gebhart/patrepeval huggingface dataset:
Histone deacetylase inhibitor treatment dramatically reduces cholesterol accumulation in Niemann-Pick type C1 mutant human fibroblasts (2011)

Niemann-Pick type C (NPC) disease is predominantly caused by mutations in the NPC1 protein that affect intracellular cholesterol trafficking and cause accumulation of unesterified cholesterol and other lipids in lysosomal storage organelles. We report the use of a series of small molecule histone deacetylase (HDAC) inhibitors in tissue culture models of NPC human fibroblasts. Some HDAC inhibitors lead to a dramatic correction in the NPC phenotype in cells with either one or two copies of the NPC1(I1061T) mutation, and for several of the inhibitors, correction is associated with increased expression of NPC1 protein. Increased NPC1(I1061T) protein levels may partially account for the correction of the phenotype, because this mutant can promote cholesterol efflux if it is delivered to late endosomes and lysosomes. The HDAC inhibitor treatment is ineffective in an NPC2 mutant human fibroblast line. Analysis of the isoform selectivity of the compounds used implicates HDAC1 and/or HDAC2 as likely targets for the observed correction, although other HDACs may also play a role. LBH589 (panobinostat) is an orally available HDAC inhibitor that crosses the blood-brain barrier and is currently in phase III clinical trials for several types of cancer. It restores cholesterol homeostasis in cultured NPC1 mutant fibroblasts to almost normal levels within 72 h when used at 40 nM. The findings that HDAC inhibitors can correct cholesterol storage defects in human NPC1 mutant cells provide the potential basis for treatment options for NPC disease.
Antioxidant activity of beta-carboline derivatives. (2011)

The investigated beta-carboline derivatives were synthesized to elucidate their activity as 5-HT(1A) and 5-HT(2A) receptor ligands. Compounds containing a carboline ring system belong to a large family of biological active indoles, which are very important for the function of the central nervous system. The research was carried out to determine antioxidative or oxidative properties of these derivatives. Analysis of antioxidative capacity as indication of oxidative stress was based on ability to scavenge free radicals by DPPH (free radical scavenging activity test) and FRAP test. The results were compared to those of standard substances like vitamin C, trolox, quercetin and curcumin. The research of derivatives of beta-carboline shows antioxidative activity comparable to vitamin C. Compounds 1, 5 and 6, but only in low concentration, have antioxidative activity. Substance 10 was classified as that with prooxidative activity.
Tyrosine kinase blocking collagen IV–derived peptide suppresses ocular neovascularization and vascular leakage (2017)

An integrin-binding peptide derived from collagen IV prevents ligand-induced activation of multiple tyrosine kinase receptors and strongly suppresses ocular neovascularization and vascular leakage.
Identification and Further Development of Potent TBK1 Inhibitors (2014)

The cytosolic Ser/Thr kinase TBK1 was discovered to be an essential element in the mediation of signals that lead to tumor migration and progression. These findings meet the need for the identification of novel tool compounds and potential therapeutics to gain deeper insights into TBK1 related signaling and its relevance in tumor progression. Herein, we undertake the activity-based screening for unique inhibitors of TBK1 and their subsequent optimization. Initial screening approaches identified a selection of TBK1 inhibitors that were optimized using methods of medicinal chemistry. Variations of the structural characteristics of a representative 2,4,6-substituted pyrimidine scaffold resulted in improved potency. Prospective use as tool compounds or basic contributions to drug design approaches are anticipated for our improved small molecules.
Cystic fibrosis and bacterial colonization define the sputum N-glycosylation phenotype (2014)

Although mucin O-glycosylation of sputum from individuals suffering from cystic fibrosis (CF) is known to be altered relative to their unaffected counterparts, protein N-glycosylation of CF sputum remains structurally and functionally under-characterized. We report the first N-glycome of soluble proteins in sputum derived from five CF patients, two pathogen-free and two pathogen-infected/colonized non-CF individuals suffering from other pulmonary conditions. N-Glycans were profiled using porous graphitized carbon-liquid chromatography-negative ion-tandem mass spectrometry following enzymatic release from sputum proteins. The composition, topology and linkage isomers of 68 N-glycans were characterized and relatively quantified. Recurring structural features in all sputum N-glycomes were terminal α2,6-sialylation, α1,6-core fucosylation, β1,4-bisecting GlcNAcylation and compositions indicating paucimannosylation. Despite covering different genotypes, age, gender and microbial flora, the sputum N-glycomes showed little interpatient and longitudinal variation within CF patients. Comparative N-glycome analysis between inter-patient group revealed that lung infection/colonization, in general, extensively enriches the CF sputum N-glycosylation phenotype with paucimannose with simultaneous over-sialylation/fucosylation and under-bisecting GlcNAcylation of complex/hybrid N-glycans. In contrast, the sputum from CF patients had only slightly increased abundance of paucimannose N-glycans relative to pathogen-infected/colonized non-CF individuals. Similar to mucin O-glycosylation, protein N-glycosylation appears to be regulated primarily as a secondary effect of bacterial infection and inflammation rather than the CF pathogenesis in sputum. This study provides new structural N-glycan information to help understand the complex cellular and molecular environment of the CF affected respiratory tract.
Ligand Recognition by E-Selectin: Synthesis, Inhibitory Activity and Conformational Analysis of Bivalent Sialyl Lewis x Analogs (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLigand Recognition by E-Selectin: Synthesis, Inhibitory Activity and Conformational Analysis of Bivalent Sialyl Lewis x AnalogsShawn A. DeFrees, Winfried Kosch, William Way, James C. Paulson, Subramanian Sabesan, Randall L. Halcomb, Dee-Hua Huang, Yoshitaka Ichikawa, and Chi-Huey WongCite this: J. Am. Chem. Soc. 1995, 117, 1, 66–79Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January 1995https://pubs.acs.org/doi/10.1021/ja00106a008https://doi.org/10.1021/ja00106a008research-articleACS PublicationsRequest reuse permissionsArticle Views380Altmetric-Citations117LEARN 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
Wireless position location: fundamentals, implementation strategies, and sources of error (2002)

This paper presents an overview of basic RF position location strategies which are feasible for ubiquitous deployment by cellular-type wireless system providers. Limitations on the practical ability to locate mobile RF transmitters and the effects of real world channel degradation on direction-finding and time difference of arrival systems are also discussed.
Structure of a Tumor Associated Antigen Containing a Tandemly Repeated Immunodominant Epitope (1995)

Human mucins are T or S glycosylated tandem repeat proteins. In breast cancer, mucins become under or unglycosylated. Two-dimensional nuclear magnetic resonance experiments are performed on chemically synthesized mucin tandem repeat polypeptides, (PDTRPAPGST-APPAHGVTSA)n the unglycosylated form for n=1,3 where (APDTR) constitutes the antigenic sites for the antibodies isolated form the tumors in the breast cancer patients. These studies demonstrate how the tandem repeats assemble in space giving rise to the overall tertiary structure, and the local structure and presentation of the antigenic site(APDTR) at the junction of two neighboring repeats. The NMR data reveal repeating knob-like structures connected by extended spacers. The knobs protrude away from the long-axis of Muc-1 and the predominant antigenic site (APDTR) forms the accessible tip of the knob. Multiple tandem repeats enhance the rigidity and presentation of the knob-like structures.
A Non Mouse-Adapted Dengue Virus Strain as a New Model of Severe Dengue Infection in AG129 Mice (2010)

The spread of dengue (DEN) worldwide combined with an increased severity of the DEN-associated clinical outcomes have made this mosquito-borne virus of great global public health importance. Progress in understanding DEN pathogenesis and in developing effective treatments has been hampered by the lack of a suitable small animal model. Most of the DEN clinical isolates and cell culture-passaged DEN virus strains reported so far require either host adaptation, inoculation with a high dose and/or intravenous administration to elicit a virulent phenotype in mice which results, at best, in a productive infection with no, few, or irrelevant disease manifestations, and with mice dying within few days at the peak of viremia. Here we describe a non-mouse-adapted DEN2 virus strain (D2Y98P) that is highly infectious in AG129 mice (lacking interferon-alpha/beta and -gamma receptors) upon intraperitoneal administration. Infection with a high dose of D2Y98P induced cytokine storm, massive organ damage, and severe vascular leakage, leading to haemorrhage and rapid death of the animals at the peak of viremia. In contrast, very interestingly and uniquely, infection with a low dose of D2Y98P led to asymptomatic viral dissemination and replication in relevant organs, followed by non-paralytic death of the animals few days after virus clearance, similar to the disease kinetic in humans. Spleen damage, liver dysfunction and increased vascular permeability, but no haemorrhage, were observed in moribund animals, suggesting intact vascular integrity, a cardinal feature in DEN shock syndrome. Infection with D2Y98P thus offers the opportunity to further decipher some of the aspects of dengue pathogenesis and provides a new platform for drug and vaccine testing.
Cell penetrating peptides: A concise review with emphasis on biomedical applications (2018)

Owing to the ability of CPPs to transport across cellular membrane, they can employ as an appropriate carrier for various cargos include nucleic acid, proteins, SiRNA, therapeutic agents, nanoparticles and so on. In this review, we describe the classifications of CPPs, their uptake mechanisms as well as biomedical applications of the CPPs.
Method for the Isolation of Intact Islets of Langerhans from the Rat Pancreas (1967)

A simple method for the isolation of intact islets from the normal rat pancreas is described. The method is based upon disruption of the acinar parenchyma by injecting Hanks solution into the pancreatic duct system followed by incubation of the pancreas in collagenase. Islets can be separated rapidly from this mixture by sedimentation. The isolated islets release insulin in vitro and appear normal by light and electron microscopy after incubation. A centrifugation method is also described for isolation of large quantities of islets for biochemical studies.
Aliasing Detection and Reduction in Plenoptic Imaging (2014)

When using plenoptic camera for digital refocusing, angular undersampling can cause severe (angular) aliasing artifacts. Previous approaches have focused on avoiding aliasing by pre-processing the acquired light field via prefiltering, demosaicing, reparameterization, etc. In this paper, we present a different solution that first detects and then removes aliasing at the light field refocusing stage. Different from previous frequency domain aliasing analysis, we carry out a spatial domain analysis to reveal whether the aliasing would occur and uncover where in the image it would occur. The spatial analysis also facilitates easy separation of the aliasing vs. non-aliasing regions and aliasing removal. Experiments on both synthetic scene and real light field camera array data sets demonstrate that our approach has a number of advantages over the classical prefiltering and depth-dependent light field rendering techniques.
Antileukemic Activity of Shepherdin and Molecular Diversity of Hsp90 Inhibitors (2006)

Shepherdin is a novel Hsp90 inhibitor with a unique mechanism of anticancer activity.
Evidence for irnnairment of energy metabofism in vivo in Huntington's disease using localized 1H NMR spectroscopy (1993)

The Huntington's disease (HD) gene mutation has recently been found; however, the biochemical defect that leads to neurodegeneration is still unknown. A progressive impairment of neuronal energy metabolism is a possible etiologic factor. We tested this possibility using localized proton nuclear magnetic resonance (NMR) spectroscopy in 18 patients at high risk for, or suffering from, HD as compared with normal controls. Lactate concentrations were increased in the occipital cortex of symptomatic HD patients when compared with normal controls, and the lactate level correlated with duration of illness. In addition, several patients showed highly elevated lactate levels in the basal ganglia. Basal ganglia levels of N-acetylaspartate were lowered and choline dramatically elevated, relative to creatine, reflecting neuronal loss and gliosis in this brain region. These findings are consistent with a possible defect in energy metabolism in HD, which could contribute to the pathogenesis of the disease. The presence of elevated lactate in HD brains may provide a simple marker that can be followed over time noninvasively and repeatedly to aid in devising and monitoring possible therapies for HD patients.
IMMUNOTHERAPY WITH NONDEPLETING ANTI-CD4 MONOCLONAL ANTIBODIES BUT NOT CD28 ANTAGONISTS PROTECTS ISLET GRAFT IN SPONTANEOUSLY DIABETIC NOD MICE FROM AUTOIMMUNE DESTRUCTION AND ALLOGENEIC AND XENOGENEIC GRAFT REJECTION1 (2001)

Nondepleting anti-CD4 mAbs but not CD28 antagonists protect islet grafts in diabetic NOD mice from autoimmune destruction and allogeneic and xenogeneic graft rejection. The efficacy of nondepleting anti-CD4 mAbs is compromised when it combines with CTLA4Ig.
Biomechanics of atherosclerotic plaque. (1997)

Atherosclerosis is the leading cause of death in the U.S. In balloon angioplasty, pressure is applied directly to atherosclerotic plaque to reopen the occluded blood vessel. The mechanical behavior of the plaque often determines the outcome of the angioplasty. Little information on the material properties of atherosclerotic plaque is available, yet the properties govern the plaque's behavior. Our discussion of the experimental testing and numerical analysis of plaque is directed toward summarizing the current knowledge of plaque material properties. Atherosclerotic plaque exhibits a wide range of behaviors consistent with the variability in the underlying composition. Overall, plaques exhibit nonlinear and inelastic mechanical behavior, although geometry and material properties are not well known. The histomorphological composition is critical in determining the plaque's mechanical response. Finite element approximations have been used to study the stresses developed in the diseased vessel; however, material properties are a critical component of a finite element analysis: the predictive capabilities depend on how accurately the material is modeled. When more information on plaque behavior is generated through careful and extensive experimental investigations, better models will be constructed to more accurately predict plaque responses. As the biomechanics community learns about plaque mechanics, we can use the knowledge to enhance the reliability of interventional procedures.
Enhanced Secretory Production of a Single-Chain Antibody Fragment from Bacillus subtilis by Coproduction of Molecular Chaperones (1998)

Formation of inclusion bodies is a major limiting factor for secretory production of an antidigoxin single-chain antibody (SCA) fragment from Bacillus subtilis. To address this problem, three new strains with enhanced production of molecular chaperones were constructed. WB600BHM constitutively produces the major intracellular molecular chaperones in an appropriate ratio without any heat shock treatment. This strain reduced the formation of insoluble SCA by 45% and increased the secretory production yield by 60%. The second strain, WB600B[pEPP], overproduces an extracytoplasmic molecular chaperone, PrsA. An increase in the total yield of SCA was observed. The third strain, WB600BHM[pEPP], coproduces both intracellular and extracytoplasmic molecular chaperones. This led to a further reduction in inclusion body formation and a 2.5-fold increase in the secretory production yield. SCA fragments secreted by this strain were biologically active and showed affinity to digoxin comparable to the affinity of those secreted by strains without overproduction of molecular chaperones. Interestingly, accumulation of a pool of periplasmic SCA was observed in the PrsA-overproducing strains. This pool is suggested to represent the secreted folding intermediates in the process of achieving their final configuration.
The relationship between carboplatin AUC and serum thrombopoietin kinetics in patients with lung cancer. (1999)

To clarify the relationship between the carboplatin AUC and the extent of damage to thrombopoiesis, we monitored both endogenous serum TPO kinetics and carboplatin pharmacokinetics after single-agent carboplatin administration. Previously untreated 12 patients with stage IV non-small-cell lung cancer were enrolled. The actual carboplatin AUC showed a significant positive correlation with the maximum increase ratio of TPO (TPOmax/TPOday1) (r = 0.74, p = 0.014). Furthermore, the increase ratio of TPO at one week after administration of carboplatin (TPOday8/TPOday1) showed a significant negative correlation with the following platelet nadir around day 19 (r = -0.84, p = 0.005). By monitoring the changes in endogenous TPO concentration, we could estimate the degree of thrombocytopenia and determine the indication, and thus the optimal timing of prophylactic administration of TPO before platelets are markedly reduced.
Directed evolution of gold nanoparticle delivery to cells (2009)

A newly selected anti-receptor (anti-EGFR) aptamer was conjugated to gold nanoparticles via a facile hybridization method and was found to specifically and quantitatively direct the delivery of gold nanoparticles to cells expressing EGFR through receptor-mediated endocytosis.
Is Age-Related Maculopathy Associated With Cataracts? (1994)

These data suggest a possible commonly shared pathogenesis between nuclear sclerotic cataract and age-related maculopathy.
Homogeneous Hydrogenation of Fatty Acid Methyl Esters and Natural Oils under Neat Conditions (2014)

A series of ruthenium- and iron-based pincer catalysts have been tested for the homogeneous hydrogenation of fatty acid methyl esters to fatty alcohols with turnover numbers (TONs) of up to 1860. These catalysts operate under neat conditions (no solvent) from the gram to the kilogram scale. The required temperature (135 °C) and H2 pressure (300–1000 psig) are much lower than those needed for current industrial processes, which rely on heterogeneous copper chromite catalysts. The fatty alcohol products can be purified through distillation, resulting in low levels of Ru (1 ppm) and P (<25 ppm). The five-coordinate Milstein catalyst and Takasago’s borane-stabilized catalyst are also effective for the direct hydrogenation of coconut oil to fatty alcohols. These results hold the promise of using homogeneous catalysts for ester hydrogenation in an industrial setting.
The shopping assistant Robot design based on ROS and deep learning (2016)

As the traditional service robots' artificial intelligence bottlenecks, there is a huge gap between service robots and human intelligence in the cognitive and learning discipline. So the service robots could not be widely applied. As deep learning theory is proposed in 2012, it may lead to a generation leap forward in machine learning discipline, so as to improving the traditional robot's cognitive algorithms. This paper studies the principle of three-dimensional Kinect sensor and the deep learning framework of CNN. We proposed a shopping assistant robot designing method which combined Robot Operation System and deep learning method. Firstly, the ROS packages for the service robot are designed. Secondly, Kinect sensors are used for acquiring the information in the robot. Finally, we use simulation to evaluated the design.
Translation initiation region sequence preferences in Escherichia coli (2007)

In E. coli the SD selection preferences are influenced by the growth temperature and not influenced by the growth rate. The A/U rich enhancers stimulate translation considerably by acting co-operatively with the SD sequences.
Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology (2003)

The phenomenon of ischemic preconditioning, in which a period of sublethal ischemia can profoundly protect the cell from infarction during a subsequent ischemic insult, has been responsible for an enormous amount of research over the last 15 years. Ischemic preconditioning is associated with two forms of protection: a classical form lasting approximately 2 h after the preconditioning ischemia followed a day later by a second window of protection lasting approximately 3 days. Both types of preconditioning share similarities in that the preconditioning ischemia provokes the release of several autacoids that trigger protection by occupying cell surface receptors. Receptor occupancy activates complex signaling cascades which during the lethal ischemia converge on one or more end-effectors to mediate the protection. The end-effectors so far have eluded identification, although a number have been proposed. A range of different pharmacological agents that activate the signaling cascades at the various levels can mimic ischemic preconditioning leading to the hope that specific therapeutic agents can be designed to exploit the profound protection seen with ischemic preconditioning. This review examines, in detail, the complex mechanisms associated with both forms of preconditioning as well as discusses the possibility to exploit this phenomenon in the clinical setting. As our understanding of the mechanisms associated with preconditioning are unravelled, we believe we can look forward to the development of new therapeutic agents with novel mechanisms of action that can supplement current treatment options for patients threatened with acute myocardial infarction.