gebhart/patrepeval huggingface dataset:
Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy (2017)

Duchenne muscular dystrophy (DMD) is an incurable X-linked muscle-wasting disease caused by mutations in the dystrophin gene. Gene therapy using highly functional microdystrophin genes and recombinant adeno-associated virus (rAAV) vectors is an attractive strategy to treat DMD. Here we show that locoregional and systemic delivery of a rAAV2/8 vector expressing a canine microdystrophin (cMD1) is effective in restoring dystrophin expression and stabilizing clinical symptoms in studies performed on a total of 12 treated golden retriever muscular dystrophy (GRMD) dogs. Locoregional delivery induces high levels of microdystrophin expression in limb musculature and significant amelioration of histological and functional parameters. Systemic intravenous administration without immunosuppression results in significant and sustained levels of microdystrophin in skeletal muscles and reduces dystrophic symptoms for over 2 years. No toxicity or adverse immune consequences of vector administration are observed. These studies indicate safety and efficacy of systemic rAAV-cMD1 delivery in a large animal model of DMD, and pave the way towards clinical trials of rAAV-microdystrophin gene therapy in DMD patients.
Caveats to Exogenous Organic Delivery from Ablation, Dilution, and Thermal Degradation (2018)

A hypothesis in prebiotic chemistry argues that organics were delivered to the early Earth in abundance by meteoritic sources. This study tests that hypothesis by measuring how the transfer of organic matter to the surface of Earth is affected by energy-dissipation processes such as ablation and airbursts. Exogenous delivery has been relied upon as a source of primordial material, but it must stand to reason that other avenues (i.e., hydrothermal vents, electric discharge) played a bigger role in the formation of life as we know it on Earth if exogenous material was unable to deliver significant quantities of organics. For this study, we look at various properties of meteors such as initial velocity and mass of the object, and atmospheric composition to see how meteors with different initial velocities and masses ablate. We find that large meteors do not slow down fast enough and thus impact the surface, vaporizing their components; fast meteors with low masses are vaporized during entry; and meteors with low velocities and high initial masses reach the surface. For those objects that survive to reach the surface, about 60 to >99% of the mass is lost by ablation. Large meteors that fragment are also shown to spread out over increasingly larger areas with increasing mass, and small meteors (~1 mm) are subjected to intense thermal heating, potentially degrading intrinsic organics. These findings are generally true across most atmospheric compositions. These findings provide several caveats to extraterrestrial delivery models that&mdash;while a viable point source of organics&mdash;likely did not supply as much prebiotic material as an effective endogenous production route.
Structure/Function Analyses of Recombinant Variants of Human Factor Xa:  Factor Xa Incorporation into Prothrombinase on the Thrombin-Activated Platelet Surface Is Not Mimicked by Synthetic Phospholipid Vesicles (1998)

This report describes the expression, purification, and characterization of a series of recombinant factor Xa variants bearing aspartate substitutions for each of the glutamate residues which normally undergo gamma-carboxylation. Factor X was expressed in human embryonic kidney cells and purified from conditioned media by immunoaffinity and hydroxylapatite chromatography. Factor X was activated with Russell's viper venom factor X activator, and single-chain unactivated factor X was removed from activated factor X by size-exclusion chromatography. Recombinant wild-type factor Xa had normal activity in a clotting assay, and mutants with aspartate substitutions for glas residues 16, 26, and 29 had no detectable clotting activity. In purified component assays, these gla variants had essentially no detectable activity in the prothrombinase complex assembled on synthetic phospholipid vesicles but had significant activity when the prothrombinase was assembled on thrombin-activated platelets. In addition, the gla 32 variant had normal activity in the platelet prothrombinase but diminished activity in prothrombinase assembled on synthetic PSPC vesicles. These differences were not accounted for by the total phospholipid composition of the thrombin-activated platelet membrane. We have produced fully active recombinant human factor Xa and demonstrated that gla residues 16, 26, and 29 are critical for normal activity of factor Xa. More importantly, this study provides an extensive characterization of macromolecular enzyme complex formation with gla variants of a vitamin K-dependent coagulation protein and provides evidence that prothrombinase complex assembly on thrombin-activated platelets is not equivalent to assembly on synthetic phospholipid vesicles. The data suggest that thrombin-activated platelets possess some element(s) (other than 30% phosphatidyl serine or factor Va), presumably either protein or phospholipid, that serves as a component of the factor Xa binding site.
ZnO Nanobridges and Nanonails (2002)

Wurtzite ZnO nanobridges and aligned nanonails have been synthesized by thermal vapor transport and condensation method. The nanobridges have two rows of c-axis ZnO nanorods epitaxailly grown on the edges of the {0001} plane of the ZnO nanobelt. Some variations of the nanobridges have also been observed. The ZnO nanonails, with crystalline cap and small diameter shafts, grow along the c-axis. The shape of the nanonail cap and shaft varies. The nanobridges have very low concentration of indium in the structure and the nanonails are pure ZnO. These materials have potential in applications such as optoelectronics, etc.
Identification and Activities of Human Carboxylesterases for the Activation of CPT-11, a Clinically Approved Anticancer Drug (2001)

CPT-11 is a clinically approved anticancer drug used for the treatment of advanced colorectal cancer. Upon administration, the carbamate side chain of the drug is hydrolyzed, resulting in the release of SN-38, an agent that has approximately 1000-fold increased cytotoxic activity. Since only a very small percentage of the injected dose of CPT-11 is converted to SN-38, there is a significant opportunity to improve its therapeutic efficacy and to diminish its systemic toxicity by selectively activating the drug within tumor sites. We envisioned that a mAb-human enzyme conjugate for CPT-11 activation would be of interest, particularly since the conjugate would likely be minimally immunogenic, and the prodrug is clinically approved. Toward this end, it was necessary to identify the most active human enzyme that could convert CPT-11 to SN-38. We isolated enzymes from human liver microsomes based on their abilities to effect the conversion and identified human carboxylesterase 2 (hCE-2) as having the greatest specific activity. hCE-2 was 26-fold more active than human carboxylesterase 1 and was 65% as active as rabbit liver carboxylesterase, the most active CPT-11 hydrolyzing enzyme known. The anti-p97 mAb 96.5 was linked to hCE-2, forming a conjugate that could bind to antigen-positive cancer cells and convert CPT-11 to SN-38. Cytotoxicity assays established that the conjugate led to the generation of active drug, but the kinetics of prodrug activation (48 pmol x min(-1) x mg(-1) was insufficient for immunologically specific prodrug activation. These results confirm the importance of hCE-2 for CPT-11 activation and underscore the importance of enzyme kinetics for selective prodrug activation.
Dynamic contributions of the components of binocular vergence (1979)

Experimental results from step stimulation of the two major dynamic components in ocular vergence showed that while fusional covergence dominated a coordinated binocular vergence movement, accomodative convergence always contributes to the dynamic response. A quantitative analysis of component dynamics, both in isolation and during coordinated movements, indicates that these components are additive at least through a portion of the movement. Two alternative hypotheses are presented for the role of accommodative convergence during the period immediately following a binocular vergence movement.
Safety and Pharmacokinetics of the Dual Action Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor, BAY 43-9006, in Patients with Advanced, Refractory Solid Tumors (2005)

The results confirm the favorable safety profile of BAY 43-9006 and support the development of this compound for the treatment of solid tumors.
The actin domain of Gardner-Rasheed feline sarcoma virus inhibits kinase and transforming activities (1989)

The transforming gene product, P70gag-actin-fgr, of Gardner-Rasheed feline sarcoma virus (GR-FeSV) is a single polypeptide composed of regions derived from cellular and viral genes. Gamma actin and c-fgr genes are the two known cellular components of the GR-FeSV genome. In the present study, sequences representing each cell-derived gene were deleted and the resulting constructs were tested for transforming activity by transfection of NIH 3T3 cells. Constructs lacking a portion of the c-fgr proto-oncogene failed to induce focus formation, demonstrating the essential nature of this component for GR-FeSV oncogenic activity. In contrast, the construct lacking the actin domain was more active than GR-FeSV DNA in transformation assays. Protein specified by the actin deletion mutant possessed a 2.4-fold greater specific protein-tyrosine kinase activity compared with that of the wild-type gene product. Furthermore, the actin domain had no detectable effect on the ability of the fgr kinase to associate with cytoskeleton or to phosphorylate unique cellular proteins on tyrosine. Our findings demonstrate that the actin domain inhibits focus formation and impairs protein-tyrosine kinase activity.
Printed covalent glycan array for ligand profiling of diverse glycan binding proteins (2004)

Here we describe a glycan microarray constructed by using standard robotic microarray printing technology to couple amine functionalized glycans to an amino-reactive glass slide. The array comprises 200 synthetic and natural glycan sequences representing major glycan structures of glycoproteins and glycolipids. The array has remarkable utility for profiling the specificity of a diverse range of glycan binding proteins, including C-type lectins, siglecs, galectins, anticarbohydrate antibodies, lectins from plants and microbes, and intact viruses.
Small diameter active catheter using shape memory alloy (2002)

Three kinds of active catheters whose outside diameters are less than 2 mm were fabricated. One uses polymer links, the other two are linkless active catheters using adhesive. Distributed shape memory alloy (SMA) coil were used as actuators for the active motion. There are endoskeletal type and exoskeletal type in the linkless active catheters. We have applied the endoskeletal type active catheter to intraureteral ultrasonography used in a kidney. Concept of an advanced multifunction active catheter is mentioned.
Temporal and Anatomic Risk Profile of Brain Injury With Neonatal Repair of Congenital Heart Defects (2007)

Specific modifiable risk factors can be identified for preoperative and postoperative white matter injury and stroke associated with neonatal surgery for CHD. The high incidence of postoperative injury observed despite new methodologies of CPB indicates the need for ongoing evaluation to optimize neurological outcome.
Accumulation of amyloid precursor protein-like immunoreactivity in rat brain in response to thiamine deficiency (1995)

Thiamine deficiency (TD) is a classical model of impaired cerebral oxidation. As in Alzheimer's disease (AD), TD is characterized by selective neuronal loss, decreased activities of thiamine pyrophosphate-dependent enzymes, cholinergic deficits and memory loss. Amyloid beta-protein (A beta), a approximately 4 kDa fragment of the beta-amyloid precursor protein (APP), accumulates in the brains of patients with AD or Down's syndrome. In the current study, we examined APP and A beta immunoreactivity in the brains of thiamine-deficient rats. Animals received thiamine-deficient diet ad libitum and daily injections of the thiamine antagonist, pyrithiamine. Immunocytochemical staining and immunoblotting utilized a rabbit polyclonal antiserum against human APP645-694 (numbering according to APP695 isoform). Three, 6 and 9 days of TD did not appear to damage any brain region nor change APP-like immunoreactivity. However, 13 days of TD led to pathological lesions mainly in the thalamus, mammillary body, inferior colliculus and some periventricular areas. While immunocytochemistry and thioflavine S histochemistry failed to show fibrillar beta-amyloid, APP-like immunoreactivity accumulated in aggregates of swollen, abnormal neurites and perikarya along the periphery of the infarct-like lesion in the thalamus and medial geniculate nucleus. Immunoblotting of the thalamic region around the lesion revealed increased APP-like holoprotein immunoreactivity. APP-like immunoreactive neurites were scattered in the mammillary body and medial vestibular nuclei where the lesion did not resemble infarcts. In the inferior colliculus, increased perikaryal APP-like immunostaining occurred in neurons surrounding necrotic areas. Regions without apparent pathological lesions showed no alteration in APP-like immunoreactivity. Thus, the oxidative insult associated with cell loss, hemorrhage and infarct-like lesions during TD leads to altered APP metabolism. This is the first report to show a relationship between changes in APP expression, oxidative metabolism and selective cell damage caused by nutritional/cofactor deficiency. This model appears useful in defining the role of APP in the reponse to central nervous system injury, and may also be relevant to the pathophysiology of Wernicke-Korsakoff syndrome and AD.
Tough, Stretchable, Compressive Novel Polymer/Graphene Oxide Nanocomposite Hydrogels with Excellent Self-Healing Performance (2017)

Designing hydrogels with high mechanical properties without sacrificing their self-healing efficiencies remains great challenges. We have fabricated cationic polyacrylamide/graphene oxide (GO) hydrogels by free-radical polymerization of acrylamide (AM) and 2-(dimethylamino)ethylacrylatemethochloride (DAC) in the presence of GO. The mechanical properties and self-healing ability can be tuned by the GO content and the mass ratio of AM and DAC. The ionic bonds between DAC and GO and the hydrogen bonds between AM and GO can efficiently dissipate energy and rebuild the networks. The resulting composite hydrogels possess high stiffness (Young's modulus: ∼1.1 MPa), high toughness (∼9.3 MJ m<sup>-3</sup>), and high fatigue resistance, as well as high self-healing efficiency (>92% of tensile strength, >99% of tensile strain and >93% of toughness). In addition, the completely dried hydrogels can recover their original mechanical values by spraying water and still possess outstanding self-healing efficiency. Our design can provide better fundamental understanding of physical properties of hydrogels and should enable the development of tough, self-healing hydrogels for practical applications.
Training support vector machines: an application to face detection (2002)

We investigate the application of Support Vector Machines (SVMs) in computer vision. SVM is a learning technique developed by V. Vapnik and his team (AT&T Bell Labs., 1985) that can be seen as a new method for training polynomial, neural network, or Radial Basis Functions classifiers. The decision surfaces are found by solving a linearly constrained quadratic programming problem. This optimization problem is challenging because the quadratic form is completely dense and the memory requirements grow with the square of the number of data points. We present a decomposition algorithm that guarantees global optimality, and can be used to train SVM's over very large data sets. The main idea behind the decomposition is the iterative solution of sub-problems and the evaluation of optimality conditions which are used both to generate improved iterative values, and also establish the stopping criteria for the algorithm. We present experimental results of our implementation of SVM, and demonstrate the feasibility of our approach on a face detection problem that involves a data set of 50,000 data points.
Low-frequency meandering piezoelectric vibration energy harvester (2012)

The design, fabrication, and characterization of a novel low-frequency meandering piezoelectric vibration energy harvester is presented. The energy harvester is designed for sensor node applications where the node targets a width-to-length aspect ratio close to 1:1 while simultaneously achieving a low resonant frequency. The measured power output and normalized power density are 118 μW and 5.02 μW/mm(3)/g(2), respectively, when excited by an acceleration magnitude of 0.2 g at 49.7 Hz. The energy harvester consists of a laser-machined meandering PZT bimorph. Two methods, strain-matched electrode (SME) and strain-matched polarization (SMP), are utilized to mitigate the voltage cancellation caused by having both positive and negative strains in the piezoelectric layer during operation at the meander's first resonant frequency. We have performed finite element analysis and experimentally demonstrated a prototype harvester with a footprint of 27 x 23 mm and a height of 6.5 mm including the tip mass. The device achieves a low resonant frequency while maintaining a form factor suitable for sensor node applications. The meandering design enables energy harvesters to harvest energy from vibration sources with frequencies less than 100 Hz within a compact footprint.
The Solution Structure of Type II Antifreeze Protein Reveals a New Member of the Lectin Family (1998)

A recombinant form of the sea raven type II antifreeze protein (SRAFP) has been produced using the Pichia pastoris expression system. The antifreeze activity of recombinant SRAFP is indistinguishable from that of the wild-type protein. The global fold of SRAFP has been determined by two-dimensional 1H homonuclear and three-dimensional 1H-¿15N¿ heteronuclear NMR spectroscopy using 785 NOE distance restraints and 47 angular restraints. The molecule folds into one globular domain that consists of two helices and nine beta-strands in two beta-sheets. The structure confirms the proposed existence of five disulfide bonds. The global fold of SRAFP is homologous to C-type lectins and pancreatic stone proteins, even though the sequence identity is only approximately 20%.
Potential antitumor agents. IX. Bisquaternary salts (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPotential antitumor agents. IX. Bisquaternary saltsB. F. Cain, G. J. Atwell, and R. N. SeelyeCite this: J. Med. Chem. 1968, 11, 5, 963–966Publication Date (Print):September 1, 1968Publication History Published online1 May 2002Published inissue 1 September 1968https://pubs.acs.org/doi/10.1021/jm00311a010https://doi.org/10.1021/jm00311a010research-articleACS PublicationsRequest reuse permissionsArticle Views52Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The serum levels of growth factors: PDGF, TGF-beta and VEGF are increased after strenuous physical exercise. (2006)

Strenuous physical exercise induces muscle fibers damage and non-specific inflammatory response. Activated by inflammatory process cells may serve as the source of wide spectrum of inflammatory mediators and growth factors. Namely Platelet Derived Growth Factor (PDGF), Transforming Growth Factor-beta (TGF-beta) and Vascular Endothelial Growth Factor (VEGF) could be released. The aim of present study was to assess the impact of physical exercise on growth factors generation in healthy young people. 14 young sportsmen were enrolled into the study. They performed strenuous physical exercise. Blood samples were drawn before, immediately after, and 2 hours after the exercise bout. Serum PDGF, TGF-beta and VEGF concentrations were measured using commercially available ELISA kit based on immunoenzimatic method. Serum level of PDGF increased significantly from 1.7 ng/ml before to 4.64 ng/ml (2.73-fold) immediately after, and to 3.3 ng/ml (1.94-fold) 2 hours after exertion. Serum level of TGF-beta increased significantly from 20.58 ng/ml before to 55.37 ng/ml (2.7-fold) immediately after, and to 40.03 ng/ml (1.95-fold) 2 hours after exertion. Serum level of VEGF increased significantly from 91.83 pg/ml before to 165.61 pg/ml (1.8-fold) immediately after the exercise. Two hours after the exertion serum level of VEGF was 137.22 pg/ml, what is 1.49-fold above the basal level; however not being significantly different. In summery, observed increased level of growth factors could be involved in the process of adaptation of human organism to physical training. In addition, in the context of the role of inflammation in the pathogenesis of various diseases, our results point to the potentially deleterious effect of strenuous physical exercise.
Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques (2013)

Emerging influenza viruses pose a serious risk to global human health. Recent studies in ferrets, macaques, and humans suggest that seasonal H1N1 (sH1N1) infection provides some cross-protection against 2009 pandemic influenza viruses (H1N1pdm), but the correlates of cross-protection are poorly understood. Here we show that seasonal infection of influenza-naïve Indian rhesus macaques (Macaca mulatta) with A/Kawasaki/173/2001 (sH1N1) virus induces antibodies capable of binding the hemagglutinin (HA) of both the homologous seasonal virus and the antigenically divergent A/California/04/2009 (H1N1pdm) strain in the absence of detectable H1N1pdm-specific neutralizing antibodies. These influenza virus-specific antibodies activated macaque NK cells to express both CD107a and gamma interferon (IFN-γ) in the presence of HA proteins from either sH1N1 or H1N1pdm viruses. Although influenza virus-specific antibody-dependent cellular cytotoxicity (ADCC)-mediated NK cell activation diminished in titer over time following sH1N1 infection, these cells expanded rapidly within 7 days following H1N1pdm exposure. Furthermore, we found that influenza virus-specific ADCC was present in bronchoalveolar lavage fluid and was able to activate lung NK cells. We concluded that infection with a seasonal influenza virus can induce antibodies that mediate ADCC capable of recognizing divergent influenza virus strains. Cross-reactive ADCC may provide a mechanism for reducing the severity of divergent influenza virus infections.