gebhart/patrepeval huggingface dataset:
Phase I clinical trial of a novel peptide vaccine in combination with UFT/LV for metastatic colorectal cancer (2010)

To test the safety and immune responses of a novel peptide vaccine derived from RNF43 (ring finger protein 43) and TOMM34 (34-kDa translocase of the outer mitochondrial membrane) administered in combination with chemotherapy in patients with metastatic colorectal cancer, a phase I clinical trial with 21 HLA-A2402-positive metastatic colorectal cancer patients was conducted. Patients received a weekly peptide vaccine (1 mg of each peptide in incomplete Freund's adjuvant) in combination with oral UFT (300 mg/m(2)/day) and UZEL (75 mg/day) for 4 weeks, followed by 1 week of rest. The protocol consisted of at least two cycles of this regimen. After the 2nd cycle, vaccinations were given biweekly or monthly, depending on the condition of the patient. Clinical responses were judged 10 weeks after the 2nd cycle by performing computed tomography (CT) scans and assessing the cytotoxic T lymphocyte (CTL) responses against RNF43 and TOMM34 in peripheral lymphocytes. The vaccinations were well tolerated without any serious adverse events. CTL responses were induced against both antigens in 8 patients and against one antigen in 12 patients, while 1 patient had no CTL response. The rate of stable disease was 83%. The group with CTL responses against both antigens had the most long-term survivors, followed by the group showing CTL responses against one antigen (p=0.0079). The patients with no CTL responses had the lowest survival. The safety and immunological responsiveness of the present combination therapy suggests that it is clinically beneficial for metastatic colorectal cancer. Further clinical trials are warranted.
Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissues. (1990)

The primary structure of rat hepatocyte growth factor (HGF) was elucidated by determining the base sequence of the complementary DNA (cDNA) of HGF. The cDNA for rat HGF was isolated by screening a liver cDNA library with oligonucleotides based on the partial N-terminal amino acid sequence of the beta subunit of purified rat HGF. HGF is encoded in an mRNA of about 6 kilobases. Both alpha and beta subunits of HGF are specified in a single open reading frame for a 728-amino acid protein with a calculated molecular weight of 82,904. The N-terminal part of HGF has a signal sequence and a prosequence with 30 and 25 amino acid residues, respectively. The mature heterodimer structure is derived proteolytically from this single pre-pro precursor polypeptide. The calculated molecular weights of the alpha and beta subunits are 50,664 and 25,883, respectively, and each subunit has two potential N-linked glycosylation sites. The amino acid sequence of HGF is 38% identical with that of plasminogen. The alpha subunit of HGF contains four "kringle" structures, and the beta subunit has 37% amino acid identity with the serine protease domain of plasmin. Northern blot analysis revealed that HGF mRNA was expressed in rat various tissues, including the liver, kidney, lung, and brain.
Recent Periodicals (1986)

Recent Periodicals Get access MICHAEL HEANEY MICHAEL HEANEY Oxford Search for other works by this author on: Oxford Academic Google Scholar The Library, Volume s6-VIII, Issue 4, December 1986, Pages 399–407, https://doi.org/10.1093/library/s6-VIII.4.399 Published: 01 December 1986
Significant enhancement of the sensing characteristics of In2O3nanowires by functionalization with Pt nanoparticles (2010)

We report a significant enhancement in the gas sensing properties of In(2)O(3) nanowires by functionalizing their surfaces with Pt nanoparticles. For Pt-functionalization, In(2)O(3)-Pt core-shell nanowires are synthesized by the sputtering deposition of Pt layers on bare In(2)O(3) nanowires. Next, continuous Pt shell layers are transformed into Pt nanoparticles of cubic phase by heat treatment. In an O(2) gas sensing test, the Pt-functionalized In(2)O(3) nanowires reveal exceptionally higher sensitivity and faster response than bare In(2)O(3) nanowires.
Administration verdirbt das Management (1996)

Schon ohne staatliche Eingriffe stellt eine Managementaufgabe hohe zeitliche Anforderungen, wenn sie als echte Verpflichtung übernommen wurde. Die Mintzberg-Unter-suchung kommt zu dem Ergebnis, „daß Manager einem unerbittlichen Arbeitstempo unterworfen sind, daß ihre Aktivitäten kurzfristig, höchst unterschiedlich und diskontinuierlich sind ... “,27 Das normale Tagesgeschäft lastet je nach Unternehmen trotz hoher Delegation zwischen acht und vierzehn Stunden aus: Gespräche mit Mitarbeitern und Kunden sowie Telefonate dienen der Information, es sind Pläne, Konzeptionen und Aktenvermerke zu lesen, Sitzungen zu leiten, Reden zu halten etc. Nur durch die Verarbeitung einer Vielzahl von Informationen läßt sich der Überblick über das laufende Geschäft behalten. Je komplexer ein Unternehmen ist, um so mehr Informationen müssen aufgenommen werden. Natürlich lassen sich die Schwerpunkte verschieben, aber vieles ist bei verantwortungsvoller Führung nicht mehr delegierbar. Obwohl die Gedanken um die Zukunft, um die Verbesserung der Organisation eigentlich die wichtigsten für die oberste Führungsebene sind, werden sie am ehesten zurückgestellt, da sie keine kurzfristige Dringlichkeit haben wie beispielsweise Maßnahmen aufgrund von Kunden- oder Mitarbeiterverlusten, aufgrund eines Versagens in einzelnen Abteilungen oder Tochtergesellschaften, durch den Kampf um größere Aufträge, durch Wettbewerbseinbrüche, bei dringenden Kreditverhandlungen, Überwachung von Planungen und Soll/Ist-Vergleichen usw.
Network of WNT and Other Regulatory Signaling Cascades in Pluripotent Stem Cells and Cancer Stem Cells (2011)

Canonical WNT signaling activation leads to transcriptional up-regulation of FGF ligand, Notch ligand, non-canonical WNT ligand, WNT antagonist, TGFβ antagonist, and MYC. Non-canonical WNT signals inhibit canonical WNT signaling by using MAP3K7-NLK signaling cascade. Hedgehog up-regulates Notch ligand, WNT antagonist, BMP antagonists, and MYCN. TGFβ up-regulates non-canonical WNT ligand, CDK inhibitors, and NANOG, while BMP up-regulates Hedgehog ligand. Based on these mutual regulations, WNT, FGF, Notch, Hedgehog, and TGFβ/BMP signaling cascades constitute the stem-cell signaling network, which plays a key role in the maintenance or homeostasis of pluripotent stem cells and cancer stem cells. Human embryonic stem cells (ESCs) are supported by FGF and TGFβ/Nodal/Activin signals, whereas mouse ESCs by LIF and canonical WNT signals. Combination of TGFβ inhibitor and canonical WNT activator alter the character of human induced pluripotent stem cells (iPSCs) from human ESC-like to mouse ESC-like. Fine-tuning of WNT, FGF, Notch, TGFβ/BMP, and Hedgehog signaling network by using small-molecule compounds could open the door for regenerative medicine utilizing pluripotent stem cells without tumorigenic potential. Because FGF, Hedgehog, TGFβ, and non-canonical WNT signals synergistically induce EMT regulators, such as Snail (SNAI1), Slug (SNAI2), TWIST, and ZEB2 (SIP1), tumor-stromal interaction at the invasion front aids cancer stem cells to acquire more malignant phenotype. Cancer stem cells occur as mimetics of normal tissue stem cells based on germ-line variation, epigenetic change, and somatic mutation of stem-cell signaling components, and then acquire more malignant phenotype based on accumulation of additional epigenetic and genetic alterations, and tumor-stromal interaction at the invasion front.
Cutting Edge: Molecular Analysis of the Negative Regulatory Function of Lymphocyte Activation Gene-3 (2002)

Lymphocyte activation gene (LAG)-3 (CD223) is a CD4-related activation-induced cell surface molecule that binds to MHC class II molecules with high affinity and negatively regulates T cell expansion and homeostasis. In this study, we show that LAG-3 inhibits CD4-dependent, but not CD4-independent, T cell function via its cytoplasmic domain. Although high affinity interaction with MHC class II molecules is essential for LAG-3 function, tailless LAG-3 does not compete with CD4 for ligand binding. A single lysine residue (K468) within a conserved "KIEELE" motif is essential for interaction with downstream signaling molecules. These data provide insight into the mechanism of action of this important T cell regulatory molecule.
Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of alpha-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation (2001)

Hurler syndrome is the most severe form of a lysosomal storage disease caused by loss of the enzyme alpha-L-iduronidase (encoded by the IDUA gene), which participates in the degradation of glycosaminoglycans (GAGs) within the lysosome. In some populations, premature stop mutations represent roughly two-thirds of the mutations that cause Hurler syndrome. In this study we investigated whether the aminoglycoside gentamicin can suppress stop mutations within the IDUA gene. We found that a Hurler syndrome fibroblast cell line heterozygous for the IDUA stop mutations Q70X and W402X showed a significant increase in alpha-L-iduronidase activity when cultured in the presence of gentamicin, resulting in the restoration of 2.8% of normal alpha-L-iduronidase activity. Determination of alpha-L-iduronidase protein levels by an immunoquantification assay indicated that gentamicin treatment produced a similar increase in alpha-L-iduronidase protein in Hurler cells. Both the alpha-L-iduronidase activity and protein level resulting from this treatment have previously been correlated with mild Hurler phenotypes. Although Hurler fibroblasts contain a much higher level of GAGs than normal, we found that gentamicin treatment reduced GAG accumulation in Hurler cells to a normal level. We also found that a reduced GAG level could be sustained for at least 2 days after gentamicin treatment was discontinued. The reduction in the GAG level was also reflected in a marked reduction in lysosomal vacuolation. Taken together, these results suggest that the suppression of premature stop mutations may provide an effective treatment for Hurler syndrome patients with premature stop mutations in the IDUA gene.
Relationship Between Regional Shortening and Asynchronous Electrical Activation in a Three‐Dimensional Model of Ventricular Electromechanics (2003)

The large variation in delay times was attributable to several factors including local anatomic variations, the location of the site relative to the activation wavefront, and regional end-diastolic strain. Therefore, we conclude that these factors, which are intrinsic to three-dimensional ventricular function, make the regional sequence of fiber shortening an unreliable surrogate for regional depolarization or electromechanical activation in the intact ventricles.
Inhibition of P210BCR/ABL Expression in K562 Cells by Electroporation with an Antisense Oligonucleotide (1990)

We designed experiments to study the effects on P210BCR/ABL expression of introducing antisense oligonucleotides into K562 cells. We used two antisense oligonucleotides: one (AS1) is complementary to the first coding codon of the BCR/ABL mRNA and the two 5' and three 3' codons, and the other (AS2) to BCR coding codons 5 to 11 inclusive. To facilitate entry of the oligonucleotides the K562 cells were subjected to electroporation on three occasions at 24 hr intervals (0, 24 and 48 hr). P210BCR/ABL expression was assayed by in vivo phosphorylation followed by immune precipitation with a BCR antibody. Introduction of AS1 inhibited P210BCR/ABL expression at 72 and 96 hrs, whereas AS2 and the control oligonucleotide had no effect. AS1 also killed K562 cells. We conclude that selected antisense oligonucleotides can modify leukaemia-specific protein expression in K562 cells. This approach could prove valuable for purging CML bone marrow cells in vitro.
Quantum Computing in the NISQ era and beyond (2018)

Noisy Intermediate-Scale Quantum (NISQ) technology will be available in the near future. Quantum computers with 50-100 qubits may be able to perform tasks which surpass the capabilities of today's classical digital computers, but noise in quantum gates will limit the size of quantum circuits that can be executed reliably. NISQ devices will be useful tools for exploring many-body quantum physics, and may have other useful applications, but the 100-qubit quantum computer will not change the world right away --- we should regard it as a significant step toward the more powerful quantum technologies of the future. Quantum technologists should continue to strive for more accurate quantum gates and, eventually, fully fault-tolerant quantum computing.
Feedback Inhibition of the Unfolded Protein Response by GADD34-Mediated Dephosphorylation of eIF2α (2001)

Phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) on serine 51 integrates general translation repression with activation of stress-inducible genes such as ATF4, CHOP, and BiP in the unfolded protein response. We sought to identify new genes active in this phospho-eIF2alpha-dependent signaling pathway by screening a library of recombinant retroviruses for clones that inhibit the expression of a CHOP::GFP reporter. A retrovirus encoding the COOH terminus of growth arrest and DNA damage gene (GADD)34, also known as MYD116 (Fornace, A.J., D.W. Neibert, M.C. Hollander, J.D. Luethy, M. Papathanasiou, J. Fragoli, and N.J. Holbrook. 1989. Mol. Cell. Biol. 9:4196-4203; Lord K.A., B. Hoffman-Lieberman, and D.A. Lieberman. 1990. Nucleic Acid Res. 18:2823), was isolated and found to attenuate CHOP (also known as GADD153) activation by both protein malfolding in the endoplasmic reticulum, and amino acid deprivation. Despite normal activity of the cognate stress-inducible eIF2alpha kinases PERK (also known as PEK) and GCN2, phospho-eIF2alpha levels were markedly diminished in GADD34-overexpressing cells. GADD34 formed a complex with the catalytic subunit of protein phosphatase 1 (PP1c) that specifically promoted the dephosphorylation of eIF2alpha in vitro. Mutations that interfered with the interaction with PP1c prevented the dephosphorylation of eIF2alpha and blocked attenuation of CHOP by GADD34. Expression of GADD34 is stress dependent, and was absent in PERK(-)/- and GCN2(-)/- cells. These findings implicate GADD34-mediated dephosphorylation of eIF2alpha in a negative feedback loop that inhibits stress-induced gene expression, and that might promote recovery from translational inhibition in the unfolded protein response.
Comparing the predictive value of neural network models to logistic regression models on the risk of death for small-cell lung cancer patients (2005)

Cancer is one of the leading causes of mortality in the developed world, and prognostic assessment of cancer patients is indispensable in medical care. Medical researchers are accustomed to using regression models to predict patient outcomes. Neural networks have been proposed as an alternative with great potential. Nonetheless, empirical evidence remains lacking to support the application of this technique as the appropriate method to investigate cancer prognosis. Utilizing data on patients from two National Cancer Institute of Canada clinical trials, we compared predictive accuracy of neural network models and logistic regression models on risk of death of limited-stage small-cell lung cancer patients. Our results suggest that neural network and logistic regression models have similar predictive accuracy. The distributions of individual predicted probabilities are very similar. On occasion, however, the prediction pairs are quite different, suggesting that they do not always give the same interpretations of the same variables.
Design and implementation of a mobile agent-based auction system (2002)

The online auction is an important e-commerce application which enables the buying and selling of goods through a dynamic pricing strategy. This paper presents the design and implementation of a multi-access and multi-functional auction system. Users can access the auction system through the Web, WAP-enabled devices and agents, particularly mobile agents. The auction system supports different types of auctions, including English auction, Dutch auction, Yankee auction, Sealed Bid auction and Double auction. In particular, we discuss the mobile agent-based approach in detail by presenting the protocol for implementing different types of auctions.
<title>Integration of deformable mirror devices with optical fibers and waveguides</title> (1993)

Deformable Mirror Devices (DMDs) have been under development at Texas Instruments for several years, primarily as spatial light modulators for free-space optical applications such as analog phase modulation and digital projection imaging. A DMD consists of one or more electrostatically deflectable micromechanical aluminum mirror elements, including both micromirrors suspended from thin flexible hinges and membranes. These devices are fabricated using low temperature silicon-compatible semiconductor processing techniques, and thus can be monolithically fabricated over any addressing circuitry. In the last few years DMDs have been integrated into optical fiber switching systems, and efforts are underway to integrate them as routing switches onto optical waveguides. The DMDs used for optical fiber switching are torsion-hinged devices similar to those used for projection imaging. These devices have been integrated with multimode fibers to construct a 4 X 4 multimode optical fiber cross-bar switch with a 19 dB optical (80:1) extinction ratio for all 16 channels. Extinction ratios of 73 dB optical (20 X 10<SUP>6</SUP>) have been achieved for single point single mode switches. The waveguide switches currently under development are deformable membranes which are monolithically fabricated on silicon wafers with phosphosilicate glass (PSG) waveguide directional couplers to form optical time delay path selection switches. In this paper we describe the fabrication of deformable mirrors, their integration with optical fibers and waveguides, and the resulting system performance.
Expression cloning of a CMP-NeuAc:NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer alpha 2,8-sialyltransferase (GD3 synthase) from human melanoma cells. (1994)

Using an expression cloning approach, we have isolated a cDNA encoding GD3 synthase (CMP-NeuAc:NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer alpha 2,8-sialyltransferase, EC 2.4.99.8), which is a key regulatory enzyme determining the prominence of the ganglioside biosynthesis pathway. The cloned cDNA encodes a 341-amino acid protein containing a single transmembrane domain at its N-terminal region, suggesting that the protein has a type II transmembrane topology. The sequence of alpha 2,8-sialyltransferase showed a high level of similarity with other sialyltransferases at two conserved regions typical in the sialyltransferase family. Transfected cells containing the cloned cDNA expressed GD3 ganglioside on the cell surface, which was detectable with specific anti-GD3 antibody by immunofluorescence and immunostaining after separation of isolated glycolipids on thin-layer chromatography. The cDNA hybridized to a single mRNA species of 2.4 kb in melanoma cells. This sialyltransferase is distinctive in catalyzing the formation of the alpha 2-8 linkage of sialic acids.
Localization, mobility and fidelity of retrotransposed Group II introns in rRNA genes (2005)

We previously showed that the group II Lactococcus lactis Ll.LtrB intron could retrotranspose into ectopic locations on the genome of its native host. Two integration events, which had been mapped to unique sequences, were localized in the present study to separate copies of the six L.lactis 23S rRNA genes, within operon B or D. Although further movement within the bacterial chromosome was undetectable, the retrotransposed introns were able to re-integrate into their original homing site provided on a plasmid. This finding indicates not only that retrotransposed group II introns retain mobility properties, but also that movement occurs back into sequence that is heterologous to the sequence of the chromosomal location. Sequence analysis of the retrotransposed introns and the secondary mobility events back to the homing site showed that the introns retain sequence integrity. These results are illuminating, since the reverse transcriptase (RT) of the intron-encoded protein, LtrA, has no known proofreading function, yet the mobility events have a low error rate. Enzymatic digests were used to monitor sequence changes from the wild-type intron. The results indicate that retromobility events have approximately 10(-5) misincorporations per nucleotide inserted. In contrast to the high RT error rates for retroviruses that must escape host defenses, the infrequent mutations of group II introns would ensure intron spread through retention of sequences essential for mobility.
C-Reactive Protein in Heart Failure (2005)

CRP is increased in heart failure. Higher levels are associated with features of more severe heart failure and are independently associated with mortality and morbidity. The ability of treatments to reduce CRP levels and the prognostic importance of reducing CRP require further study.
Chitin Synthesis in Saccharomyces cerevisiae in Response to Supplementation of Growth Medium withGlucosamine and Cell WallStress (2003)

In Saccharomyces cerevisiae most chitin is synthesized by Chs3p, which deposits chitin in the lateral cell wall and in the bud-neck region during cell division. We have recently found that addition of glucosamine (GlcN) to the growth medium leads to a three- to fourfold increase in cell wall chitin levels. We compared this result to the increases in cellular chitin levels associated with cell wall stress and with treatment of yeast with mating pheromone. Since all three phenomena lead to increases in precursors of chitin, we hypothesized that chitin synthesis is at least in part directly regulated by the size of this pool. This hypothesis was strengthened by our finding that addition of GlcN to the growth medium causes a rapid increase in chitin synthesis without any pronounced change in the expression of more than 6,000 genes monitored with Affymetrix gene expression chips. In other studies we found that the specific activity of Chs3p is higher in the total membrane fractions from cells grown in GlcN and from mutants with weakened cell walls. Sucrose gradient analysis shows that Chs3p is present in an inactive form in what may be Golgi compartments but as an active enzyme in other intracellular membrane-bound vesicles, as well as in the plasma membrane. We conclude that Chs3p-dependent chitin synthesis in S. cerevisiae is regulated both by the levels of intermediates of the UDP-GlcNAc biosynthetic pathway and by an increase in the activity of the enzyme in the plasma membrane.
Three-channel, high-speed transmission over 8 km installed, 1300 nm optimised single-mode fibre using 800 nm CD laser and 1300/1500 nm LED transmitters (1988)

The feasibility of wavelength division multiplexing 800, 1300 and 1500 nm channels over an 8 km long, installed, 1300nm optimised single-mode fibre loop has been demonstrated. A 780 nm CD-laser and Si-APD receiver were used to transmit data at 150 Mbit/s on one of the channels. A 0.25 metre long, 800 nm optimised SM fibre section was used at the receiver to filter the LP11 mode propagating in 1300 nm optimised SM fibre at 800 nm. The mode filter significantly reduced intermodal distortion, thus allowing high-speed 800 nm transmission over the loop. Edge-emitting, 1300 and 1500 nm LEDs were used to transmit 140 and 90 Mbit/s data, respectively.
Measurement-based evaluation of a printer dot model for halftone algorithm tone correction (1993)

The <i>Journal of Electronic Imaging</i> (JEI), copublished bimonthly with the Society for Imaging Science and Technology, publishes peer-reviewed papers that cover research and applications in all areas of electronic imaging science and technology.