gebhart/patrepeval huggingface dataset:
Efficacy of enzyme replacement therapy in -mannosidosis mice: a preclinical animal study (2004)

Alpha-mannosidosis is a lysosomal storage disorder which manifests itself in the excessive storage of mannose-containing oligosaccharides in the lysosomes of multiple peripheral tissues and in the brain. Here we report on the correction of storage in a mouse model of alpha-mannosidosis after intravenous administration of lysosomal acid alpha-mannosidase (LAMAN) from bovine kidney, and human and mouse recombinant LAMAN. The bovine and the human enzyme were barely phosphorylated, whereas the bulk of the mouse LAMAN contained mannose 6-phosphate recognition markers. The clearance decreased from bovine to human to mouse LAMAN with plasma half-times of 4, 8 and 12 min, respectively. The apparent half-life of the internalized enzyme was dependent on the enzyme source as well as tissue type and varied between 3 and 16 h. The corrective effect on the storage of neutral oligosaccharides was time-, tissue- and dose-dependent, and the effects were observed to be transient. After a single dose of LAMAN the maximum corrective effect was observed between 2 and 6 days after injection. In general the corrective effect of the human LAMAN was higher than that of the mouse LAMAN and lowest for the bovine LAMAN. Injection of 250 mU human LAMAN/g body weight followed by a subsequent injection 3.5 days later was sufficient to clear liver, kidney and heart from neutral oligosaccharides. Surprisingly a decrease in mannose containing oligosaccharides was also observed in the brain, with storage levels reported at <30% than that found in controls. These data clearly underline the efficacy of enzyme replacement therapy for the correction of storage in alpha-mannosidosis and suggest that this treatment can substantially decrease storage in the brain.
Preventing PCR amplification carryover contamination in a clinical laboratory. (2004)

During the past two decades PCR and several other DNA/RNA amplification techniques have become important diagnostic tools in clinical laboratories. Amplification products contamination has been the main impediment to using these techniques routinely in diagnostic laboratories. Over the years, several creative pre- and post-amplification methods have been developed that prevent amplicon carryover contamination. These procedures, coupled with automated systems that employ real-time amplification and simultaneous detection in a closed system, have substantially reduced the possibility of false positive results due to amplification products carryover contamination.
Kinesin Family Deregulation Coordinated by Bromodomain Protein ANCCA and Histone Methyltransferase MLL for Breast Cancer Cell Growth, Survival, and Tamoxifen Resistance (2014)

These findings support the development of novel inhibitors of cancer-associated kinesins and their regulator ANCCA for effective treatment of cancers including tamoxifen-resistant breast cancers.
Characterization of the Interaction between Neuronal RNA-binding Protein HuD and AU-rich RNA (2003)

Hu proteins have been shown to bind to AU-rich elements (AREs) in the 3'-untranslated region of unstable mRNAs. They can thereby inhibit the decay of labile transcripts by antagonizing destabilizing proteins that target these AU-rich sequences. Here we examine the sequence preferences of HuD to elucidate its possible role in counteracting mRNA decay. Using repeats of the prototype destabilizing sequence UU(AUUU)nAUU, we show that all three HuD RNA-binding domains participate in binding to AU-tracts that can be as short as 13 residues, depending on the position of the remaining As. Removal of the A residues, resulting in a poly(U)-tract, increased the affinity of HuD for RNA, suggesting that the presence of As in destabilizing elements might favor the recruitment of other proteins and/or prevent HuD from binding too tightly to AREs. In vitro selection experiments with randomized RNAs confirmed the preference of HuD for poly(U). RNA binding analysis of the related protein HuB showed a similar preference for poly(U). In contrast, tristetraprolin, an mRNA destabilizing protein, strongly prefers AU-rich RNA. Many labile mRNAs contain U-tracts in or near their AREs. Individual AREs may thus differentially affect mRNA half-life by recruiting a unique complement of stabilizing and destabilizing factors.
Effect of beta-blockade on baroreceptor and autonomic function in heart failure. (1999)

Although beta-adrenoreceptor antagonists appear to be beneficial in chronic heart failure there is little information on their effects on autonomic and baroreceptor function which may have important prognostic implications. We sought to determine first whether beta-adrenoreceptor blockade will improve baroreceptor function and vagal tone in chronic heart failure, and second whether there were any differences between standard therapy with metoprolol and the second-generation vasodilating beta-blocker celiprolol. In this double-blind randomized placebo-controlled study 50 patients with stable chronic heart failure received either celiprolol 200 mg daily, metoprolol 50 mg twice daily or placebo for 12 weeks after a 4-week dose titration period. Thirty-five healthy normal subjects were also studied. Baroreceptor gain was assessed non-invasively by cross-spectral analysis of R-R and systolic blood pressure low- and high-frequency components (the alpha angle) during controlled respiration. High-frequency power was used as a measure of vagal modulation. Satisfactory recordings for analysis were obtained in 31 patients with heart failure. The results showed that at baseline baroreceptor gain (alphaHF) was significantly depressed in patients with heart failure compared with the normal control group (4.95+/-0. 55 versus 11.73+/-1.32 ms/mmHg, P<0.0001). After 12 weeks of treatment with metoprolol baroreceptor gain improved significantly whether measured while supine (P=0.03) or standing (P=0.009), and this was associated with a significant increase in R-R HF power (P=0. 008). There were no significant changes after treatment with celiprolol or placebo. We conclude that metoprolol but not celiprolol therapy restores baroreceptor gain towards normal and increases vagal tone in chronic heart failure. The ancillary properties of celiprolol do not appear to provide any advantages over metoprolol for the restoration of autonomic and baroreceptor function in heart failure.
A p‐Type Amorphous Oxide Semiconductor and Room Temperature Fabrication of Amorphous Oxide p–n Heterojunction Diodes (2003)

Oxide electronics , which together with amorphous semiconductors could become a rapid‐growth field, have come a step closer with the first report of a p‐type amorphous oxide semiconductor, ZnO·Rh 2 O 3 . The thin‐film deposition of this material at room temperature and the fabrication of p–n heterojunction diodes on flexible plastic sheets (see Figure) are demonstrated.
3-O-Deacylation of Lipid A by PagL, a PhoP/PhoQ-regulated Deacylase of Salmonella typhimurium, Modulates Signaling through Toll-like Receptor 4 (2004)

Toll-like receptor 4 (TLR4)-mediated responses, which are induced by the lipid A portion of lipopolysaccharide, are important for host defense against Salmonellae infection. A variety of different data indicate that the acylation state of lipid A can alter TLR4-mediated responses. The S. typhimurium virulence gene product PhoP/PhoQ signals the presence of host microenvironments to regulate the expression of a lipid A 3-O-deacylase, PagL, and a lipid A palmitoyltransferase, PagP. We now demonstrate that 3-O-deacylation and palmitoylation of lipid A decreases its ability to induce TLR4-mediated signaling. Deacylated lipid A, deacylated and palmitoylated lipid A, palmitoylated lipid A, and unmodified lipid A species were purified from Escherichia coli heterologously expressing PagL and/or PagP. The purified lipid A preparations showed spectra of a single lipid A species on mass spectrometry and gave a single band on thin layer chromatography. The activity of purified lipid A species was examined using human and mouse cell lines that express recombinant human TLR4. Compared with unmodified lipid A, the modified lipid A species are 30-100-fold less active in the ability to induce NF-kappaB-dependent reporter activation. These results suggest that the lipid A modifications reduce TLR4-signaling as part of Salmonellae adaptation to host environments.
Regulation of Lymphokine Messenger RNA Stability by a Surface-Mediated T Cell Activation Pathway (1989)

Quiescent T cells can be induced to express many genes by mitogen or antigen stimulation. The messenger RNAs of some of these genes undergo relatively rapid degradation compared to messenger RNAs from constitutively expressed genes. A T cell activation pathway that specifically regulates the stability of messenger RNAs for the lymphokines interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor is induced by stimulation of the CD28 surface molecule. This pathway does not directly affect the steady-state messenger RNA level, transcription, or messenger RNA half-life of other T cell activation genes, including c-myc, c-fos, IL-2 receptor, and the 4F2HC surface antigen. These data show that stimuli received at the cell surface can alter gene expression by inducing specific changes in messenger RNA degradation.
Passive mode locking in erbium fiber lasers with negative group delay (1993)

100 fs pulses are generated in passively mode-locked erbium fiber lasers with small negative group-velocity dispersion. The pulses are obtained at a pump power significantly higher than the mode-locking threshold. An optimization of fiber lengths leads to the elimination of pedestal formation and the generation of stable pulse trains with high contrast ratios.
A New Ground Resistivity Method For Engineering And Environmental Geophysics (1994)

Several years ago, a capacitive-coupled resistivity system was developed in Russia by one of us&lt;br&gt;(V.M.T.), for engineering geophysical applications in permafrost areas of Siberia. This system,&lt;br&gt;called VCHEP (cyrillic acronym for high frequency capacitive-coupled resistivity) uses both&lt;br&gt;transmitter and receiver antennas operating in the range of several kilohertz. Measurements of&lt;br&gt;applied current and received voltage potential are converted to apparent resistivity using a&lt;br&gt;geometrical factor related to the antenna array. The transmitter and receiver type and geometry&lt;br&gt;can be varied depending upon a particular application; however, the most cost-effective array&lt;br&gt;is the in-line double dipole line antenna configuration. Using such a, drag-cable design of&lt;br&gt;antennas, data acquisition rates may far exceed those techniques requiring galvanic electrode&lt;br&gt;contact. Considerable experience with this method has been obtained in northern areas of&lt;br&gt;Siberia; and as part of the Canada/Russia Northern Scientific Exchange Program, testing has also&lt;br&gt;been conducted in the Canadian western arctic.
Structural insights into the promiscuity and function of the human pregnane X receptor. (2002)

The pregnane X receptor (PXR) is a promiscuous nuclear receptor that responds to a wide variety of drugs, xenobiotics and endogenous compounds, and plays a critical role in mediating drug-drug interactions in humans. PXR is the master regulator of the expression of the CYP3A4 gene, which encodes for the most abundant and promiscuous drug-metabolizing enzyme in humans. PXR also regulates the expression of other genes involved in xenobiotic metabolism, including CYP2C8, CYP2C9, CYP2B6, GSTA2 and MDR1, as well as genes critical to bile acid metabolism. While PXR functions as a xenobiotic sensor in numerous vertebrates, its relatively low sequence conservation across species causes the PXRs from different organisms to respond to distinct subsets of xenobiotics. Thus, PXR promiscuity is directed and not random. The recent determination of crystal structures of the ligand binding domain of human PXR has provided the first detailed molecular view of this promiscuous receptor, and has advanced our understanding of its varied biological functions. We review the evidence establishing the binding promiscuity of PXR and its directed specificity in different species, and analyze the structural determinants of these characteristics. In addition, we examine the relationship between the interaction of PXR with ligands and the manner in which CYP3A4 is thought to bind to substrate molecules. The accumulating structural and functional data on PXR may facilitate the development of improved methods for in vitro, in vivo and in silico screening for PXR activation.
Flat panel detector-based cone-beam volume CT angiography imaging: system evaluation (2000)

Preliminary evaluation of recently developed large-area flat panel detectors (FPDs) indicates that FPDs have some potential advantages: compactness, absence of geometric distortion and veiling glare with the benefits of high resolution, high detective quantum efficiency (DQE), high frame rate and high dynamic range, small image lag (< 1%), and excellent linearity (approximately 1%). The advantages of the new FPD make it a promising candidate for cone-beam volume computed tomography (CT) angiography (CBVCTA) imaging. The purpose of this study is to characterize a prototype FPD-based imaging system for CBVCTA applications. A prototype FPD-based CBVCTA imaging system has been designed and constructed around a modified GE 8800 CT scanner. This system is evaluated for a CBVCTA imaging task in the head and neck using four phantoms and a frozen rat. The system is first characterized in terms of linearity and dynamic range of the detector. Then, the optimal selection of kVps for CBVCTA is determined and the effect of image lag and scatter on the image quality of the CBVCTA system is evaluated. Next, low-contrast resolution and high-contrast spatial resolution are measured. Finally, the example reconstruction images of a frozen rat are presented. The results indicate that the FPD-based CBVCT can achieve 2.75-lp/mm spatial resolution at 0% modulation transfer function (MTF) and provide more than enough low-contrast resolution for intravenous CBVCTA imaging in the head and neck with clinically acceptable entrance exposure level. The results also suggest that to use an FPD for large cone-angle applications, such as body angiography, further investigations are required.
Ketonization Reactions of Carboxylic Acids and Esters over Ceria−Zirconia as Biomass-Upgrading Processes (2010)

Carboxylic acids and esters are common intermediate products formed in biomass conversion processes. Reaction kinetics studies for upgrading mixtures containing carboxylic acids and esters by ketonization reactions (to achieve C−C coupling) over a ceria−zirconia catalyst have been carried out using butanoic acid, pentanoic acid, and hexanoic acid at temperatures of 548, 573, 598, and 623 K. The results from these experimental studies have been consolidated and described using kinetic models. For the ketonization of hexanoic acid, a kinetic model, previously developed for hexanoic acid, has been modified and extended to describe a wider and more applicable concentration range, between 2.5 and 75 mol %. Furthermore, the homo- and the cross-ketonization of butanoic acid, pentanoic acid, and hexanoic acid have been studied, showing that the rate of cross-ketonization is faster than the rate of homo-ketonization. Because esters are common side products of biomass conversion processes, formed by the esterification of acids with primary and second alcohols, the reaction kinetics for the direct ketonization of esters has also been studied, showing that ester ketonization is slower than ketonization of the corresponding acid. Finally, a kinetic model has been developed to describe the experimentally observed product distribution obtained by reacting a mixture of different biomass-derived species over a ceria−zirconia catalyst. The model includes the ketonization of acids and the ketonization of esters as well as the esterification of acids with primary and secondary alcohols.
Immunolocalization and pharmacological relevance of oligopeptide transporter PepT1 in intestinal absorption of β‐lactam antibiotics (1996)

A polyclonal antibody (anti-PepT1/C) was raised against the rabbit intestinal H(+)-coupled oligopeptide transporter, PepT1. Anti-PepT1/C detected 70-80-kDa protein in crude membranes obtained from rabbit duodenum, jejunum and ileum. PepT1 was localized in the brush-border of the absorptive epithelial cells by subcellular fractionation of membranes on a sucrose density gradient and by immunohistochemistry using light and electron microscopy. Transport activity for cephalosporins and dipeptide expressed in Xenopus laevis oocytes injected with total mRNA obtained from rabbit small intestine was eliminated completely by prehybridization of the mRNA with antisense oligonucleotide against the 5'-coding region of rabbit PepT1 cDNA.
Soybean b-Conglycinin Genes Are Clustered in Several DNA Regions and Are Regulated by Transcriptional and Posttranscriptional Processes (1989)

John J. Harada, Susan J. Barker, Robert B. Goldberg, Soybean β-Conglycinin Genes Are Clustered in Several DNA Regions and Are Regulated by Transcriptional and Posttranscriptional Processes, The Plant Cell, Vol. 1, No. 4 (Apr., 1989), pp. 415-425
SIRT1 Acts as a Nutrient-sensitive Growth Suppressor and Its Loss Is Associated with Increased AMPK and Telomerase Activity (2008)

SIRT1, the mammalian homolog of SIR2 in Saccharomyces cerevisiae, is an NAD-dependent deacetylase implicated in regulation of lifespan. By designing effective short hairpin RNAs and a silent shRNA-resistant mutant SIRT1 in a genetically defined system, we show that efficient inhibition of SIRT1 in telomerase-immortalized human cells enhanced cell growth under normal and nutrient limiting conditions. Hematopoietic stem cells obtained from SIRT1-deficient mice also showed increased growth capacity and decreased dependency on growth factors. Consistent with this, SIRT1 inhibition was associated with increased telomerase activity in human cells. We also observed a significant increase in AMPK levels up on SIRT1 inhibition under glucose limiting conditions. Although SIRT1 suppression cooperated with hTERT to promote cell growth, either overexpression or suppression of SIRT1 alone had no effect on life span of human diploid fibroblasts. Our findings challenge certain models and connect nutrient sensing enzymes to the immortalization process. Furthermore, they show that in certain cell lineages, SIRT1 can act as a growth suppressor gene.
Hemolytic Activity of pH-Responsive Polymer-Streptavidin Bioconjugates (1999)

Drug delivery systems that increase the rate and/or quantity of drug release to the cytoplasm are needed to enhance cytosolic delivery and to circumvent nonproductive cell trafficking routes. We have previously demonstrated that poly(2-ethylacrylic acid) (PEAAc) has pH-dependent hemolytic properties, and more recently, we have found that poly(2-propylacrylic acid) (PPAAc) displays even greater pH-responsive hemolytic activity than PEAAc at the acidic pHs of the early endosome. Thus, these polymers could potentially serve as endosomal releasing agents in immunotoxin therapies. In this paper, we have investigated whether the pH-dependent membrane disruptive activity of PPAAc is retained after binding to a protein. We did this by measuring the hemolytic activity of PPAAc-streptavidin model complexes with different protein to polymer stoichiometries. Biotin was conjugated to amine-terminated PPAAc, which was subsequently bound to streptavidin by biotin complexation. The ability of these samples to disrupt red blood cell membranes was investigated for a range of polymer concentrations, a range of pH values, and two polymer-to-streptavidin ratios of 3:1 and 1:1. The results demonstrate that (a) the PPAAc-streptavidin complex retains the ability to lyse the RBC lipid bilayers at low pHs, such as those existing in endosomes, and (b) the hemolytic ability of the PPAAc-streptavidin complex is similar to that of the free PPAAc.
Improvement of Fc–erythropoietin structure and pharmacokinetics by modification at a disulfide bond (2005)

Erythropoietin (Epo) is a cytokine that controls the production of red blood cells (RBCs). Epo acts continuously on RBC precursors to prevent apoptosis, so it is important to maintain high levels of Epo activity when treating anemic patients. We describe here modified human Epo [Epo(NDS)] with mutations His32Gly, Cys33Pro, Trp88Cys and Pro90Ala that result in the rearrangement of the disulfide bonding pattern from Cys29-Cys33 to Cys29-Cys88 and that, in the context of an Fc-Epo(NDS) fusion protein, lead to significantly improved properties. Fc-Epo was secreted from NS/0 myeloma cells as about 35% high molecular weight aggregates, was unstable upon removal of N-linked oligosaccharides and showed poor pharmacokinetics and little efficacy in mice. In contrast, a corresponding Fc-Epo(NDS) was secreted almost exclusively as a unit dimer, was relatively stable to removal of N-linked oligosaccharides, had much improved pharmacokinetic properties and had a significantly improved effect on RBC production. These results indicate that rearrangement of the disulfide bonding pattern in a therapeutic protein can have a significant effect on pharmacokinetics and, potentially, the dosing schedule of a protein drug.
Smart antennas for wireless systems (1998)

In this article we discuss current and future antenna technology for wireless systems and the improvement that smart and adaptive antenna arrays can provide. We describe standard cellular antennas, smart antennas using fixed beams, and adaptive antennas for base stations, as well as antenna technologies for handsets. We show the potential improvement that these antennas can provide, including range extension, multipath diversity, interference suppression, capacity increase, and data rate increase. The issues involved in incorporating these antennas into wireless systems using CDMA, GSM, and IS-136 in different environments, such as rural, suburban, and urban areas, as well as indoors, are described. Theoretical, computer simulation, experimental, and field trial results are also discussed that demonstrate the potential of this technology.
Field‐Effect Nanoparticle‐Based Glucose Sensor on a Chip: Amplification Effect of Coimmobilized Redox Species (2008)

Abstract A capacitive EIS (electrolyte‐insulator‐semiconductor) structure was modified with gold nanoparticles together with glucose oxidase and used as field‐effect‐based glucose biosensor using the constant capacitance mode. Co‐immobilization of ferrocene redox species resulted in a two‐fold increase of the biosensor sensitivity. The effect was explained by the hydrogen peroxide‐mediated oxidation of ferrocene resulting in a pool of charged species at the interface increasing the sensor response towards glucose. The studied approach was suggested as a general means to amplify signals from Si chip‐based field‐effect enzyme biosensors.