gebhart/patrepeval huggingface dataset:
Matrix Metalloproteinases Cleave Connective Tissue Growth Factor and Reactivate Angiogenic Activity of Vascular Endothelial Growth Factor 165 (2002)

Vascular endothelial growth factor (VEGF), a potent angiogenic mitogen, plays a crucial role in angiogenesis under various pathophysiological conditions. We have recently demonstrated that VEGF(165), one of the VEGF isoforms, binds connective tissue growth factor (CTGF) and that its angiogenic activity is inhibited in the VEGF(165).CTGF complex form (Inoki, I., Shiomi, T., Hashimoto, G., Enomoto, H., Nakamura, H., Makino, K., Ikeda, E., Takata, S., Kobayashi, K. and Okada, Y. (2002) FASEB J. 16, 219-221). In the present study, we further examined the susceptibility of the VEGF(165).CTGF complex to matrix metalloproteinases (MMP-1, -2, -3, -7, -9, and -13), ADAMTS4 (aggrecanase-1), and serine proteinases, and evaluated the recovery of the angiogenic activity of VEGF(165) after the treatment. Among the MMPs, MMP-1, -3, -7, and -13 processed CTGF of the complex into the major NH(2)- and COOH-terminal fragments, whereas VEGF(165) was completely resistant to the MMPs. On the other hand, elastase and plasmin cleaved both CTGF and VEGF(165) of the complex, but they were completely resistant to ADAMTS4. By digestion of the immobilized VEGF(165).CTGF complex with MMP-3 or MMP-7, both NH(2)- and COOH-terminal fragments of CTGF were dissociated and released from the complex into the liquid phase. The in vitro angiogenic activity of VEGF(165) blocked in the VEGF(165).CTGF complex was reactivated to original levels after CTGF digestion of the complex with MMP-1, -3, and -13. Recovery of angiogenic activity was further confirmed by in vivo angiogenesis assay using a Matrigel injection model in mice. These results demonstrate for the first time that CTGF is a substrate of MMPs and that the angiogenic activity of VEGF(165) suppressed by the complex formation with CTGF is recovered through the selective degradation of CTGF by MMPs. MMPs may play a novel role through CTGF degradation in VEGF-induced angiogenesis during embryonic development, tissue maintenance, and/or pathological processes of various diseases.
Local Injection of Deferoxamine Improves Neovascularization in Ischemic Diabetic Random Flap by Increasing HIF-1α and VEGF Expression (2014)

Local injection of DFO could exert preventive effects against skin flap necrosis in STZ-induced diabetic mice by elevating the expression of HIF-1α and VEGF, increased EPC mobilization, which all contributed to promote ischemic diabetic flap survival.
Discovery of (1 R ,5 S )- N -[3-Amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2( S )-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2( S )-carboxamide (SCH 503034), a Selective, Potent, Orally Bioavailable Hepatitis C Virus NS3 Protease Inhibitor:  A Potential Therapeutic Agent for the Treatment of Hepatitis C Infection (2006)

Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.
CD45-protein tyrosine phosphatase cross-linking inhibits T cell receptor CD3-mediated activation in human T cells. (1989)

Activation of peripheral blood T cells, and the leukemic T cell line Jurkat, as measured by mobilization of intracellular calcium, by an anti-TCR antibody is blocked by mAb (T191) to the leukocyte common Ag (CD45). T191 also blocked down-regulation of the CD3-TCR complex induced by an anti-CD3 mAb. Vanadate, a phosphotyrosine phosphatase inhibitor, partially blocks the effect of T191 and restored mobilization of intracellular calcium. Assays of the immunoprecipitates of T191 and CD45 from both Jurkat-BM1 and peripheral T cells showed that the immune complexes had intrinsic phosphatase activity. A parallel immunoprecipitate using a mAb (4-10) against HLA class I showed no such activity. Further analysis of the T191 immunocomplex revealed activity against phosphotyrosine, p-nitrophenylphosphate, and [32P-poly-glu-tyr, but not against phosphoserine. Phosphatase activity was inhibited by Vanadate, but not by Zn2+ or F-. These results show that CD45 is a phosphotyrosine phosphatase, and strongly suggest that tyrosine phosphorylation/dephosphorylation is critically involved in activation of T cells through the TCR-CD3 complex.
Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain (2002)

Phenotypic modification of dorsal root ganglion (DRG) neurons represents an important mechanism underlying neuropathic pain. However, the nerve injury-induced molecular changes are not fully identified. To determine the molecular alterations in a broader way, we have carried out cDNA array on the genes mainly made from the cDNA libraries of lumbar DRGs of normal rats and of rats 14 days after peripheral axotomy. Of the 7,523 examined genes and expressed sequence tags (ESTs), the expression of 122 genes and 51 expressed sequence tags is strongly changed. These genes encompass a large number of members of distinct families, including neuropeptides, receptors, ion channels, signal transduction molecules, synaptic vesicle proteins, and others. Of particular interest is the up-regulation of gamma-aminobutyric acid(A) receptor alpha5 subunit, peripheral benzodiazepine receptor, nicotinic acetylcholine receptor alpha7 subunit, P2Y1 purinoceptor, Na(+) channel beta2 subunit, and L-type Ca(2+) channel alpha2delta-1 subunit. Our findings therefore reveal dynamic and complex changes in molecular diversity among DRG neurons after axotomy. Sequences reported in this paper have been deposited in the GenBank database (accession numbers BG 662484-BG 673712)
The Structural Diversity of Phthalides from the Apiaceae (2007)

Phthalides, and their corresponding dihydro and tetrahydro analogues, are components of several genera of the plant family Apiaceae. These taxa have been reported as exhibiting a wide range of bioactivities against experimental models of several illnesses and physiological conditions, including microbial and viral infections, stroke, tuberculosis, and vasoconstriction. Many of these genera are purported to possess medicinal values, and of these several are considered to be traditional herbal medicines. This review provides an overview of the methods of investigation, the structural diversity, and the bioactivity of phthalides, dihydrophthalides, tetrahydrophthalides, and dimers from plants in the Apiaceae.
Gene Linked to Faulty Cholesterol Transport (1999)

CELL BIOLOGYIn the August issue of Nature Genetics , three groups report that they have nabbed the gene at fault in Tangier disease, a rare hereditary condition in which a defect in cholesterol management leaves the patients with yellow tonsils, oversized spleens, and scant amounts of the heart-protective high density lipoprotein (HDL) cholesterol in their bloodstreams. The discovery not only sheds light on this disorder, but may also lead to a better understanding of familial HDL deficiency syndrome, a much more common genetic deficiency characterized by low blood levels of HDL cholesterol and a high risk of heart attack. The gene found by the three groups encodes a protein known as ABC1. It apparently transports cholesterol from inside cells to the cholesterol-enveloping proteins waiting outside to carry it as HDL cholesterol particles to the liver for recycling back to cells in the body--the first time that researchers have shown how cholesterol gets out of cells.
Titanium and rare earth chloride catalysts for ethylene polymerization (1984)

Abstract Anhydrous chlorides of Mg, Mn, Y, and selected lanthanides were reacted with tri‐ n ‐butylphosphate and finally TiCI 4 to prepare ethylene polymerization catalysts. With triethylaluminum as cocatalyst the highest activities were observed with Mg, Nd, and Pr, which correlate with the peak activity for Nd and Pr in diene polymerization catalysts prepared from the lanthanides. At a given hydrogen concentration molecular weights and molecular weight distributions and catalyst activities were similar for these three metals. The high activity for Nd and Pr is surprising because NdCI 3 and PrCI 3 adopt the UCI 3 structure rather than a layer lattice structure common to MgCI 2 and TiCI 3 .
Polycystin 1 is required for the structural integrity of blood vessels (2000)

Autosomal dominant polycystic kidney disease (ADPKD), often caused by mutations in the PKD1 gene, is associated with life-threatening vascular abnormalities that are commonly attributed to the frequent occurrence of hypertension. A previously reported targeted mutation of the mouse homologue of PKD1 was not associated with vascular fragility, leading to the suggestion that the vascular lesion may be of a secondary nature. Here we demonstrate a primary role of PKD1 mutations in vascular fragility. Mouse embryos homozygous for the mutant allele (Pkd1(L)) exhibit s.c. edema, vascular leaks, and rupture of blood vessels, culminating in embryonic lethality at embryonic day 15.5. Kidney and pancreatic ductal cysts are present. The Pkd1-encoded protein, mouse polycystin 1, was detected in normal endothelium and the surrounding vascular smooth muscle cells. These data reveal a requisite role for polycystin 1 in maintaining the structural integrity of the vasculature as well as epithelium and suggest that the nature of the PKD1 mutation contributes to the phenotypic variance in ADPKD.
Extensive Sequence Variation in the Attachment (G) Protein Gene of Avian Pneumovirus: Evidence for Two Distinct Subgroups (1994)

The putative attachment protein of the avian pneumovirus that causes turkey rhinotracheitis is, by analogy with mammalian pneumoviruses, expected to be the major antigenic determinant. We report the nucleotide sequence of the attachment (G) protein genes of five different continental European isolates and compare them with the previously published sequence of the G gene for the focal variant of a U.K. isolate. The nucleotide sequences and the predicted amino acid sequences indicate that there are at least two distinct subgroups, similar to the grouping described for human respiratory syncytial (RS) virus. The U.K. and French isolates form one group and the isolates from Spain, Italy and Hungary form a second. The two subgroups can be easily distinguished on the basis of restriction enzyme digestion of PCR-generated products representing the full-length gene. Within the subgroups the predicted G proteins were highly conserved (98.5 to 99.7% amino acid identity) compared to the levels of identity of RS virus G proteins in the same subgroup (80 to 95%). Between the avian pneumovirus subgroups described here there was an unexpected degree of divergence, the average amino acid identity between members of the two groups being only 38%. This compares with the 53% conservation seen between members of the RS virus subgroups A and B. Comparison of the predicted amino acid sequences showed that the G proteins of members of the two avian pneumovirus subgroups had similar structural features. All proteins had an amino-terminal membrane anchor and the positions of cysteine residues were highly conserved. The potential importance of the high level of variation between the two subgroups in terms of epidemiology of the disease is discussed.
Interactions of neosaxitoxin with the sodium channel of the frog skeletal muscle fiber. (1991)

Neosaxitoxin (neoSTX) differs structurally from saxitoxin (STX) in that the hydrogen on N-1 is replaced by a hydroxyl group. On single frog skeletal muscle fibers in the vaseline-gap voltage clamp, the concentrations for reducing the maximum sodium current by 50% (ED50) at pH's 6.50, 7.25, and 8.25 are, respectively, 4.9, 5.1, and 8.9 nM for STX and 1.6, 2.7, and 17.2 nM for neoSTX. The relative potencies of STX at the different pH's closely parallel the relative abundance of the protonated form of the 7,8,9 guanidinium function, but the relative potencies of neoSTX at the same pH's vary with the relative abundance of the deprotonated N-1 group. In constant-ratio mixtures of the two toxins, the observed ED50's are consistent with the notion that the two toxins compete for the same site. At pH's 6.50 and 7.25, the best agreement between observed and computed values is obtained when the efficacy term (epsilon) for either toxin is 1. At pH 8.25 the best agreement is obtained if the efficacy is 1 for STX but 0.75 for neo-STX. The marked pH dependence of the actions of neoSTX probably reflects the presence of a site in the receptor that interacts with the N-1 -OH, in addition to those interacting with the 7,8,9 guanidinium and the C-12 hydroxyl groups. Considering the three-dimensional structure of the STX and neoSTX molecules, the various site points are probably located in a fold or a crevice of the channel protein, where the extracellular orifice of the sodium channel is located.
Bioluminescent imaging of a marking transgene and correction of Fabry mice by neonatal injection of recombinant lentiviral vectors (2004)

Successful therapy for many inherited disorders could be improved if the intervention were initiated early. This is especially true for lysosomal storage disorders. Earlier intervention may allow metabolic correction to occur before lipid buildup has irreversible consequences and/or before the immune system mounts limiting responses. We have been developing gene therapy to treat lysosomal storage disorders, especially Fabry disease. We describe studies directed toward metabolic correction in neonatal animals mediated by recombinant lentiviral vectors. To develop this method, we first injected a marking lentiviral vector that engineers expression of luciferase into the temporal vein of recipient neonatal animals. The use of a cooled charged-coupled device camera allowed us to track transgene expression over time in live animals. We observed intense luciferase expression in many tissues, including the brain, that did not diminish over 24 weeks. Next, we injected neonatal Fabry mice a single time with a therapeutic lentiviral vector engineered to express human alpha-galactosidase A. The injection procedure was well tolerated. We observed increased plasma levels of alpha-galactosidase A activity starting at our first plasma collection point (4 weeks). Levels of alpha-galactosidase A activity were found to be significantly elevated in many tissues even after 28 weeks. No immune response was observed against the corrective transgene product. Increased levels of enzyme activity also led to significant reduction of globotriaosylceramide in the liver, spleen, and heart. This approach provides a method to treat lysosomal storage disorders and other disorders before destructive manifestations occur.
The problem of self-calibration of fluorescence signal in microscale sensor systems (2005)

Most recent developments in fluorescent molecular sensor devices are based on "ON-OFF" switching, which is an operation with a single measurable parameter, commonly the quenching of total intensity. In the meantime, with this approach self-calibration on the molecular level is not achievable. This calibration is strongly needed in all kinds of microscale applications, including microarrays, microfluidic systems and living cell imaging. Different possibilities are discussed for overcoming this difficulty and an "OR-OR" switching concept is suggested that involves the two-channel detection as a promising solution. For achieving the desired efficiency specific conditions are needed: it should be a single reporter dye exhibiting rapid reversible excited-state reaction and providing two-band wavelength ratiometric response.
Respiratory Syncytial Virus Infections in Previously Healthy Working Adults (2001)

During 1975-1995, a total of 2960 healthy adults, 18-60 years of age, were prospectively evaluated for respiratory virus infections. Of these subjects, 211 (7%) acquired respiratory syncytial virus (RSV) infection. The infections were symptomatic in 84% of subjects, involved only the upper respiratory tract in 74%, and included lower respiratory tract symptoms in 26%. Overall, 40% of the subjects were febrile. Lower respiratory tract signs developed in 26%. RSV illnesses were more prolonged than non-RSV respiratory illnesses. Compared with influenza, RSV infections were less frequently associated with fever and headache, but were associated significantly more often with nasal congestion, ear and sinus involvement, and productive cough. Absence from work during the acute phase of the illness resulted from 38% of RSV infections and 66% of influenza cases. The mean duration of RSV illness (9.5 days), however, was significantly longer than that of influenza (6.8 days). The occurrence of annual epidemics of RSV, the virus' potential to reinfect all age groups, and the morbidity associated with these reinfections suggest that RSV infections in working adults may result in appreciable costs for medical visits and absence from work.
Differentiation of Human Motion Data Using Combined Spline and Least Squares Concepts (1991)

A differentiation method, which combines the concepts of least squares and splines, has been developed to analyze human motion data. This data smoothing technique is not dependent on a choice of a cut-off frequency and yet it closely reflects the nature of the phenomenon. Two sets of published benchmark data were used to evaluate the new algorithm.
Development of a granular media model for finite element analysis (2001)

Today's pavement design calls for more emphasis on pavement performance prediction. This is a far more complex task than traditional designs that strive to provide safe thickness and specifications for the material. Modern computational mechanics provide application tools to deal with this new challenge, provided material models are created that predict cumulative deformations under traffic loading. This paper describes an ongoing research effort to create material models for granular base course material that may be implemented within general-purpose finite element computer programs. The model was evolved from a mechanistic interpretation of endochronic theory, which creates a modular system that can accommodate plasticity, visco-elasticity/plasticity, and damage within a single modeling format. The performance of the model is illustrated with the analysis of permanent deformations in a flexible pavement caused by repeated tire loads.
Carbon−Silicon Core−Shell Nanowires as High Capacity Electrode for Lithium Ion Batteries (2009)

We introduce a novel design of carbon-silicon core-shell nanowires for high power and long life lithium battery electrodes. Amorphous silicon was coated onto carbon nanofibers to form a core-shell structure and the resulted core-shell nanowires showed great performance as anode material. Since carbon has a much smaller capacity compared to silicon, the carbon core experiences less structural stress or damage during lithium cycling and can function as a mechanical support and an efficient electron conducting pathway. These nanowires have a high charge storage capacity of approximately 2000 mAh/g and good cycling life. They also have a high Coulmbic efficiency of 90% for the first cycle and 98-99.6% for the following cycles. A full cell composed of LiCoO(2) cathode and carbon-silicon core-shell nanowire anode is also demonstrated. Significantly, using these core-shell nanowires we have obtained high mass loading and an area capacity of approximately 4 mAh/cm(2), which is comparable to commercial battery values.
Human beta-hexosaminidase alpha chain: coding sequence and homology with the beta chain. (1985)

We have isolated a cDNA clone, p beta H alpha-5, from an adult human liver library that contains the entire coding sequence of the alpha chain of beta-hexosaminidase. The cDNA insert of p beta H alpha-5 is 1944 base pairs long and contains a 168-base-pair 5' untranslated region, a 186-base-pair 3' untranslated region, and an open reading frame of 1587 base pairs corresponding to 529 amino acids (Mr, 60,697). The first 17-22 amino acids satisfy the requirements of a signal sequence. A striking sequence homology with a published partial amino acid sequence for the beta chain [O'Dowd, B. F., Quan, F., Willard, H. F., Lamhonwah, A. M., Korneluk, R. G., Lowden, J. A., Gravel, R. A. & Mahuran, D. J. (1985) Proc. Natl. Acad. Sci. USA 82, 1184-1188] suggests that both chains may have evolved from a common ancestor. A shorter alpha-chain cDNA was found to hybridize to the long arm of chromosome 15, the known location for the alpha-chain gene. In addition, we isolated another alpha-chain cDNA clone, p beta H alpha-4, from a simian virus 40-transformed human fibroblast library that contained an extra 453-base-pair piece at its 3' end. A probe consisting of this additional sequence hybridized exclusively to a single mRNA species (2.6 kilobases) in mRNA preparations from cultured human fibroblasts. In contrast, p beta H alpha-5 hybridized to both a 2.1-kilobase major and a 2.6-kilobase minor mRNA species in these same mRNA preparations, indicating the presence of two distinct alpha-chain mRNA species differing at the 3' end. Fibroblasts from an Ashkenazi Jewish patient with classic Tay-Sachs disease were deficient in both species of mRNA, confirming their genetic relationship.
Perforating and non-perforating indications for repeated operations in Crohn's disease: evidence for two clinical forms. (1988)

The surgical indications in 770 patients with Crohn's disease undergoing intestinal resection at The Mount Sinai Hospital from 1960-83 have been reviewed. Surgical indications were divided into two principal categories: 375 cases with perforating indications and 395 cases non-perforating. Among 292 patients who underwent second operations for recurrent Crohn's disease, the indications for second operation were closely dependent on the indication for primary resection. Second operations were undertaken for perforating indications much more often among cases where the initial indication had been perforating, than among those whose initial indications had been non-perforating (73% v 29%, p less than 0.00001). This trend to similarities in the indications which bring patients to surgery was maintained within each anatomical category of Crohn's disease and even between second and third operations (p less than 0.001). Operations for perforating indications were followed by reoperation approximately twice as fast as operations for non-perforating indications, whether going from first to second operation (perforating 4.7 v non-perforating 8.8 years, p less than 0.001), or from second to third (perforating 2.3 v non-perforating 5.2 years, p less than 0.005). Crohn's disease thus seems to occur in two different clinical patterns, independent of anatomic distribution. These are a relatively aggressive perforating type and a more indolent non-perforating type, which tend to retain their identities between repeated operations and to influence the speed with which reoperation occurs.