gebhart/patrepeval huggingface dataset:
JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34+ cells in vitro and in vivo (2014)

Chronic myeloid leukemia (CML) stem cell survival is not dependent on BCR-ABL protein kinase and treatment with ABL tyrosine kinase inhibitors cures only a minority of CML patients, thus highlighting the need for novel therapeutic targets. The Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)5 pathway has recently been explored for providing putative survival signals to CML stem/progenitor cells (SPCs) with contradictory results. We investigated the role of this pathway using the JAK2 inhibitor, ruxolitinib (RUX). We demonstrated that the combination of RUX, at clinically achievable concentrations, with the specific and potent tyrosine kinase inhibitor nilotinib, reduced the activity of the JAK2/STAT5 pathway in vitro relative to either single agent alone. These effects correlated with increased apoptosis of CML SPCs in vitro and a reduction in primitive quiescent CML stem cells, including NOD.Cg-Prkdc(scid) IL2rg(tm1Wjl) /SzJ mice repopulating cells, induced by combination treatment. A degree of toxicity toward normal SPCs was observed with the combination treatment, although this related to mature B-cell engraftment in NOD.Cg-Prkdc(scid) IL2rg(tm1Wjl) /SzJ mice with minimal effects on primitive CD34(+) cells. These results support the JAK2/STAT5 pathway as a relevant therapeutic target in CML SPCs and endorse the current use of nilotinib in combination with RUX in clinical trials to eradicate persistent disease in CML patients.
Unexpected Healability of an <i>ortho</i>-Blocked Polybenzoxazine Resin (2019)

Ring-opening polymerization of bifunctional benzoxazine has long been thought to produce a permanent network structure without reprocessing ability. Here, we demonstrate that surprising healability can be achieved by a controlled polymerization of an <i>ortho</i>-blocked bifunctional benzoxazine poly(<i>o</i>C-hda). The cured resin possesses a cross-linked structure, but can be deformed, remolded from crushed pieces or healed from mechanical damage. Based on a series of intensive experiments, we show that the healability can be explained by a dynamic bonding exchange mechanism between the phenoxy structures existing during the curing process. Moreover, we verify the possibility to heal the fatigue damaged poly(<i>o</i>C-hda) based composite to extend its service life. Our study provides another dynamic covalent bond to synthesize healable polymers, offering a broad platform for combining healability and desired thermosetting features together.
Discoidin domain receptor 2 deficiency predisposes hepatic tissue to colon carcinoma metastasis (2011)

DDR2 deficiency fosters the myofibroblast transdifferentiation of tumour-activated HSCs, generating a prometastatic microenvironment in the liver via HSC-derived factors. These findings underscore the role of stromal cells in conditioning the hepatic microenvironment for metastases through altered receptor-stroma interactions.
Pharmacological management of epilepsy. Mechanism of action, pharmacokinetic drug interactions, and new drug discovery possibilities. (1998)

Despite recent advances in neurobiology and significant insight into the molecular dysfunction of epilepsy, about 25% of patients do not completely respond to current frontline therapeutic agents such as carbamazepine, phenytoin, valproic acid, ethosuximide, phenobarbital, and benzodiazepine. Recently, much effort has been made to discover new antiepileptic drugs effective in refractory seizures. Two major groups of drugs have emerged of which felbamate, gabapentin, lamotrigine, oxcarbazepine, and vigabatrin are among the most promising. The mechanism of action of the first group works by enhancing brain GABA activity (e.g. vigabatrin) while the second group inhibits excitatory amino acids (e.g. lamotrigine and felbamate). Oxcarbazepine acts in a similar manner to carbamazepine while gabapentin's mode of action is still unclear. The major clinical indications of these new antiepileptics are partial complex seizures. They exhibit limited drug interactions with few adverse effects. A rational approach to the drug discovery process is necessary in order to lead to novel effective therapy. Another line of research is the use of the structure-activity relationship to fine-tune the pharmacology of existing antiepileptics providing less adverse effects with the same or better efficacy. Clinical perspectives from the discovery of new drugs such as fosphenytoin and valproyl glycinamide look promising. Rapid development in molecular biologic techniques for the study of the neurophysiology of epilepsy and the neurotransmitters which are the target for the antiepileptic drugs may also provide better insight into the interactions of antiepileptics with either ion channels or brain receptors.
Sustainable Films and Coatings from Hemicelluloses: A Review (2008)

This review summarizes the results of past research on films and coatings from hemicelluloses, biopolymers that are as yet relatively unexploited commercially. The targeted uses of hemicelluloses have primarily been packaging films and coatings for foodstuffs as well as biomedical applications. Oxygen permeability of hemicellulose films, an important characteristic for food packaging, was typically comparable to values found for other biopolymer films such as amylose and amylopectin. As expected, the modification of hemicelluloses to create more hydrophobic films reduced the water vapor permeability. However, modified hemicellulose coatings intended for food still exhibited water vapor permeabilities several magnitudes higher than those of other polymers currently used for this purpose. Research on hemicelluloses for biomedical applications has included biocompatible hydrogels and coatings and material surfaces with enhanced cell affinity. Numerous possibilities exist for chemically modifying hemicelluloses, and fundamental studies of films from modified hemicelluloses have identified other potential applications, including selective membranes.
Evaluation of Two Magnetic-Bead-Based Viral Nucleic Acid Purification Kits and Three Real-Time Reverse Transcription-PCR Reagent Systems in Two TaqMan Assays for Equine Arteritis Virus Detection in Semen (2011)

This study showed that under specifically defined conditions with respect to nucleic acid extraction method and testing reagents, a previously described real-time reverse transcription-PCR (rRT-PCR) assay (T1 assay) provides sensitivity equal to or higher than that of virus isolation for the detection of equine arteritis virus in semen.
Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to teniposide. (1991)

Nuclear extracts from teniposide (VM-26)-resistant sublines of the human leukemic cell line CCRF-CEM have decreased levels of DNA topoisomerase II catalytic activity and decreased capacity to form drug-stabilized covalent protein-DNA complexes. The ATP concentration required for equivalent activity in a DNA-unknotting assay is 2- to 8-fold higher in nuclear extracts from drug-resistant cell lines as compared with the parental line. When adenosine 5'-[beta,gamma-imido]triphosphate is substituted for ATP in complex-formation assays, no significant change is seen with drug-sensitive cells, but a 50-65% reduction is seen with VM-26-resistant cells. Collectively, these results indicate that an alteration in ATP binding may be involved in the resistance phenotype. Therefore, we identified regions of the topoisomerase II sequence that conform to previously identified nucleotide-binding sites. Starting with cDNA as the template we determined the sequence of the topoisomerase II mRNA surrounding these sites by sequencing DNA fragments produced by the polymerase chain reaction. In the region corresponding to the consensus B ATP-binding sequence described by Walker et al. [Walker, J. E., Saraste, M., Runswick, M. J. & Gay, N. J. (1982) EMBO J. 1, 945-951], the cDNA from the two VM-26-resistant sublines contained an altered sequence having a G----A base change. This base substitution results in the replacement of the conserved arginine at position 449 with a glutamine. Hybridization with allele-specific oligonucleotides confirmed the presence of both the normal and the altered sequence in the resistant cell lines, whereas only the normal sequence was found in the sensitive CEM cells. A chemical mismatch cleavage procedure for the detection of mispaired bases in DNA duplexes identified no other alterations in the 5' third of the mRNA coding sequence, which contains the complete ATP-binding domain of topoisomerase II. The presence of mRNA encoding topoisomerase II with Gln449 correlates both with the presence of a topoisomerase II protein whose interaction with ATP is altered and with increased resistance to the cytotoxicity of VM-26.
CYP3A activity: towards dose adaptation to the individual (2016)

While ample data is available on the choice appropriate phenotyping drugs (midazolam, alfentanil, aplrazolam, buspirone, triazolam), less clinical trial data is available concerning strategies to usefully guide dosing in the clinical practice. Implementation into the clinical routine necessitates further research to identify (1) an easy-to-use and cheap test for CYP3A activity that (2) adequately predicts drug exposure to (3) allow a sound decision on dose adaptation and hence (4) improve clinical outcome and/or reduce the intensity or frequency of adverse drug effects.
A quick intelligent program architecture for 3 V-only NAND-EEPROMs (2003)

A quick program/program verify architecture with an intelligent verify circuit for 3-V-only NAND-EEPROMs is described. The verify circuit, which is composed of two transistors, provides a simple, intelligent program algorithm for 3-V-only operation. The total programming time is reduced to 50%. By using intelligent verify circuits, the memory cells which require more time to reach the program state are automatically detected. Verify-read, the modification of program data, and data reload are performed simultaneously. The chip size penalty is estimated to be only 1% for a 16-Mb NAND-EEPROM.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Long‐term expression of the human glucocerebrosidase gene <i>in vivo</i> after transplantation of bone‐marrow‐derived cells transformed with a lentivirus vector (2005)

The recombinant lentiviral vector transduces HSCs that are capable of long-term gene expression in vivo. This approach is potentially useful for the treatment of patents with Gaucher disease and other lysosomal storage disorders.
S‐100a<sub>0</sub> protein stimulates Ca<sup>2+</sup> ‐induced Ca<sup>2+</sup> release from isolated sarcoplasmic reticulum vesicles (1989)

S-100a0 protein, the alpha alpha-isoform of the S-100 family, stimulates Ca2+-induced Ca2+ release from terminal cisternae isolated from rat skeletal muscle cells. The stimulatory effect of S-100a0 is maximal at approximately 5 microM S-100a0 and half maximal at approximately 0.1 microM S-100a0, at 1.8 microM free Ca2+ in the presence of 5 mM Mg2+ plus 0.1 M KCl. The effect of the protein on Ca2+-induced Ca2+ release is completely inhibited by the calcium release blocker, ruthenium red.
Intra- and extra-cranial effects of transient blood pressure changes on brain near-infrared spectroscopy (NIRS) measurements (2011)

Brain near-infrared spectroscopy (NIRS) is an emerging neurophysiological tool that combines straightforward activity localization with cost-economy, portability and patient compatibility. NIRS is proving its empirical utility across specific cognitive and emotional paradigms. However, a potential limitation is that it is not only sensitive to haemodynamic changes taking place in the cortex, and task-related cardiovascular responses expressed in the perfusion of extracranial layers may be confounding. Existing literature reports correlations between brain NIRS and systemic blood pressure, yet it falls short of establishing whether in normal participants the blood pressure changes encountered in experimental settings can have confounding effects. Here, we tested this hypothesis by performing two experimental manipulations while recording from superficial occipital cortex, encompassing striate and extrastriate regions. Visual stimulation with reversing chequerboards evoked cortical haemodynamic responses. Simultaneously and independently, transient systemic blood pressure changes were generated through rapid arm-raising. Shallow-penetration NIRS recordings, probing only extra-cerebral tissues, highlighted close haemodynamic coupling with blood pressure. A different coupling pattern was observed in deep-penetration recordings directed at haemodynamic signals from visual cortex. In absence of blood-pressure changes, NIRS signals tracked differences in visual stimulus duration. However when blood pressure was actively manipulated, this effect was absent and replaced by a very large pressure-related response. Our observations demonstrate that blood pressure fluctuations can exert confounding effects on brain NIRS, through expression in extracranial tissues and within the brain itself. We highlight the necessity for continuous blood pressure monitoring alongside brain NIRS, and for further research on methods to correct for physiological confounds.
Pivaloylnitrene (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPivaloylnitreneG. Thomas. Tisue, Siegfried. Linke, and Walter. LwowskiCite this: J. Am. Chem. Soc. 1967, 89, 24, 6303–6307Publication Date (Print):November 1, 1967Publication History Published online1 May 2002Published inissue 1 November 1967https://pubs.acs.org/doi/10.1021/ja01000a056https://doi.org/10.1021/ja01000a056research-articleACS PublicationsRequest reuse permissionsArticle Views431Altmetric-Citations39LEARN 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
Performance and Variability Comparisons between Multi-Gate FETs and Planar SOI Transistors (2006)

This paper compares the performance and inter-die variability of doped and undoped channel multiple-gate FETs (MUGFETs) with respect to planar SOI devices. We show that doped-channel FinFETs have equivalent variability to narrow-width planar devices. As such, transitions to FinFETs for narrow-width devices will likely incur minimal variability impact. To match the low variability of wide-width planar devices, conversions to undoped channel FinFETs is necessary. Furthermore, good short-channel control has to be maintained since undoped channel devices exhibit increase sensitivity to Tbody relative to doped channel FinFETs due to enhanced fully-depleted channel electrostatics
Ratio of serum ?-GT/ALT rather than ISDR variability is predictive for initial virological response to IFN-? in chronic HCV infection (1999)

Chronic hepatitis C virus (HCV) infection in humans is treated at present with interferon (IFN)-alpha. Because the proportion of patients responding to therapy with sustained or even just with transient elimination of viral RNA is low, several potential prognostic parameters have been evaluated to predict the outcome of the therapy. The present study aimed to prove the validity of a predictive parameter described previously for initial virological response, namely the ratio of serum gamma-glutamyltransferase/alanine transaminase (gamma-GT/ALT) activity in connection with virus genotypes 1a, 1b, and 3a, prospectively and to compare the predictive value of these combined parameters with amino acid variability within the interferon sensitivity determining region (ISDR). The prospective analysis confirmed previous data on the predictive value of the serum gamma-GT/ALT ratio. Concerning ISDR variability, the majority of ISDR sequences obtained from the mostly nonresponding type 1b-infected individuals (23/28) resembled nonmutant types (27/ 28). Isolates from type 3a-infected patients responding to therapy in the majority of cases (13/ 20) exclusively resembled nonmutant types when compared with databank type 3a sequences, but were mutant when compared with the prototype sequence HCV-J. However, the initial virological responsiveness among both type 1b- and type 3a-infected patients did not correlate to ISDR variability. In contrast, virological responsiveness was closely related to serum gamma-GT/ALT ratio. The data are not necessarily contrary to the concept that the number of amino acid exchanges within the ISDR compared with the prototype HCV-J sequence is related to some extent to IFN-alpha sensitivity. The ratio of serum gamma-GT/ALT in combination with HCV genotype, however, was found to be a more reliable and stringent predictive parameter.
PI3K/AKT/PTEN Signaling as a Molecular Target in Leukemia Angiogenesis (2012)

PI3K/AKT/PTEN pathway is important in the regulation of angiogenesis mediated by vascular endothelial growth factor in many tumors including leukemia. The signaling pathway is activated in leukemia patients as well as leukemia cell lines together with a decrease in the expression of PTEN gene. The mechanism by which the signaling pathway regulates angiogenesis remains to be further elucidated. However, it has become an attractive target for drug therapy against leukemia, because angiogenesis is a key process in malignant cell growth. In this paper, we will focus on the roles and mechanisms of PI3K/AKT/PTEN pathway in regulating angiogenesis.
The aging spine: the role of inflammatory mediators in intervertebral disc degeneration. (2007)

Human intervertebral disc undergoes multifactorial biochemical and morphologic degenerative changes during the process of aging. The frequency of degeneration, especially lumbar degeneration increases sharply with age and is regarded as a major cause of discogenic low back pain. Since degenerative discs are often asymptomatic, the pathobiology of discogenic back pain remains unclear. Degenerated discs spontaneously produce increased amounts of inflammatory mediators suggesting their role in the degenerative process of the intervertebral disc. However, the relationship between aging, degenerative processes, and actual illness is far from clear. Basic science research has demonstrated that the intervertebral disc is an avascular tissue element occupied by inadequately characterized cells in an extensive extracellular matrix. While the annulus fibrosus is predominantly collagenous, the matrix of the central nucleus pulposus is rich in proteoglycans. With aging, the substance of proteoglycans significantly decreases which is believed to be a critical factor in intervertebral disc degeneration. A variety of inflammatory mediators have been implicated in the degeneration of the intervertebral disc including nitric oxide (NO), interleukins, matrix metalloproteinases (MMP), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-alpha) and a group of cytokines. MMPs, PGE2, and a variety of cytokines have been already been shown to play a role in the degradation of articular cartilage. Nitric oxide is a novel mediator that is drawn into much attention recently for its role in disc abnormalities. Elevated nitric oxide production derived from NO synthase activity has been manifested in cerebrospinal fluid in patients with degenerative lumbar disease. However, the regulatory mechanism of NO and its relationship to the clinical manifestations are unclear. The biochemical events that occur with the 'aging spine' and in particular, the role of inflammatory mediators in intervertebral disc degeneration have not been studied assertively. Correspondingly, the association between degeneration of the intervertebral disc and the nociceptive mechanism of back pain is also not fully elucidated. However, there is high incidence of degenerated disc disorders manifested as back and neck pain and are among the most commonly encountered complaints in elderly population. It is hypothesized that the degenerative cascade ultimately leads to extensive structural defects and loss of normal motion segment function and configuration.
IQGAP1 regulates cell proliferation through a novel CDC42-mTOR pathway (2009)

Cell proliferation requires close coordination of cell growth and division to ensure constant cell size through the division cycles. IQGAP1, an effector of CDC42 GTPase has been implicated in the modulation of cell architecture, regulation of exocytosis and in human cancers. The precise mechanism underlying these activities is unclear. Here, we show that IQGAP1 regulates cell proliferation, which requires phosphorylation of IQGAP1 and binding to CDC42. Expression of the C-terminal region of IQGAP1 enhanced cellular transformation and migration, but reduced the cell size, whereas expression of the N-terminus increased the cell size, but inhibited cell transformation and migration. The N-terminus of IQGAP1 interacts with mTOR, which is required for IQGAP1-mediated cell proliferation. These findings are consistent with a model where IQGAP1 serves as a phosphorylation-sensitive conformation switch to regulate the coupling of cell growth and division through a novel CDC42-mTOR pathway, dysregulation of which generates cellular transformation.
A flexible circuit switched NOC for FPGA based systems (2005)

Increases in chip density due to Moore's Law allow for the implementation of ever larger and more complex systems on a single chip. The communication mechanisms employed in such SOC's is an important contribution to their overall performance. Networks on chip promise to overcome the scalability problems found in bus-based interconnect. Most work to this point has focused on packet-switched NOC's. Circuit-switched networks are a lightweight alternative that promise high communication rates and predictable communication latencies. This paper describes PNoC, a very flexible circuit-switched NOC suitable for use in FPGA-based systems. Implementation results on a Virtex-il Pro device are given using an image binarization demonstration which resulted in a 2 - 23x speedup with a 29% area overhead compared to a shared bus implementation.