gebhart/patrepeval huggingface dataset:
Superparamagnetic Iron Oxide Nanotheranostics for Targeted Cancer Cell Imaging and pH-Dependent Intracellular Drug Release (2010)

Studies were conducted to develop antibody- and fluorescence-labeled superparamagnetic iron oxide nanoparticle (SPIO) nanotheranostics for magnetic resonance imaging (MRI) and fluorescence imaging of cancer cells and pH-dependent intracellular drug release. SPIO nanoparticles (10 nm) were coated with amphiphilic polymers and PEGylated. The antibody HuCC49ΔCH2 and fluorescent dye 5-FAM were conjugated to the PEG of iron oxide nanoparticles (IONPs). Anticancer drugs doxorubicin (Dox), azido-doxorubicin (Adox), MI-219, and 17-DMAG containing primary amine, azide, secondary amine, and tertiary amine, respectively, were encapsulated into IONPs. The encapsulation efficiency and drug release at various pHs were determined using LC-MS/MS. The cancer targeting and imaging were monitored using MRI and fluorescent microscopy in a colon cancer cell line (LS174T). The pH-dependent drug release, intracellular distribution, and cytotoxicity were evaluated using microscopy and MTS assay. The PEGylation of SPIO and conjugation with antibody and 5-FAM increased SPIO size from 18 to 44 nm. Fluorescent imaging, magnetic resonance imaging (MRI) and Prussian blue staining demonstrated that HuCC49ΔCH2-SPIO increased cancer cell targeting. HuCC49ΔCH2-SPIO nanotheranostics decreased the T(2) values in MRI of LS174T cells from 117.3 ± 1.8 ms to 55.5 ± 2.6 ms. The loading capacities of Dox, Adox, MI-219, and 17-DMAG were 3.16 ± 0.77%, 6.04 ± 0.61%, 2.22 ± 0.42%, and 0.09 ± 0.07%, respectively. Dox, MI-219 and 17-DMAG showed pH-dependent release while Adox did not. Fluorescent imaging demonstrated the accumulation of HuCC49ΔCH2-SPIO nanotheranostics in endosomes/lysosomes. The encapsulated Dox was released in acidic lysosomes and diffused into cytosol and nuclei. In contrast, the encapsulated Adox only showed limited release in endosomes/lysosomes. HuCC49ΔCH2-SPIO nanotheranostics target-delivered more Dox to LS174T cells than nonspecific IgG-SPIO and resulted in a lower IC(50) (1.44 μM vs 0.44 μM). The developed HuCC49ΔCH2-SPIO nanotheranostics provides an integrated platform for cancer cell imaging, targeted anticancer drug delivery and pH-dependently drug release.
A direct role of SRY and SOX proteins in pre-mRNA splicing (2002)

The mammalian testis determining factor SRY and its related Sox factors are critical developmental regulators. They share significant similarity in their high mobility group (HMG) domain and display discrete patterns of tissue-specific expression. Here we show that SRY and the Sox protein SOX6 colocalize with splicing factors in the nucleus and are dynamically redistributed following the blockage of splicing in living cells. Anti-SOX6 antibodies supershift the spliceosomal complex from assembled splicing reactions and inhibit splicing in vitro of multiple pre-mRNA substrates. Most importantly, SOX6-depleted nuclear extracts have impaired splicing activity, which is efficiently restored by addition of the recombinant SOX6 HMG domain and also by recombinant SRY and the SOX9 HMG domain. These results reveal an unexpected biological function of the SRY, SOX6, and SOX9 gene products and provide a functional link to the biochemical mechanisms operating in mammalian sex determination and in other developmental processes regulated by Sox genes.
An evaluation framework for Multicast Ordering Protocols (1992)

A new framework for evaluating Multicast Ordering protocols is presented. It allows to compare solutions to the problem of ordering multicast messages in an identical way at all receiving sites when multiple senders operate concurrently. A new type of delay measure called Synchronization Delay forms the basis for this framework. It filters out network-dependent factors and accounts precisely for the excess delay that user messages suffer in order to achieve the ordering property. The usefulness of the evaluation framework is demonstrated by applying it to three protocols covered in the literature. As an example their delay behavior is analyzed for low-traffic environments. The evaluation results allow a user to choose the most suitable protocol for his application.
Progress in circulating tumor cell capture and analysis: implications for cancer management (2012)

The hematogenous dissemination of cancer and development of distant metastases is the cause of nearly all cancer deaths. Detection of circulating tumor cells (CTCs) as a surrogate biomarker of metastases has gained increasing interest. There is accumulating evidence on development of novel technologies for CTC detection, their prognostic relevance and their use in therapeutic response monitoring. Many clinical trials in the early and metastatic cancer setting, particularly in breast cancer, are including CTCs in their translational research programs and as secondary end points. We summarize the progress of detection methods in the context of their clinical importance and speculate on the possibilities of wider implementation of CTCs as a diagnostic oncology tool, the likelihood that CTCs will be used as a useful biomarker, especially to monitor therapeutic response, and what may be expected from the future improvements in technologies.
A new class of tobacco chitinases homologous to bacterial exo-chitinases displays antifungal activity (1994)

A novel chitinase gene of tobacco was isolated and characterized by DNA sequence analysis of a genomic clone and a cDNA clone. Comparative sequence analysis of both clones showed an identity of 94%. The proteins encoded by these sequences do not correspond to any of the previously characterized plant chitinases of classes I-IV and are designated as class V chitinases. Comparison of the chitinase class V peptide sequence with sequences in the Swiss Protein databank revealed significant sequence similarity with bacterial exo-chitinases from Bacillus circulans, Serratia marcescens and Streptomyces plicatus. It was demonstrated that class V chitinase gene expression is induced after treatment of tobacco with different forms of stress, like TMV-infection, ethylene treatment, wounding or ultraviolet irradiation. Two related chitinase class V proteins of 41 and 43 kDa were purified from Samsun NN tobacco leaves inoculated with tobacco mosaic virus. The proteins were purified by Chelating Superose chromatography and gel filtration. In vitro assays demonstrated that class V chitinases have endo-chitinase activity and exhibit antifungal activity toward Trichoderma viride and Alternaria radicina. In addition, it was shown that class V chitinase acts synergistically with tobacco class I beta-1,3-glucanase against Fusarium solani germlings.
Binding of Phosphatidic Acid to the Protein-Tyrosine Phosphatase SHP-1 as a Basis for Activity Modulation (1999)

Activation of the SH2 domain-possessing protein-tyrosine phosphatase SHP-1 by acidic phospholipids as phosphatidic acid (PA) has been described earlier and suggested to participate in regulation of SHP-1 activity toward cellular substrates. The mechanism of this activation is poorly understood. Direct binding of phosphatidic acid to recombinant SHP-1 could be demonstrated by measuring the extent of [(14)C]PA binding in a chromatographic assay, by measuring the extent of binding of SHP-1 to PA-coated ELISA plates or silica beads (TRANSIL), and by spectroscopic assays employing fluorescently labeled PA liposomes. In addition to PA, phosphatidylinositol 3,4, 5-trisphosphate (PIP3), dipalmitoylphosphatidylglycerol, phosphatidylinositol 4,5-bisphosphate, and phosphatidylserine (PS) were found to bind to SHP-1, albeit to a lesser extent. A high-affinity binding site for PA and PIP3 was mapped to the 41 C-terminal amino acids of SHP-1. This site was absent from the related protein-tyrosine phosphatase SHP-2 and conferred activation of SHP-1 by PA toward two different substrates at low lipid concentrations. A SHP-1 mutant missing this binding site could, however, still be activated toward phosphorylated myelin basic protein as a substrate at high PA concentrations. This activation is likely to be mediated by a second, low-affinity binding site for PA in the N-terminal part of SHP-1 within the SH2 domains. High-affinity phospholipid binding to the C-terminus of SHP-1 may present a specific mechanism of regulating activity and/or cellular localization.
Browsing and keyword-based profiles: a cautionary tale (2005)

In the research presented, adaptive user profiles are used to rate Web pages with respect to possible user interest. The user profiles consist of weighted keywords and the adaptation is based on the Hebbian Learning Model with direct user feedback. A user study was conducted to determine if the system would "learn" over a series of five sessions when there was no explicit task other than to browse. The results are analogous to reading the news, i.e., it is not possible to predict what pages a user will read if there is no explicit task. We suggest that a shift away from content to document style (genre) and other user characteristics may be more effective.
Primitive Cardiac Cells from Human Embryonic Stem Cells (2011)

Pluripotent stem cell-derived cardiomyocytes are currently being investigated for in vitro human heart models and as potential therapeutics for heart failure. In this study, we have developed a differentiation protocol that minimizes the need for specific human embryonic stem cell (hESC) line optimization. We first reduced the heterogeneity that exists within the starting population of bulk cultured hESCs by using cells adapted to single-cell passaging in a 2-dimensional (2D) culture format. Compared with bulk cultures, single-cell cultures comprised larger fractions of TG30(hi)/OCT4(hi) cells, corresponding to an increased expression of pluripotency markers OCT4 and NANOG, and reduced expression of early lineage-specific markers. A 2D temporal differentiation protocol was then developed, aimed at reducing the inherent heterogeneity and variability of embryoid body-based protocols, with induction of primitive streak cells using bone morphogenetic protein 4 and activin A, followed by cardiogenesis via inhibition of Wnt signaling using the small molecules IWP-4 or IWR-1. IWP-4 treatment resulted in a large percentage of cells expressing low amounts of cardiac myosin heavy chain and expression of early cardiac progenitor markers ISL1 and NKX2-5, thus indicating the production of large numbers of immature cardiomyocytes (~65,000/cm(2) or ~1.5 per input hESC). This protocol was shown to be effective in HES3, H9, and, to a lesser, extent, MEL1 hESC lines. In addition, we observed that IWR-1 induced predominantly atrial myosin light chain (MLC2a) expression, whereas IWP-4 induced expression of both atrial (MLC2a) and ventricular (MLC2v) forms. The intrinsic flexibility and scalability of this 2D protocol mean that the output population of primitive cardiomyocytes will be particularly accessible and useful for the investigation of molecular mechanisms driving terminal cardiomyocyte differentiation, and potentially for the future treatment of heart failure.
Tailored Porous Silicon Microparticles: Fabrication and Properties (2010)

The use of mesoporous silicon particles for drug delivery has been widely explored thanks to their biodegradability and biocompatibility. The ability to tailor the physicochemical properties of porous silicon at the micro- and nanoscale confers versatility to this material. A method for the fabrication of highly reproducible, monodisperse, mesoporous silicon particles with controlled physical characteristics through electrochemical etching of patterned silicon trenches is presented. The particle size is tailored in the micrometer range and pore size in the nanometer range, the shape from tubular to discoidal to hemispherical, and the porosity from 46 to over 80%. In addition, the properties of the porous matrix are correlated with the loading of model nanoparticles (quantum dots) and their three-dimensional arrangement within the matrix is observed by transmission electron microscopy tomography. The methods developed in this study provide effective means to fabricate mesoporous silicon particles according to the principles of rational design for therapeutic vectors and to characterize the distribution of nanoparticles within the porous matrix.
Quantitative measurement of lipoprotein surface charge by agarose gel electrophoresis. (1992)

The electrophoretic mobilities of low density lipoprotein (LDL) and six pure proteins in a 0.5% agarose gel have been compared to literature electrophoretic mobility values determined by the Tiselius moving boundary method. There is a strong correlation (r = 0.99) between the electrophoretic mobilities determined by the two techniques. The electrophoretic behavior of charged particles smaller than very low density lipoproteins (VLDL) is not markedly perturbed by a 0.5% agarose matrix, and variations in mobility primarily reflect differences in particle valence and density of surface charge. Application of electrokinetic theory to derive protein and lipoprotein net charges from the electrophoretic mobilities in agarose yields a quantitative delineation of lipoprotein electrophoretic migration patterns wherein the beta mobility region comprises a surface potential range of -4.5 to -7.0 mV; the pre-beta region a range of -7.0 to -10.5 mV; the alpha mobility region a range of -10.5 to -12.5 mV and the serum albumin region a range of -12.5 to -14.0 mV. Because protein conformation and charge are critical in metabolic regulation, the agarose gel electrophoresis technique provides a valuable analytical tool that should help to elucidate further details of the structure-function relationships of serum lipoprotein particles.
Species‐specific measurement of the second group of Dermatophagoides mite allergens, Der p 2 and Der f 2, using a monoclonal antibody‐based ELISA (1996)

The MoAb-ELISA for Der p 2 and Der f 2, as well as that of Der p 1 and Der f 1, will be useful for the standardization of mite extracts and for the assessments of mite allergen exposure.
Two-photon-absorbed photopolymerization for three-dimensional microfabrication (2002)

We report a method for three-dimensional microfabrication with photopolymerization stimulated by two-photon absorption. An experimental system for the microfabrication has been developed with a Ti:sapphire laser that has an oscillating wavelength as 770 nm and a 130 fs pulse width. The usefulness of the proposed method has been verified by fabrication of several kinds of microstructure by use of a resin consisting of photoinitiators, urethane acrylate monomers and urethane acrylate oligomers.
Role of Melatonin in Schizophrenia (2013)

Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia's biological etiology is multifactorial and is still under investigation. Melatonin has been involved in schizophrenia since the first decades of the twentieth century. Research into melatonin regarding schizophrenia has followed two different approaches. The first approach is related to the use of melatonin as a biological marker. The second approach deals with the clinical applications of melatonin as a drug treatment. In this paper, both aspects of melatonin application are reviewed. Its clinical use in schizophrenia is emphasized.
Differences in the rates of gene amplification in nontumorigenic and tumorigenic cell lines as measured by Luria-Delbrück fluctuation analysis. (1989)

It has been hypothesized that genomic fluidity is an important component of tumorigenesis. Previous studies described the relationship between tumorigenicity and one marker for genomic fluidity, gene amplification. In this report, these studies are extended with the rat liver epithelial cell lines to show that: (i) the amplification in these cells arises in a spontaneous fashion in the population (i.e., the variants detected are not preexisting in the population), and (ii) the rate of spontaneous amplification (mutation), as measured by Luria-Delbrück fluctuation analysis, is significantly lower in the nontumorigenic cells than in the tumorigenic cells. The rate was estimated by using the Po method and the method of means. The rate of spontaneous amplification of the gene encoding the multifunctional protein CAD (containing the enzymatic activities carbamoyl-phosphate synthase, aspartate transcarbamylase, and dihydroorotase) in the highly tumorigenic cells was significantly greater than that for the nontumorigenic cells, reaching almost 1 x 10(-4) events per cell per generation. The rate of this mutagenic event is high compared to the rate of point mutations usually reported in mammalian cells, and its potential contribution to the tumorigenic process will be discussed.
Inference-based ambiguity management in decentralized decision-making: decentralized diagnosis of discrete event systems (2006)

The task of decentralized decision-making involves interaction of a set of local decision-makers, each of which operates under limited sensing capabilities and is thus subjected to ambiguity during the process of decision-making. In a prior work by R. Kumar and S. Takai (2005) we made a key observation that such ambiguities are of differing gradations and presented a framework for inferencing over various local control decisions of varying ambiguity levels to arrive at a global control decision. We develop a similar framework for performing diagnosis in a decentralized setting. For each event-trace executed by a system being monitored, each local diagnoser issues its own diagnosis decision (failure or non-failure or unsure), tagged with a certain ambiguity level zero being the minimum). A global diagnosis decision is taken to be a "winning" local diagnosis decision, i.e., one with a minimum ambiguity level. The computation of an ambiguity level for a local decision requires an assessment of the self-ambiguities as well as the ambiguities of the others, and an inference based up on such knowledge. In order to characterize the class of systems for which any fault can be detected within a uniformly bounded delay, we introduce the notion of N-inference-diagnosability for failures (also called N-inference-diagnosability), where the index N represents the maximum ambiguity level of any winning local decision. We show that the codiagnosability introduced by W. Qiu and R. Kumar (2006) is the same as 0-inference F-diagnosability; the conditional F-codiagnosability introduced by Y. Wang et al.(2004), Y. Wang et al. (2005) is a type of 1-inference F-diagnosability; and the class of higher-index inference F-diagnosable systems strictly subsumes the class of lower-index ones
A Petri Net-Based Novel Scheduling Approach and Its Cycle Time Analysis for Dual-Arm Cluster Tools With Wafer Revisiting (2012)

For some wafer fabrication processes, such as an atomic layer deposition (ALD) process, the wafers need to visit some process modules for a number of times. Using the existing swap-based strategy scheduling method in such systems leads to a 3-wafer cyclic schedule. Unfortunately, it is not optimal in the sense of cycle time. Aiming at searching for a better schedule, this paper models the system by a timed Petri net. With this model, the properties of the 3-wafer schedule are analyzed. Then, based on the analysis, it is found that, to improve the performance, it is necessary to reduce the number of wafers completed in a cycle. Hence, a 1-wafer schedule is developed by using a new swap-based strategy. By using the Petri net model, its cycle time is analyzed and shown to be optimal. Also, an effective method is presented to implement it. Illustrative examples are given to verify the research results obtained in this paper.
Kinetic mechanism of the DNA-dependent DNA polymerase activity of human immunodeficiency virus reverse transcriptase. (1993)

The kinetic pathway of DNA-dependent DNA polymerase activity of human immunodeficiency virus reverse transcriptase (HIV RT) as determined by pre-steady-state methods using a defined primer/template is as follows, [formula: see text] where E is RT, Dn,n+1 is primer/template, dNTP is deoxyribonucleoside triphosphate, and PPi is pyrophosphate. The rate-determining step for enzyme turnover in single nucleotide addition is the dissociation of enzyme from DNA (k6 = 0.11 s-1). The observation of an E'.DNA.dNTP intermediate by pulse-chase analysis and the absence of a phosphorothioate elemental effect identified the rate-limiting step for nucleotide addition as a conformational change of the E.DNA.dNTP complex (k3 = 83 s-1) prior to the chemical step. Biphasic kinetics of single-turnover pyrophosphorolysis suggested that this conformational change (k-3 = 0.3 s-1) is also rate-limiting for the reverse reaction. The equilibrium constant for the chemical step (K4) is 3.8, in slight favor of the forward reaction. The large equilibrium constant (K3 = 280) for the conformational change effectively renders nucleotide addition kinetically irreversible. The dissociation constant for primer/template is 26 nM, and the association rate of enzyme and DNA (k1) is 2.3 x 10(6) M-1 s-1. Equilibrium dissociation constants for dTTP and PPi are 18 microM and 7.2 mM, respectively. Mg2+ enhances productive interaction of RT with DNA as judged by a 50% increase in burst amplitude in the single nucleotide addition reaction and by an 8-fold decrease in KD for the RT.DNA complex as determined by gel mobility shift assay. Secondary interactions of the RT.DNA complex with free DNA were observed in the absence of Mg2+.
놀이치료에서 의미분석법에 의한 모형동물 이미지 연구 (2000)

The purpose of this study is to investigate the difference between the significance attached by children to miniature animals used in play therapy and the attitudes of therapists to the miniature animals which the children choose. The object of this study were 210 3th, 4th, 5th graders selected from 2 elementary schools in Seoul. Thirty one 3th, 4th, 5th graders experienced play therapy with 41 play therapists. The research instruments used for this study were the Semantic Differential Techniques relation to miniature animals. The Semantic Differential Technique and has three main factors-namely Potency factor, Evaluation factor, and Activity factor. The results of this study were as follow: There were significant differences attached 0 the meaning of miniature animals amongst the thee groups. First There were significant differences in the Potency factors of dinosaurs, spiders, elephants, turtles, and lizards, in the Evaluation factor of the dolphin, and the horse, and in the Activity factor of elephants between general children and play therapy children. Secondly, There were significant differences in the Potency factors of dinosaurs, makes, lions, tigers, and turtles, in the Evaluation factors of makes, dolphins, lizards, and the Activity factors of lions, elephants, whales, turtles between the children involved and their play therapists.
Inhibitors of CXC chemokine receptor type 4 (2013)

Based on these findings, blocking CXCR4 seems to be a therapeutic strategy in inflammatory diseases. Several promising CXCR4 antagonists are in different stages of development and clinical trials. Currently, only plerixafor (AMD3100) has been approved for short-term application.