gebhart/patrepeval huggingface dataset:
An Experimental Investigation of Drilling-Fluid Filter-Cake Removal by Acid Jetting (2008)

Abstract Acid jetting from ports near the end of a tubing string is a common method being applied to remove drilling or completion fluid filter cakes and to stimulate near-wellbore permeability. To be effective, the acid jet must remove enough of the filter cake to eliminate any significant filter cake Δp, and should stimulate some distance into the formation if internal damage has occurred. In this study, we experimentally evaluated the efficiency of acid jetting at conditions similar to those being applied in the field. The results obtained with acid jetting were compared with those obtained jetting with water alone to determine the relative importance of the mechanical removal of the filter cake by the liquid jet and the dissolution of filter cake and formation solids by the acid. We first created a drilling fluid filter cake and internal damage by circulating a typical drill-in fluid containing sized CaCO3 particles past the face of a 4-inch diameter by 18-inch long core for up to 18 hours. A pressure differential of 500 psi was held across the core to drive filtrate and possibly solids invasion into the rock. Acid (15% HCl) was then jetted from a small port on to the center of the core face at velocities typical of field applications. The velocity and duration of jetting was varied systematically in the experiments. In each experiment, we measured the evolving permeability of the filter cake/core system by measuring the pressure drop across the system. In this paper, we show how the key parameters of jet velocity and duration of jetting affect jetting efficiency. Comparison of the acid jetting results with those obtained jetting with water alone show how much of the cleanup is accomplished by the mechanical action of the liquid jet compared with the chemical dissolution of the solids by the acid. In many cases, the jetting action provides the primary restoration of productivity with less effect caused by acid dissolution.
DNA-Mediated Interferon Signature Induction by SLE Serum Occurs in Monocytes Through Two Pathways: A Mechanism to Inhibit Both Pathways (2018)

A primary mechanism for activation of innate immunity is recognition of damage or pathogen associated molecular patterns by pattern recognition receptors (PRRs). Nucleic acid is a damage associated molecular pattern molecule that when internalized into a monocyte and recognized by intracellular nucleic acid sensing toll like receptors will cause production of type 1 interferon. The process by which DNA or RNA is delivered into the cytosol of monocytes in systemic lupus erythematosus remains incompletely understood, and therapeutic approaches to prevent DNA-mediated monocyte activation are needed. We identified two mechanisms for internalization of DNA by monocytes. IgG-bound DNA was internalized by interacting with Fc gamma receptor IIa, while high-mobility group box-1 protein-bound DNA was internalized by interacting with the receptor for advanced glycation end products. Both pathways contribute to an inflammatory phenotype in monocytes exposed to serum from patients with SLE. Moreover, both of these pathways can be inhibited by a pentapeptide, DWEYS, which is a DNA mimetope. In one instance DWEYS directly competes with DNA for antibody binding and in the other DWEYS binds high-mobility group box-1 and blocks its interaction with RAGE. Our data highlight distinct pathways involved in nucleic acid enters monocytes in SLE, and identify a potential therapeutic to prevent nucleic acid internalization in SLE.
The lack of RNA‐dependent protein kinase enhances susceptibility of mice to genital herpes simplex virus type 2 infection (2006)

Mice deficient in RNA-dependent protein kinase (PKR-/-) or deficient in PKR and a functional 2',5'-oligoadenylate synthetase (OAS) pathway (PKR/RL-/-) are more susceptible to genital herpes simplex virus type 2 (HSV-2) infection than wild-type mice or mice that are deficient only in a functional OAS pathway (RL-/-) as measured by survival over 30 days. The increase in susceptibility correlated with an increase in virus titre recovered from vaginal tissue or brainstem of infected mice during acute infection. There was also an increase in CD45+ cells and CD8+ T cells residing in the central nervous system of HSV-2-infected PKR/RL-/- mice in comparison with RL-/- or wild-type control animals. In contrast, there was a reduction in the HSV-specific CD8+ T cells within the draining lymph node of the PKR/RL-/- mice. Collectively, activation of PKR, but not of OAS, contributes significantly to the local control and spread of HSV-2 following genital infection.
Roles of Pim‐3, a novel survival kinase, in tumorigenesis (2011)

Pim-3 is a member of the Provirus integrating site Moloney murine leukemia virus (Pim) family, which belongs to the Ca(2+) /calmodulin-dependent protein kinase (CaMK) group and exhibits serine/threonine kinase activity. Similar to other members of the Pim family (i.e. Pim-1 and Pim-2), Pim-3 can prevent apoptosis and promote cell survival and protein translation, thereby enhancing cell proliferation of normal and malignant cells. Pim-3 is expressed in vital organs, such as the heart, lung, and brain. However, minimal phenotypic changes in Pim-3-deficient mice suggest that Pim-3 may be physiologically dispensable. Pim-3 expression is enhanced in several cancer tissues, particularly those of endoderm-derived organs, including the liver, pancreas, colon, and stomach. The development of hepatocellular carcinoma is accelerated in mice expressing the Pim-3 gene selectively in the liver only when these mice are treated with a hepatocarcinogen, indicating that Pim-3 can act as a promoter but not as an initiator. Moreover, inhibition of Pim-3 expression can retard in vitro cell proliferation of hepatocellular, pancreatic, and colon carcinoma cell lines by promoting cell apoptosis. Furthermore, a Pim-3 kinase inhibitor has been reported to inhibit cell proliferation in an in vivo xenograft model using a human pancreatic cancer cell line without inducing any major adverse effects. Thus, Pim-3 kinase may be a candidate molecule for the development of molecular targeting drugs against cancer.
Benzimidazole Derivatives as Potent JAK1-Selective Inhibitors (2015)

The Janus kinase (JAK) family comprises four members (JAK1, JAK2, JAK3, and Tyk2) that play a key role in mediating cytokine receptor signaling. JAK inhibition thus modulates cytokine-mediated effects. In particular, selective inhibition of JAK1 or JAK3 may provide an efficient therapeutic agent for the treatment of inflammatory diseases, with minimized side effects. In this study, as part of our continued efforts to develop a selective JAK1 inhibitor, a series of 1,2-disubstituted benzimidazole-5-carboxamide derivatives was prepared and their inhibitory activities against all four JAK isozymes were evaluated. A clear structure-activity relationship was observed with respect to JAK1 selectivity; this highlighted the importance of hydrogen bond donors at both N(1) and R2 positions located within a specific distance from the benzimidazole core. One of the synthesized compounds, 1-(2-aminoethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole-5-carboxamide (5c), showed remarkable JAK1 selectivity (63-fold vs JAK2, 25-fold vs JAK3, and 74-fold vs Tyk2). Molecular docking revealed that the 2-aminoethyl and piperidin-4-yl substituents of 5c function as probes to differentiate the ATP-binding site of JAK1 from that of JAK2, resulting in preferential JAK1 binding. A kinase panel assay confirmed the JAK1 selectivity of 5c, which showed no appreciable inhibitory activity against 26 other protein kinases at 10 μM.
Identifying prostate carcinoma by MALDI-Imaging (2007)

Prostate cancer has become one of the most common malignancies worldwide. Although lacking in specificity its diagnosis is still based partially on the serum-based test for prostate-specific antigen. As its pathogenesis has not yet been deciphered, the ongoing search for new and more reliable biomarkers remains a challenge to stratify disease onset and progression. Matrix-assisted laser desorption/ionization (MALDI)-Imaging is a promising technique to assist in this endeavor. It delivers accurate mass spectrometric information of the sample's proteins and enables the visualization of the spatial distribution of protein expression profiles and correlation of the information with the histomorphological features of the same tissue section. This study describes the analysis of 22 prostate sections (11 with and 11 without prostate cancer) by MALDI-Imaging. Specific protein expression patterns were obtained for normal and cancerous regions within the tissue sections. Applying a 'support vector machine' algorithm to classify the cancerous from the non-cancerous regions, an overall cross-validation, a sensitivity and specificity of 88, 85.21 and 90.74%, respectively, was achieved. Additionally four distinctively overexpressed peaks were identified: 2,753 and 6,704 Da for non-cancerous glands, and 4,964 and 5,002 Da for cancerous glands. The results of this first clinical study utilizing the new technique of MALDI-Imaging underline its vast potential to identify candidates for more reliable prostate cancer tumor markers and to enlighten the pathogenesis of prostate cancer.
Rare‐event analysis methods for detection of fetal red blood cells in maternal blood (1984)

Methods for analyzing very small subpopulations of cells ("rare-event analysis methods") are of interest in many areas of biology. In this paper we demonstrate the ability to detect one Rh-positive erythrocyte per 100,000 Rh-negative erythrocytes. This is the level needed to detect human fetal red blood cells in the maternal circulation in the case of fetal-maternal Rh-incompatibility. Erythrocytes stained with fluorescent immunobeads are more than 100 times as bright as the same cells stained by indirect immunofluorescence (or almost 40 times as bright as cells stained by the biotin-avidin technique). More importantly there is greater than a sevenfold increase in signal-to-noise (S/N) ratio, which proves critical in detecting very low frequency ("rare event") cell subpopulations. Although equal mixtures of positive and negative cells can easily be detected, positives cannot be easily distinguished from negatives when they are present in relative frequencies of 1:1000 or less as measured by either indirect immunofluorescence or biotin-fluorescent avidin labeling of D antigens. However, use of fluorescent immunobeads and high-speed flow cytometry allows detection of subpopulations of the same cells at relative frequencies of less than 1:100,000. Based on calibrations using free-fluorescent immunobeads, the average Rh-positive cell (when present in a relative frequency of 1:100,000) labeled with 36 +/- 19 fluorescent immunobeads. Rh-positive cells of relative frequencies 1:10,000 and 1:100,000 can be detected above background (Rh-negative red blood cells treated with the same amount of fluorescent immunobeads). Using defined mixtures of Rh-positive and negative cells, the expected numbers of positive cells were observed over a range of 1:100 to 1:100,000 relative Rh-positive cell frequencies. These methods should prove of general use in applications where original frequency information about rare cell subpopulations is important and would be lost if enrichment procedures were to be used.
Selective Self-Organization of Colloids on Patterned Polyelectrolyte Templates (2000)

Submicron-sized colloidal particles have been self-organized into patterned arrangements on a substrate using a novel technique. At the substrate, a polyelectrolyte multilayer film has been deposited onto a chemically patterned surface; subsequently, the polyelectrolyte surface is immersed in an aqueous colloidal suspension of bare SiO2 microspheres or functionalized polystyrene latex particles. The colloids self-organize at the surface, driven by the spatially varied electrostatic and secondary interactions between the colloid and the substrate. The polyelectrolyte platform provides a strong bond to the colloids, imparting mechanical robustness which enables postprocessing of the patterned assemblies. An important advantage to this approach is that the use of a polyelectrolyte multilayer platform opens up the possibility of introducing functionality into the underlying layers. We have demonstrated control over the density and selectivity of particle adsorption. Three mechanisms have been used to control adsorption: (i) pH of the colloid suspension, which determines the ionization of the uppermost surface of the polyelectrolyte multilayer; (ii) ionic strength of the suspension, which determines the extent of charge screening about the colloid and polyelectrolyte; and (iii) concentration of added surfactant, which causes charge screening and introduces hydrophobic interactions between the surfactant and polyelectrolyte. Finally, an energy adsorption model is presented.
Tumorigenicity of human breast cancer is associated with loss of the Ca2+-activated chloride channel CLCA2. (1999)

The human Ca2+-activated chloride channel-2 (CLCA2) is expressed in normal breast epithelium but not in breast tumors of different stages of progression. Northern analysis of nontransformed and transformed breast epithelial cell lines revealed CLCA2 expression in the nontransformed cell line MCF10A and the nontumorigenic cell line MDA-MB-453, whereas all tumorigenic cell lines were negative (MDA-MB-231, MDA-MB-435, MDA-MB-468, and MCF7). When stably reintroduced into CLCA2-negative MDA-MB-231 and MDA-MB-435 cells, CLCA2 expression reduced Matrigel invasion in vitro and inducibility of s.c. and metastatic tumors of MDA-MB-231 cells in nude mice. Our results suggest that CLCA2 may act as a tumor suppressor in breast cancer.
Factor XI Activation by Meizothrombin: Stimulation by Phospholipid Vesicles Containing both Phosphatidylserine and Phosphatidylethanolamine (1997)

The activation of factor XI by meizothrombin was investigated using recombinant meizothrombin (R155A meizothrombin) that is resistant to autocatalytic removal of fragment 1. Meizothrombin was capable of activating factor XI at an activation rate similar to that of thrombin. Dextran sulphate and heparin, known cofactors of thrombin-mediated factor XI activation, did not stimulate the activation of factor XI by meizothrombin. However, the activation of factor XI by meizothrombin was markedly enhanced by vesicles containing phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylethanolamine (PE), whereas PC/PS or PC/PE vesicles only had a minor effect on the activation. Thrombin-mediated factor XI activation was not influenced by phospholipids. The effect of PC/PS/PE and PC/PS vesicles was studied in a factor XI dependent clot lysis assay. In this assay, factor XI inhibits clot lysis by a feedback loop in the intrinsic pathway via thrombin-mediated factor XI activation. Removal of endogenous phospholipids in plasma by centrifugation resulted in an increased clot lysis, which could be restored to the pre-centrifugation level by the addition of PC/PS/PE vesicles, but not by PC/PS vesicles. When clot lysis was initiated by factor IXa in the presence of a factor XIa blocking antibody, there was no difference in inhibitory effect of PC/PS/PE or PC/PS vesicles. These data suggested that the differences in clot lysis inhibition observed between PC/PS/PE and PC/PS vesicles were caused by factor XI activation by meizothrombin. Meizothrombin-mediated factor XI activation may therefore play an important role in the antifibrinolytic feedback loop in the intrinsic pathway.
Physiological Role of Gap-Junctional Hemichannels (2000)

Hemichannels in the overlapping regions of apposing cells plasma membranes join to form gap junctions and provide an intercellular communication pathway. Hemichannels are also present in the nonjunctional regions of individual cells and their activity is gated by several agents, including calcium. However, their physiological roles are unknown. Using techniques of atomic force microscopy (AFM), fluorescent dye uptake assay, and laser confocal immunofluorescence imaging, we have examined the extracellular calcium-dependent modulation of cell volume. In response to a change in the extracellular physiological calcium concentration (1.8 to </=1.6 mM) in an otherwise isosmotic condition, real-time AFM imaging revealed a significant and reversible increase in the volume of cells expressing gap-junctional proteins (connexins). Volume change did not occur in cells that were not expressing connexins. However, after the transient or stable transfection of connexin43, volume change did occur. The volume increase was accompanied by cytochalasin D-sensitive higher cell stiffness, which helped maintain cell integrity. These cellular physical changes were prevented by gap-junctional blockers, oleamide and beta-glycyrrhetinic acid, or were reversed by returning extracellular calcium to the normal level. We conclude that nongap-junctional hemichannels regulate cell volume in response to the change in extracellular physiological calcium in an otherwise isosmotic situation.
Rescue by cytokines of apoptotic cell death induced by IL-2 deprivation of human antigen-specific T cell clones (1997)

The control of cell survival and cell death is of central importance in tissues with high cell turnover such as the lymphoid system. We have examined the effect of cytokines on IL-2 deprivation-induced apoptosis of human antigen-specific T helper clones with different cytokine production profiles. We found that IL-2, interferon-alpha (IFN-alpha), and IFN-beta inhibited IL-2 deprivation apoptosis in Th0, Th1, and Th2 clones. We also found that IL-2 protects T cell clones from IL-2 deprivation apoptosis accompanying active proliferation and enhanced expression of P53, Rb and Bcl-xL proteins. In contrast, IFN-alpha/beta rescued T cell clones from apoptosis without active proliferation, and expression of apoptosis-associated proteins tested so far was unaffected. This may be due to the fact that T cells treated with IL-2 contained those located in S + G2/M phases of the cell cycle, whereas the vast majority of T cells treated with IFN-alpha/beta were located in G0/G1 phase. IFN-alpha/beta specifically induced tyrosine phosphorylation and translocation into nucleus of signal transducers and activators of transcription (STAT) 2 protein in the T cell clones. In addition, over-expression of STAT2 by transfection of the cDNA prevented apoptosis of the T cell clones. Our present study shows that IFN-alpha and -beta mediate anti-apoptotic effect through other pathways than that of IL-2 in growth factor deprivation apoptosis.
Human adipocyte lipid-binding protein: purification of the protein and cloning of its complementary DNA (1989)

Human adipocyte lipid-binding protein (H-ALBP) was purified from normal subcutaneous adipose tissue to greater than 98% homogeneity, utilizing a combination of acid fractionation, gel filtration, covalent chromatography on activated thiol-Sepharose 4B, and anion-exchange chromatography. Human ALBP comprised about 1% of total cytosolic protein in human adipose tissue, had a relative molecular mass of about 15 kDa, and existed as a monomer in solution. The amino terminus of H-ALBP was blocked to sequencing. When a liposome ligand delivery assay was used, H-ALBP saturably bound oleic acid with about 1 mol of ligand bound per mole of protein. Additionally, H-ALBP saturably bound retinoic acid as determined by the quenching of intrinsic tryptophan fluorescence. A full-length H-ALBP cDNA has been cloned; the sequence predicts a 649-base mRNA comprised of a 62-base 5'-noncoding region containing an 18S ribosome-binding site, a single 396-base open-reading frame, and a 191-base 3'-noncoding region. Comparative sequence analysis indicated that the 132 amino acid H-ALBP is a member of a multigene family of intracellular lipid-binding proteins and contains the consensus substrate phosphorylation sequence for tyrosyl kinases.
Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis (2014)

National Medical Research Council, Singapore.
The action of proteolytic enzymes on the glycoprotein from pig gastric mucus (1977)

A glycoprotein of mol.wt. 2x10(6) was isolated in homogeneous form from pig gastric mucus by isopycnic centrifugation in CsCl but without enzymic digestion or reductive cleavage of disulphide bonds. Digestion of the purified glycoprotein with trypsin, pepsin or Pronase resulted in the formation of glycoprotein subunits, of mol.wt. 5.2x10(5)-5.8x10(5), one-quarter that of the undigested glycoprotein. The glycoprotein subunits were isolated by gel filtration and shown to contain all the carbohydrate present in the undigested glycoprotein, but 18.6-25.6% of the total amino acids originally present were lost on digestion. The relative amount of threonine, serine and proline had increased from 41% (w/w) in the undigested glycoprotein to 61-67% of the total amino acids in the glycoprotein subunits after digestion. The results support the previously proposed structure for the glycoprotein, namely that of four subunits joined by disulphide bridges. These results show the presence of two distinct regions in the glycoprotein molecule, one rich in threonine, serine and proline, which is glycosylated and resistant to proteolyis, whereas the other, with an amino acid composition more characteristic of a globular protein, is not glycosylated and is susceptible to proteolysis. In addition, the region that is susceptible to proteolysis contains the disulphide bridges which join the glycoprotein subunits together to form the gastric glycoprotein.
<title>Optical coherence microscopy for the in-depth study of biological structures: system based on a parallel detection scheme</title> (1998)

We present a new microscopy system based on the OCT principle, that uses a multiplexed lock-in detection scheme to generate a 2D head-on image in parallel without lateral scanning. Our 'full-field optical coherence microscopy' comprises a Michelson interferometer built with a polarizing beam splitter, and uses a photoelastic birefringence modulator to modulate the optical path difference between the two orthogonal polarizations. A novel signal processing method is used to achieve a demodulation in parallel on every pixel of a 256 X 256 CCD camera. A 840 nm electroluminescent diode with 20 micrometers coherence length is used to illuminate the field of view through the microscope objective lens. In-depth exploration of the sample is realized by changing the plane of focus. The lateral resolution of the images is limited by the camera pixel size and is 2 micrometers . The axial sectioning ability is approximately 8 micrometers . Having validated our setup on model samples, we now evaluate its performance on biological structures. As an example, images of onion cells from 50-400 micrometers below the surface are obtained in 1 s with 100 dB sensitivity.