gebhart/patrepeval huggingface dataset:
miR-150 enhances apoptotic and anti-tumor effects of paclitaxel in paclitaxel-resistant ovarian cancer cells by targeting Notch3 (2017)

Tumor recurrence by obtaining chemoresistance is a major obstacle to treating ovarian cancer. By TargetScan database and a luciferase reporter assay, we identified miR-150 directly targets <i>Notch3</i>, which is a key oncogene in ovarian cancer. We, therefore, investigated the role of miR-150 in ovarian cancer cells, and the usefulness of miR-150 as a therapeutic target in chemoresistant ovarian cancer, through examining miR-150 expression by qRT-PCR in ovarian cancer cell lines and tissues, and assessing the gain-of-function effect by WST, colony forming, TUNEL, wound healing and angiogenesis assays. Western blotting was performed to evaluate its downstream targets. The miR-150 expression was significantly downregulated in ovarian cancers. Treatment with pre-miR-150 significantly inhibited cancer cell proliferation, and induced apoptosis in PTX (paclitaxel) -resistant SKpac cells, which was not seen by PTX only treatment. On spheroid forming assay, an additional pre-miR-150 treatment with PTX decreased cancer stem cell activation in PTX-resistant SKpac cells. An experimental upregulation of miR-150 also decreased cancer cell migration and angiogenesis in SKpac cells. The Notch3 downstream proteins(NICD3 and HEY2), and cell cycle-related proteins (cyclinD3, pS6, and NF-kB), and apoptosis-related proteins (BCL-2 and BCL-W) were significantly downregulated by pre-miR-150 transfection. Taken together, miR-150 is related with PTX-resistance in ovarian cancer, and treatment with pre-miR-150 resensitizes cancer cells to PTX. Therefore, it may be a promising treatment strategy in chemoresistant and recurrent ovarian cancer.
Plasminogen‐activator inhibitor type 2 (PAI‐2) is a spontaneously polymerising SERPIN (1993)

Plasminogen-activator inhibitor type 2 (PAI-2) is a specific inhibitor of plasminogen activators (PA) that exists in an intracellular, low-molecular-mass form and a secreted, high-molecular-mass form that varies with respect to glycosylation. Here we have developed expression systems for both forms of PAI-2 and biochemically characterised the purified proteins. In order to obtain efficient secretion, we constructed an artificial signal sequence and fused it to the coding region of PAI-2. With this construct, more than 90% of PAI-2 was secreted as a glycosylated, 60-kDa molecular-mass form, but the level of expression was low and unstable. To obtain higher expression of secreted PAI-2, a novel expression vector based on the Semliki-forest-virus replicon was used. Secreted PAI-2 was purified to homogeneity and N-terminal sequence analysis showed that the artificial signal peptide was correctly removed. The intracellular, non-glycosylated form of PAI-2 was expressed in Escherichia coli and purified to homogeneity. Both the secreted and the intracellular forms of PAI-2 were found to inhibit plasminogen activators by forming SDS-resistant complexes and the second-order rate constants were similar for both forms, ranging over 2.4-2.7 x 10(6) M-1s-1 for urokinase-type PA, 2.5-2.7 x 10(5) M-1s-1 for two-chain tissue-type PA and 0.8-1.2 x 10(4) M-1s-1 for single-chain tissue-type PA. None of the purified PAI-2 forms bound to vitronectin. Circular-dichroism spectral analysis revealed that PAI-2 has a CD spectrum that resembles ovalbumin more than PA-inhibitor type 1, confirming the greater similarity between these two members of the serine-protease inhibitor family. Similar to what has been described for the Z-form of alpha 1-antitrypsin, purified PAI-2 was found to spontaneously form polymers during incubation at room temperature. Attempts to convert PAI-2 to a stable locked conformation resembling the conformation of latent PAI-1 by treatment with diluted guanidinium chloride were unsuccessful. Instead, this treatment enhanced the formation of PAI-2 polymers, possibly by the loop-sheet polymerisation mechanism described for alpha 1-antitrypsin.
The linear effects of <i>α</i>‐thalassaemia, the <i>UGT1A1</i> and <i>HMOX1</i> polymorphisms on cholelithiasis in sickle cell disease (2007)

Serum bilirubin levels and predisposition to gallstones in sickle cell disease (SCD) are influenced by genetic variation in the hepatic uridine diphosphate (UDP)-glucuronosyltransferase (UGT1A1) gene, but the association is not consistent. This study investigated whether variation in the gene encoding haem oxygenase (HMOX1), a rate-limiting enzyme upstream of UGT1A in the haem catabolic pathway, and alpha-thalassaemia could explain some of the inconsistent effects. The UGT1A1 [TA](n) and HMOX1 [GT](n) promoter polymorphisms and alpha globin genotypes were determined in 263 SCD patients (199 HbSS, 5 HbS/beta(0), 59 HbSC). Detection of gallstones was based on ultrasound of the liver/biliary tree. Regression analysis showed that serum bilirubin levels and the incidence of gallstones were strongly associated with the number of UGT1A1 [TA] repeats in all subjects (P < 0.0001 and P < 0.01, respectively). While HMOX1 genotype had no effect, co-inheritance of alpha-thalassaemia reduced serum bilirubin levels in all SCD patients independently of the number of UGT1A1 [TA] repeats. Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD.
Chemokine modulation of high‐conductance Ca<sup>2+</sup>‐sensitive K<sup>+</sup> currents in microglia from human hippocampi (2003)

During acute pathological processes, microglia transform into an activated state characterized by a defined morphology and current profile, and are recruited to injury sites by chemokines. No information is available on the ion channels and the mode of action of chemokines in microglia in brain slices from humans with a chronic pathology. Thus, patch-clamp recordings of microglia were performed in hippocampal slices from seven patients who underwent surgery for pharmaco-resistant epilepsy. Cells were identified as microglia by positive labelling with fluorescein-conjugated tomato lectin before recording. All the recorded cells had an ameboid morphology characteristic of activated microglia. However, they had a high input resistance (3.6 G omega), a zero-current resting potential of -16 mV, and lacked Na+ currents, inwardly rectifying and delayed rectifying K+ currents such as non-activated microglia. Importantly, recorded cells expressed Ca2+-sensitive outward currents that activated at 0 mV with non-buffered intracellular Ca2+ and were sensitive to 1 mm tetraethylammonium (TEA). The estimated single-channel conductances were 187 pS in cell-attached and 149 pS in outside-out patches, similar to those of high-conductance Ca2+-dependent K+ channels. The chemokine MIP1-alpha increased whole-cell outward current amplitudes measured at +60 mV by a factor of 3.3. Thus, microglia in hippocampi from epileptic patients express high-conductance Ca2+-dependent K+ channels that are modulated by the chemokine MIP1-alpha. This modulation may contribute to the migratory effect of MIP1-alpha on microglia.
Solid-State <sup>13</sup>C NMR and Raman Studies of Cellulose Triacetate:  Oligomers, Polymorphism, and Inferences about Chain Polarity (1996)

13C CPMAS NMR and Raman spectra have been taken for oligomers (DP = 2−9) and several preparations of cellulose triacetate (CTA). CTA exhibits polymorphism and the NMR spectra of the CTA(I) and CTA(II) allomorphs along with the spectrum of noncrystalline CTA have been isolated. Magnetic inequivalence within the unit cell of CTA(II) is greater than for CTA(I), indicating a lower symmetry in the CTA(II) unit cell. An attempt is made to correlate some of the NMR resonances with proposed X-ray crystal structures for each of these allomorphs. From both the Raman and the NMR spectra of the oligomers, in comparison with the different CTA preparations, it is determined that the pentamer and higher oligomers crystallize into the CTA(I) lattice. On the basis of the Raman spectra, it is argued that CTA(I) and CTA(II) are distinguished by backbone conformational differences. In a single attempt to explore the role of the solvent in determining the crystal habit of the oligomers, the pentamer persisted in the CTA(I) lattice even when crystallization took place in dibenzyl ether, the solvent out of which the CTA polymer forms CTA(II) crystallites. Based on these findings, an approach to obtaining a definitive crystal structure of CTA(I) would be to grow and perform a structural determination on a single crystal of an oligomer of DP > 4. Spectra of these oligomers indicated partial crystallinity; hence, care must be taken in growing single crystals. Since it is known that there is a correlation between the allomorphs of CTA formed by heterogeneous acetylation and the allomorphs of the precursor, cellulose, and since there are still points of ambiguity regarding the crystal structures of the allomorphs of cellulose and CTA, the topic of chain polarity (directionality) is addressed herein. As a contribution to the dialogue on the structure of these materials, we present plausibility arguments, i.e., not definitive arguments, that CTA(I) has parallel and CTA(II) antiparallel chain character.
Genetic Analysis of Azole Resistance by Transposon Mutagenesis in <i>Saccharomyces cerevisiae</i> (1999)

The increasing resistance of Candida species to fluconazole is cause for concern. To determine the molecular mechanisms involved in resistance to fluconazole, I used a scheme of transposon mutagenesis in Saccharomyces cerevisiae, a genetically tractable yeast that is closely related to Candida albicans. This technique, which permits the generation and analysis of multiple random Tn3::LEU2::lacZ fusions, can be used as a disruption mutagen (N. B. Burns et al., Genes Dev. 8:1087-1105, 1994). By using the Tn3::LEU2::lacZ library as a disruption mutagen, I found recessive mutations in genes that were previously found to be involved in azole resistance, e.g., PDR5 and CPR1, and in genes previously found to be involved in azole sensitivity, e.g., ERG3. This approach also enabled me to identify recessive mutations in three genes not previously known to be involved in azole sensitivity. Two of the genes, ADA3 and SPT7, are general transcriptional regulators; the third, YMR034c, is a putative sterol transporter. Finally, by screening the Tn3::LEU2::lacZ library for lacZ fusions induced by a low concentration of fluconazole, I identified genes known to be induced by azoles as well as a variety of other genes not previously known to be induced by the drug. In conclusion, transposon mutagenesis is a promising screening tool for use in identifying novel drug targets and in uncovering the mechanisms involved in the response of S. cerevisiae to antifungal drugs.
Metabolic engineering of morphinan alkaloids by over‐expression and RNAi suppression of salutaridinol 7‐<i>O</i>‐acetyltransferase in opium poppy (2007)

We demonstrate that both over-expression and suppression of the gene encoding the morphinan pathway enzyme salutaridinol 7-O-acetyltransferase (SalAT) in opium poppy affects the alkaloid products that accumulate. Over-expression of the gene in most of the transgenic events resulted in an increase in capsule morphine, codeine and thebaine on a dry-weight basis. The transgenic line with the highest alkaloid content had 41%, 37% and 42% greater total alkaloids than the control in three independent trials over 3 years. DNA-encoded hairpin RNA-mediated suppression of SalAT resulted in the novel accumulation of the alkaloid salutaridine at up to 23% of total alkaloid; this alkaloid is not detectable in the parental genotype. Salutaridine is not the substrate of SalAT but the substrate of the previous enzyme in the pathway, salutaridine reductase. RNA transcript analysis of 16 primary T0 transformants and their segregating T1 progeny revealed an average reduction in SalAT transcript to about 12% of the control. Reduction in SalAT transcript was evident in both leaves and latex. Reverse transcriptase PCR and high-performance liquid chromatography analyses confirmed cosegregation of the expressed transgene with the salutaridine accumulating phenotype.
ChemInform Abstract: REACTIVITY OF CO‐ORDINATED LIGANDS PART 23, PREPARATION OF SOME CYCLIC KETONES USING TRICARBONYLIRON COMPLEXES IN THE PRESENCE OF ALUMINIUM TRICHLORIDE (1975)

Abstract Die Reaktion der Cyclooctatetraen‐Fe‐carbonyle (I) mit wasserfreiem A1‐trichlorid führt zu den Oxobicyclononadienyl‐Fe‐Komplexen (II).
Inverted Organic Solar Cells (2017)

Intense research has been carried out to obtain high-efficiency, stable, low-cost, and high-speed production of organic solar cells. Organic photovoltaics (OPVs) devices are based on carbon-based organic semiconductors in which charge transport is mainly by the delocalization of electrons along conjugated polymer backbones. At early stages, most organic solar cells, including single layer, bilayer, and bulk heterojunction devices, were fabricated using normal device structure by sandwiching photoactive layers between two electrodes. Generally, higher work function electrode indium tin oxide (ITO) served as the anode and the low work function electrode Al as cathode. However, efficiency of organic solar cells with both a single layer and bilayers was limited by exciton diffusion length and the area of donor– acceptor interface. Device fabrication using solution processing techniques of all involved layers is the ultimate goal of organic solar cells so that roll-to-roll processing and mass production are viable, which can reduce the cost to a great extent.
Clearance and Glomerular Localization of Preformed DNP Anti‐DNP Immune Complexes (1979)

The in vivo behaviour of well-defined immune complexes in rats was studied using complexes derived from DNP-conjugated bovine thyroglobulin (DNP-BTG) and purified specific goat anti-DNP IgG. Both clearance and glomerular localization were mainly dependent on the nature of the antigen. Soluble immune complexes formed with DNP17-BTG were cleared faster and showed a more marked localization in the glomerular mesangium than complexes formed with DNP3.4-BTG. A slight increase in the antibody to antigen ratio seemed to facilitate mesangial localization of soluble immune complexes. Insoluble immune complexes showed temporary localization as microemboli in the lumina of glomerular and peritubular capillaries. This study thus shows that not only the size and composition of the complexes but also the nature of the antigen within the complex can influence the clearance and organ localization of circulating immune complexes.
An aerial radiological survey of the Double Track Site and surrounding area. Central Nevada (1995)

An aerial radiological survey of the Double Track Site was conducted in December 1993. An interim report was issued. That report described survey procedures and presented terrestrial exposure rate and wide-area-averaged plutonium isopleth plots. This letter report presents additional plutonium plots and some ``rule-of-thumb`` calculations which should help the reader to properly interpret the data presented. Attached to this report are three isopleth plots produced from the Double Track data. No one processing method provides all the answers regarding a particular surveyed area. Where peak values are most important, isopleth {number_sign}1, created from the original unsmoothed data, is the presentation of choice. Isopleth {number_sign}2, from smoothed data, is superior for the detection of areas of widespread low-level contamination. Isopleth {number_sign}3, also smoothed data, satisfied a particular early mission goal but is not as useful for cleanup operations as the other two.
Crystal structure of 7-chloropyrrolo[1,2-b][1,2,5]benzothiadiazepin- 10(11H)-one-5,5-dioxide, C11H7N2O3ClS (2001)

Ci 1H7CIN2O3S, monoclinic, P12i/al (No. 14), a = 7.066(9) , b = 21.069(5) k,c = 7.663(1) , = 93.69(1), V= 1138.5 3 , Z= 4, R gl (F) = 0.049, wR^F 2 ) = 0.060, T= 293 K.
Powdered Cyclotron Targets for Stacked Foil Activation Experiments (1966)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation J. B. Natowitz, F. Pement, R. L. Wolke; Powdered Cyclotron Targets for Stacked Foil Activation Experiments. Rev. Sci. Instrum. 1 January 1966; 37 (1): 121–122. https://doi.org/10.1063/1.1719932 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioReview of Scientific Instruments Search Advanced Search |Citation Search
Expression of immunomodulating genes in prostate cancer and benign prostatic tissue. (2009)

Our data suggest that arginine metabolism may be involved in prostate cancer immune response evasion, whereas COX-2 may play a role in pathogenesis. We provide a snapshot of immunosuppressive gene expression at the transcriptional level in the prostate tumor microenvironment.
Processor Modeling and Design Tools (2016)

Architecture description languages (ADL) have been successfully used as a specification language for processor development. Modeling plays a central role in the design automation of processors. This chapter aims to cover the entire spectrum of processor design tools, from the perspective of ADL-based design methodology. More specifically, the ADL specification is used to derive a processor toolsuite such as instruction-set simulator, compiler, debugger, profiler, assembler, and linker. In principle, ADLs differ from programming languages because the latter bind all architectural abstractions to specific point solutions whereas ADLs intentionally suppress or vary such binding. ADLs can be classified into four categories based on the nature of the information: structural, behavioral, mixed, and partial. ADLs are used to specify processor and memory architectures and generate software toolkit including compiler, simulator, assembler, profiler, and debugger. One of the main purposes of an ADL is to support automatic generation of a high-quality software toolkit including a cycle-accurate simulator.
The Relationship between Cyclic Fatigue Properties and Microstructures of Sintered Silicon Nitride Ceramics (1990)

The present study deals with the relationship between the microstructures and the fatigue failure mechanisms in five different kinds of sintered silicon nitride ceramics. Static fatigue test and cyclic fatigue test were conducted with a stress ratio (R) condition of 0.1 using flex specimens at room temperature, as a means to determine the effects of microstructures on crack propagation. Also, the accelerative effects upon the propagation velocity of fatigue cracking in cyclic loading conditions were discussed quantitatively using the estimation method applied to the empirical equation for subcritical crack growth.The results indicated that the accelerative effects on propagation velocity under cyclic fatigue conditions were observable in samples in which the matrix was composed of microcrystalline grains of the sintered silicon nitride ceramics, but not in those with a matrix composed of amorphous materials. Thus, under cyclic loading, the fatigue crack propagation was found to be governed by the microstructure of the sample, in particular by the matrix filling the gaps between the coarse grains.
Evaluation of human neutrophil peptide-1, -2 and -3 as serum markers for colorectal cancer (2010)

Increased total serum concentrations of human neutrophil peptide-1, -2 and -3 (HNP-1, -2 and -3) have been associated with colorectal cancer (CRC). Owing to a recently developed and fully validated liquid-chromatography coupled to tandem-mass spectrometry (LC-MS/MS) assay, individual serum concentrations of these antimicrobial peptides were quantified to evaluate their role as serum markers in CRC. Serum was obtained from patients with indications for colonoscopy, subsequently diagnosed as normal colon or hyperplastic polyp (CON; n= 368), adenomatous polyp (AP; n = 179) or colorectal cancer (CRC; n = 69). Comparison of HNP-1, -2 and -3 concentrations between CRC and CON (130 ± 90 vs. 105 ± 80; 264 ± 140 vs. 206 ± 99 and 62 ± 56 vs. 54 ± 59 for HNP-1, -2 and -3, respectively) revealed that reported up-regulated total HNP-concentrations can be largely attributed to increased HNP-2 (P=0.0006) and HNP-1 (P=0.024) levels. Although receiver operating characteristics (ROC) analyses showed low specificity of the peptides for CRC and no significant changes in serum levels were observed after surgical removal of the tumor (n=23), the established differentiation between the HNP-subtypes may be particularly useful to completely elucidate the role of these antimicrobial peptides in CRC.
P3‐344: γ‐secretase‐dependent APP processing occurs either at the plasma membrane or in the endocytic compartments independent of the APP wild‐type or APP Swedish variant (2008)

Sequential cleavages of the amyloid precursor protein (APP) by β- and γ-secretase leads to the release of Aβ. An unresolved question is the precise location where Aβ is generated and how access of these enzymes to APP is regulated. In contrast to previous reports we observed a robust decrease of Aβ secretion in cells stably expressing APP695swe with a deletion of the internalization motif NPXY. Expression of several mutations of APPswe revealed that β-secretase cleavage ofAPPswe is independent of the YENPTY motif and therefore presumably occurs in the secretory pathway. On the other hand, secretion of APPsβwt is abrogated by destruction of this endocytosis signal, indicating that β-secretase cleavage of APPwt occurs in endocytic compartments. These observations suggest the existence of two different sites of BACE activity for APPswe and APPwt, respectively. While the levels of APPsβswe were virtually unchanged by any C-terminal mutation, we observed a dramatic decrease of βCTF levels, manifested by a decline in the βCTF to αCTF ratio, indicating that the decrease of Aβ secretion is caused by a destabilisation of βCTF. Stable expression of C99 confirmed the observation that Aβ production from βCTF overall demands a functional endocytosis motif. Investigating βCTF reduction in C99 and APPswe expressing cells revealed that βCTF generated in the secretory pathway can be subsequently processed by α-secretase at the cell surface, thereby preventing Aβ generation from βCTF. Inhibition of α-secretase cleavage restored beta-CTF levels and Aβ secretion. Thus, while access of β-secretase to APPwt and APPswe might be locally segregated to endocytic and secretory pathways, respectively, γ-secretase cleavage and Aβ generation from both WT and Swe APP isoforms depends on internalization from the surface into endocytic compartment. While Aβ secretion from APPwt depends on endocytosis of holoAPP, internalization of βCTF is demanded for a large fraction of Aβ generation from APPswe. Given a six to eight fold increase in Aβ secretion from APPswe, a decrease of 60% by specific inhibition of βCTF internalisation might have a profound impact on clinical outcome by lowering Aβ levels in swedish familial AD patients to non familial AD levels.
On the Inside State of the Lumpy Zone of Blast Furnace (1976)

Hirohata No. 1 BF and Kukioka No. 4 BF of Nippon Steel Corporation were blown down in a usual operating state and dissected very cautiously after quenched with water. The conditions in the reducing zone of the furnace shaft are explained in this report.From these investigations burden distribution, gas flow at the shaft deduced from the burden distribution, changes of burden properties according to the progress of reduction, and the behaviors of Zn, S and alkali materials in the shaft were clarified. Both furnace conditions were carefully compared to the respective operating conditions. The relation between the operating conditions and the changes of burden properties at the shaft were cleared.Based on the results of dissection, burden testing methods and necessary burden properties are discussed.