gebhart/patrepeval huggingface dataset:
P-selectin-mediated attachment of small cell lung carcinoma to endothelial cells (1996)

Small cell lung carcinoma (SCLC) frequently metastasizes early in the course of the disease. P-selectin (P-sel), a cell adhesion molecule expressed on activated platelets and endothelial cells (EC), has previously been demonstrated to mediate binding of platelets to SCLC. We hypothesized that P-sel facilitates attachment of SCLC to EC, acting as an important factor in SCLC metastasis. To test this hypothesis, attachment of H82 cells (SCLC cell line) to EC was quantified. Attachment of H82 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated EC was increased compared with control EC. Increased attachment of H82 cells to EC was apparent after 10 min of TPA activation, reached a peak after 30 min, and returned to baseline after 120 min of exposure. The TPA-induced increase in H82 cell attachment to EC was inhibited by addition of anti-P-sel antibodies but not by addition of anti-E-selectin antibodies. The TPA-induced increase in H82 cell attachment was likely mediated by activation of EC protein kinase C (PKC). Pretreatment of the EC with PKC inhibitors effectively blocked the TPA-mediated increase in H82 cell attachment. In addition, prolonged exposure of EC to TPA resulted in decreased expression of the PKC-alpha and PKC-epsilon isoforms. These data indicate for the first time that attachment of SCLC to activated EC appears to be mediated by increased expression of P-sel on the EC surface, which may result from activation of specific isoforms of PKC.
Rapid and sensitive detection of antibiotic resistance on a programmable digital microfluidic platform (2015)

The widespread dissemination of CTX-M extended spectrum β-lactamases among Escherichia coli bacteria, both in nosocomial and community environments, is a challenge for diagnostic bacteriology laboratories. We describe a rapid and sensitive detection system for analysis of DNA containing the blaCTX-M-15 gene using isothermal DNA amplification by recombinase polymerase amplification (RPA) on a digital microfluidic platform; active matrix electrowetting-on-dielectric (AM-EWOD). The devices have 16,800 electrodes that can be independently controlled to perform multiple and simultaneous droplet operations. The device includes an in-built impedance sensor for real time droplet position and size detection, an on-chip thermistor for temperature sensing and an integrated heater for regulating the droplet temperature. Automatic dispensing of droplets (45 nL) from reservoir electrodes is demonstrated with a coefficient of variation (CV) in volume of approximately 2%. The RPA reaction is monitored in real-time using exonuclease fluorescent probes. Continuous mixing of droplets during DNA amplification significantly improves target DNA detection by at least 100 times compared to a benchtop assay, enabling the detection of target DNA over four-order-of-magnitude with a limit of detection of a single copy within ~15 minutes.
New and emerging topical approaches for actinic keratoses. (2003)

Actinic keratoses (AKs) are intraepidermal foci of malignancy and represent the earliest clinical stage in the continuum of squamous cell carcinoma (SCC). A variety of topical, physical, and surgical modalities are available for treatment. Until recently, topical 5-fluorouracil was the only topical agent approved by the US Food and Drug Administration (FDA) for the treatment of AK. Topical diclofenac 3% gel, an inhibitor of arachidonic acid, is the second topical approved for the treatment of AK. Although not currently approved in the United States, multiple studies have substantiated the efficacy of topical imiquimod for AKs. This article reviews the efficacy and safety of topical diclofenac and topical imiquimod for the treatment of AKs.
A Specific Endoplasmic Reticulum Export Signal Drives Transport of Stem Cell Factor (Kitl) to the Cell Surface (2004)

Stem cell factor, also known as Kit ligand (Kitl), belongs to the family of dimeric transmembrane growth factors. Efficient cell surface presentation of Kitl is essential for the migration, proliferation, and survival of melanocytes, germ cells, hemopoietic stem cells, and mastocytes. Here we demonstrate that intracellular transport of Kitl to the cell surface is driven by a motif in the cytoplasmic tail that acts independently of the previously described basolateral sorting signal. Transport of Kitl to the cell surface is controlled at the level of the endoplasmic reticulum (ER) and requires a C-terminal valine residue positioned at a distance of 19-36 amino acids from the border between the transmembrane and cytoplasmic domains. Deletion or substitution of the valine with other hydrophobic amino acids results in ER accumulation and reduced cell surface transport of Kitl at physiological expression levels. When these mutant proteins are overexpressed in the ER, they are transported by bulk flow to the cell surface albeit at lower efficiency. A fusion construct between Kitl and the green fluorescent protein-labeled extracellular domain of a temperature-sensitive mutant of vesicular stomatitis virus G protein revealed the valine-dependent recruitment into coat protein complex II-coated ER exit sites and vesicular ER to Golgi transport in living cells. Thus the C-terminal valine defines a specific ER export signal in Kitl. It is responsible for the capture of Kitl at coat protein complex II-coated ER exit sites, leading to subsequent cell surface transport under physiological conditions.
Selective Golgi export of Kir2.1 controls the stoichiometry of functional Kir2.x channel heteromers (2005)

Surface expression of ion channels and receptors often depends on intrinsic sequence motifs that control their intracellular transport along the secretory pathway. Although members of the Kir2.x subfamily share two such motifs - a diacidic ER export motif and a positively charged Golgi export motif - they strongly differ in their surface expression. Whereas Kir2.1 shows prominent plasma membrane localization, Kir2.4 channels accumulate within the Golgi complex. By constructing chimeras between Kir2.1 and Kir2.4 subunits, a stretch of 20 amino acids was identified in the Kir2.1 C-terminus that is both necessary and sufficient to promote anterograde transport of Kir channel subunits at the level of trafficking from the Golgi to the plasma membrane. The core element of the identified sequence bears a tyrosine-dependent YXXPhi consensus motif for adaptin binding, with the flanking residues determining its functional efficiency. As the signal is dominant in promoting surface transport of Kir2.1/Kir2.4 channel heteromers and is recognized by both the epithelial and neuronal intracellular sorting machinery, the preferential Golgi export of Kir2.1 will control the stoichiometry of Kir2.x heteromers expressed on the cell surface.
Correlation between encoded protein overexpression and copy number of the HER2 gene with survival in non‐small cell lung cancer (2002)

The HER2 oncogene, which encodes the tyrosine kinase receptor, is commonly overexpressed in several types of cancer. Treatment using a humanized monoclonal antibody bound to HER2 product is becoming standard therapy for advanced breast cancer. Overexpression occurs in approximately 30% of non-small cell lung cancers (NSCLCs) and has been associated with poor prognosis. However, the frequency of a genetic aberration in the HER2 gene in lung cancer and the association between gene amplification and prognosis are poorly defined. To clarify these relationships, we simultaneously analyzed protein overexpression by immunohistochemistry (IHC) and determined the gene copy number by FISH in 50 surgical specimens of NSCLC. A low-grade increase in the copy number (3 to 8 copies) of the HER2 gene was detected in 44% of tumors. Most represented polysomy of chromosome 17. Protein overexpression was observed in 26%. Overexpression was detected in adenocarcinoma more frequently than in squamous cell carcinoma. No significant correlation was observed between copy number increase and overexpression. Neither gene copy number increase nor overexpression correlated with survival. We conclude that the significance of HER2 status in NSCLC is different from that in breast cancer because high-grade amplification occurs rarely.
A Practical Approach for Evaluating New Antibodies in the Clinical Immunohistochemistry Laboratory (2001)

Abstract Paraffin section immunohistochemistry (IHC) is widely used in diagnostic surgical pathology. Today, it is difficult to imagine the practice of surgical pathology without IHC. The availability of automated immunostainers with reagent rental contracts makes this technology commonplace. One potential danger is that many laboratories are now offering immunostains without significant prior knowledge or experience in IHC. As part of its mission, the Cell Markers Committee of the College of American Pathologists offers this manuscript as a basic guide to introducing new antibodies in the clinical IHC laboratory. Issues relating to regulatory developments, antibody selection, staining optimization, and test validation are addressed.
The Double-Stranded RNA-Binding Protein Staufen Is Incorporated in Human Immunodeficiency Virus Type 1: Evidence for a Role in Genomic RNA Encapsidation (2000)

Human Staufen (hStau), a double-stranded RNA (dsRNA)-binding protein that is involved in mRNA transport, is incorporated in human immunodeficiency virus type 1 (HIV-1) and in other retroviruses, including HIV-2 and Moloney murine leukemia virus. Sucrose and Optiprep gradient analyses reveal cosedimentation of hStau with purified HIV-1, while subtilisin assays demonstrate that it is internalized. hStau incorporation in HIV-1 is selective, is dependent on an intact functional dsRNA-binding domain, and quantitatively correlates with levels of encapsidated HIV-1 genomic RNA. By coimmunoprecipitation and reverse transcription-PCR analyses, we demonstrate that hStau is associated with HIV-1 genomic RNA in HIV-1-expressing cells and purified virus. Overexpression of hStau enhances virion incorporation levels, and a corresponding, threefold increase in HIV-1 genomic RNA encapsidation levels. This coordinated increase in hStau and genomic RNA packaging had a significant negative effect on viral infectivity. This study is the first to describe hStau within HIV-1 particles and provides evidence that hStau binds HIV-1 genomic RNA, indicating that it may be implicated in retroviral genome selection and packaging into assembling virions.
Point of View (2009)

From the Cecil G. Sheps Center for Health Services Research, UNC Chapel Hill, NC. The manuscript submitted does not contain information about medical device(s)/drug(s). No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. Address correspondence and reprint requests to Timothy Carey, Cecil G. Sheps Center for Health Services Research, UNC Chapel Hill, NC; E-mail: [email protected]
Serological evidence of Ureaplasma urealyticum infection in neonatal respiratory disease. (1984)

Since up to 80 percent of pregnant women and 30 percent of neonates may be colonized with genital mycoplasmas, it is difficult to determine whether true infection occurs. The antibody responses to eight serotypes of U. urealyticum were assessed in mothers and infants in 21 cases of neonatal respiratory disease (RD) and 24 normal cases. Among the normal population of mothers and infants, a titer of greater than or equal to 1:32 occurred in 0.25 percent (1/394). In mother-infant paired titers, a fourfold difference occurred in 2.6 percent (5/192). Among 54 RD neonates, 55.6 percent had a titer of greater than or equal to 1:32 compared to only 4.2 percent of normal neonates (p less than .001). Fourfold elevations in antibody titers of greater than 1:32 were observed in the neonate in 52.4 percent of RD cases compared to 0 percent of 24 normal pairs (p less than .001) and in 28.6 percent of mothers of RD neonates compared to 0 percent in normal cases (p = .013). We observed that 43.3 percent of RD neonates with titers greater than or equal to 1:32 died compared to 16.6 percent of RD neonates exhibiting no elevation of antibody response over the maternal level. Among the six who died, 66.7 percent of neonates and 16.7 percent of their mothers had elevated titers, compared to 33.3 percent of 15 surviving infants and 40.0 percent of their mothers. These elevated antibody responses strongly support the concept that U. urealyticum causes infection in the perinatal period in association with neonatal respiratory disease. Since the elevation in titers was detected close to delivery in many cases, the infection may occur in utero.
Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells (2014)

Overexpression of transcription factors has been used to directly reprogram somatic cells into a range of other differentiated cell types, including multipotent neural stem cells (NSCs), that can be used to generate neurons and glia. However, the ability to maintain the NSC state independent of the inducing factors and the identity of the somatic donor cells remain two important unresolved issues in transdifferentiation. Here we used transduction of doxycycline-inducible transcription factors to generate stable tripotent NSCs. The induced NSCs (iNSCs) maintained their characteristics in the absence of exogenous factor expression and were transcriptionally, epigenetically, and functionally similar to primary brain-derived NSCs. Importantly, we also generated tripotent iNSCs from multiple adult cell types, including mature liver and B cells. Our results show that self-maintaining proliferative neural cells can be induced from nonectodermal cells by expressing specific combinations of transcription factors.
Shear and extensional viscosity characteristics of a series of hydrophobically associating polyelectrolytes (1995)

The shear and extensional viscosity characteristics of aqueous solutions of a series of hydrophobically associating polyelectrolytes have been investigated and compared. The polymers studied consisted of a methacrylic acid/ethyl acrylate copolymer backbone containing varying levels of incorporation (0–2 mol%) of a pendant C18 hydrophobe. The extensional viscosities of all solutions were found to be higher than their corresponding shear viscosities, with the calculated Trouton ratio tending towards the predicted value of three at low strain rates but increasing with increasing extensional strain rate thereafter. In both flow modes, the viscosities of the solutions increased with increasing concentration and hydrophobe content of the polymers. In contrast to the purely shear-thinning characteristics of the polymer solutions observed in shear flow, the extensional viscosity–strain rate profiles of a number of systems were found to contain an initial region of strain-thickening, although strain-thinning behaviour was observed at higher strain rates. For any given system, the strain rate at which the evident maxima in extensional viscosity occurred decreased with increasing polymer concentration. In the presence of additives such as excess surfactant or a miscible alcoholic non-solvent, which are known to disrupt regions of intermolecular hydrophobic associations, the extensional viscosity of a typical solution of an associative polyelectrolyte was found to be significantly reduced and no longer to exhibit a maximum in the viscosity–strain rate profile.
Clostridium difficile toxin A binding to human intestinal epithelial cells (1997)

Clostridium difficile radiolabelled toxin A ([3H]-toxin A) bound to human duodenal and colonic epithelial cells isolated from endoscopic biopsies. Binding was greater at 4 degrees C than 37 degrees C, consistent with the thermal binding characteristic of toxin A to a carbohydrate moiety. At 37 degrees C colonic cells bound significantly more [3H]-toxin A than duodenal cells. The amount of [3H]-toxin A binding varied considerably between individuals. [3H]-toxin A was displaced by unlabelled toxin A by 50% for duodenal cells and 70% for colonic cells with 94.3 nM unlabelled toxin A. Low non-displacable binding was observed in some samples at 4 degrees C and 37 degrees C, suggesting that these cells came from individuals incapable of specifically binding toxin. Pre-treating cells with alpha- or beta-galactosidases to cleave terminal alpha- and beta-galactose residues reduced [3H]-toxin A binding. There was also a reduction in [3H]-toxin A binding after heat treating cells, which is suggestive of protein binding. The reduction in binding varied between individuals. The reduction of [3H]-toxin A binding, after the removal of beta-linked galactose units, implicates these as components of the receptor and adds credence to the idea that the Lewis X, Y and I antigens may be involved in toxin A binding to human intestinal epithelial cells. However, because the Lewis antigens do not possess terminal alpha-galactose units, the reduction in binding after alpha-galactosidase treatment suggests that other receptors may be involved in toxin A binding to some human intestinal cells. These data are the first demonstration of direct toxin A binding to human intestinal epithelial cells.
Structural Conservation between the Actin Monomer-binding Sites of Twinfilin and Actin-depolymerizing Factor (ADF)/Cofilin (2002)

Twinfilin is an evolutionarily conserved actin monomer-binding protein that regulates cytoskeletal dynamics in organisms from yeast to mammals. It is composed of two actin-depolymerization factor homology (ADF-H) domains that show approximately 20% sequence identity to ADF/cofilin proteins. In contrast to ADF/cofilins, which bind both G-actin and F-actin and promote filament depolymerization, twinfilin interacts only with G-actin. To elucidate the molecular mechanisms of twinfilin-actin monomer interaction, we determined the crystal structure of the N-terminal ADF-H domain of twinfilin and mapped its actin-binding site by site-directed mutagenesis. This domain has similar overall structure to ADF/cofilins, and the regions important for actin monomer binding in ADF/cofilins are especially well conserved in twinfilin. Mutagenesis studies show that the N-terminal ADF-H domain of twinfilin and ADF/cofilins also interact with actin monomers through similar interfaces, although the binding surface is slightly extended in twinfilin. In contrast, the regions important for actin-filament interactions in ADF/cofilins are structurally different in twinfilin. This explains the differences in actin-interactions (monomer versus filament binding) between twinfilin and ADF/cofilins. Taken together, our data show that the ADF-H domain is a structurally conserved actin-binding motif and that relatively small structural differences at the actin interfaces of this domain are responsible for the functional variation between the different classes of ADF-H domain proteins.
Energy consumption in optical modulators for interconnects (2012)

We analyze energy consumption in optical modulators operated in depletion and intended for low-power interconnect applications. We include dynamic dissipation from charging modulator capacitance and net energy consumption from absorption and photocurrent, both in reverse and small forward bias. We show that dynamic dissipation can be independent of static bias, though only with specific kinds of bias circuits. We derive simple expressions for the effects of photocurrent on energy consumption, valid in both reverse and small forward bias. Though electroabsorption modulators with large reverse bias have substantial energy penalties from photocurrent dissipation, we argue that modulator diodes with thin depletion regions and operating in small reverse and/or forward bias could have little or no such photocurrent energy penalty, even conceivably being more energy-efficient than an ideal loss-less modulator.
Design and Fabrication of Digital Oil Level Indicator (2014)

The aim of our project is to monitor the level of the oil in the vehicle oil tank and to automatically indicate the level information through LCD display.The main blocks are micro controller unit, oil level sensor and LCD display unit. The oil level detection circuit is used to detect the level of the oil in the tank here sensors are placed at certain places to find out the oil level and the signals are sent to the micro controller unit for further operations. Here sensors are placed at various places to sense the oil level and the signals from these sensors are sent to the micro controller unit to decide the exact level information. When the oil level reaches the top level sensor which means that the tank is full and this will be indicated to the user by means of the level information is indicated through LCD. By this same method the other sensors are working accordingly. The temperature sensor will sense the temperature of the oil. The viscous meter will sense the viscosity of the oil. Here the level information is displayed in terms of percentage and this information is preprogrammed according to the sensor position. The oil level indication is set to execute once for medium level and for high level and it will repeat continu- ously for the low level until the user fills the level of the oil correctly.
Genotyping Porcine Circovirus 3 (PCV-3) Nowadays: Does It Make Sense? (2020)

The discovery of a globally distributed porcine circovirus (<i>Porcine circovirus 3</i>; PCV-3) has led to intense research activity and the production of a large amount of molecular data. Different research groups have proposed several, not always concordant, genotypes for this virus. While such categories could aid an easier interpretation of PCV-3 molecular epidemiology, any classification, to be useful in practical settings, must be univocal and of help in the understanding of underlying biological features and epidemiology. Based on these premises, the possibility of defining PCV-3 genotypes was evaluated on the broadest available dataset of PCV-3 complete genome (<i>n</i> = 357) and open reading frame 2 (ORF2, <i>n</i> = 653) sequences. Genetic distance and phylogenetic clustering were selected as the main objective criteria. Additional factors, including the number of within-cluster sequences, host and geographic clustering, concordance between different genomic regions, and analysis method were also taken in account to generate a classification that could be effectively applied in research and diagnostic settings. A maximum within-genotype genetic distance of 3% at the complete genome and 6% at the ORF2 levels, bootstrap support higher than 90%, and concordance between analysis methods allowed us to clearly define two clades which could be potentially defined as genotypes. Further subdivision was not suggested due to the absence of a meaningful association between PCV-3 and its biological/epidemiological features. Nevertheless, since one of the clades included two strains only, thus far we formally propose the definition of only one PCV-3 genotype (PCV-3a). The established criteria will allow us to automatically recognize other genotypes when more strain sequences are characterized.