gebhart/patrepeval huggingface dataset:
Mechanism of glycosylation in the Golgi apparatus. (1983)

A major role of the Golgi apparatus in liver is the terminal glycosylation of secreted serum proteins and of plasma membrane glycoproteins. Galactosyltransferase is a membrane-bound Golgi enzyme that transfers galactose directly from uridine diphosphogalactose (UDP-Gal) to terminal N-acetylglucosamine groups of N-asparagine-linked glycoproteins during secretion. Sialytransferase then transfers sialic acid from cytidine monophosphosialic acid (CMP-NAN) to the newly added terminal galactose of the glycoprotein. In the cell, the transfer reaction must occur on the lumen side of the Golgi membrane. UDP-Gal is synthesized mainly in the cytoplasm and CMP-NAN is synthesized in the nucleus in liver. An important question for understanding the mechanism is, how do these nucleotide sugars gain access to the transferases? A second question involves uridine diphosphate (UDP), a highly inhibitory product of galactosyltransferase. How is UDP removed from the lumen of the Golgi fast enough to prevent product inhibition of the galactosyltransferase? We have shown that isolated Golgi, although vesiculated, retains its original orientation. The vesicles are oriented with greater than 90% of both galactosyltransferase and sialyl-transferase on the luminal side of the vesicles. Using intact vesicles, we can show that UDP-Gal is taken up via a saturable carrier system present in the Golgi membrane. During galactosylation in vitro, UDP formed in the lumen of Golgi vesicles is rapidly converted to UMP by a nucleoside diphosphatase in the lumen. Uridine monophosphate, which is much less inhibitory to the galactosyltransferase than UDP, is then transported out of the lumen by a second carrier and is broken down further to uridine by 5'-nucleotidase on the cytoplasmic side of the Golgi vesicles. The transport of nucleotides appears unique to the Golgi membranes, since neither rough endoplasmic reticulum nor plasma membrane vesicles from rat liver accumulate these nucleotides.
Analysis of Tumor-Host Interactions by Gene Expression Profiling of Lung Adenocarcinoma Xenografts Identifies Genes Involved in Tumor Formation (2005)

Tumor cell lines are relied on extensively for cancer investigations, yet cultured cells in an in vitro environment differ considerably in behavior compared with those of the same cancer cells that proliferate and form tumors in vivo. To uncover gene expression changes related to tumor formation, gene expression profiles of human lung adenocarcinoma (A549) cells grown as lung tumors in immune-compromised mice were compared with profiles of the same cells grown in vitro. Additionally, profiles of uninvolved adjacent mouse tissue were determined. A profound interplay between cancer cells and the host was shown that affected a complex protein interaction network involving processes of extracellular interaction, growth factor signaling, hemostasis, immune response, and transcriptional regulation. Growth in vivo of A549 cells, which carry an activating k-ras mutation, induced changes in gene expression that corresponded highly to a pattern characteristic of human lung tumors with k-ras mutation. Cytokines interleukin-4, interleukin-6, and IFN-gamma each induced distinct in vitro genomic responses in cancer cells that emulated many of the changes in gene expression observed in vivo. Genes that were both selectively induced in vivo and overexpressed in human lung adenocarcinoma tumors included CSPG2, which has not been associated previously with tumor formation. Knockdown in A549 of CSPG2 by RNA interference significantly inhibited tumor growth in vivo but not in vitro. Thus, analysis of tumor xenografts by gene expression profiling has the potential for identifying genes involved in tumor development that may not be expressed in cancer cells grown in vitro.
Characterization of the antigen (CAK1) recognized by monoclonal antibody K1 present on ovarian cancers and normal mesothelium. (1992)

K1 is a monoclonal antibody that reacts with a cell surface antigen (CAK1) found in human mesothelia and nonmucinous ovarian tumors. In this article, the characteristics of the CAK1 antigen have been examined in detail. Using immunofluorescence microscopy, we have found that the CAK1 signal is removed from the cell surface by treatment with proteases or by phosphatidylinositol-phospholipase C, but not by neuraminidase and beta-galactosidase. The phosphatidylinositol-phospholipase C-released material was found to contain the CAK1 antigen which was detected by a competition radioimmunoassay. The phosphatidylinositol-phospholipase C-released CAK1 antigen was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting and found to be approximately 40 kDa protein. The CAK1-K1 antibody complex remains on the cell surface and is poorly internalized, as shown by an acid wash immunofluorescence internalization assay. An immunotoxin composed of K1 and Lys-PE40, a mutant form of Pseudomonas exotoxin lacking the cell binding domain, was not cytotoxic, supporting the conclusion that the CAK1-K1 antibody complex is not internalized. However, an immunotoxin composed of K1 and native Pseudomonas exotoxin was selectively cytotoxic to cells expressing the CAK1 antigen. This cytotoxicity is due to the fact that domain I of Pseudomonas exotoxin promotes internalization of antigens which are not internalized or bound to antibody alone. Our results suggest that CAK1 is a polypeptide that is expressed on mesothelial cells and many ovarian cancers, and that K1 may be useful as a targeting agent for the immunotherapy of human ovarian cancer.
Acylguanidines as Small-Molecule β-Secretase Inhibitors (2006)

BACE1 is an aspartyl protease responsible for cleaving amyloid precursor protein to liberate Abeta, which aggregates leading to plaque deposits implicated in Alzheimer's disease. We have identified small-molecule acylguanidine inhibitors of BACE1. Crystallographic studies show that these compounds form unique hydrogen-bonding interactions with the catalytic site aspartic acids and stabilize the protein in a flap-open conformation. Structure-based optimization led to the identification of potent analogs, such as 10d (BACE1 IC(50) = 110 nM).
ARIES (1992)

DB2 TM , IMS, and Tandem TM systems. ARIES is applicable not only to database management systems but also to persistent object-oriented languages, recoverable file systems and transaction-based operating systems. ARIES has been implemented, to varying degrees, in IBM's OS/2 TM Extended Edition Database Manager, DB2, Workstation Data Save Facility/VM, Starburst and QuickSilver, and in the University of Wisconsin's EXODUS and Gamma database machine.
Recombinant Human Interleukin–11 Improves Thrombocytopenia in Patients With Cirrhosis (2003)

To elucidate the hematopoietic activity of recombinant human interleukin-11 (rhIL-11, [Neumega, Cambridge, MA]) in patients with cirrhosis and thrombocytopenia, we administered rhIL-11 at 50 microg/kg/d subcutaneously to 10 patients for 10 days with a 30-day follow-up period. All treated patients (n = 9) experienced a gradual, yet significant increase in their platelet count above the baseline value (P < or =.01) reaching the peak value (median, 93,000/microL; range, 60,000-206,000/microL) at a median of 13 days (range, 6-23 days). Eight patients (89%) had a significant increase of > or =50% over the baseline value (P <.05). Moreover, further increases to > or =60,000/microL, > or =80,000/microL, and > or =100,000/microL were observed in 100%, 78%, and 33% of the patients, respectively. A subsequent decline in platelet count was observed at a median of 19 days (range, 7-26 days) after the occurrence of peak concentration. A significant increase in neutrophil count was also demonstrated starting on the third day of treatment (P < or =.01). Concurrent with an increase in the serum level of fibrinogen, transaminase levels declined significantly during treatment period, while bilirubin levels continued to drop for up to 20 days after the initiation of treatment (P <.05). The most frequent effects were due to plasma volume expansion, including conjunctival redness and edema. In conclusion, rhIL-11 can improve platelet counts in patients with early cirrhosis and these patients could benefit from rhIL-11 treatment. However, given the high frequency of regimen-related toxicity, the use of rhIL-11 in patients with cirrhosis should be administered with caution.
Gum arabic is a kind of arabinogalactan-protein. (1984)

Arabinogalactan-proteins (AGPs) are widely distributed in the plant kingdom.1>2) In previous paper,3>4) we
Correlation of ASN2 Gene Expression with Ammonium Metabolism in Arabidopsis (2004)

Abstract In Arabidopsis, asparagine (Asn) synthetase is encoded by a small gene family (ASN1, ASN2, and ASN3). It has been shown that ASN1 and ASN2 exhibit reciprocal gene expression patterns toward light and metabolites. Moreover, changes in total free Asn levels parallel the expression of ASN1, but not ASN2. In this study, we show that ASN2 expression correlates with ammonium metabolism. We demonstrate that the light induction of ASN2 is ammonium dependent. The addition and removal of ammonium exerted fast and reciprocal effects on the levels of ASN2 mRNA, specifically under light-grown conditions. NaCl and cold stress increased cellular free ammonium and ASN2 mRNA levels in a coordinated manner, suggesting that the effects of stress on ASN2 expression may be mediated via accumulation of ammonium. The correlation between ASN2 and cellular ammonium metabolism was further demonstrated by analysis of ASN2 transgenic plants. When plants were grown on Murashige and Skoog medium containing 50 mm ammonium, ASN2 overexpressors accumulated less endogenous ammonium compared with the wild-type Colombia-0 and ASN2 underexpressors. When plants were subjected to high-light irradiance, ammonium levels built up. Under such conditions, ASN2 underexpressors accumulated more endogenous ammonium than the wild-type Colombia-0 and ASN2 overexpressors. These results support the notion that ASN2 is closely correlated to ammonium metabolism in higher plants.
Single Quantum Dot-Micelles Coated with Silica Shell as Potentially Non-Cytotoxic Fluorescent Cell Tracers (2006)

The present study describes a stabilization of single quantum dot (QD) micelles by hydrophobic silica precursors and an extension of the silica layer to form a silica shell around the micelle. The obtained product consists of up to 92% of single nanocrystals (CdSe, CdSe/ZnS, or CdSe/ZnSe/ZnS quantum dots) in the silica micelles, coated with silica shell. The thickness of silica shell could vary, starting from 3 to 4 nm. Increasing the shell thickness increases the photoluminescent characteristics of QDs in aqueous solution. The silica-shelled single CdSe/ZnS QD micelles possess a high quantum yield in aqueous solution, a controlled small size, sharp photoluminescence spectra (fwhm approximately 30 nm), an absence of aggregation, and a high transparency. The presence of a hydrophobic layer between the QD and silica shell ensures an incorporation of other hydrophobic molecules (with interesting properties) in the close proximity of nanocrystal. Thus, it is possible to combine the characteristics of hybrid material with the priority of small size. The nanoparticles are amino functionalized and ready for conjugation. A comparatively good biocompatibility is demonstrated. The nanoparticles show ability for intracellular delivery and are noncytotoxic during long-term incubation with viable cells in the absence of light exposure, which makes them appropriate for cell tracing and drug delivery.
Laboratory and Field Evaluation of a Combined Fluid-Loss-Control Additive and Gel Breaker for Fracturing Fluids (1990)

Summary More than 200% increase in fracture conductivity and permeability was obtained when a new degradable fluid-loss-control additive was used in place of silica flour (SF) in 40-lbm crosslinked hydroxypropyl-guar (HPG) fracturing-fluid systems. The new additive, an organic acid particulate (OAP), slowly degraded into water-soluble monomeric units at temperatures &amp;gt; 150°F after fracture stimulation experiments. The high-acid-content degradation product then acted as an excellent HPG gel breaker and effectively cleaned the proppant packs. As a fluid-loss-control additive, the measured wall-building coefficients were as good as, or better than, those of SF in crosslinked-gel, linear-gel, and N2-foam systems. This paper summarizes a 2-year study of the evaluation and application of this new product in fracturing-fluid systems.
MECHANICAL PROPERTIES OF SiO2 - AEROGELS (1989)

The mechanical behavior of SiO2 - aerogels was investigated in ultrasonic and static compression experiments. In our paper we present data on the sound velocity as a function of density, of external load and internal gas pressure. We also demonstrate local variation of sound velocity over distances of a few mm. Furthermore we investigated the sintering behavior of aerogels with respect to temperature and duration of treatment and derived scaling laws for the elastic constants.
Continuous-Flow Left Ventricular Assist Device Thrombosis: A Danger Foreseen is a Danger Avoided (2015)

Left ventricular assist devices (LVAD) are an increasingly implemented therapeutic intervention for patients with end-stage heart failure. A growing body of evidence, however, has shown an elevated risk of device thrombosis, a major complication jeopardizing the patient's post-implantation survival. To date, multiple causative factors for LVAD thrombosis have been identified, such as internal shear stress, device material, infection, and inadequate anticoagulation. Understanding the mechanisms leading to LVAD thrombosis will not only enable device optimization, but also allow for better patient handling, hence improving post-implantation outcome. In this review we highlight the most commonly identified factors leading to LVAD thrombosis and discuss their mechanisms.
Transcription By RNA Polymerase III (1988)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
DNA sequencing by capillary electrophoresis: use of a two-laser-two-window intensified diode array detection system (1993)

This paper presents the principles of an instrument designed for DNA sequencing using the standard four-dye-labeled primer approach. The method is based on capillary electrophoresis with laser-induced fluorescence and an intensified diode array detector. An important goal of the instrument design has been a detection system that possesses high sensitivity and high spectral resolution. Based on an analysis of the spectral characteristics of the four standard dye-labeled primers, FAM, JOE, ROX, and TAMRA, the strategy has been to use a two-laser-two-window approach, in which a 488-nm argon ion laser illuminates one window, followed by a 543-nm helium-neon laser illuminating the second window. The two-window approach has no moving parts and permits continuous illumination. Spectral resolution is provided by a grating spectrograph and a cooled intensified diode array. The estimated limit of detection for the standard four dye-labeled primers was found to be in the sample concentration range of 1 x 10(-12) M. To achieve these low levels, complete free-radical polymerization of polyacrylamide has been found to be necessary in order to reduce background noise. In addition, reduction in background noise was accomplished by continual purging of the anodic reservoir in order to prevent electrolysis products from entering the capillary. Separation of DNA sequencing reaction products is demonstrated on a 9% T linear polyacrylamide column.
Macitentan: entry-into-humans study with a new endothelin receptor antagonist (2011)

The pharmacokinetic and tolerability profile of macitentan is consistent with a once-a-day dosing regimen and warrants further investigation in clinical studies.
Targeting Akt3 Signaling in Malignant Melanoma Using Isoselenocyanates (2009)

Synthetic isoselenocyanates are therapeutically effective for inhibiting melanoma tumor development by targeting Akt3 signaling to increase apoptosis in melanoma cells with negligible associated systemic toxicity.
Modulation of IgE reactivity of allergens by site‐directed mutagenesis: potential use of hypoallergenic variants for immunotherapy (1998)

Specific immunotherapy is an efficient treatment for patients suffering from type I allergy. The mechanisms underlying successful immunotherapy are assumed to operate at the level of T helper cells, leading to a modulation of the immune response to allergens. During immunotherapy, increasing doses of allergens are given on a regular basis, and the beneficial effects for the patient depend on the concentration of allergen used. On the other hand, the risk of IgE-mediated anaphylactic side effects also increase with the amount of allergen applied per injection. Therefore, we have proposed the use of hypoallergenic (low IgE binding activity) forms of allergens for immunotherapy. We evaluated by site-directed mutagenesis the contributions of individual amino acid residues/positions for IgE binding to Bet v 1, the major allergen of birch pollen. We found that IgE binding to Bet v 1 depended on at least six amino acid residues/positions. Immunoblot analyses and inhibition experiments showed that the multiple-point Bet v 1 mutant exhibited extremely low reactivity with serum IgE from birch pollen-allergic patients. In vivo (skin prick) tests showed that the potency of the multiple-point mutant to induce typical urticarial type I reactions in pollen-allergic patients was significantly lower than for wild-type Bet v 1. Proliferation assays of allergen-specific T cell clones demonstrated that these six amino acid exchanges in the Bet v 1 sequence did not influence T cell recognition. Thus, the Bet v 1 six-point mutant displayed significantly reduced IgE binding activity, but conserved T cell activating capacity, which is necessary for immunomodulation. The approach described here may be generally applied to produce allergen variants to be used in a safe therapy form of immediate-type allergies.
Prospective Evaluation of Sacral Nerve Modulation in Children with Validated Questionnaires (2013)

Patients undergoing sacral neuromodulation had significant improvement in NLUTD/DES scores, and psychosocial and overall total quality of life. Results were durable at 1 month. Continuing to follow these patients in a prospective manner with validated questionnaires will strengthen the current evidence supporting sacral neuromodulation in the pediatric population.
Improvement in hemolysis and pulmonary arterial systolic pressure in adult patients with sickle cell disease during treatment with hydroxyurea (2009)

Elevated pulmonary arterial systolic pressure is strongly associated with mortality in patients with sickle cell disease (SCD). A tricuspid regurgitant velocity (TRV) of 2.5 m/s or greater by trans-thoracic echocardiogram is a key marker of risk [1–3]. The pathophysiologic mechanism involves release from the red cell during intravascular hemolysis of cell-free plasma hemoglobin and arginase [4]. Hydroxyurea is the only drug approved by the Food and Drug Administrations specifically for SCD. It acts by increasing levels of fetal hemoglobin, which inhibits sickling, and has been shown to reduce the incidence of vaso-occlusive crisis (VOC), and prolong survival in patients with sickle cell disease [5,6]. Because fetal hemoglobin also reduces the rate of hemolysis in SCD, hypothetically, hydroxyurea might also reduce the severity of hemolysis-linked vascular dysfunction and pulmonary hypertension. Herein, we describe five patients with sickle cell disease having elevated pulmonary arterial systolic pressure who exhibited improvement in their baseline laboratory parameters of hemolysis, accompanied by reduced TRV, during treatment with hydroxyurea. Hydroxyurea may have a role in the management of selected patients with elevated TRV.
Stentenna: a micromachined antenna stent for wireless monitoring of implantable microsensors (2004)

This paper reports on a micromachined stent that has been developed to serve as an antenna for wireless monitoring of implantable microsensors. A 4 mm long, 3.5 mm diameter design is fabricated from 50 /spl mu/m thick stainless steel foil using a batch-compatible micro electro-discharge machining process. As it is expanded during deployment, the stent transforms from a mesh that fits snugly around the angioplasty balloon into an inductive coil. This is accomplished by strategically located breakable links which change its electrical characteristics during the plastic deformation into its final shape. This 20 nH coil is coupled to a capacitive pressure microsensor that is approximately 1.2/spl times/4/spl times/0.5 mm/sup 3/ in dimensions. Wireless monitoring is demonstrated by showing that the resonant electrical loading provided by this LC tank to a separate transmitting coil shifts by 400 KHz over a pressure change of 800 Torr. The tests are performed in a liquid environment.
A Prospective, Open-Label Trial Assessing Dexamethasone Pulse Therapy in Moderate to Severe Ulcerative Colitis (2002)

Dexamethasone pulse therapy is highly effective in inducing remission in patients with ulcerative colitis, but randomized controlled trials are needed to compare dexamethasone pulse therapy with standard oral continuous corticosteroid regimens.
Transcriptome analysis of LuxS‐deficient Streptococcus mutans grown in biofilms (2010)

We previously reported that LuxS in Streptococcus mutans is involved in stress tolerance and biofilm formation. In this study, flowcells and confocal laser scanning microscopy were used to further examine the effects of LuxS-deficiency on biofilm formation. Similar to the wild-type strain (UA159), a strain deficient in LuxS (TW26D) bound efficiently to the flowcells and formed microcolonies 4 h after inoculation. Unlike UA159, which accumulated and formed compact, evenly distributed biofilms after 28 h, TW26D showed only loose, sporadic, thin biofilms. DNA microarray analysis revealed alterations in transcription of more than 60 genes in TW26D biofilms by at least 1.5-fold (P < 0.001). Among the upregulated genes were those for sugar-specific enzymes II of the phosphotransferase (PTS) system and the atp operon, which codes for the proton-pumping F-ATPase. Of the downregulated genes, several encode proteins with putative functions in DNA repair. Mutation of selected genes caused severe defects in the ability of the mutants to tolerate low pH and oxidative stress. These results provide additional proof that LuxS-deficiency causes global alterations in the expression of genes central to biofilm formation and virulence of S. mutans, including those involved in energy metabolism, DNA repair and stress tolerance.
Scanning fiber angle-resolved low coherence interferometry (2009)

We present a fiber-optic probe for Fourier-domain angle-resolved low coherence interferometry for the determination of depth-resolved scatterer size. The probe employs a scanning single-mode fiber to collect the angular scattering distribution of the sample, which is analyzed using the Mie theory to obtain the average size of the scatterers. Depth sectioning is achieved with low coherence Mach-Zehnder interferometry. In the sample arm of the interferometer, a fixed fiber illuminates the sample through an imaging lens and a collection fiber samples the backscattered angular distribution by scanning across the Fourier plane image of the sample. We characterize the optical performance of the probe and demonstrate the ability to execute depth-resolved sizing with subwavelength accuracy by using a double-layer phantom containing two sizes of polystyrene microspheres.