificity, were assayed. Mutations that affect residues near 8 to 18, 74 to 82, and 118 to 121 were found to affect starch binding and maltodextrin-selective functions strongly, confirming and extending previous results with substitutions at these regions. Substitutions and insertions in two previously undefined regions in the protein, in or near residues 194 and 360, also resulted in defects in maltodextrin-specific functions and indicate that C-terminal parts of the protein also contribute to the discontinuous binding and pore domains. There was a detectable transport defect in all binding-affected mutants, and one mutation caused near-total pore blocking towards both maltose and nonmaltoside. The highly discontinuous phage lambda-binding site was affected by mutations near residues 9 and 10 and 194, as well as previously established regions near residues 18, 148 to 165, 245 to 259, and 380 to 400. The significance of these mutations is discussed in the context of a model of the functional topology of maltoporin. The additional role of regions near residues 10 and 120 in maltoporin assembly, as well as starch binding, was suggested by the temperature-sensitive biogenesis of maltoporin in strains with one- or two-codon insertion at these sites.
Learning about blood component therapy (2009)

Lynda S. Cook works as an independent vascular access consultant in Greensboro, N.C. Find out how blood products are used, and learn about the latest developments in this field.