gebhart/patrepeval huggingface dataset:
Iron Availability Influences Aggregation, Biofilm, Adhesion and Invasion of Pseudomonas Aeruginosa and Burkholderia Cenocepacia (2005)

Pseudomonas aeruginosa and Burkholderia cenocepacia are predominant opportunistic pathogens in cystic fibrosis (CF) patients. In healthy humans the lower respiratory tract as well as all mucosa, contains a very low free iron concentration (10(-18) M), while in CF patients sputum iron concentration is very high, showing a median value of 63x10(-6) M. Accumulation of catalytic reactive iron heavily contributes to subsequent clinical complications in the lung disorders by the production of reactive oxygen species and increases bacterial growth and virulence. The data reported in this study indicate that low iron concentration (Fe3+ 1 microM)induced free-living forms and motility both in P. aeruginosa and B. cenocepacia, while high iron concentrations (Fe3+ 10 and 100 microM) stimulated aggregation and biofilm formation already in the fluid phases, so demonstrating that aggregation and biofilm formation are positively iron-modulated in these bacteria. Moreover, the different morphological forms (free-living, aggregates and biofilm) showed different capabilities of adhering and invading the bronchial cell line A549. P. aeruginosa PAO1 aggregates, and mostly biofilm, exerted the highest adhesion efficiency, while B. cenocepacia PV1 aggregates or biofilm the lowest. A significant reduction in invasion efficiency by P. aeruginosa biofilm and a significant increase in cell internalization by B. cenocepacia biofilm has been reported. Therefore, the iron availability is an important signal to which P. aeruginosa and B. cenocepacia counteract by leaving the motile free-living forms and entering into a new lifestyle, i.e. biofilm. These data could contribute to explain that the iron-overload of the sputum of CF patients, inducing nonmotile forms, aggregates and biofilm, may facilitate penetration of host epithelial barriers contributing to the establishment of infection, colonization, persistence and systemic spread of these opportunistic pathogens.
The Structure and Function of Estrogens. XI. Synthesis of (±)-7(8→11α) abeo -Estradiol and Its 9,11-Didehydro Derivative (1992)

Two approaches to the synthesis of (±)-7(8?11a)abeo-estra-1,3,5(10)-triene-3,17 ß- diol (2a) from (±)-1 ß-t-butoxy-7a ß-methy1-2,3,3a a,6,7,7a-hexahydro-1H-inden-5(4H)-one (11) were studied. A pathway involving 6-alkylation of (11) with 2-(3'-methoxyphenyl)ethyl halides or sulfonate esters was unsuccessful, but conjugate addition of 3-methoxybenzyl nucleophiles with (±)-1ß-t-butoxy-7a ß-methyl-6-methylene-2,3,3a,6,7,7a-hexahydro-1H-inden-5(4H)-one (18), prepared from (11), led to ( ±)-1ß-t-butoxy-6 a-[2'-(3"-methoxyphenyl)ethy1]-7a ß a,6,7,7a-hexahydro-1H-inden-5(4H-one (10a). Acid-catalysed cyclization of (10a) afforded (±)-17ß-t-butoxy-3-methoxy-7(8 ?11)abeo-estra-l,3,5(10),9(11)-tetraene (29) which upon lithium/ammonia reduction in the presence of diphenylmethane gave ( ±)-17 ß- t-butoxy-3-methoxy-7(8 ?11a)abeo-estra,1,3,5(10)- triene (31). Deprotection of (31) and (29) afforded (±)-7(8 ?11 a)abeo-estra-1,3,5(10)-triene-3,17 ß- diol (2a) and (±)-7(8 ?1l)abeo-estra-1,3,5(10),9(11)-tetraene-3,17ß-diol (32), respectively. Alternatively, reaction of (±)-1ß-t-butoxy-7a ß-methyl-6-methylene-2,3,3a a,6,7,7a-hexahydro-1H-inden-5(4H)-one (18) with 3-methoxybenzyl phenyl sulfoxide (23a) gave (1RS,3'SR,2RS,-3a'SR,7a'SR)-3'-t-butoxy-2-(3"-methoxyphenyl)-3a'-methyl-2',3',3a',4'7',7a'-hexahydrospiro- [cyclopropane-1,5'-[5H]inden ]-6'(1'H)-one (26), reductive cleavage of which with lithium/ammonia afforded (10a). The relative stereochemistries of (31) and of the spiro cyclopropyl ketone intermediate (26) were established unambiguously by X-ray crystallography.
Design, Preparation, and Implementation of an Imidazole-Based Chiral Biaryl P,N-Ligand for Asymmetric Catalysis (2013)

A new strategy for increasing the barrier to rotation in biaryls has been developed that allows for the incorporation of 5-membered aromatic heterocycles into chiral atropisomers. Using this concept, an imidazole-based biaryl P,N-ligand has been designed and prepared as a single enantiomer. This ligand performs exceptionally well in the enantioselective A(3)-coupling, demonstrating the potential of this new design element.
Inhibition of B16-BL6 Melanoma Lung Colonies by Semisynthetic Sulfaminoheparosan Sulfates fromE. coliK5 Polysaccharide (2002)

Heparin (H), heparan sulfate (HS), and related glycosaminoglycans can inhibit cancer cell invasion, possibly due to their ability to interact with vascular growth factors, adhesion molecules, endoglycosidases, and signaling proteins, in addition to the well-known effects on the clotting system. We evaluated the antitumor activity of a series of semisynthetic sulfaminoheparosan sulfates (SAHSs) with different degree and distribution of sulfates, obtained by chemical modifications of the E. coli K5 polysaccharide, namely type A, B, and C compounds. B16-BL6 melanoma cells (10 5 cells/mouse) were injected intravenously (i.v.) in a lateral tail vein of C57BL6 mice at a dose of 0.5 mg/ mouse together with test compounds. Tumor lung nodules were significantly reduced as compared with controls only by H (95.5 +/- 1.0% inhibition), SAHS-2 (84.2 +/- 5.0% inhibition), and SAHS-4 (91.1 +/- 4.2% inhibition), among compounds tested. SAHS-2 and SAHS-4 are type B compounds, with a sulfate/carboxylate ratio similar to that of H. A typical mammalian HS showed only 54.8% inhibition. Supersulfated low-molecular-weight heparin and heparan sulfate (ssLMWH and ssLMWHS) showed an activity similar to that of unfractionated compounds. H and SAHS-4 inhibited dose dependently B16-BL6 lung colonies, with IC-50 values of 0.05 and 0.1 mg/mouse, respectively. The relationship with ex vivo anticoagulant potency was evaluated by activated partial thromboplastin time (aPTT) on mouse plasma at different time intervals after i.v. injection (0.1 to 0.5 mg/mouse) of the compound. H showed a dose-dependent anticoagulant activity lasting up to 2 hours, whereas SAHS-4 showed a potent anticoagulant effect only at a dose of 0.5 mg/mouse. Accordingly, H but not SAHS-4 consistently inhibited B16-BL6 lung colonies when given 1 hour before tumor cells. SAHS-4 derivatives, with different size and/or affinity depleted of AT binding sites, showed an inhibitory effect on B16-BL6 melanoma similar to that of SAHS-4, suggesting that the greater antitumor effect of H was not due to AT-mediated inhibition of blood clotting. Interactions with other blood inhibitors, such as heparin cofactor II or tissue factor pathway inhibitory protein cannot be ruled out. The better effect of H may be due to persistence in the circulation and/or ability to inhibit tumor neoangiogenesis.
Surface-plasmon-assisted resonant tunneling of light through a periodically corrugated thin metal film (2000)

We present experimental results and a numerical model confirming that surface plasmons can resonantly enhance light transmission through a corrugated metal film. A new interpretation in terms of plasmon-assisted light tunneling is given to recent experiments on light penetration through periodic subwavelength holes in a thin metal film. We designed a narrow-band filter suitable for applications in optical communication by optimizing the film and the grating parameters.
Insights into G Protein Structure, Function, and Regulation (2003)

In multicellular organisms from Caenorhabditis elegans to Homo sapiens, the maintenance of homeostasis is dependent on the continual flow and processing of information through a complex network of cells. Moreover, in order for the organism to respond to an ever-changing environment, intercellular signals must be transduced, amplified, and ultimately converted to the appropriate physiological response. The resolution of the molecular events underlying signal response and integration forms the basis of the signal transduction field of research. An evolutionarily highly conserved group of molecules known as heterotrimeric guanine nucleotide-binding proteins (G proteins) are key determinants of the specificity and temporal characteristics of many signaling processes and are the topic of this review. Numerous hormones, neurotransmitters, chemokines, local mediators, and sensory stimuli exert their effects on cells by binding to heptahelical membrane receptors coupled to heterotrimeric G proteins. These highly specialized transducers can modulate the activity of multiple signaling pathways leading to diverse biological responses. In vivo, specific combinations of G alpha- and G beta gamma-subunits are likely required for connecting individual receptors to signaling pathways. The structural determinants of receptor-G protein-effector specificity are not completely understood and, in addition to involving interaction domains of these primary acting proteins, also require the participation of scaffolding and regulatory proteins.
MC 1288 ? A vitamin D analogue with immunosuppressive effects on heart and small bowel grafts (1994)

The vitamin D analogue MC 1288 (20-epi-1 alpha,25-dihydroxycholecalciferol) was tested here for its possible immunosuppressive properties in vivo using different rat transplantation models. MC 1288, in a dose of 0.1 microgram/kg daily, administered intraperitoneally for 10 days, was found to be effective in prolonging cardiac allograft survival. Untreated recipients rejected their grafts around day 8 while MC 1288 treatment delayed rejection until day 22 (P < 0.001). Addition of the immunostimulatory drug LS-2616 (Linomide) reduced the immunosuppressive effect of MC 1288 and rejection occurred around day 11. The immunosuppressive effect of MC 1288 on rejection following small bowel transplantation was determined by measuring the amounts of hyaluronan (HA) secreted into the intestinal lumen. On day 6 post-transplantation the amounts of intraluminal HA in untreated animals was 29.2 +/- 5.3 ng/min and cm, while in MC 1288-treated animals it was just 5.0 +/- 1.6 ng/min and cm (P < 0.01). We conclude that MC 1288 has immunosuppressive effects that may make it suitable for the prevention of graft rejection.
Current Therapy for Infrarenal Aortic Aneurysms (1997)

In 1951 the treatment of abdominal aortic aneurysms was revolutionized when Dubost et al. successfully replaced such an aneurysm with a homograft.1 Before that seminal operation, the treatment of abdominal aortic aneurysms was ineffective because there was no treatment that could prevent the lethal rupture of these aneurysms. The goal of surgical treatment was to prevent rupture, with acceptable rates of operative morbidity and mortality. Over the ensuing 46 years, surgical therapy has been refined so that aortic reconstruction has become a safe and frequently performed procedure, with approximately 46,000 repairs carried out in 1992 in the United States.2 Such . . .
Sequence Variants at 22q13 Are Associated with Prostate Cancer Risk (2008)

To search for genetic variants that are associated with prostate cancer risk in the genome, we combined the data from our genome-wide association study (GWAS) in a population-based case-control study in Sweden with publicly available GWAS data from the Cancer Genetic Markers of Susceptibility (CGEMS) study. We limited the cases to those with aggressive disease in an attempt to identify risk variants that are associated with this most clinically relevant form of the disease. Among the most likely candidate single nucleotide polymorphisms (SNP) identified from the two GWAS, we sequentially confirmed one SNP at 22q13 in two independent study populations: the remaining subjects in Cancer of the Prostate in Sweden and a hospital-based case-control study at Johns Hopkins Hospital. Association of aggressive prostate cancer with the SNP at 22q13 was also observed in the publicly available data of four additional study populations from the second stage of the CGEMS study. In all seven study populations examined, the frequency of allele "C" of rs9623117 at 22q13 was consistently higher in aggressive cases than in controls. The combined allelic test was highly significant, with P = 5.0 x 10(-7). The odds ratio (OR) of allele C for aggressive prostate cancer was estimated to be 1.18 [95% confidence interval (95% CI), 1.11-1.26]. However, the SNP was also associated with nonaggressive prostate cancer, with an estimated OR of 1.11 (95% CI, 1.04-1.19; P = 0.004). The risk-associated variants are located within the genomic region of TNRC6B, a gene involved in miRNA-mediated mRNA degradation. Additional studies are warranted to further confirm the association.
Influenza virus hemagglutinin-specific antibodies isolated from a combinatorial expression library are closely related to the immune response of the donor. (1990)

Antibodies specific for the influenza virus hemagglutinin have been isolated from a combinatorial expression library generated using mRNA obtained from an immunized donor mouse. Sequence analysis indicates that the antibody heavy chain variable regions were derived from members of an expanded hemagglutinin-specific B-cell clone, in conjunction with one of two light chain variable regions. Moreover, the most frequently identified heavy chain variable/light chain variable combination is extremely similar to a heavy chain variable/light chain variable combination that has previously been identified among hemagglutinin-specific hybridoma antibodies. The results, therefore, demonstrate that these antibodies bear a close relationship to the immune status of the donor mouse and suggest that simple adaptations of this procedure might allow evaluation of the immune responses of species, such as man, in which conventional hybridoma techniques have to date proven ineffective.
GENETIC AND PHENOTYPIC VARIATION OF WEST NILE VIRUS IN NEW YORK, 2000–2003 (2004)

West Nile virus (WNV) strains circulating during the first five years of WNV transmission in New York were collected, partial nucleotide sequences were determined, and in vitro and in vivo phenotypic analyses of selected strains were undertaken to determine whether observed increases in the intensity of enzootic and epidemic transmission in New York State during 2002 and 2003 were associated with viral genetic changes. Functionally diverse regions of the WNV genome were also compared to determine whether some regions may be more or less variable than others. The complete envelope coding regions of 67 strains and fragments of the nonstructural protein 5 (NS5) and 3' noncoding regions of 39 strains collected during 2002 and 2003 were examined. West Nile virus in New York remains relatively genetically homogeneous. Viral genetic diversity was greater in 2002 and 2003 at both the nucleotide and amino acid levels than in previous years due to the emergence of a new WNV genotype in 2002. This genotype persisted and became dominant in 2003. Envelope and NS5 coding regions were approximately two-fold more likely than the 3' untranslated region to contain nucleotide substitutions, and the envelope region was approximately three-fold more likely to contain amino acid substitutions than the NS5 region. Variation was noted in in vivo mosquito transmission assays, but not in in vitro growth studies. Strains belonging to the epizootiologically dominant clade were transmitted after approximately two fewer days of extrinsic incubation, providing a possible mechanism for the dominance of this clade. The observed increase in the intensity of WNV transmission beginning in 2002 was associated with an increase in viral genetic diversity that was the result of the emergence of an additional phylogenetic clade. This genotype seems to possess an advantage over previously recognized WNV strains in mosquito transmission phenotype.
Flow Cytometric Screening of cDNA Expression Libraries for Fluorescent Proteins (2004)

Fluorescence-activated cell sorting (FACS) was applied for quantitative screening of cDNA expression libraries in bacteria for rare fluorescent protein encoding cDNAs. Rare fluorescent cells, observed at a frequency of 1 in 200,000 bacteria in a cDNA expression library constructed from Astrangia lajollaensis, were detected, enriched, and purified by sorting, yielding three distinct green fluorescent proteins. Two of the isolated fluorescent proteins were found to be 2.5-fold brighter in whole cell fluorescence than the widely used and already optimized EGFP variant and possessed a novel cysteine-containing chromophore. FACS can possess significant advantages in the screening of cDNA libraries in bacteria, since desired genes may occur at low frequencies and possess unexpected properties. This strategy provides a high-throughput, quantitative approach for isolating fluorescent proteins from a more diverse range of organisms and should be extendable to proteins that are not intrinsically fluorescent with the use of available fluorescent indicators.
Comparative Analysis of Prokaryotic Communities Associated with Organic and Conventional Farming Systems (2015)

One of the most important challenges in agriculture is to determine the effectiveness and environmental impact of certain farming practices. The aim of present study was to determine and compare the taxonomic composition of the microbiomes established in soil following long-term exposure (14 years) to a conventional and organic farming systems (CFS and OFS accordingly). Soil from unclared forest next to the fields was used as a control. The analysis was based on RT-PCR and pyrosequencing of 16S rRNA genes of bacteria and archaea. The number of bacteria was significantly lower in CFS than in OFS and woodland. The highest amount of archaea was detected in woodland, whereas the amounts in CFS and OFS were lower and similar. The most common phyla in the soil microbial communities analyzed were Proteobacteria (57.9%), Acidobacteria (16.1%), Actinobacteria (7.9%), Verrucomicrobia (2.0%), Bacteroidetes (2.7%) and Firmicutes (4.8%). Woodland soil differed from croplands in the taxonomic composition of microbial phyla. Croplands were enriched with Proteobacteria (mainly the genus Pseudomonas), while Acidobacteria were detected almost exclusively in woodland soil. The most pronounced differences between the CFS and OFS microbiomes were found within the genus Pseudomonas, which significantly (p<0,05) increased its number in CFS soil compared to OFS. Other differences in microbiomes of cropping systems concerned minor taxa. A higher relative abundance of bacteria belonging to the families Oxalobacteriaceae, Koribacteriaceae, Nakamurellaceae and genera Ralstonia, Paenibacillus and Pedobacter was found in CFS as compared with OFS. On the other hand, microbiomes of OFS were enriched with proteobacteria of the family Comamonadaceae (genera Hylemonella) and Hyphomicrobiaceae, actinobacteria from the family Micrococcaceae, and bacteria of the genera Geobacter, Methylotenera, Rhizobium (mainly Rhizobium leguminosarum) and Clostridium. Thus, the fields under OFS and CFS did not differ greatly for the composition of the microbiome. These results, which were also confirmed by cluster analysis, indicated that microbial communities in the field soil do not necessarily differ largely between conventional and organic farming systems.
Functional Characterization of MHC Class II-Restricted CD8+CD4− and CD8−CD4− T Cell Responses to Infection in CD4−/− Mice (2004)

Abstract Classical CD4+ and CD8+ T cells recognize Ag presented by MHC class II (MHCII) and MHC class I (MHCI), respectively. However, our results show that CD4−/− mice mount a strong, readily detectable CD8+ T cell response to MHCII-restricted epitopes after a primary bacterial or viral infection. These MHCII-restricted CD8+CD4− T cells are more similar to classical CD8+ T cells than to CD4+ T cells in their expression of effector functions during a primary infection, yet they also differ from MHCI-restricted CD8+ T cells by their inability to produce high levels of the cytolytic molecule granzyme B. After resolution of a primary infection, epitope-specific MHCII-restricted T cells in CD4−/− mice persist for a long period of time as memory T cells. Surprisingly, upon reinfection the secondary MHCII-restricted response in CD4−/− mice consists mainly of CD8−CD4− T cells. In contrast to CD8+ T cells, MHCII-restricted CD8−CD4− T cells are capable of producing IL-2 in addition to IFN-γ and thus appear to have attributes characteristic of CD4+ T cells rather than CD8+ T cells. Therefore, MHCII-restricted T cells in CD4−/− mice do not share all phenotypic and functional characteristics with MHCI-restricted CD8+ T cells or with MHCII-restricted CD4+ T cells, but, rather, adopt attributes from each of these subsets. These results have implications for understanding thymic T cell selection and for elucidating the mechanisms regulating the peripheral immune response and memory differentiation.
Efficient time series matching by wavelets (1999)

Time series stored as feature vectors can be indexed by multidimensional index trees like R-Trees for fast retrieval. Due to the dimensionality curse problem, transformations are applied to time series to reduce the number of dimensions of the feature vectors. Different transformations like Discrete Fourier Transform (DFT) Discrete Wavelet Transform (DWT), Karhunen-Loeve (KL) transform or Singular Value Decomposition (SVD) can be applied. While the use of DFT and K-L transform or SVD have been studied on the literature, to our knowledge, there is no in-depth study on the application of DWT. In this paper we propose to use Haar Wavelet Transform for time series indexing. The major contributions are: (1) we show that Euclidean distance is preserved in the Haar transformed domain and no false dismissal will occur, (2) we show that Haar transform can outperform DFT through experiments, (3) a new similarity model is suggested to accommodate vertical shift of time series, and (4) a two-phase method is proposed for efficient n-nearest neighbor query in time series databases.
Cross-Linking of CD32 Induces Maturation of Human Monocyte-Derived Dendritic Cells Via NF-κB Signaling Pathway (2003)

Dendritic cells (DC) represent a unique set of APCs that initiate immune responses through priming of naive T cells. Maturation of DC is a crucial step during Ag presentation and can be induced by triggering a broad spectrum of DC surface receptors. Although human DC express several receptors for the Fc portion of IgG which were described to play an important role in Ag internalization, little is known about the effects of IgG or immune complexes on DC maturation. In this study, we show that cross-linking of FcgammaR-type II (CD32) with immobilized IgG (imIgG) can induce maturation of human monocyte-derived DC via the NF-kappaB signaling pathway. IgG-mediated maturation was accompanied by a moderate increase of IL-10 secretion, whereas no IL-12 production was observed. Involvement of CD32 was further supported by experiments with the anti-CD32 mAb, which blocked IgG-triggered DC maturation and cytokine secretion significantly. Furthermore, DC cultivated in the presence of imIgG induced allogeneic T cell proliferation. Because this imIgG-induced maturation was considerably impaired in monocyte-derived DC from systemic lupus erythematosus patients, we suggest that DC, which matured in the presence of immune complexes, may contribute to prevention of pathological immune responses.