gebhart/patrepeval huggingface dataset:
THE PATHOGENESIS OF RHEUMATOID ARTHRITIS: FROM MOLECULES TO THE WHOLE PATIENT (1993)

The pathogenesis of RA has now been worked out in considerable detail. The cell types involved have been characterized: monocyte/macrophages, T and B cells, synoviocytes and endothelial cells. The processes which are involved include cell adhesion and migration, T and B cell activation, cytokine release and joint destruction. The molecules which participate in these complex interactions have, for the most part, been cloned and sequenced and the function of their products studied intensively. However, despite the knowledge gathered by this reductionist approach we still do not understand fully the pathogenesis of the disease. This problem is resolvable by considering the fact that the synovitis is taking place within an individual in whom a number of other complex systems are interacting with the immune system. Of these, the neuroendocrine system is probably one of the most important as it has the ability to downregulate inflammation through the secretion of cortisol. Study of the hypothalamic-pituitary-adrenal axis in patients with RA has shown that it responds poorly to inflammatory stimuli. This defect may not only be an important factor in determining the severity of joint inflammation but could be an important early event in the switch from acute to joint inflammation. These findings reinforce the belief that exciting and high quality clinical research is still of crucial importance in our understanding of complex biological processes such as RA.
An Adenovirus Recombinant that Expresses the Human Cytomegalovirus Major Envelope Glycoprotein and Induces Neutralizing Antibodies (1990)

The gene of the human cytomegalovirus (HCMV) major envelope glycoprotein, gB, was cloned from the Towne strain and inserted into adenovirus type 5 downstream of the E3 promoter. The recombinant virus, Ad-gB, expressed antigenically related proteins of 58, 30, 25, and 23 kDa in A549 and MRC-5 cells; the 58-kDa protein had the same mobility as the native gB from HCMV-infected MRC-5 cells and virions. All four proteins were detected by a monospecific polyclonal antiserum and by a monoclonal antibody in immunoblot and immunofluorescence assays. Hamsters infected intranasally with live Ad-gB developed protein-specific and HCMV-neutralizing antibody. This study confirms the importance of gB in the generation of the neutralizing immune response to HCMV and demonstrates the potential of live adenoviruses as vaccine vectors.
Preparation and properties of poly 2'-O-ethylcytidylic acid. (1976)

Poly 2*-O-ethylcytidylic acid (poly (Ce)) was prepared by polymerization of 2'-0-ethylcytidine-5 l -pyrophosphate with Escherichia c o l l polynucleotide phospharyla.se i n the presence of I&i ++ , and i t s properties compared with those of poly (rC), poly (Cm) and poly ( d C ) . The neutral form of poly (Ce) e x h i b i t s properties similar t o those of poly (rC) and poly (Cm). I t a l s o forms an acid twin-stranded h e l i x with a t r a n s i t i o n pH of 5 . 9 i n 0.1 M NaCl. The neutral farm readily forms a double-stranded h e l i c a l complex with poly ( r l ) . Relative t o poly (Cm), replacement of the 2'-0-methyl by 2'-O-ethyl leads t o increased enhancement of the thermal s t a b i l i t i e s of both the acid h e l i c a l form of poly (Ce) and i t s complex with poly ( r l ) .
Synthesis and Characterization of Titania-Sugar Alcohol Complex Nanoparticles (2006)

Complexes between TiO2 and sugar alcohol molecules or polyol molecules were prepared by heating the mixture of titanium isopropoxide (TIP) and ethylene glycol, glycerin, meso-erythritol, or D-mannitol aqueous solution at 368 K for 24 h. The degree of crystallization of TiO2 in the obtained TiO2-sugar alcohol or polyol complex depended on the concentration of the polyol and sugar alcohol aqueous solution. When the TiO2-sugar alcohol or polyol complex was prepared by using the same concentration of the sugar alcohol or polyol aqueous solution, the degree of crystallization of the TiO2 in the complex decreased with increase in the number of OH groups per molecule. According to the results of the DTA measurements and the element analysis, the strength of the interaction between Ti4+ ions and polyol or sugar alcohol molecules increased with increases in the number of OH groups in the molecules. The heat treatment of TiO2-D-mannitol complex in 0.5 mol/l HNO3 aqueous solution at more than 318 K enabled to obtain TiO2-D-mannitol complex nanoparticles by breaking the bonds between the D-mannitol molecules and Ti4+ ions. The obtained TiO2-D-mannitol complex nanoparticles had large surface area which was more than 300 m2/g and showed photocatalytic activity. Furthermore, the complex nanoparticles can be dispersed into the distilled water with high stability.
Rapid and Efficient DNA Strand Cross‐Linking by Click Chemistry (2008)

Click chemistry has been used to covalently cross-link complementary DNA strands between bases to form very stable duplexes. Several alkyne- and azide-modified uracil monomers were used to evaluate the effect of the linkers on the efficiency of the click reaction. All cross-linked duplexes had much higher thermal stabilities than non-cross-linked ones, with increases in melting temperature of up to 30 degrees C. In some cases, the conversion was near-quantitative, and the reaction was complete in 5 min.
The role of the right ventricle in pulmonary arterial hypertension (2011)

Although changes in the pulmonary vasculature are the primary cause of pulmonary arterial hypertension (PAH), severity of symptoms and survival are strongly associated with right ventricular function, and right heart failure is the main cause of death in patients with PAH. Echocardiography and cardiac magnetic resonance imaging allow noninvasive evaluation of right ventricular function and structure, and a number of indices have been shown to have potential prognostic value in PAH. Given the importance of the right ventricle in PAH, preservation and improvement of its function should be important aspects of therapy; however, there are currently few data specifically related to this aspect of treatment response. Simple, reproducible, noninvasive measures of right ventricular function would help to improve the management of patients with PAH, and to provide tools with which to help establish the optimal therapeutic approach to manage not only the effects of the disease on the pulmonary vasculature, but also to support and improve right ventricular function.
Gingko biloba (Rökan) therapy in tinnitus patients and measurable interactions between tinnitus and vestibular disturbances. (2000)

Tinnitus is one of the most important symptoms in neurootology after vertigo, nausea, and hearing loss. In most cases, the origin of the tinnitus remains inexplicable. Well-known, however, is that tinnitus may arise in any part of the hearing pathway (i.e., both within the cochlea receptor and in the temporal lobe and projections). Tinnitus also is associated frequently with vertigo, nausea and hearing loss. An age predominance exists, with tinnitus more common among those older than 40 years. From this starting point, a great demand exists today for new ideas and developments in the diagnosis and treatment of tinnitus.
Low-loss semiconductor waveguide bends (1988)

An experimental comparison is made between the losses of waveguide bends in disorder-delineated waveguides in semiconductor superlattices composed of GaAs and AlAs layers for simple abrupt bends and abrupt bends with an additional half-angle guiding wall proposed by Shiina et al. [Opt. Lett. 11, 736 (1986)]. For light above the band gap of bulk GaAs, the abrupt and Shiina bends were found to have to 3-dB loss angles of 3 and 7 deg, respectively. This improved performance suggests that the specific geometry of the bends is yet another degree of freedom in designing guiding structure for planar routing.
Glycosylation and intracellular transport of membrane glycoproteins encoded by murine leukemia viruses. Inhibition by amino acid analogues and by tunicamycin. (1982)

Addition of asparagine-linked oligosaccharides to nascent murine leukemia virus (MuLV)-encoded membrane glycoproteins was inhibited either completely by tunicamycin or specifically at Asn-X-Thr glycosylation sites by incorporation of the threonine analogue beta-hydroxynorvaline. In conditions of partial analogue substitution, a series of subglycosylated components is formed which are related by a constant apparent Mr difference when assayed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The total number of asparagine-linked oligosaccharides is then estimated by dividing the measured apparent Mr of one oligosaccharide into the total apparent Mr difference between the complete glycoprotein and the polypeptide chain that is synthesized in cells incubated with tunicamycin. Correct results were obtained using glycoproteins with known numbers of oligosaccharides. Our analyses indicate that the gp70 membrane envelope glycoproteins of certain ecotropic MuLVs contain seven oligosaccharides, whereas the GIX+ antigen-containing variant gp70 contains one fewer Asn-X-Thr-linked oligosaccharide. The membrane glycoprotein encoded by the gag gene of Friend MuLV contains only one asparagine-linked oligosaccharide. Similarly, the gp55 membrane glycoprotein encoded by Friend erythroleukemia virus contains four asparagine-linked oligosaccharides. Pulse-chase and cell surface iodination analyses indicate that MuLV membrane envelope glycoprotein processing by partial proteolysis and transport to the cell surface can be efficiently blocked by structural perturbations caused by incorporation of different amino acid analogues or by loss of oligosaccharides. Our data also suggest that loss of oligosaccharides may expose new antigenic sites in viral membrane glycoproteins and increase their susceptibility to intracellular proteolysis.
Microbiota Downregulates Dendritic Cell Expression of miR-10a, Which Targets IL-12/IL-23p40 (2011)

Commensal flora plays important roles in the regulation of the gene expression involved in many intestinal functions and the maintenance of immune homeostasis, as well as in the pathogenesis of inflammatory bowel diseases. The microRNAs (miRNAs), a class of small, noncoding RNAs, act as key regulators in many biological processes. The miRNAs are highly conserved among species and appear to play important roles in both innate and adaptive immunity, as they can control the differentiation of various immune cells, as well as their functions. However, it is still largely unknown how microbiota regulates miRNA expression, thereby contributing to intestinal homeostasis and pathogenesis of inflammatory bowel disease. In our current study, we found that microbiota negatively regulated intestinal miR-10a expression, because the intestines, as well as intestinal epithelial cells and dendritic cells of specific pathogen-free mice, expressed much lower levels of miR-10a compared with those in germ-free mice. Commensal bacteria downregulated dendritic cell miR-10a expression via TLR-TLR ligand interactions through a MyD88-dependent pathway. We identified IL-12/IL-23p40, a key molecule for innate immune responses to commensal bacteria, as a target of miR-10a. The ectopic expression of the miR-10a precursor inhibited, whereas the miR-10a inhibitor promoted, the expression of IL-12/IL-23p40 in dendritic cells. Mice with colitis expressing higher levels of IL-12/IL-23p40 exhibited lower levels of intestinal miR-10a compared with control mice. Collectively, our data demonstrated that microbiota negatively regulates host miR-10a expression, which may contribute to the maintenance of intestinal homeostasis by targeting IL-12/IL-23p40 expression.
Ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic acid. Repression of IFN-γ-induced MHC class II gene expression via a glucocorticoid receptor-dependent pathway (1996)

The therapeutic effectiveness of ursodeoxycholic acid (UDCA) for various autoimmune liver diseases strongly indicates that UDCA possesses immunomodulatory activities. Experimental evidence also supports this notion, since, for example, UDCA has been shown to suppress secretion of IL-2, IL-4, and IFN-gamma from activated T lymphocytes, and Ig production from B lymphocytes. To investigate the mechanical background of UDCA-mediated immunomodulation, we asked whether UDCA interacts with the intracellular signal transduction pathway, especially whether it is involved in immunosuppressive glucocorticoid hormone action. For this purpose, we used a cloned Chinese hamster ovary cell line, CHOpMTGR, in which glucocorticoid receptor cDNA was stably integrated. In immunocytochemical analysis, we found that treatment with UDCA promoted the nuclear translocation of the glucocorticoid receptor in a ligand-independent fashion, which was further confirmed by immunoprecipitation assays. Moreover, the translocated glucocorticoid receptor demonstrated sequence-specific DNA binding activity. Transient transfection experiments revealed that treatment of the cells with UDCA marginally enhanced glucocorticoid-responsive gene expression. We also showed that UDCA suppressed IFN-gamma-mediated induction of MHC class II gene expression via the glucocorticoid receptor-mediated pathway. Together, UDCA-dependent promotion of translocation of the glucocorticoid receptor may be associated with, at least in part, its immunomodulatory action through glucocorticoid receptor-mediated gene regulation.
Autocrine regulation of cell proliferation by the insulin-like growth factor (IGF) and IGF binding protein-3 protease system in a human prostate carcinoma cell line (PC-3) (1995)

PC-3 cells, whose growth is androgen-independent, were shown to be capable of slow proliferation in serum-free medium and in the absence of added growth factor for 7 days. They secreted insulin-like growth factor (IGF)-II but no detectable IGF-I. This IGF-II, although produced in small amounts, plays a role in their proliferation because growth could be inhibited dose dependently by up to 80% in the presence of monoclonal antibodies directed against IGFs or the type 1 IGF receptor. PC-3 cells also secreted IGF binding proteins (IGFBPs) -2, -3, -4, and -6. Immunoblot analysis revealed selective proteolysis of IGFBP-3, yielding fragments of the same molecular size as those generated from IGFBP-3 in vivo. With the addition to the culture medium of a serine protease inhibitor, 4-(2-aminoethyl)-benzenesulfonyl fluoride (Pefabloc-SC), at concentrations < 0.2 mM that were nontoxic to the cells, cell proliferation was dose dependently inhibited up to 80% and, at the same time, proteolysis of the IGFBP-3 secreted by the cells was depressed. Urokinase activity detected in the conditioned media was depressed by Pefabloc, suggesting that the urokinase-type plasminogen activator was involved in the proteolysis of IGFBP-3. In addition, 0.01-5 micrograms/ml plasminogen induced a dose-dependent increase in both proliferation and the proportions of proteolysed IGFBP-3 in the media. The stimulation of proliferation was totally blocked in the presence of anti-type 1 IGF receptor antibody. Recombinant human IGF-II (5-200 ng/ml) added to cell-free medium conditioned by 48 h of culture dose dependently stimulated PC-3 cell proliferation. At concentrations < or = 100 ng/ml, its mitogenic action was potentiated when medium had been conditioned by cells cultured in the presence of plasminogen but inhibited when medium had been conditioned by cells cultured in the presence of Pefabloc. We conclude from these results 1) that IGF-II is involved in the autocrine control of PC-3 cell proliferation via the type 1 IGF receptor; and 2) that this proliferation is directly dependent on IGF-II bioavailability that itself is modulated by the limited IGFBP-3 proteolysis induced, at least in part, by urokinase-type plasminogen activator and plasmin.
Successful use of eculizumab for treatment of an acute hemolytic reaction after ABO‐incompatible red blood cell transfusion (2014)

A low isoagglutinin titer and blood group A2 of the erroneously transfused cells most likely were the reason for the absence of clinical signs during and immediately after the ABO-incompatible transfusion. In the further course, eculizumab successfully protected the incompatible RBCs from hemolysis for several weeks.
RNA structure at high resolution (1995)

Studies of RNA structural motifs at high resolution by NMR and X-ray crystallographic methods have provided many insights into the fundamental forces that give rise to the unique structural characteristics of RNA. Non-Watson-Crick purine-pyrimidine, purine-purine, and pyrimidine-pyrimidine base pairing, as well as base-phosphate and base-ribose hydrogen bonding, are important forces for folding and stabilizing RNA structures. Base stacking is as important in determining RNA conformations as hydrogen bonding interactions. With the noncanonical interactions, many single-stranded loop regions such as hairpin loops, bulge loops, and internal loops fold into well-defined secondary structures. Loop-loop and loop-helix interactions can produce tertiary structures such as pseudoknots. Also, single strands adjacent to helical regions can form tertiary contacts with base-paired nucleotides of the helices. As we learn more about the structures of the important motifs we can ask more specific questions about the mechanisms of RNA-mediated functions. Conformational flexibility rather than a specific shape of the RNA may be important for some biological reactions. However, knowledge of the structures and the ease of conformational change of the molecules involved in any process are essential for understanding and eventually controlling the process.
Detection of point mutations by capillary electrophoresis in liquid polymers in temporal thermal gradients (1994)

A new and fast method is described for detection of point mutations in polymerase-chain reaction (PCR)-amplified DNA, based on capillary electrophoresis in sieving liquid polymers in presence of temporal thermal gradients. The background electrolyte contains a constant amount of denaturing agent (e.g., 6 M urea) and the DNA fragments are injected in a constant-temperature plateau below the melting temperature (Tm). After loading, a temperature ramp is activated (typically from 0.2 to 0.6 degrees C/min, according to the melting profiles of the DNA duplexes under investigation) with resultant branching of homo- and heteroduplexes at different times along the migration path. In the case of individuals heterozygous for a point mutation, the expected four-band pattern is obtained. The temperature gradient is not produced externally, via circulating coolant and a thermostat, but is generated internally by using a dedicated computer program able to calculate the precise inner temperature under given electric conditions. The method is applied to the identification of three point mutations located in exon 17b (R1066H, R 1066C, F1052V) and of two polymorphisms located in exon 14a (V868V, T854T) of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Coronin Function Is Required for Chemotaxis and Phagocytosis in Human Neutrophils (2007)

Coronins are a family of conserved actin-associated proteins that have been implicated in a variety of cellular processes dependent on actin rearrangements. In this study, we show that in primary human neutrophils, coronins-1-4 and -7 are expressed. Coronin-1 accumulates at the leading edge of migrating neutrophils and at the nascent phagosome. Inhibition of coronin function by transduction of a dominant-negative form of the protein leads to inhibition of chemotaxis and a reduction in neutrophil spreading and adhesion. This inhibition appears to correlate with changes in the distribution of F-actin structures within the cell. In addition, phagocytosis is inhibited, but neither secretion nor activation of the NADPH oxidase appears to be affected. Together, these results show that coronins are required for actin-dependent changes in cell morphology that lead to migration and phagocytosis.
Binding to heparan sulfate or heparin enhances neutrophil responses to interleukin 8. (1993)

The interaction of interleukin 8 (IL-8) with heparin was studied by using synthetic IL-8 analogs with C- and N-terminal truncations. Elimination of the N-terminal region preceding the first cysteine, which constitutes the IL-8 receptor binding site, did not affect the affinity to heparin-Sepharose. Affinity, however, decreased with progressive truncation at the C terminus, and no binding was observed when the C-terminal alpha-helix was eliminated. The effect of heparin and other glycosaminoglycans on IL-8 activity was also tested. When IL-8 was applied together with heparan sulfate, neutrophil chemotaxis in vitro was enhanced up to 4-fold, and the stimulus-dependent increase in cytosolic free Ca2+ increased markedly in both rate and peak value. Heparin had a similar effect on the Ca2+ response but did not enhance chemotaxis. The glycosaminoglycans by themselves did not elicit neutrophil responses. Their enhancing effect was restricted to stimulation with IL-8 and was not observed when the unrelated chemoattractant fMet-Ile-Phe-Leu was used as the stimulus. Elastase released from stimulated neutrophils was inhibited by heparin, heparan sulfate, and, to a lesser extent, chondroitin sulfate B, confirming previous observations. Taken together, these results suggest that heparan sulfate, which is present on the endothelial cell surface and in the basement membrane, may have a dual function in diapedesis, promotion of IL-8-dependent transmigration of neutrophils, and protection of the tissue microenvironment from damage by lytic enzymes released from the migrating cells.
Global Contrast Based Salient Region Detection (2014)

Automatic estimation of salient object regions across images, without any prior assumption or knowledge of the contents of the corresponding scenes, enhances many computer vision and computer graphics applications. We introduce a regional contrast based salient object detection algorithm, which simultaneously evaluates global contrast differences and spatial weighted coherence scores. The proposed algorithm is simple, efficient, naturally multi-scale, and produces full-resolution, high-quality saliency maps. These saliency maps are further used to initialize a novel iterative version of GrabCut, namely SaliencyCut, for high quality unsupervised salient object segmentation. We extensively evaluated our algorithm using traditional salient object detection datasets, as well as a more challenging Internet image dataset. Our experimental results demonstrate that our algorithm consistently outperforms 15 existing salient object detection and segmentation methods, yielding higher precision and better recall rates. We also show that our algorithm can be used to efficiently extract salient object masks from Internet images, enabling effective sketch-based image retrieval (SBIR) via simple shape comparisons. Despite such noisy internet images, where the saliency regions are ambiguous, our saliency guided image retrieval achieves a superior retrieval rate compared with state-of-the-art SBIR methods, and additionally provides important target object region information.
HTRA3 expression in non-pregnant rhesus monkey ovary and endometrium, and at the maternal-fetal interface during early pregnancy (2008)

We propose that HTRA3 may be involved in folliculogenesis and luteinisation in the primate ovary. Furthermore, similar to previous findings in the human, HTRA3 is possibly a factor involved in and potentially important for primate placentation.