gebhart/patrepeval huggingface dataset:
Role of Receptor Proteins for Enterobactin and 2,3-Dihydroxybenzoylserine in Virulence of Salmonella enterica (2003)

Single, double, and triple mutants of an enterobactin-deficient mutant strain of Salmonella enterica serovar Typhimurium were constructed that were defective in the expression of the iron-regulated outer membrane proteins (IROMPs) FepA, IroN, and Cir, which are proposed to function as catecholate receptors. Uptake of naturally occurring and chemically synthesized catecholate molecules by these mutants was assessed in standard growth promotion assays. Unique patterns of uptake were identified for each IROMP; specifically, FepA and IroN were confirmed to be required for transport of enterobactin, and all three proteins were shown to function as receptors for the enterobactin breakdown product 2,3-dihydroxybenzoylserine. The fepA, iroN, and cir alleles were transduced to enterobactin-proficient strains of S. enterica serovar Typhimurium and S. enterica serovar Enteritidis, and the resulting phenotypes were confirmed by analysis of outer membrane protein profiles, by sensitivity to KP-736, a catecholate-cephalosporin conjugate, and by growth promotion tests on egg white agar. Intragastric infections of mice with the S. enterica serovar Typhimurium strains indicated that the parental strain and the fepA iroN double mutant were similarly virulent but that the fepA iroN cir triple mutant was significantly attenuated. Moreover, in mixed infections, the fepA iroN mutant showed similar cecal colonization and invasion of the liver to the parental strain, while the triple mutant showed significantly reduced cecal colonization and no measurable spread to the liver. Infections of 4-day-old chicks with S. enterica serovar Enteritidis strains also indicated that mutation of the fepA iroN genes did not significantly reduce cecal colonization and systemic spread compared with those of the parental strain. The results indicate that, while enterobactin uptake is not essential for the virulence of S. enterica serovars in mouse and chicken infection models, the ability to take up 2,3-dihydroxybenzoylserine via any of the three catecholate siderophore receptors appears to play an important role, since the S. enterica serovar Typhimurium triple mutant was significantly attenuated in the mouse model. Salmochelins appear not to be involved in the virulence of S. enterica.
Quantitative Fluorescence Imaging Approach for the Study of Polyploidization in Hepatocytes (2003)

We applied automatic quantitative fluorescence imaging of nuclear DNA to rat liver cells obtained from animals at various times after birth up to 3 months of age. We show that, in conditions best preserving the native cellular structures, DNA content measurements, performed on whole single cells in situ after Hoechst staining, were precise and accurate. Cells in the various ploidy and nuclearity classes could thus be identified correctly and their percentages were estimated on a total of 300 cells or more. DNA synthesis was shown to occur asynchronously in all ploidy and nuclearity classes around weaning time. Observation of the labeling patterns, after in vivo BrdU pulse and short-term culture (chase), showed that the cell cycle was shorter in diploid cells compared with cells undergoing polyploidization. These results show that the approach of fluorescence imaging is well suited to investigations on polyploidization mechanisms.
Protection against aerosol Mycobacterium tuberculosis infection using Mycobacterium bovis Bacillus Calmette Guérin-infected dendritic cells (1999)

In the lung, dendritic cells (DC) are key antigen-presenting cells capable of triggering specific cellular responses to inhaled pathogens, and thus, they may be important in the initiation of an early response to mycobacterial infections. The ability of DC to enhance antigen presentation to naive T cells within the lungs was characterized with respect to Mycobacterium bovis Bacillus Calmette Guérin (BCG) vaccination against M. tuberculosis infection. In vitro derived DC were infected with BCG, which induced their maturation, as shown by the increased expression of MHC class II antigens, CD80 and CD86 co-stimulatory molecules. The synthesis of mRNA for IL-1, IL-6, IL-12, IL-10 and IL-1 receptor antagonist was also enhanced. When administered intratracheally in mice, infected DC induced a potent T cell response and the production of IFN-γ to mycobacterial antigens in the mediastinal lymphnodes, leading to a significant protection against aerosol M. tuberculosis infection. Intriguingly, although the vaccination schedule for BCG-infected DC was much shorter than subcutaneous BCG vaccination (7 days as compared to 100 days), both types of vaccination showed similar levels of protection. These data confirm that DC can be potent inducers of a cellular immune response against mycobacteria and support the concept of combining DC strategies with mycobacterial vaccines for protective immunity against tuberculosis.
Structural and functional relationships among the RTX toxin determinants of Gram-negative bacteria (1992)

The RTX (repeats in toxin) cytolytic toxins represent a family of important virulence factors that have disseminated widely among Gram-negative bacteria. They are characterised by a series of glycine-rich repeat units at the C-terminal end of each protein. They also have other features in common. Secretion from the cell occurs without a periplasmic intermediate by a novel mechanism which involves recognition of a signal sequence at the C-terminus of the toxin by membrane-associated proteins that export the toxin directly to the outside of the cell. The structural gene for each protein encodes an inactive toxin which is modified post-translationally to an active cytotoxic form by another gene product before secretion. The genes for toxin synthesis, activation and secretion are for the most part grouped together on the chromosome and form an operon. The toxins all create pores in the cell membrane of target cells leading to eventual cell lysis and they appear to require Ca2+ for cytotoxic activity. Although the toxins have a similar mode of action, they vary in target cell specificity. Some are cytotoxic for a wide variety of eukaryotic cell types while others exhibit precise target cell specificity and are only active against leukocytes from certain host species. The characteristic glycine-rich repeat units have been identified in other exoproteins besides those with cytotoxic activity and it is likely that the novel secretory mechanism has been harnessed by a variety of pathogens to release important virulence-associated factors from the cell or to locate them on the cell surface.
Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects (2013)

Invasion of microbial DNA into the cytoplasm of animal cells triggers a cascade of host immune reactions that help clear the infection; however, self DNA in the cytoplasm can cause autoimmune diseases. Biochemical approaches led to the identification of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) as a cytosolic DNA sensor that triggers innate immune responses. Here, we show that cells from cGAS-deficient (cGas(-/-)) mice, including fibroblasts, macrophages, and dendritic cells, failed to produce type I interferons and other cytokines in response to DNA transfection or DNA virus infection. cGas(-/-) mice were more susceptible to lethal infection with herpes simplex virus 1 (HSV1) than wild-type mice. We also show that cGAMP is an adjuvant that boosts antigen-specific T cell activation and antibody production in mice.
Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study (2001)

The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis) to be treated by topical PDT of skin cancer.
Active-Site Models for Iron Hydrogenases:  Reduction Chemistry of Dinuclear Iron Complexes (2006)

Reduction of Fe2(mu-S2C3H6)(CO)6 (1) in tetrahydrofuran with 1 equiv of decamethylcobaltocene (Cp*2Co) affords a tetranuclear dianion 2. The IR spectra of samples of 2 in solution and in the solid state exhibit a band at 1736 cm(-1), suggestive of the presence of a bridging carbonyl (CO) ligand. X-ray crystallography confirms that the structure of 2 consists of two Fe2 units bridged by a propanedithiolate moiety formulated as [Fe2(mu-S2C3H6)(CO)5(SCH2CH2CH2-mu-S)Fe2(mu-CO)(CO)6](2-). One of the Fe2 units has a bridging CO ligand and six terminal CO ligands. The second subunit exhibits a bridging propanedithiolate moiety. One CO ligand has been replaced by a terminal thiolate ligand, replicating the basic architecture of Fe-only hydrogenases. The reduction reaction can be reversed by treatment of 2 with 2 equiv of [Cp2Fe][PF6], reforming complex 1 in near-quantitative yield. Complex 2 can also be oxidized by acids such as p-toluenesulfonic acid, regenerating complex 1 and forming H2.
Estimating the number of people in crowded scenes by MID based foreground segmentation and head-shoulder detection (2008)

This paper proposes a novel method to address the problem of estimating the number of people in surveillance scenes with people gathering and waiting. The proposed method combines a MID (mosaic image difference) based foreground segmentation algorithm and a HOG (histograms of oriented gradients) based head-shoulder detection algorithm to provide an accurate estimation of people counts in the observed area. In our framework, the MID-based foreground segmentation module provides active areas for the head-shoulder detection module to detect heads and count the number of people. Numerous experiments are conducted and convincing results demonstrate the effectiveness of our method.
Terminal structure and heterogeneity in human cytomegalovirus strain AD169 (1986)

We have characterized the heterogeneity occurring at the junction of the long (L) and short (S) segments and at the termini of the strain AD169 human cytomegalovirus (HCMV) genome by restriction endonuclease mapping and nucleotide sequence analyses. The HCMV a sequence was identified by its position at both termini and inverted orientation at the L-S junction. Heterogeneity at both termini and the L-S junction was generated by the presence of fused and tandem a sequences. Some S termini lacked an a sequence. In addition, near the L terminus and at the L-S junction there were a variable number of 217-base-pair (bp) XhoI fragments arranged in tandem. The 217-bp fragments consisted of a portion of the a and adjacent b sequences (in the L-segment repeat) bounded by the same direct repeats (DR1) found at the boundaries of the a sequence. A model for the generation of these heterogeneous fragments is presented. We also determined the sequence of seven cloned terminal fragments, five from the L terminus and two from the S terminus. All L termini contained identical terminal sequences ending with base 32 of a 33-bp DR1. The S termini differed from each other and from the L-segment termini. One S terminus lacked an a sequence and terminated within S-segment repeat (c) sequences. The second S terminus contained an a sequence and terminated with bases 20 to 33 of a 33-bp DR1. A comparison of the cloned L and S terminal sequences with cloned L-S junction sequences suggested that the termini contained 3' single base extensions which were removed during the cloning. We also show that the herpesvirus conserved sequence is in a similar position relative to the termini of HCMV and several other herpesviruses, thus adding further support for the role of the sequence in the maturation of viral DNA.
Ff-nano, short functionalized nanorods derived from Ff (f1, fd, or M13) filamentous bacteriophage (2015)

F-specific filamentous phage of Escherichia coli (Ff: f1, M13 or fd) are long thin filaments (860 nm x 6 nm). They have been a major workhorse in display technologies and bionanotechnology; however, some applications are limited by the high length-to-diameter ratio of Ff. Furthermore, use of functionalized Ff outside of laboratory containment is in part hampered by the fact that they are genetically modified viruses. We have now developed a system for production and purification of very short functionalized Ff-phage-derived nanorods, named Ff-nano, that are only 50 nm in length. In contrast to standard Ff-derived vectors that replicate in E. coli and contain antibiotic-resistance genes, Ff-nano are protein DNA complexes that cannot replicate on their own and do not contain any coding sequences. These nanorods show an increased resistance to heating at 70 °C in 1 % SDS in comparison to the full-length Ff phage of the same coat composition. We demonstrate that functionalized Ff-nano particles are suitable for application as detection particles in sensitive and quantitative “dipstick” lateral flow diagnostic assay for human plasma fibronectin.
Design and Implementation of an Application. Programming Interface for Volume Rendering (2002)

To efficiently examine volumetric data sets from CT or MRI scans good volume rendering applications are needed. This thesis describes the design and implementation of an application programming interface (API) to be used when developing volume-rendering applications. A complete application programming interface has been designed. The interface is designed so that it makes writing application programs containing volume rendering fast and easy. The interface also makes created application programs hardware independent. Volume rendering using 3d-textures is implemented on Windows and Unix platforms. Rendering performance has been compared between different graphics hardware.
Complexities of CD28/B7: CTLA-4 Costimulatory Pathways in Autoimmunity and Transplantation (2001)

Recent advances in the understanding of T cell activation have led to new therapeutic approaches in the treatment of immunological disorders. One attractive target of intervention has been the blockade of T cell costimulatory pathways, which result in more selective effects on only those T cells that have encountered specific antigen. In fact, in some instances, costimulatory pathway antagonists can induce antigen-specific tolerance that prevents the progression of autoimmune diseases and organ graft rejection. In this review, we summarize the current understanding of these complex costimulatory pathways including the individual roles of the CD28, CTLA-4, B7-1 (CD80), and B7-2 (CD86) molecules. We present evidence that suggests that multiple mechanisms contribute to CD28/B7-mediated T cell costimulation in disease settings that include expansion of activated pathogenic T cells, differentiation of Th1/Th2 cells, and the migration of T cells into target tissues. Additionally, the negative regulatory role of CTLA-4 in autoimmune diseases and graft rejection supports a dynamic but complex process of immune regulation that is prominent in the control of self-reactivity. This is most apparent in regulation of the CD4(+)CD25(+)CTLA-4(+) immunoregulatory T cells that control multiple autoimmune diseases. The implications of these complexities and the potential for use of these therapies in clinical immune intervention are discussed.
Heterogeneous Nuclear Ribonucleoprotein A1 Interferes with the Binding of the Human T Cell Leukemia Virus Type 1 Rex Regulatory Protein to Its Response Element (2002)

The human T cell leukemia virus, type 1 (HTLV-1), Rex protein mediates the nuclear export of unspliced and incompletely spliced viral mRNAs. This post-transcriptional activity is dependent in part on the binding of this protein to cis-regulatory sequences termed the Rex-response element (XRE). We have proposed previously that the decreased functionality exhibited by Rex in human lymphoblastoid Jurkat T cells may be linked to alterations in the Rex/XRE interactions. The analysis of the ribonucleoprotein complexes formed between Jurkat nuclear proteins and XRE-RNA led to the identification of a 36-kDa protein as heterogeneous nuclear ribonucleoprotein (hnRNP) A1. In vitro binding assays revealed that hnRNP A1 proteins were found to interfere with the binding of Rex to XRE, whereas nuclear extracts depleted of these proteins were unable to disrupt Rex-XRE complexes. Furthermore, A1 proteins from Jurkat cells were acting in a concentration-dependent manner, suggesting that the amount of these RNA-binding proteins is a critical parameter in controlling Rex activity. We indeed observed a lower level of hnRNP A1 in in vitro HTLV-1-transformed virus-producing T cells than that detected in Jurkat cells. Likewise, overexpression of hnRNP A1 proteins in 293T cells and in Jurkat cells led to a decrease in the expression of a reporter gene dependent on Rex/XRE interactions. Such a decrease was not observed when the expression of the same reporter gene by cells overexpressing hnRNP A1 was dependent on the interactions of human immunodeficiency virus Rev protein with the Rev-response element. These findings indicate that hnRNP A1 by competing with Rex for the formation of REX-XRE complexes is specifically involved in the modulation of the post-transcriptional activity of Rex.
The MARCKS Protein Plays a Critical Role in Phosphatidylinositol 4,5-Bisphosphate Metabolism and Directed Cell Movement in Vascular Endothelial Cells (2010)

The MARCKS protein (myristoylated alanine-rich C kinase substrate) is an actin- and calmodulin-binding protein that is expressed in many mammalian tissues. The role of MARCKS in endothelial signaling responses is incompletely understood. We found that siRNA-mediated knockdown of MARCKS in cultured endothelial cells abrogated directed cell movement in a wound healing assay. We used biochemical and cell imaging approaches to explore the role of MARCKS in endothelial signal transduction pathways activated by insulin. Insulin treatment of vascular endothelial cells promoted the dose- and time-dependent phosphorylation of MARCKS. Cell imaging and hydrodynamic approaches revealed that MARCKS is targeted to plasmalemmal caveolae and undergoes subcellular translocation in response to insulin. Insulin treatment promoted an increase in levels of the signaling phospholipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) in plasmalemmal caveolae. The insulin-stimulated increase in caveolar PIP(2) was blocked by siRNA-mediated knockdown of MARCKS, as determined using both biochemical assays and imaging studies using FRET-based PIP(2) biosensors. The critical role of PIP(2) in MARCKS responses was explored by examining the PIP(2)- and actin-binding proteins Arp2/3 and N-WASP. Insulin promoted the rapid and robust phosphorylation of both N-WASP and Arp2/3, but these phosphorylation responses were markedly attenuated by siRNA-mediated MARCKS knockdown. Moreover, MARCKS knockdown effectively abrogated N-WASP activation in response to insulin, as determined using a FRET-based N-WASP activity biosensor. Taken together, these studies show that MARCKS plays a key role in insulin-dependent endothelial signaling to PIP(2) and is a critical determinant of actin assembly and directed cell movement in the vascular endothelium.
The Influence of Feature Selection Methods on Accuracy, Stability and Interpretability of Molecular Signatures (2011)

Biomarker discovery from high-dimensional data is a crucial problem with enormous applications in biology and medicine. It is also extremely challenging from a statistical viewpoint, but surprisingly few studies have investigated the relative strengths and weaknesses of the plethora of existing feature selection methods. In this study we compare 32 feature selection methods on 4 public gene expression datasets for breast cancer prognosis, in terms of predictive performance, stability and functional interpretability of the signatures they produce. We observe that the feature selection method has a significant influence on the accuracy, stability and interpretability of signatures. Surprisingly, complex wrapper and embedded methods generally do not outperform simple univariate feature selection methods, and ensemble feature selection has generally no positive effect. Overall a simple Student's t-test seems to provide the best results.
The presence of codon-anticodon pairs in the acceptor stem of tRNAs. (1996)

A total of 1268 available (excluding mitochondrial) tRNA sequences was used to reconstruct the common consensus image of their acceptor domains. Its structure appeared as a 11-bp-long double-stranded palindrome with complementary triplets in the center, each flanked by the 3'-ACCD and NGGU-5' motifs on each strand (D, base determinator). The palindrome readily extends up to the modern tRNA-like cloverleaf passing through an intermediate hairpin having in the center the single-stranded triplet, in supplement to its double-stranded precursor. The latter might represent an original anticodon-codon pair mapped at 1-2-3 positions of the present-day tRNA acceptors. This conclusion is supported by the striking correlation: in pairs of consensus tRNAs with complementary anticodons, their bases at the 2nd position of the acceptor stem were also complementary. Accordingly, inverse complementarity was also evident at the 71st position of the acceptor stem. With a single exception (tRNA(Phe)-tRNA(Glu) pair), the parallelism is especially impressive for the pairs of tRNAs recognized by aminoacyl-tRNA synthetases (aaRS) from the opposite classes. The above complementarity still doubly presented at the key central position of real single-stranded anticodons and their hypothetical double-stranded precursors is consistent with our previous data pointing to the double-strand use of ancient RNAs in the origin of the main actors in translation- tRNAs with complementary anticodons and the two classes of aaRS.
A comparison of trace-sampling techniques for multi-megabyte caches (1994)

The paper compares the trace-sampling techniques of set sampling and time sampling. Using the multi-billion reference traces of A. Borg et al. (1990), we apply both techniques to multi-megabyte caches, where sampling is most valuable. We evaluate whether either technique meets a 10% sampling goal: a method meets this goal if, at least 90% of the time, it estimates the trace's true misses per instruction with /spl les/10% relative error using /spl les/10% of the trace. Results for these traces and caches show that set sampling meets the 10% sampling goal, while time sampling does not. We also find that cold-start bias in time samples is most effectively reduced by the technique of D.A. Wood et al. (1991). Nevertheless, overcoming cold-start bias requires tens of millions of consecutive references.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
IVIg‐mediated amelioration of ITP in mice is dependent on sialic acid and SIGNR1 (2012)

Intravenous immunoglobulin G (IVIg) therapy is widely used to treat autoimmune and inflammatory diseases. Recent evidence suggests that in mice, splenic resident cells might be important for the anti-inflammatory activity of IVIg in a model of serum transfer arthritis. Splenectomized human immunothrombocytopenia (ITP) patients, however, still respond to IVIg therapy. To investigate whether the requirement of the spleen is essential for mouse ITP, we used a passive model of induced ITP and demonstrated that IVIg activity was functional in splenectomized animals. Further analysis showed that the IVIg-mediated amelioration of platelet phagocytosis was fully dependent on terminal sialic acid residues in the IVIg preparation and could be blocked with a specific ICAM3 grabbing nonintegrin-related 1 (SIGNR1) specific antibody. These results suggest that, similar to the human system, a spleen-independent but sialic acid- and SIGNR1-dependent pathway is responsible for IVIg-mediated suppression of autoantibody-dependent platelet depletion in mice.