gebhart/patrepeval huggingface dataset:
Alterations of 3p21.31 tumor suppressor genes in head and neck squamous cell carcinoma: Correlation with progression and prognosis (2008)

The aim of our study was to analyze the alterations of some candidate tumor suppressor genes (TSGs) viz. LIMD1, LTF, CDC25A, SCOTIN, RASSF1A and CACNA2D2 located in the chromosomal region 3p21.31 associated with the development of early dysplastic lesions of head and neck. In analysis of 72 dysplastic lesions and 116 squamous cell carcinoma of head and neck, both deletion and promoter methylation have been seen in these genes except for CDC25A and SCOTIN where no methylation has been detected. The alteration of LIMD1 was highest (50%) in the mild dysplastic lesions and did not change significantly during progression of tumor indicating its association with this stage of the disease. It was evident that alterations of LTF, CDC25A and CACNA2D2 were associated with development of moderate dysplastic lesions, while alterations in RASSF1A and CACNA2D2 were needed for progression. Novel somatic mutations were seen in exon 1 of LIMD1 (7%), intron 3/exon4 splice junction of LTF (2%) and exon 7 of cdc25A (10%). Quantitative RT-PCR analysis revealed mean reduced expression of the genes in the following order: LTF (67.6 +/- 16.8) > LIMD1 (53.2 +/- 20.1) > CACNA2D2 (23.7 +/- 7.1) > RASSF1A (15.1 +/- 5.6) > CDC25A (5.3 +/- 2.3) > SCOTIN (0.58 +/- 0.54). Immunohistochemical analysis of CDC25A showed its localization both in cytoplasm and nucleus in primary lesions and oral cancer cell lines. In absence of HPV infection, LTF and RASSF1A alterations jointly have adverse impact on survival of tobacco addicted patients. Thus, our data suggested that multiple candidate TSGs in the chromosomal 3p21.31 region were differentially associated with the early dysplastic lesions of head and neck.
Fresh Frozen Plasma Lessens Pulmonary Endothelial Inflammation and Hyperpermeability After Hemorrhagic Shock and Is Associated With Loss of Syndecan 1 (2013)

We have recently demonstrated that injured patients in hemorrhagic shock shed syndecan 1 and that the early use of fresh frozen plasma (FFP) in these patients is correlated with improved clinical outcomes. As the lungs are frequently injured after trauma, we hypothesized that hemorrhagic shock-induced shedding of syndecan 1 exposes the underlying pulmonary vascular endothelium to injury resulting in inflammation and hyperpermeability and that these effects would be mitigated by FFP. In vitro, pulmonary endothelial permeability, endothelial monolayer flux, transendothelial electrical resistance, and leukocyte-endothelial binding were measured in pulmonary endothelial cells after incubation with equal volumes of FFP or lactated Ringer's (LR). In vivo, using a coagulopathic mouse model of trauma and hemorrhagic shock, pulmonary hyperpermeability, neutrophil infiltration, and syndecan 1 expression and systemic shedding were assessed after 3 h of resuscitation with either 1× FFP or 3× LR and compared with shock alone and shams. In vitro, endothelial permeability and flux were decreased, transendothelial electrical resistance was increased, and leukocyte-endothelial binding was inhibited by FFP compared with LR-treated endothelial cells. In vivo, hemorrhagic shock was associated with systemic shedding of syndecan 1, which correlated with decreased pulmonary syndecan 1 and increased pulmonary vascular hyperpermeability and inflammation. Fresh frozen plasma resuscitation, compared with LR resuscitation, abrogated these injurious effects. After hemorrhagic shock, FFP resuscitation inhibits endothelial cell hyperpermeability and inflammation and restores pulmonary syndecan 1 expression. Modulation of pulmonary syndecan 1 expression may mechanistically contribute to the beneficial effects FFP.
Hormonal Regulation of Hyaluronate Synthesis in Cultured Human Fibroblasts: Evidence for Differences between Retroocular and Dermal Fibroblasts (1989)

Fibroblasts derived from retroocular connective tissue and skin were propagated in culture in an effort to identify structural and functional differences in connective tissue which might explain the apparent region-specific involvement in Graves' disease. Striking morphological differences existed between cultured cells from the two anatomical sites. Inhibition of glycosaminoglycan (GAG) accumulation by T3 and dexamethasone in these cultures was compared. Confluent cultures were labeled with [3H]acetate, and total [3H]GAG was quantitated. Fibroblasts from the skin responded to T3 (100 nmol/L) and dexamethasone (100 nmol/L) with 27% and 55% inhibition of [3H]GAG accumulation, respectively (n = 12). In contrast, retroocular fibroblasts responded with 12% and 8% inhibition (n = 6) to the two hormones. When cultures from abdominal skin and retroocular tissue were treated with n-butyrate (10 mM), a compound known to inhibit hyaluronate specifically, they responded similarly with 78% and 83% inhibition, respectively. A pulse-chase study was performed using fibroblasts from both sites, and no [3H]GAG degradation could be detected for the duration of the chase period (up to 72 h). These results suggest that retroocular fibroblasts, likely participants in the pathogenesis of Graves' ophthalmopathy, do not respond vigorously to T3 or glucocorticoids in terms of inhibition of [3H]GAG synthesis as do their dermal counterparts.
Reactive Block Copolymers for Modification of Thermosetting Epoxy (2000)

Block copolymers incorporating epoxy-reactive functionality in one block have been studied as modifiers for model epoxy resins. As observed previously with nonreactive poly(ethylethylene)-b-poly(ethylene oxide) (OP) copolymers, reactive poly(epoxyisoprene)-b-polybutadiene (BIxn) copolymers and poly(methyl acrylate-co-glycidyl methacrylate)-b-polyisoprene (MG-I) copolymers form ordered microstructures in blends with epoxy precursors as evidenced by small-angle X-ray scattering and transmission electron microscopy. Like OP copolymers, both types of reactive copolymer remain well-dispersed within the epoxy matrix during cure. Additionally, DSC and solubility studies suggest that these copolymers can react with the curing epoxy resin to form covalent linkages between the copolymeric microstructures and the cross-linked epoxy resin. The capability of these types of copolymers to template epoxy resin is proposed to arise from a combination of (1) the miscibility of one block with the epoxy components well into the curing process and (2) the energetic barriers to nucleation and growth of copolymer-rich regions in the epoxy matrix as network formation occurs and the epoxy molecular weight diverges.
Electrical insulation of implantable devices by composite polymer coatings. (1987)

Protection of implanted integrated circuits has required hermetic sealing, usually in metal containers and usually in package sizes that would preclude implantation in small and confined areas of the body. We have developed a method whereby ultrathin (10 micron) composite films consisting of glow discharge and vapor deposited polymers can be placed directly over integrated circuit substrates to provide protection from water and ions for up to 30 days (our present test limits). Our paper describes the reactor, surface preparation, and polymerization conditions necessary to obtain the water/ion resistant coatings. Results indicate little change in leakage current when comb patterns with 10 micron line widths and our insulating composite coatings are exposed to physiological saline solution and a 3 VDC bias.
Protein Radical Involvement In Biological Catalysis? (1989)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Synthetic multi‐epitope peptides identified in silico induce protective immunity against multiple influenza serotypes (2007)

Influenza causes yearly epidemics of mild disease and, occasionally, pandemics with millions of fatalities. Currently, no vaccine is effective against all influenza strains. Analysis of influenza sequences from animal and human isolates using CLUSTALW and a novel proprietary epitope prediction algorithm identified six conserved T cell-reactive regions in several proteins. Immunisation of transgenic mice with a preparation of these six regions as chemically synthesised peptides (FLU-v) induced a specific HLA-A*0201-mediated CD8(+) T cell response. This T cell population also reacted against human cells infected with three non-related influenza strains, confirming that the identified regions contain epitopes naturally presented by infected human cells and conserved amongst non-related viruses. Moreover, FLU-v immunisation significantly increased survival of transgenic mice against lethal challenge with influenza. Overall, FLU-v represents a promising influenza vaccine candidate, obviating the need for yearly vaccinations and allowing the stockpiling and initiation of a worldwide vaccination program in advance of a pandemic outbreak.
The Akt/PKB Family of Protein Kinases: A Review of Small Molecule Inhibitors and Progress Towards Target Validation: A 2009 Update (2010)

This article describes recent advances in the development and biological evaluation of small molecule inhibitors for the serine/threonine kinase Akt (PKB) as a reprise of our 2005 review with new data from the 2006-2009 time period. Akt plays a pivotal role in cell survival and proliferation through a number of downstream effectors. Recent studies indicate that unregulated activation of the PI3K/Akt pathway is a prominent feature of many human cancers and Akt is over-expressed or activated in all major cancers. Akt is considered an attractive target for cancer therapy and inhibition of Akt alone or in combination with standard cancer chemotherapeutics has been postulated to reduce the apoptotic threshold and preferentially kill cancer cells. Recently, several series of small molecule, ATP-competitive inhibitors have been reported with a range of Akt potencies and selectivities. Phosphatidylinositol (PI) analogs have been reported to inhibit Akt, but these inhibitors may also have specificity problems with respect to other pleckstrin homology (PH) domain containing proteins and may have poor bioavailability. In addition, novel allosteric inhibitors have been reported which are PH domain dependent, exhibit selectivity for the individual Akt isozymes and inhibit the activity and the activation of Akt. Compounds within these classes Akt inhibitors have sufficient potency and specificity which have culminated in recent reports of efficacy in tumor xenograft models. Moreover, Merck just disclosed positive Phase I data with an oral allosteric Akt inhibitor (MK-2206).
Studies on the syntheses of analgesics. IV. Syntheses of 1,2,3,4-tetrahydro-5H-benzazepine derivatives. (1975)

In order to examine more advantageous syntheses and the structure activity relationship, derivatives of 1, 2, 3, 4-tetrahydro-5H-benzazepine were synthesized via two routes from 3, 4-dihydro-1(2H)-naphthalenone. First, these compounds were synthesized via Beckmann rearrangement of 3, 4-dihydro-1(2H)-naphthalenone oximes and second, via 2-(2-cyano-1, 1-dimethylethyl)-4-methoxybenzoic acid. The synthesized compounds were tested for analgesic activity in mice.
Antisense inhibition of Chk2/hCds1 expression attenuates DNA damage‐induced S and G2 checkpoints and enhances apoptotic activity in HEK‐293 cells (2001)

The cellular response to DNA damage involves checkpoint controls that delay cell cycle progression in order to provide time for repair of damaged DNA. Chk2/hCds1 is a recently identified homolog of the yeast Cds1 kinase that is involved in cell cycle checkpoint response to DNA damage. To investigate the functions of Chk2/hCds1 in response to DNA damage in mammalian cells, we established a stable human kidney embryonic cell line (HEK-293) that expresses antisense Chk2/hCds1 (Chk2AS) under the control of an inducible promoter. Cells that express Chk2AS display defective S-phase delay in response to DNA replication-mediated DNA damage induced by the topoisomerase I inhibitor camptothecin. The defective G2 checkpoint was also observed in Chk2AS cells exposed to the DNA damaging agent VP-16 or gamma-radiation. Enhanced apoptosis was observed in Chk2AS cells after exposure to gamma-radiation or camptothecin. No p53 activation was observed after DNA damage in HEK-293 or Chk2AS cells. Our results indicate that perturbation of Chk2/hCds1 expression adversely affects the S- and G2-phase checkpoints following DNA damage or DNA replication block, and suggest that reduced expression of Chk2/hCds1 might promote a p53-independent apoptotic response.
Control of the function of substrate-bound C4b-C3b by the complement receptor Cr1. (1984)

The complement fragments C3b and C4b are the main ligands for the membrane receptor CR1. We showed elsewhere that CR1 functions as an essential cofactor for the factor I-mediated enzymatic breakdown of membrane-bound C3b (*C3b) into C3c and * C3dg . One of the main findings of the present paper is that CR1 also promotes the degradation of bound C4b (*C4b) into C4c and *C4d. On a weight basis, the cofactor activity of CR1 in the cleavage of *C4b present on the cell intermediate EAC14 is 10(3)-fold greater than that of the serum cofactor C4-binding protein ( C4bp ). An additional finding is that the effect of CR1 on either *C3b or *C4b is modulated by the presence of the other ligand in its vicinity; that is, *C4b degradation by CR1 plus I is enhanced by neighboring *C3b and vice versa. For example, upon uptake of optimal amounts of *C3b onto EAC142 and the assembly of the C3-convertase EAC1423 , the activity of CR1 in generating C4c is enhanced 5-10 times further. Conversely, when the number of *C3b molecules on EAC1423 is relatively small (or when EAC1423 has been converted by I plus H into EAC1423i ), the presence of neighboring *C4b enhances the conversion of *C3b (or *iC3b) into C3c plus * C3dg . The enhancing effect of *C3b on the cleavage of *C4b by I is observed only if the cofactor of this reaction is CR1. Indeed, the activity of I or I plus C4bp on *C4b is significantly inhibited when *C3b is fixed and the main product of the reaction is * iC4b . Taken together, these findings suggest that degradation of *C4b will be more effective when enough C3b molecules are fixed nearby, thus facilitating the interaction of *C4b*3b clusters with CR1-bearing cells, and that under physiological conditions, *C4b activity can be efficiently controlled by CR1.
Neutral endopeptidase inhibition enhances substance P mediated inflammation due to hypomagnesemia (2009)

During dietary deficiency of magnesium neurogenic inflammation is mediated, primarily, by elevated levels of substance P (SP). The enzyme most specific for degrading this neuropeptide is neutral endopeptidase (NEP). In recent studies we found that pharmacological inhibition of NEP by phosphoramidon resulted in elevated plasma levels of SP and greater oxidative stress. We also observed that hypomagnesemia reduced cardiac and intestinal expression of NEP. In these magnesium-deficient rats increased intestinal permeability and impaired cardiac contractility occurred. In our colony of genetically-engineered NEP knockout mice that have reduced ability to degrade SP, we found increased oxidative stress that was prevented by SP (neurokinin-1) receptor blockade. Thus, we submit that inhibition of NEP by pharmacological, genetic and dietary approaches (magnesium restriction), causes greater neurogenic inflammation that may result in increased intestinal and cardiac dysfunction.
ADAM17 as a Therapeutic Target in Multiple Diseases (2009)

As a metalloproteinase specialized in releasing membrane-tethered proteins, A Disintegrin and A Metalloproteinase 17 (ADAM17), also known as Tumor necrosis factor-alpha Converting Enzyme (TACE) or less commonly CD156q, has received more than its share of attention. This is mainly because major contemporary pathologies like cancer, inflammatory and vascular diseases seem to be connected to its cleavage abilities. The involvement in such a broad spectrum of diseases is due to the large variety of substrates that ADAM17 is able to cut. ADAM17 can activate growth factors or inactivate receptors by shedding their extracellular domain from the cell membrane. Similarly, it can detach cells by cleaving cell adhesion molecules. Some of these proteolytic events are part of cleavage cascades known as Regulated Intramembrane Proteolysis and lead to intracellular signaling. It is therefore clear that ADAM17 literally fulfills a key role in diverse processes and pathologies, making it a prime target for developing therapies. Here we review the role of ADAM17 in health and disease and highlight the problems to overcome for ADAM17 to mature towards a therapeutically valuable target.
Fast video super-resolution using artificial neural networks (2012)

In this study, video super-resolution using artificial neural network (ANN) is proposed to enlarge low-resolution (LR) frames. The proposed super-resolution method consists of three main modules, i.e., motion-trace volume collection, ANN training, and ANN prediction. In the proposed method, the LR frames are super-resolved to HR frames through ANN. The traditional motion estimation is used to catch the motion-trace volume which eliminates the unfathomable object motion in the video. Then, the complex spatio-temporal detail between LR and HR data is learned by ANN. Using the ANN training results, the optimal weights can be determined for frame resolution enhancement in video. Simulation results show that the proposed method successfully improves the average peak signal-to-noise ratio (PSNR) and perceptual quality in super-resolved frames.
Genetically engineered brain drug delivery vectors: cloning, expression and in vivo application of an anti-transferrin receptor single chain antibody–streptavidin fusion gene and protein (1999)

A single chain Fv antibody-streptavidin fusion protein was expressed and purified from bacterial inclusion bodies following cloning of the genes encoding the variable region of the heavy chain and light chain of the murine OX26 monoclonal antibody to the rat transferrin receptor. The latter undergoes receptor mediated transcytosis through the brain capillary endothelial wall in vivo, which makes up the blood-brain barrier (BBB); therefore, the OX26 monoclonal antibody and its single chain Fv analog may act as brain drug delivery vectors in vivo. Attachment of biotinylated drugs to the antibody vector is facilitated by production of the streptavidin fusion protein. The bi-functionality of the OX26 single chain Fv antibody-streptavidin fusion protein was retained, as the product both bound biotin and the rat transferrin receptor in vitro and in vivo, based on pharmacokinetic and brain uptake analyses in anesthetized rats. The attachment of biotin-polyethyleneglycol-fluorescein to the OX26 single chain Fv antibody-streptavidin fusion protein resulted in illumination of isolated rat brain capillaries in confocal fluorescent microscopy. In conclusion, these studies demonstrate that genetically engineered single chain Fv antibody-streptavidin fusion proteins may be used for non-invasive neurotherapeutic delivery to the brain using endogenous BBB transport systems such as the transferrin receptor.
Cloning of DNA sequences encoding foreign peptides and their expression in the K88 pili (1989)

A genetic system that allows the cloning of a peptide-coding sequence in the Escherichia coli K88ac and K88ad pilin genes and their expression as recombinant pili has been constructed. Two insertion vectors were created by subcloning the pilin genes in a pBR322 plasmid and replacing the coding sequence of two nonconserved clusters by a linker. The K88ac helper genes were subcloned in the compatible pACYC184 plasmid, and expression of pili by bacteria carrying both plasmids occurred by complementation. Two peptide-coding sequences of the influenza hemagglutinin were cloned in both insertion vectors, and recombinant pilins were shown to be assembled in pili. One recombinant pilus was shown to elicit antibodies against the synthetic peptide in immunized rats. The somatostatin-coding sequence was cloned in both vectors and led in one case to detectable pilus production. The fused somatostatin was shown to be recognized by specific monoclonal and polyclonal antibodies.
Reblastatin, a Novel Benzenoid Ansamycin-type Cell Cycle Inhibitor. (2000)

In the course of our screening for compounds which inhibit Rb protein phosphorylation at the cell level and cause cell cycle arrest at the Gl phase1}, reblastatin (Fig. hygroscopicus SANK 61995 deposited as FERM BP-5140.
Ghost-imaging experiment by measuring reflected photons (2008)

A CCD array is placed facing a chaotic light source and gated by a photon counting detector that simply counts all randomly scattered and reflected photons from an object. A ``ghost'' image of the object is then observed in the gated CCD. Differing from all published ghost-imaging experiments, this setup captures ghosts from scattered and reflected light of an object, instead of the transmitted ones. This new feature is not only useful for practical applications, but is also important fundamentally. It further explores the nonclassical interference nature of thermal light ghost imaging.
The stem-loop binding protein forms a highly stable and specific complex with the 3′ stem-loop of histone mRNAs (2001)

Replication-dependent histone mRNAs end in a highly conserved 26-nt stem-loop structure. The stem-loop binding protein (SLBP), an evolutionarily conserved protein with no known homologs, interacts with the stem-loop in both the nucleus and cytoplasm and mediates nuclear-cytoplasmic transport as well as 3'-end processing of the pre-mRNA by the U7 snRNP. Here, we examined the affinity and specificity of the SLBP-RNA interaction. Nitrocellulose filter-binding experiments showed that the apparent equilibrium dissociation constant (Kd) between purified SLBP and the stem-loop RNA is 1.5 nM. Binding studies with a series of stem-loop variants demonstrated that conserved residues in the stem and loop, as well as the 5' and 3' flanking regions, are required for efficient protein recognition. Deletion analysis showed that 3 nt 5' of the stem and 1 nt 3' of the stem contribute to the binding energy. These data reveal that the high affinity complex between SLBP and the RNA involves sequence-specific contacts to the loop and the top of the stem, as well the base of the stem and its immediate flanking sequences. Together, these results suggest a novel mode of protein-RNA recognition that forms the core of a ribonucleoprotein complex central to the regulation of histone gene expression.
Infrequency of detection of particle‐associated MSRV/HERV‐W RNA in the synovial fluid of patients with rheumatoid arthritis (2000)

MSRV/HERV-W RNA sequences are detectable in the synovial fluid of a small proportion of RA patients, but this phenomenon may not be specific to RA.