gebhart/patrepeval huggingface dataset:
Evidence that Resistance to Nilotinib May Be Due to BCR-ABL, Pgp, or Src Kinase Overexpression (2008)

Targeting the tyrosine kinase activity of Bcr-Abl is an attractive therapeutic strategy in chronic myeloid leukemia (CML) and in Bcr-Abl-positive acute lymphoblastic leukemia. Whereas imatinib, a selective inhibitor of Bcr-Abl tyrosine kinase, is now used in frontline therapy for CML, second-generation inhibitors of Bcr-Abl tyrosine kinase such as nilotinib or dasatinib have been developed for the treatment of imatinib-resistant or imatinib-intolerant disease. In the current study, we generated nilotinib-resistant cell lines and investigated their mechanism of resistance. Overexpression of BCR-ABL and multidrug resistance gene (MDR-1) were found among the investigated mechanisms. We showed that nilotinib is a substrate of the multidrug resistance gene product, P-glycoprotein, using verapamil or PSC833 to block binding. Up-regulated expression of p53/56 Lyn kinase, both at the mRNA and protein level, was found in one of the resistant cell lines and Lyn silencing by small interfering RNA restored sensitivity to nilotinib. Moreover, failure of nilotinib treatment was accompanied by an increase of Lyn mRNA expression in patients with resistant CML. Two Src kinase inhibitors (PP1 and PP2) partially removed resistance but did not significantly inhibit Bcr-Abl tyrosine kinase activity. In contrast, dasatinib, a dual Bcr-Abl and Src kinase inhibitor, inhibited the phosphorylation of both BCR-ABL and Lyn, and induced apoptosis of the Bcr-Abl cell line overexpressing p53/56 Lyn. Such mechanisms of resistance are close to those observed in imatinib-resistant cell lines and emphasize the critical role of Lyn in nilotinib resistance.
Adaptive dynamics with hybrid response (2012)

This paper describes a hybrid technique to produce physically plausible response for animated character. The approach includes the automatic, adaptive selection of the dynamic articulation necessary for local-body responses based on the changing conditions of the character. This method is combined with a whole-body reaction to disturbances which is computed and controlled separately. Combined, the resulting response effects the entire body as well as the local area of a disturbance without the need for an explicit full-body controller and the response computed is both deliberate (controlled) and passive (uncontrolled). The results showcase a variety of scenarios including fast and sustained contact.
A Novel Calibration Algorithm With Unknown Line-Series-Shunt Standards for Broadband S-Parameter Measurements (2008)

This paper presents a novel calibration algorithm using unknown line-series-shunt standards that are suitable for planar transmission line structures for the broadband S-parameter measurements of microwave vector network analyzers. The derivations are based on the eight-term error model with the matched line standard and the lumped assumptions for the series and shunt calibration kits, respectively. With the self-calibration technique, the line propagation constant and the impedance/admittance of the lumped elements are evaluated for further deembedding processes. Simulated and measured results for the conductor-backed coplanar waveguide calibration kit are shown with the additional noise-effect simulation and the two-line thru-reflect-line calibration measurement to validate the proposed approach.
Ovulatory and Metabolic Effects of d-Chiro-Inositol in the Polycystic Ovary Syndrome (1999)

D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.
Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities (2005)

The paraoxonase (PON) gene family in humans has three members, PON1, PON2, and PON3. Their physiological role(s) and natural substrates are uncertain. We developed a baculovirus-mediated expression system, suitable for all three human PONs, and optimized procedures for their purification. The recombinant PONs are glycosylated with high-mannose-type sugars, which are important for protein stability but are not essential for their enzymatic activities. Enzymatic characterization of the purified PONs has revealed them to be lactonases/lactonizing enzymes, with some overlapping substrates (e.g., aromatic lactones), but also to have distinctive substrate specificities. All three PONs metabolized very efficiently 5-hydroxy-eicosatetraenoic acid 1,5-lactone and 4-hydroxy-docosahexaenoic acid, which are products of both enzymatic and nonenzymatic oxidation of arachidonic acid and docosahexaenoic acid, respectively, and may represent the PONs' endogenous substrates. Organophosphates are hydrolyzed almost exclusively by PON1, whereas bulky drug substrates such as lovastatin and spironolactone are hydrolyzed only by PON3. Of special interest is the ability of the human PONs, especially PON2, to hydrolyze and thereby inactivate N-acyl-homoserine lactones, which are quorum-sensing signals of pathogenic bacteria. None of the recombinant PONs protected low density lipoprotein against copper-induced oxidation in vitro.
A Simple and Efficient Method for the Preparation of Binaltrorphimine and Derivatives and determination of their K opioid antagonist selectivity (1989)

Abstract The bimorphinans 1 (binaltrorphimine), 3 , and 7 have been prepared by treatment of the parent morphinan‐6‐ones naltrexone ( 5 ), naloxone ( 4 ), and dihydrocodeinone ( 6 ), respectively, with N ‐methylhydrazine sulfate in AcOH at room temperature. Compound 3 showed opioid antagonist potency and selectivity for K receptors which were somewhat lower in comparison to 1 .
Increased lipogenesis in cancer cells: new players, novel targets (2006)

The same disturbances in signaling pathways responsible for oncogenic transformation may also contribute to the increased lipogenesis observed in tumor cells. Increased lipogenesis involves modulation of multiple lipogenic enzymes at both transcriptional and posttranscriptional level and is linked to other cancer-associated metabolic changes. Not only fatty acid synthase, but in fact all key enzymes involved in fatty acid synthesis as well as key metabolic regulators are potential targets for antineoplastic intervention.
Computer-aided Diagnosis Scheme for Detection of Polyps at CT Colonography (2002)

Colon cancer is one of the leading causes of cancer deaths in the United States. However, most colon cancers can be prevented if precursor colonic polyps are detected and removed. An advanced computer-aided diagnosis (CAD) scheme was developed for the automated detection of polyps at computed tomographic (CT) colonography. A region encompassing the colonic wall is extracted from an isotropic volume data set obtained by interpolating CT colonographic scans along the axial direction. Polyp candidates are detected with computation of three-dimensional (3D) geometric features that characterize polyps, followed by extraction of polyps with hysteresis thresholding and fuzzy clustering using these geometric features. The number of false-positive findings is reduced by extracting 3D texture features from polyp candidates and applying quadratic discriminant analysis to the candidates. This CAD scheme was applied in 71 patients who underwent CT colonography, 14 of whom had colonoscopically confirmed polyps (n = 21). At by-patient analysis, sensitivity was 100%, with an average false-positive rate of 2.0 per patient. At by-polyp analysis, the scheme detected 90% of the polyps at the same false-positive rate. This CAD scheme permits accurate detection of suspicious lesions and thus has the potential to reduce radiologists' interpretation time and improve their diagnostic accuracy in the detection of polyps at CT colonography.
Noncovalent Functionalization of Graphene and Graphene Oxide for Energy Materials, Biosensing, Catalytic, and Biomedical Applications (2016)

This Review focuses on noncovalent functionalization of graphene and graphene oxide with various species involving biomolecules, polymers, drugs, metals and metal oxide-based nanoparticles, quantum dots, magnetic nanostructures, other carbon allotropes (fullerenes, nanodiamonds, and carbon nanotubes), and graphene analogues (MoS2, WS2). A brief description of π-π interactions, van der Waals forces, ionic interactions, and hydrogen bonding allowing noncovalent modification of graphene and graphene oxide is first given. The main part of this Review is devoted to tailored functionalization for applications in drug delivery, energy materials, solar cells, water splitting, biosensing, bioimaging, environmental, catalytic, photocatalytic, and biomedical technologies. A significant part of this Review explores the possibilities of graphene/graphene oxide-based 3D superstructures and their use in lithium-ion batteries. This Review ends with a look at challenges and future prospects of noncovalently modified graphene and graphene oxide.
Chitin: New Facets of Research (1981)

Research on chitin as a marine resource is pointing to novel applications for this cellulose-like biopolymer. Discovery of nondegrading solvent systems has permitted the spinning of filaments, for example, for use as surgical sutures. New methods for preparing the bioactive alkyl glycoside of N-acetyl-D-glucosamine (the monomer unit of chitin) and a microcrystalline chitin has encouraged their use as promoters for growth of bifidobacteria and as an aid in digestion of high-lactose cheese whey by domestic animals. Chitin-protein complexes of several crustacean species show great variability in ratios of chitin to covalently bound protein and in residual protein in the "purified" chitins.
Application of GIS in site selection for nuclear waste disposal facility (1996)

Whether designing a new facility or investigating, potential contaminant migration at an existing site, proper characterization of the subsurface conditions and their interaction with surface features is critical to the process. The Atomic Energy Control Board, states in its regulatory document R-104 that, {open_quotes}For the long-term management of radioactive wastes, the preferred approach is disposal, a permanent method of management in which there is no intention of retrieval and which, ideally uses techniques and designs that do not rely for their success on long-term institutional control beyond a reasonable period of time{close_quotes}. Thus although storage is safe, eventually disposal is necessary to avoid long-term reliance on continuing care and attention, such as monitoring and maintenance. In Canada, the concept being proposed by Atomic Energy of Canada Limited (AECL) involves disposal in deep underground repositories in intrusive igneous rock. The aim of this concept as a disposal method is to build multiple barriers that would protect humans and the natural environment from contaminants in the radioactive waste. The multiple barriers include the geosphere, which consists of the rock, any sediments overlying the rock, and the groundwater. Nevertheless, immediate, as well as long-term, consequences, including, risk involved with technological systems and themore » inherent uncertainty of any forecast, make the prediction and analysis tasks of increasing importance. This uncertainty in the area of nuclear waste disposal is leading to growing concerns about nuclear waste site selection.« less
Immunity in the absence of CD28 and CD137 (4‐1BB) molecules (2003)

We report the generation and immune regulation of mice that are deficient in CD28 and 4-1BB (CD137) genes. These mice were viable, fertile and did not display any overt abnormalities and had a normal T cell phenotype in thymus and spleen. Proliferative responses to anti-CD3 and ConA were enhanced in 4-1BB-/- but not in either CD28-/- or double mutant mice, while levels of interleukin-2 were decreased in all mutant mice. Although the 4-1BB-/- mice displayed increased basal levels of most immunoglobulin isotypes tested, the plateau levels of immunoglobulin G2a, immunoglobulin G2b and immunoglobulin A were particularly high compared to wild type controls. The immunoglobulin class switch to T-dependent antigen was normal in 4-1BB-/- mice but was greatly affected in both CD28-/- and 4-1BB-/- CD28-/- mice. Vesicular stomatitis virus-specific cytotoxic T lymphocyte responses and plaque reduction neutralizing ability was differentially reduced in all mutant mice. Contact sensitivity to allergens showed marginal but not significant change in ear thickness in 4-1BB-/- mice, but an ability to mount contact hypersensitivity to the same antigens was greatly curtailed in CD28-/- and double mutant mice.
Abnormal development of embryonic and extraembryonic cell lineages in parthenogenetic mouse embryos (1994)

Parthenogetically activated, diploid mouse oocytes can develop to midgestation stages in utero. However, even these advanced parthenogenones appear to die because of much reduced trophoblast and yolk sac development. Previous studies have compared the general features of parthenogenetic and androgenetic development and determined the fate of uniparental cells in chimeras with normal embryos. These studies led to the concept of genomic imprinting as the cause for developmental failure when either the maternal or the paternal genome is duplicated, with the corresponding deficiency of the other. Genomic imprinting appears to arise during gametogenesis and to act through dosage effects in a set of imprinted genes, whose expression depends on their parental origin. In this study we undertook a more detailed morphological analysis of parthenogenetic development in the mouse and established a classification system to quantify the developmental extent of parthenogenones. We found that the failure of parthenogenones occurred at different times during early postimplantation development, generating a spectrum of concepti which had developed to different extents, with only a small fraction of the embryos reaching advanced somite stages. In all parthenogenones differentiation and proliferation of the trophectoderm and primitive endoderm lineages (both extraembryonic) was abnormal, and in all, even the best-developed parthenogenones, we observed similar deficiencies in the embryonic lineages, especially the mesoderm. Common to all abnormally developed lineages was that the proportion of undifferentiated precursor cells was much reduced, while their differentiated descendants were relatively abundant. We propose, therefore, that the failure of parthenogenones to develop to term is due to abnormal regulation of differentiation and proliferation in both embryonic and extraembryonic lineages. In this hypothesis, the apparent tissue specific defects observed in parthenogenones arise as a consequence of the functional importance of certain tissues (like the trophoblast) early in development. The spectrum of parthenogenones thus appears to reflect critical events in early development, whose regulation are affected by genomic imprinting.
A Randomized, Double‐Blind, Placebo‐Controlled Study of Botulinum Toxin Type A for the Treatment of Glabellar Lines (2007)

Reloxin (Dysport/botulinum toxin type A) treatment resulted in a significant improvement in glabellar lines, and the 50-U dose was identified as optimal. All doses were well tolerated.
Sleep Loss Reduces Diurnal Rhythm Amplitude of Leptin in Healthy Men (2003)

The aim of the current study was to investigate the effects of sleep loss on the diurnal rhythm of circulating leptin levels. An indwelling forearm catheter was used to sample blood at 90-min intervals for a total of 120 h, which included 88 h of sustained sleeplessness, in 10 healthy men. The diurnal amplitude of leptin was reduced during total sleep deprivation and returned toward normal during the period of recovery sleep. This finding provides evidence that sleep influences the nocturnal leptin profile, and may have implications for the understanding of the role of sleep in metabolic regulation and the aetiologies of obesity and the night eating syndrome.
Problém počátku letopočtu a spontánní narušení symetrie (2001)

Problem roku 0, casto diskutovaný v souvislosti s pocatkem
letopoctu, je projevem spontanniho naruseni symetrie, znameho z
fyziky.
A fast hierarchical motion-compensation scheme for video coding using block feature matching (1996)

This paper presents a fast hierarchical feature matching-motion estimation scheme (HFM-ME) that can be used in H.263, H.261, MPEG 1, MPEG 2, and HDTV applications. In the HFM-ME scheme, the sign truncated feature (STF) is defined and used for block template matching, as opposed to the pixel intensity values used in conventional block matching methods. The STF extraction process can be considered as a zero-crossing phase detection with the mean as the bias and binary sign pattern as the phase deviation. Using the STF definition, a data block can be represented by a mean and a set of binary features with a much reduced data set. The block matching motion estimation is then divided into mean matching and binary phase matching. The proposed technique enables a significant reduction in computational complexity compared with the conventional full-search block matching ME because binary phase matching only involves Boolean logic operations. This feature also significantly reduces the data transfer time between the frame buffer and motion estimator. The proposed HFM-ME algorithm is implemented and compared with the conventional full-search block matching schemes. Our test results using three full-motion MPEG sequences indicate that the performance of the HFM-ME is comparable with the full-search block matching under the same search ranges, however, HFM-ME can be implemented about 64 times faster than the conventional full-search schemes. The proposed scheme can be combined with other fast algorithms to further reduce the computational complexity, at the expense of picture quality.
Clinical Scale Expansion of Human Pluripotent Stem Cells. (2005)

Abstract Research studies of adherent stem cell populations, primarily isolated from bone marrow but also cord blood, adipose and other tissues, have shown cultures capable of regenerating more than one primitive germ layer in vitro or in vivo. This raises exciting possibilities for tissue repair in acute injury or degenerative disease, provided scalable processes for cell expansion can be developed. We have optimized an expansion process based on the Multi-potent Adult Progenitor Cell (MAPC) platform first described by Dr. C. Verfaillie. Termed Multistem, these adherent stem cell cultures have the capacity to differentiate into many different primary tissue types including but not limited to endothelial, hepatic, neuronal, adipogenic, and osteogenic lineages cells. Three fresh marrow aspirates were obtained from healthy donors and the mononuclear cells isolated using the COBE 2991 Cell Processor. Once the mononuclear cells were isolated, they were subsequently placed into Nunc cell factories that had been coated with 10 ng/ml Fibronectin A (Day 0). Serum containing media supplemented with PDGF and EGF was used, with cells incubated under low oxygen tension (5%). Cells were expanded to Day six, and then every two to three days until greater than 100 million cells were obtained (routinely Day 15–17). The growth rate was linear through approximately 24 population doublings, (yielding a theoretical 1011 cells) with a doubling rate of 24–30 hours. Release criteria qualifying successfully expansion to clinical scale include sterility, identity/purity, and tissue lineage potency. In addition, the cells were analyzed at approximately population doubling 20 for cytogenetic abnormalities and out of 20 spreads, 0 abnormal cells were detected for each of the three samples. All cultures tested positive by qPCR for expression of Oct4, a marker of pluripotency in ES cell systems. Telomerase levels were analyzed using a TRAP QPCR assay and the levels ranged from between 15 and 22 times higher than that measured in commercially purchased mesenchymal stem cells (MSC) at about population doubling 20 FACS analysis was performed on cells expanded using these conditions, with all cultures being positive for CD49c, CD90 and negative for CD45 and HLA class II surface markers. Current process improvements have allowed for the growth of human cells out to greater than 60 population doublings. These results demonstrate that large numbers of human stem and progenitor cells can be obtained using these culturing techniques, and that the cell products are consistent between donors. Donor ages ranged between 19 and 57. This is the first report of a scalable and consistent process for expansion of human stem cell cultures with pluripotent lineage capacity.
Double-Stranded RNA Unwinding and Modifying Activity Is Detected Ubiquitously in Primary Tissues and Cell Lines (1990)

A double-stranded RNA unwinding and modifying activity was found to be present in a wide range of tissues and cell types. The level of activity did not vary significantly with respect to the state of cell differentiation, cell cycle, or transformation. Thus, the unwinding and modifying activity, localized in the nucleus in somatic cells and capable of converting many adenosine residues to inosine, appears to be one of the housekeeping genes.
Tissue-Engineered Three-Dimensional Tumor Models to Study Tumor Angiogenesis (2010)

Cell-microenvironment interactions play a critical role in the transformation of normal cells into cancer; however, the underlying mechanisms and effects are far from being well understood. Tissue Engineering provides innovative culture tools and strategies to study tumorigenesis under pathologically relevant culture conditions. Specifically, integration of biomaterials, scaffold fabrication, and micro/nano-fabrication techniques offers great promise to reveal the dynamic role of chemical, cell-cell, cell-extracellular matrix, and mechanical interactions in the pathogenesis of cancer. Due to the central importance of blood vessel formation in tumor growth, progression, and drug response, this review will discuss specific design parameters for the development of culture microenvironments to study tumor angiogenesis. Tumor engineering approaches have the potential to revolutionize our understanding of cancer, provide new platforms for testing of anti-cancer drugs, and may ultimately result in improved treatment strategies.
Contemporary Heterocyclic Chemistry: Syntheses, Reactions and Applications (1982)

Partial table of contents: Nomenclature. Electronic Division of Aromatic Heterocyclic Compounds. Synthetic Routes to Selected Monocyclic Five-Membered Pi-Excessive Heteroaromatic Compounds. Synthetic Routes and Reactions of Some Common Benzo-fused Five Membered Pi-Excessive Heteroaromatic Compounds.
Interpretation of Europe Society of Parental and Enteral Nutrition Guidelines on percutaneous endoscopic gastrostomy (2011)

Percutaneous endoscopic gastrostomy (PEG) is an convenient, effective, and safe technique, and is especially useful for the nutritional support of patients who are unable to befedorally. PEG should be carefully arranged based on indications, ethical criteria, and contraindications. Early PEG can remarkably improve the quality of life.


Key words: 
Percutaneous endoscopic gastrostomy; Europe Society of Parentral and Enteral Nutrition; Guideline