gebhart/patrepeval huggingface dataset:
GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation (2020)

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.
The Inhibitor of Cyclin-Dependent Kinase 4a/Alternative Reading Frame ( INK4a/ARF ) Locus Encoded Proteins p16INK4a and p19ARF Repress Cyclin D1 Transcription through Distinct cis Elements (2004)

The Ink4a/Arf locus encodes two structurally unrelated tumor suppressor proteins, p16(INK4a) and p14(ARF) (murine p19(ARF)). Invariant inactivation of either the p16(INK4a)-cyclin D/CDK-pRb pathway and/or p53-p14(ARF) pathway occurs in most human tumors. Cyclin D1 is frequently overexpressed in breast cancer cells contributing an alternate mechanism inactivating the p16(INK4a)/pRb pathway. Targeted overexpression of cyclin D1 to the mammary gland is sufficient for tumorigenesis, and cyclin D1-/- mice are resistant to Ras-induced mammary tumors. Recent studies suggest cyclin D1 and p16(INK4a) expression are reciprocal in human breast cancers. Herein, reciprocal regulation of cyclin D1 and p16(INK4a) was observed in tissues of mice mutant for the Ink4a/Arf locus. p16(INK4a) and p19(ARF) inhibited DNA synthesis in MCF7 cells. p16(INK4a) repressed cyclin D1 expression and transcription. Repression of cyclin D1 by p16(INK4a) occurred independently of the p16(INK4a)-cdk4-binding function and required a cAMP-response element/activating transcription factor-2-binding site. p19(ARF) repressed cyclin D1 through a novel distal cis-element at -1137, which bound p53 in chromatin-immunoprecipitation assays. Transcriptional repression of the cyclin D1 gene through distinct DNA sequences may contribute to the tumor suppressor function of the Ink4a/Arf locus.
Neoplastic Transformation of Human Small Airway Epithelial Cells Induced by Arsenic (2008)

Human small airway epithelial cells (SAECs) previously immortalized with human telomerase reverse transcriptase (h-TERT) were continuously treated with sodium arsenite at a dose of 0.5 microg/mL in culture for up to 6 months. Arsenic-treated cells progressively displayed an increase in transformed phenotype including enhanced growth saturation density, plating efficiency, and anchorage-independent growth and invasion capability compared with their nontreated control cells. To determine whether arsenic-induced cell transformation was associated with genomic instability, treated and control cells were also analyzed for micronuclei formation. A 4.8-fold increase in micronuclei incidence in arsenic-treated cells was detected in conjunction with increased N-phosphonacetyl-l-aspartate (PALA)-resistant characteristics. In addition, arsenic-treated cells showed an increase in c-H-ras, c-myc, and c-fos protein expression relative to controls. The change in oncoprotein expression correlated with a decrease in wild-type p53 expression and hyperphosphorylated retinoblastoma. Taken together, these results strongly suggest that h-TERT immortalized human small airway epithelial cells underwent step-wise transformation after inorganic arsenic treatment.
Southwest Pacific Ocean Water-Mass Changes between 1968/69 and 1990/91*† (1997)

Abstract Water-mass changes are estimated in the southwest Pacific Ocean by comparing a meridional hydrographic section along 170°W between 60°S and the equator occupied in 1968/69 during the Southern Cross cruise and again in 1990 during a NOAA Climate and Global Change cruise. Another comparison is made using a hydrographic section along 35°S between the date line and 169°W occupied in 1969 during USNS Eltanin cruise 40 and again in 1991 during a Mapkiwi cruise. The most robust change consists of cooling (and freshening) on isopycnals, with peak differences exceeding −1.0°C (−0.25 pss) at the base of the subtropical thermocline. The cooling and freshening starts above the stratification minimum of the Subantarctic Mode Water and persists to below the salinity minimum of the Antarctic Intermediate Water. Amplitudes are largest at 48°S, near where these water masses subduct, and decay toward 20°S, near the axis of the Subtropical Gyre. This change is likely the result of surface warming and/or freshening ...
Microarray analysis of apoptosis resistance mediated by dexamethasone in ovarian cancer (2004)

5037 Background: Dexamethasone is widely used as a supportive drug to reduce side-effects of chemotherapy in ovarian cancer. This study identified apoptosis-inhibiting genes responsible for the anti-apoptotic effect of dexamethasone in ovarian cancer. Methods: Microarray analysis was performed using chips comprising 8,000 human genes. RT-PCR and Western Blot analysis were utilized for confirmation. Samples from solid tumors and from ascites of ovarian cancer patients have been used to establish tissue culture. Dexamethasone was used at serum-equivalent doses of 10 to 100 nM. After induction of apoptosis, activition of caspase 3 and PARP cleavage were analyzed. Results: Thirty genes were identified to be upregulated by more than 4-fold following dexamethasone treatment. Major anti-apoptotic genes were upregulated: 7fold upregulation of MIHC (major inhibitor of human caspases), 4.5fold upregulation of bcl-XL and 5.4fold upregulation of bcl-2. Activity of apoptosis-executing caspase 3 was reduced by 40% after dexamethasone treatment. Conclusion: Administration of dexamethasone in ovarian cancer patients could reduce the therapeutic efficacy of systemic cancer therapies by upregulation of anti-apoptotic genes. No significant financial relationships to disclose.
Nonenzymatic free radical-catalyzed generation of 15-deoxy-Δ12,14-prostaglandin J2-like compounds (deoxy-J2-isoprostanes) in vivo (2010)

15-Deoxy-Δ(12,14)-prostaglandin J₂ (15-d-PGJ₂) is a reactive cyclopentenone eicosanoid generated from the dehydration of cyclooxygenase-derived prostaglandin D₂ (PGD₂). This compound possesses an α,β-unsaturated carbonyl moiety that can readily adduct thiol-containing biomolecules such as glutathione and cysteine residues of proteins via the Michael addition. Due to its reactivity, 15-d-PGJ₂ is thought to modulate inflammatory and apoptotic processes and is believed to be an endogenous ligand for peroxisome proliferator-activated receptor-γ. However, the extent to which 15-d-PGJ₂ is formed in vivo and the mechanisms that regulate its formation are unknown. Previously, we have reported the formation of PGD₂ and PGJ₂-like compounds, termed D₂/J₂-isoprostanes (D₂/J₂-IsoPs), produced in vivo by the free radical-catalyzed peroxidation of arachidonic acid (AA). Based on these findings, we investigated whether 15-d-PGJ₂-like compounds are also formed via this nonenzymatic pathway. Here we report the generation of novel 15-d-PGJ₂-like compounds, termed deoxy-J₂-isoprostanes (deoxy-J₂-IsoPs), in vivo, via the nonenzymatic peroxidation of AA. Levels of deoxy-J₂-IsoPs increased 12-fold (6.4 ± 1.1 ng/g liver) in rats after oxidant insult by CCl₄ treatment, compared with basal levels (0.55 ± 0.21 ng/g liver). These compounds may have important bioactivities in vivo under conditions associated with oxidant stress.
Increased resistance to multiple drugs by introduction of the Enterobacter cloacae romA gene into OmpF porin-deficient mutants of Escherichia coli K-12 (1991)

Introduction of the romA gene cloned from Enterobacter cloacae into Escherichia coli K-12 resulted in almost complete inhibition of OmpF expression and a concomitant increase in resistance to quinolones, beta-lactams, chloramphenicol, and tetracyclines. In addition, the romA gene reduced the susceptibility to these multiple drugs even in the OmpF porin-deficient mutants of E. coli K-12. Results indicate the presence of romA-sensitive penetration pathway(s) for these multiple drugs other than the OmpF porin in E. coli.
Comparison of proline and N‐methylnorleucine induced conformational equilibria in cyclic pentapeptides (1996)

The cyclic, imido acid containing pentapeptides cyclo(Asp-Trp-(NMe)Nle-Asp-Phe) (cpp[NMeNle(3)]) and cyclo(Asp-Trp-Pro-Asp-Phe) (cpp[Pro(3)]) have been investigated by 1H-NMR spectroscopy in DMSO and by restrained molecular dynamics methods. The spectra indicate the existence of at least four cis/trans isomers for cpp[NMeNle(3)] and two cis/trans isomers for cpp[Pro(3)]. In addition to the imido peptide bonds, cpp[NMeNle(3)] shows cis/trans isomerization of the Asp4-Phe5 and Phe5-Asp1 peptide bonds whereas only the Phe5-Asp1 peptide bond isomerizes in the Pro-containing peptide. In cpp[Pro(3)] all cis bonds are centred in betaVIb turns. Also, cpp[NMeNle(3)] prefers backbone angles around the cis bonds which are rather similar to the angles of a betaVIb turn. The higher number of cis/trans isomers and slight deviations in the backbone angles of comparable isomers of both peptides are caused by an enhanced flexibility of cpp[NMeNle(3)] due to the possibility of the phi-(NMe)Nle rotation.
Unconventional media and technologies for starch etherification and esterification (2018)

This review summarizes recent advances in starch etherification and esterification in unconventional media and by unconventional technologies.
Tailoring Explanations for the User (1985)

In order for an expert system to provide the most effective explanations, it should be able to tailor its responses to the concerns of the user. One way in which explanations may be tailored is by point of view A method is presented for representing the knowledge to support different points of view in the current domain. In addition, we present a method for determining the point of view to take by inferring the user's goal within a brief discourse segment. The advising system's response to the derived goal depends on the strength of its belief in the inference for which a method of determination is also provided. This information enables the system to decide what answer to give to a question, which kind of justification is relevant, and when to provide it. Some details of the current implementation are included.
Discovery, Validation, and Application of Novel Methylated DNA Markers for Detection of Esophageal Cancer in Plasma (2019)

Novel MDMs assayed from plasma detect esophageal cancer with moderate accuracy. Further optimization and clinical testing are warranted.
Toward Understanding Phage:Host Interactions in the Rumen; Complete Genome Sequences of Lytic Phages Infecting Rumen Bacteria (2017)

The rumen is known to harbor dense populations of bacteriophages (phages) predicted to be capable of infecting a diverse range of rumen bacteria. While bacterial genome sequencing projects are revealing the presence of phages which can integrate their DNA into the genome of their host to form stable, lysogenic associations, little is known of the genetics of phages which utilize lytic replication. These phages infect and replicate within the host, culminating in host lysis, and the release of progeny phage particles. While lytic phages for rumen bacteria have been previously isolated, their genomes have remained largely uncharacterized. Here we report the first complete genome sequences of lytic phage isolates specifically infecting three genera of rumen bacteria: <i>Bacteroides, Ruminococcus</i>, and <i>Streptococcus</i>. All phages were classified within the viral order Caudovirales and include two phage morphotypes, representative of the Siphoviridae and Podoviridae families. The phage genomes displayed modular organization and conserved viral genes were identified which enabled further classification and determination of closest phage relatives. Co-examination of bacterial host genomes led to the identification of several genes responsible for modulating phage:host interactions, including CRISPR/<i>Cas</i> elements and restriction-modification phage defense systems. These findings provide new genetic information and insights into how lytic phages may interact with bacteria of the rumen microbiome.
Turbulence observations in the Gulf of Trieste under moderate wind forcing and different water column stratification (2016)

Abstract. The oceanographic campaign CARPET2014 (Characterizing Adriatic Region Preconditionig EvenTs), (30 January–4 February 2014) collected the very first turbulence data in the Gulf of Trieste (northern Adriatic Sea) under moderate wind (average wind speed 10 m s−1) and heat flux (net negative heat flux ranging from 150 to 400 W m−2). Observations consisted of 38 CTD (Conductivity, Temperature, Depth) casts and 478 microstructure profiles (grouped into 145 ensembles) with three sets of yoyo casts, each lasting for about 12 consecutive hours. Averaging closely repeated casts, such as the ensembles, can lead to a smearing effect when in the presence of a vertical density structure with strong interfaces that can move up or down between subsequent casts under the influence of tides and internal waves. In order to minimize the smearing effect of such displacements on mean quantities, we developed an algorithm to realign successive microstructure profiles to produce sharper and more meaningful mean profiles of measured turbulence parameters. During the campaign, the water column in the gulf evolved from well-mixed to stratified conditions due to Adriatic waters intruding at the bottom along the gulf's south-eastern coast. We show that during the warm and relatively dry winter, the water column in the Gulf of Trieste, even under moderate wind forcing, was not completely mixed due to the influence of bottom waters intruding from the open sea. Inside the gulf, two types of water intrusions were found during yoyo casts: one coming from the northern coast of the Adriatic Sea (i.e. cooler, fresher and more turbid) and one coming from the open sea in front of the Po Delta (i.e. warmer, saltier and less turbid). The two intrusions had different impacts on turbulence kinetic energy dissipation rate profiles. The former, with high turbidity, acted as a barrier to wind-driven turbulence, while the latter, with low sediment concentrations and a smaller vertical density gradient, was not able to suppress downward penetration of turbulence from the surface.
The Gas Permeability of Plasma Sprayed Ceramic Coatings (1997)

Abstract A simple test procedure, based on steady state flow through a membrane, has been developed for measurement of the gas permeability of specimens over a range of temperature. The reliability of this equipment has been verified by testing solid disks containing single perforations and comparing the measured flow rates with those expected on the basis of laminar flow. Coatings of yttria-stabilised zirconia have been produced by plasma spraying in vacuum and in air. The specific permeability of these coatings has been measured at temperatures ranging up to 600°C, using hydrogen gas. It has been found that permeability is increased for coatings produced with longer stand-off distances and at higher pressures. Porosity levels have been measured using densitometry and microstructural features have been examined using SEM. A model has been developed for prediction of the permeability from such microstructural features, based on percolation theory. Agreement between predicted and measured permeabilities is good, although it is clear that more comprehensive data are needed in order to validate the model systematically.
Estimation of multipath propagation parameters from measured channel data (2002)

An antenna array at the base station can be used for mobile source localization and to unravel multipath propagation structures in terms of angles and delays. A previously proposed technique for this purpose is the shift-invariance joint angle-delay estimation (SIJADE) algorithm. We extend this algorithm to a hexagonal array and apply it to measured indoor channel data.
Quantification of Proteins by Functionalized Gold Nanoparticles Using Click Chemistry (2012)

This letter presents a click-chemistry-based assay for proteins (CAP) that allows quantitative determination of the concentration of proteins, using azide- and alkyne-functionalized gold nanoparticles (AuNPs). Compared with conventional methods, CAP has a broader linear range for detection of proteins with good selectivity. CAP enables the analysis of total proteins in various sera and milk samples.
Selective Incision of Mucosa and Less-Invasive Dissection of Sub-Mucosa Using Carbon Dioxide Laser- Translational Research from Basic Laser Tissue Interaction to Clinical Research - (2011)

Endoscopic submucosal dissection (ESD) has attracted a great deal of attention as a new treatment for
Impact of preinterventional tricuspid regurgitation on outcome of MitraClip therapy in patients with severely reduced ejection fraction (2020)

In patients with HFrEF treated with MitraClip for FMR, moderate-to-severe FTR was an independent predictor of cardiac death within 1 year. To improve survival, additional therapy to residual FTR should be considered in early phase after MitraClip therapy.
Deletion Mutants of Chlorophyll a/b Binding Proteins Are Efficiently Imported into Chloroplasts but Do Not Integrate into Thylakoid Membranes (1992)

Chlorophyll a/b binding polypeptides (CABp) are integral thylakoid membrane proteins containing three membrane-spanning helices. We have created a series of mutations in tomato CABp to test whether individual membrane helices with hydrophilic flanking sequences, when fused to a transit peptide, can be imported into chloroplasts and correctly targeted to thylakoid membranes. All of the mutated precursors, including those with large C-terminal and internal deletions, were imported successfully, showing that these regions of the mature CABp are not required for import into chloroplasts. All mutants tested, containing either one or two membrane helices, were found primarily in the stroma and not in the thylakoids. The small amount of protein found associated with the thylakoids was largely resistant to alkali extraction but was sensitive to protease, unlike wild-type protein, which is resistant to both treatments. When incubated with thylakoids in the absence of stroma and/or ATP, a significant amount of wild-type protein assumes a form that is resistant to alkali extraction but is protease sensitive, like the imported deletion proteins. This form of the wild-type protein is not chased into a protease-resistant form by adding stroma and/or ATP. These results suggest that CABp can spontaneously associate with membranes as an aberrant species that is not an intermediate in the process of integration. The inability of the deletion forms of CABp to assume a protease-resistant conformation suggests that correct integration is afforded by elements within the entire protein that collectively contribute to the proper conformation of the protein. The ability of deletion mutants to associate with thylakoids in a nonphysiological way suggests that the study of such mutants may not be useful in elucidating thylakoid-targeting signals.
Amelioration of Pancreatic Fibrosis in Mice With Defective TGF-?? Signaling (2005)

Conditional loss of TGF-beta signaling selectively in the pancreas led to a failure in fibrogenic responses of repeated injections of cerulein, signifying that the modulation of TGF-beta signaling could be the therapeutic target for the prevention of chronic fibrosing pancreatitis.
A Case of Oral Mucosa Ulcer Induced by Nicorandil in Diabetic Nephropathy Patient Accompanied by a Dementia (2018)

Nicorandil is an antianginal drug that was developed in Japan in 1975 and has been widely used. The drug has also been widely used in European countries and North America, but the side effect of oral ulceration induced by Nicorandil has been reported in these countries. The etiology of this side effect remains unknown.In this report, we describe our experience of a case of oral mucosa ulcer induced by Nicorandil in a dialysis patient, and also review the Japanese literature.
Preparation and characteriszation of nanocellular poly(phenylquinoxaline)foams. A new approach to nanoporous high-performance polymers (2007)

International audience
Expression cloning of a rat B2 bradykinin receptor. (1991)

A cDNA encoding a functional bradykinin receptor was isolated from a rat uterus library by a clonal selection strategy using Xenopus laevis oocytes to assay for expression of bradykinin responses. The predicted protein is homologous to the seven transmembrane G protein-coupled superfamily of receptors. Bradykinin and its analogs stimulate a Cl- current oocytes expressing the receptor with the rank order of potency: bradykinin approximately Lys-bradykinin greater than [Tyr8]-bradykinin much greater than [Phe6]bradykinin. This is the rank order of potency observed for these compounds in competitive binding assays on soluble receptor from rat uterus. Des-Arg9-bradykinin (10 microM) elicits no response when applied to oocytes expressing the receptor; thus, the cDNA encodes a B2 type bradykinin receptor. [Thi5,8,DPhe7]bradykinin, where Thi is beta-(2-thienyl)-alanine, is a very weak partial agonist and inhibits the bradykinin-mediated ion flux, suggesting the cDNA encodes a smooth muscle, rather than a neuronal, B2 receptor subtype. Receptor message has a distribution consistent with previous reports of bradykinin function and/or binding in several tissues and is found in rat uterus, vas deferens, kidney, lung, heart, ileum, testis, and brain. Receptor subtypes are a possibility because several tissues contain two or three message species (4.0, 5.7, and 6.5 kilobases). Southern blot high-stringency analysis demonstrated that the rat, guinea pig, and human genomes contain a single gene. As bradykinin is a key mediator of pain, knowledge of the primary structure of this receptor will allow a molecular understanding of the receptor and aid the design of antagonists for pain relief.
Thyroid Dysfunction in Patients With Type 1 Diabetes (2003)

This longitudinal study confirms the association between autoimmune thyroid dysfunction and type 1 diabetes. Our results indicate that all subjects with type 1 diabetes should undergo annual screening by serum TSH measurement to detect asymptomatic thyroid dysfunction, particularly those with positive TPO antibodies.