gebhart/patrepeval huggingface dataset:
Roles of E-NTPDase1 and 5'-eNT in the regulation of microglial phagocytosis (2013)

Purinergic signaling plays a major role in the regulation of phagocytosis in microglia. Interplay between P2 and P1 receptor activation is controlled by a cascade of extracellular enzymes which dephosphorylate purines resulting in the formation of adenosine. The ATP and ADP degrading capacity of cultured microglia depends on the expression of E-NTPDase1 (CD39) and is several times higher when compared to astrocytes which lack this enzyme. In brain slices, deletion of cd39 resulted in a 50 % decrease of ADP-degrading ability, while the degradation of ATP was decreased to about 75 % of the values measured in wild-type brain tissue. Microglia in acute slices from cd39 -/- animals had increased constitutive phagocytic activity which could not be further enhanced by ATP in contrast to control animals. Pharmacological blockage of P2 receptors decreased the constitutive phagocytic activity to a similar base level in wild type and cd39 -/- microglia. Activation of P1 receptors by non- hydrolysable adenosine analog significantly decreased phagocytic activity. Deletion of cd73 , an enzyme expressed by microglia which converts AMP to adenosine did not affect phagocytic activity. Taken together, these data show that CD39 plays a prominent role in controlling ATP levels and thereby microglial phagocytosis.
A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β (2012)

Because it lacks a lymphatic circulation, the brain must clear extracellular proteins by an alternative mechanism. The cerebrospinal fluid (CSF) functions as a sink for brain extracellular solutes, but it is not clear how solutes from the brain interstitium move from the parenchyma to the CSF. We demonstrate that a substantial portion of subarachnoid CSF cycles through the brain interstitial space. On the basis of in vivo two-photon imaging of small fluorescent tracers, we showed that CSF enters the parenchyma along paravascular spaces that surround penetrating arteries and that brain interstitial fluid is cleared along paravenous drainage pathways. Animals lacking the water channel aquaporin-4 (AQP4) in astrocytes exhibit slowed CSF influx through this system and a ~70% reduction in interstitial solute clearance, suggesting that the bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport. Fluorescent-tagged amyloid β, a peptide thought to be pathogenic in Alzheimer's disease, was transported along this route, and deletion of the Aqp4 gene suppressed the clearance of soluble amyloid β, suggesting that this pathway may remove amyloid β from the central nervous system. Clearance through paravenous flow may also regulate extracellular levels of proteins involved with neurodegenerative conditions, its impairment perhaps contributing to the mis-accumulation of soluble proteins.
RRBSMAP: a fast, accurate and user-friendly alignment tool for reduced representation bisulfite sequencing (2011)

Supplementary data are available at Bioinformatics online.
Abstract 15823: PCSK-9 Monoclonal Antibody Alirocumab Dose-Dependently Decreases Atherosclerosis Development and Enhances the Effects of Atorvastatin in APOE*3Leiden.CETP Mice (2013)

Introduction: Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease responsible for low density lipoprotein receptor (LDLR) degradation in the liver, thereby increasing LDL cholesterol levels. PCSK9 inhibition is a potential novel strategy for treatment of CVD, especially in combination with statins which increase PCSK9 expression. Alirocumab (also known as SAR236553/REGN727) is a fully human PCSK9 monoclonal antibody currently in phase 3 clinical development. Hypothesis: Alirocumab alone reduces progression of atherosclerosis in APOE*3Leiden.CETP mice and adds to the atheroprotective effect of atorvastatin in this model. Methods: Mice were fed a Western-type diet alone or were treated by weekly subcutaneous injection with alirocumab (3 or 10 mg/kg) with or without atorvastatin (3.6 mg/kg/d) for 18 weeks. Effects on plasma lipids, hepatic LDLR expression and atherosclerotic lesion size and severity were assessed. Results: Alirocumab dose-dependently decreased total cholesterol (TC) (-37% to -46%, P Conclusions: A PCSK9 monoclonal antibody, alirocumab, dose-dependently decreases plasma lipids and progression of atherosclerosis and enhances the beneficial effects of atorvastatin in APOE*3Leiden.CETP mice.
Circulating Tumor-Specific DNA: A Marker for Monitoring Efficacy of Adjuvant Therapy in Cancer Patients (2005)

Adjuvant systemic therapy (a strategy that targets potential disseminated tumor cells after complete removal of the tumor) has clearly improved survival of patients with cancer. To date, no tool is available to monitor efficacy of these therapies, unless distant metastases arise, a situation that unavoidably leads to death. We analyzed RASSF1A DNA methylation in pretherapeutic sera and serum samples collected 1 year after surgery from 148 patients with breast cancer who were receiving adjuvant tamoxifen; 19.6% and 22.3% of patients with breast cancer showed RASSF1A DNA methylation in their pretherapeutic and 1-year-after serum samples, respectively. RASSF1A methylation 1 year after primary surgery (and during adjuvant tamoxifen therapy) was an independent predictor of poor outcome, with a relative risk (95% confidence interval) for relapse of 5.1 (1.3-19.8) and for death of 6.9 (1.9-25.9). Measurement of serum DNA methylation allows adjuvant systemic treatment to be monitored for efficacy: disappearance of RASSF1A DNA methylation in serum throughout treatment with tamoxifen indicates a response, whereas persistence or new appearance means resistance to adjuvant tamoxifen treatment. It remains to be seen whether modifications made in adjuvant therapeutic strategies based on detection of circulating nucleic acids will improve survival as well as quality of life.
Quantitative Methods for Anthocyanins. (1968)

SUMMARY— The evaluation of the various purification methods was based, in the order of their importance, on the recovery of individual and total anthocyanins and on the concentrating power. Amberlite CG‐50 ion exchange resin was the best, but basic lead acetate was also satisfactory. Polyamide did not concentrate the anthocyanins and the use of neutral lead acetate resulted in poor recoveries.
Promoting Healing With Recombinant Human Platelet‐Derived Growth Factor–BB in a Previously Irradiated Problem Wound (2003)

In previously irradiated tissue, rhPDGF can be useful in helping refractory wounds to heal by inducing further granulation formation. If such treatment is planned, the patient should be informed of the possible theoretical risks of its use when it is in proximity to a previously treated neoplastic site.
Electronic Cigarettes: Effective Nicotine Delivery After Acute Administration (2012)

User experience and/or device characteristics likely influence EC nicotine delivery and other effects. Systematic manipulation of these and other variables could elucidate conditions that produce intended effects.
Topology Aware Performance Prediction of Collective Communication Algorithms on Multi-Dimensional Mesh/Torus (2014)

Abstract—As the scale of computers becomes large, tech-nologies for appropriate selection of collective communication algorithm have become important. Especially, on Multi Dimen-sional Mesh/Torus topology, which is popularly used on large-scale supercomputers, this selection is one of the most important issues for achieving sufficient scalability. Currently, the authors are developing a method that combines performance prediction models and runtime measurement to enable efficient algorithm selection. This paper introduces a performance prediction model of algorithms on Multi-Dimensional Mesh/Torus topology. This model considers effects of collisions on links to increase the preciseness of the prediction. Some experiments have been done
The Establishment and Evaluation of Luminescent-Labelled Immunometric Assays for Prostate-Speciflc Antigen-α1-Antichymotrypsin Complexes in Serum (1991)

Prostate-specific antigen is found in the prostate in two forms, one with a low (30,000) and one with a high (100,000) relative molecular mass. The latter has recently been found to be a complex of prostate-specific antigen with alpha 1-antichymotrypsin. Immunoluminometric assays were designed for the prostate-specific antigen-alpha 1-antichymotrypsin complex as well as for alpha 1-antichymotrypsin, the former being compared with a commercially available radioimmunoassay for prostate-specific antigen (ProsChek RIA-Yang Laboratories). The precision of the immunoluminometric assays was acceptable (intra-assay variation less than 7%; inter-assay variation less than 8.5%) in the measuring ranges 0-90 micrograms/l for the prostate-specific antigen-alpha 1-antichymotrypsin complex and 0-12 g/l for alpha 1-antichymotrypsin. The correlation between the assays for prostate-specific antigen and prostate-specific antigen-alpha 1-antichymotrypsin complex was acceptable, showing a correlation coefficient r = 0.83 after double logarithmic transformation, or r = 0.85 using the Spearman rank correlation on 131 data pairs. Extremely high alpha 1-antichymotrypsin levels (above 2 g/l) caused interference in the prostate-specific antigen-alpha 1-antichymotrypsin complex assay. Such levels, although rare, are encountered in pulmonary inflammatory disease. The reference ranges for the three assays were found to be as follows: prostate-specific antigen 0.13-4.63 micrograms/l, prostate-specific antigen-alpha 1-antichymotrypsin complex 0.08-1.78 microgram/l, and for alpha 1-antichymotrypsin 0.27-0.61 g/l. These values were obtained from 82 hospitalised males for the first two assays and from 80 males and females free from infection for the latter.(ABSTRACT TRUNCATED AT 250 WORDS)
Power output monitoring for vehicles equipped with electronic throttle (2001)

Vehicles equipped with electronic throttle control (ETC) systems are entering the automotive marketplace for several reasons, including improved fuel economy (early transmission upshifts, lean-burn combustion, variable displacement engines), drivability (improved pedal response, altitude compensation, traction control), and emissions (controlled tip-in/tip-out, cold start). These improvements come at the cost of increased complexity. One of the issues is related to engine power output detection and mitigation in case of operation under exceptional conditions. The authors propose a method that monitors the operation of the powertrain based on the amount of injected fuel and provides a natural mitigating action.
Cell Culture Models in Microfluidic Systems (2008)

Microfluidic technology holds great promise for the creation of advanced cell culture models. In this review, we discuss the characterization of cell culture in microfluidic systems, describe important biochemical and physical features of the cell microenvironment, and review studies of microfluidic cell manipulation in the context of these features. Finally, we consider the integration of analytical elements, ways to achieve high throughput, and the design constraints imposed by cell biology applications.
Fas ligand is targeted to secretory lysosomes via a proline-rich domain in its cytoplasmic tail (2001)

Fas ligand (FasL) induces apoptosis through its cell surface receptor Fas. T lymphocytes and natural killer cells sort newly synthesised FasL to secretory lysosomes but, in cell types with conventional lysosomes, FasL appears directly on the plasma membrane. Here, we define a proline-rich domain (PRD) in the cytoplasmic tail of FasL that is responsible for sorting FasL to secretory lysosomes. Deletion of this PRD results in cell surface expression of FasL in cells with secretory lysosomes. Positively charged residues flanking the PRD are crucial to the sorting motif and changing the charge of these residues causes mis-sorting to the plasma membrane. In cells with conventional lysosomes, this motif is not recognised and FasL is expressed at the plasma membrane. The FasL PRD is not required for endocytosis in any cell type, as deletion mutants lacking this motif are endocytosed efficiently to the lysosomal compartment. Endogenous FasL cannot internalise extracellular antibody, demonstrating that FasL does not transit the plasma membrane en route to the secretory lysosomes. We propose that an interaction of the PRD of FasL with an SH3-domain-containing protein, enables direct sorting of FasL from the Golgi to secretory lysosomes.
Potential inhibitors of collagen biosynthesis. 5,5-Difluoro-DL-lysine and 5,5-dimethyl-DL-lysine and their activation by lysyl-tRNA ligase (1977)

The synthesis of lysine analogues wherein blocking groups are substituted at position 5, the site of hydroxylation by peptidyl lysine hydroxylase, is described. Thus, 5,5-difluorolysine (1) and 5,5-dimethylysine (2) were synthesized via a four- and six-step sequence, respectively, starting from ketone precursors. The propensity for these lysine analogues to be incorporated into procollagen protein in vivo was assessed by their ability to stimulate the lysine-dependent ATP-PPi exchange reaction in the presence of lysyl-tRNA ligase in vitro. The difluoro analogue 1 stimulated exchange, but at a Km (1.3 X 10(-3) M) 1000 times greater than that for lysine itself. The dimethyl analogue 2 did not stimulate exchange, but at high concentrations was a competitive inhibitor of lysine, with an apparent Ki of 1.6 X 10(-2) M. Thus, electronegative and/or bulky substituents at the 5 position of lysine cannot be tolerated by lysyl-tRNA ligase, and this position must be kept free in lysine analogues specifically designed to block collagen biosynthesis.
Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA (2004)

Interferons (IFNs) are critical for protection from viral infection, but the pathways linking virus recognition to IFN induction remain poorly understood. Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.
Elimination of bcl-2-IgH-positive follicular lymphoma cells from blood transplants with high recovery of hematopoietic progenitors by the miltenyi CD34+ cell sorting system. (1996)

Contamination of autologous blood cell transplants with cells of follicular non-Hodgkin's lymphoma (F-NHL) may contribute to relapse of the malignancy after potentially curative high doses of chemotherapy and radiotherapy. In an attempt to circumvent this limitation, we have evaluated various techniques of selection of CD34+ cells to eliminate malignant cells from blood cell transplants of five patients with F-NHL undergoing high-dose sequential therapy. The contamination of F-NHL cells was evaluated using a nested PCR assay for the detection of bcl-2-IgH rearrangement with a sensitivity of one F-NHL cell in 10(5) normal cells. In two experiments with blood cell transplant fractions of 0.5 x 10(9) nucleated cells, negative selection of CD34+ cells by removal of B cells and other mature cells that naturally adhere to nylon wool fibers decreased the number of CD19+ B cells detectable by flow cytometry but failed to eliminate bcl-2-IgH-positive F-NHL cells detectable by PCR. In contrast, positive selection of CD34+ cells by the Miltenyi MiniMACS high gradient magnetic cell sorting system in five separate experiments resulted in: (1) the elimination of F-NHL cells in four out of five cases as detected both flow cytometry and bclk-2-IgH PCR; (2) a highly purified population of hematopoietic progenitors comprising 90.8% +/- 2.3% CD34+ cells; and (3) the recovery of 77.9% +/- 3.2% CD34+ cells. These favorable results were confirmed on a large-scale with a blood cell transplant comprising 5.8 x 10(9) nucleated cells in which positive selection of CD34+ cells by the Miltenyi SuperMACS system resulted in: (1) the elimination of F-NHL cells as detected both by flow cytometry and bcl-2-IgH PCR; (2) a highly purified population of hematopoietic progenitors comprising 94.6% CD34+ cells; and (3) the recovery of 62.7% CD34+ cells. These results, attained with the newly available Super MACS system, compare favorable with previous techniques because they show the feasibility of eliminating F-NHL cells from blood cell transplants without relevant nonspecific loss of hematopoietic progenitors.
Possible role of flanking nucleotides in recognition of the AUG initiator codon by eukaryotic ribosomes (1981)

Sequences flanking the initiator codon in eukaryotic mRNAs are not random. Out of 153 messages examined, 151 have either a purine in position -3, or a G in position +4, or both. Thus, [A/G]XXAUGG emerges as the favored sequence for eukaryotic initiation sites. Nucleotides flanking nonfunctional AUG triplets, which occur in the 5'-noncoding region of a few eukaryotic messages, are different from those found at most functional sites. Whereas most authentic initiator codons are preceded by a purine (usually A) in position -3, most nonfunctional AUGs have a pyrimidine in that position. The observed asymmetry suggests that purines in positions -3 and +4 might facilitate recognition of the AUG condon during formation of initiation complexes. To test this idea, in vitro binding studies were carried out with 32P-labeled oligonucleotides. Binding of AUG-containing oligonucleotides to wheat germ ribosomes was significantly enhanced by placing a purine in position -3 or +4. The scanning model, which postulates that 40S ribosomal subunits attach at the 5'-end of a message and migrate down to the AUG codon, is discussed in light of these new observations. A modified version of the scanning mechanism is proposed.
Involvement of Endothelial Nitric Oxide in Sphingosine-1-Phosphate–Induced Angiogenesis (2002)

Nitric oxide (NO) has been implicated as a critical signaling molecule of angiogenesis. Recently, sphingosine-1-phosphate (S1P) has emerged as a mediator of angiogenesis, and S1P-induced NO synthesis in endothelial cells (ECs) has been reported. To analyze the signaling pathways involved in S1P-induced angiogenesis and clarify the role of NO in this process, we performed in vivo and in vitro angiogenesis assays. S1P activated the phosphatidylinositol-3-kinase (PI3K)/Akt/endothelial NO synthase (eNOS) pathway in ECs, since S1P-stimulated eNOS phosphorylation and NO production were blocked by inhibition of activities of PI3K and Akt. S1P increased capillary ingrowth into subcutaneously implanted Matrigel plugs in mice, and the effect of S1P was significantly reduced in mice that received N(G)-nitro- L-arginine methyl ester (L-NAME), an inhibitor of NOS. S1P stimulated EC migration and tube formation on Matrigel, which processes were significantly decreased by inhibition of activities of PI3K, Akt, or eNOS, whereas treatment with LY294002, a PI3K inhibitor, but not L-NAME, inhibited EC viability and proliferation. Thus, our results demonstrate the crucial role of NO in S1P-induced angiogenesis in vivo and in vitro and suggest the divergent roles of NO in the S1P-induced angiogenic response.
Systematic Mutational Mapping of Sites on Human Interferon-β-1a That Are Important for Receptor Binding and Functional Activity (2000)

A systematic mutational analysis of human interferon-beta-1a (IFN-beta) was performed to identify regions on the surface of the molecule that are important for receptor binding and for functional activity. The crystal structure of IFN-beta-1a was used to design a panel of 15 mutant proteins, in each of which a contiguous group of 2-8 surface residues was mutated, in most instances to alanine. The mutants were analyzed for activity in vitro in antiviral and in antiproliferation assays, and for their ability to bind to the type I IFN (ifnar1/ifnar2) receptor on Daudi cells and to a soluble ifnar2 fusion protein (ifnar2-Fc). Abolition of binding to ifnar2-Fc for mutants A2, AB1, AB2, and E established that the ifnar2 binding site on IFN-beta comprises parts of the A helix, the AB loop, and the E helix. Mutations in these areas, which together define a contiguous patch of the IFN-beta surface, also resulted in reduced affinity for binding to the receptor on cells and in reductions in activity of 5-50-fold in functional assays. A second receptor interaction site, concluded to be the ifnar1 binding site, was identified on the opposite face of the molecule. Mutations in this region, which encompasses parts of the B, C, and D helices and the DE loop, resulted in disparate effects on receptor binding and on functional activity. Analysis of antiproliferation activity as a function of the level of receptor occupancy allowed mutational effects on receptor activation to be distinguished from effects on receptor binding. The results suggest that the binding energy from interaction of IFN-beta with ifnar2 serves mainly to stabilize the bound IFN/receptor complex, whereas the binding energy generated by interaction of certain regions of IFN-beta with ifnar1 is not fully expressed in the observed affinity of binding but instead serves to selectively stabilize activated states of the receptor.
Smoking is associated with chronic sympathetic activation in hypertension (2010)

In patients with essential hypertension, smoking is independently associated with chronic increase in MSNA. These findings may have implications for our understanding of the mechanisms linking smoking to cardiovascular events.
Use of Recombinant Cellulose-Binding Domains of Trichoderma reesei Cellulase as a Selective Immunocytochemical Marker for Cellulose in Protozoa (2002)

Some unicellular organisms are able to encyst as a protective response to a harmful environment. The cyst wall usually contains chitin as its main structural constituent, but in some cases, as in Acanthamoeba, it consists of cellulose instead. Specific cytochemical differentiation between cellulose and chitin by microscopy has not been possible, due to the similarity of their constituent beta-1,4-linked hexose backbones. Thus, various fluorescent brightening agents and lectins bind to both cellulose and chitin. We have used a recombinant cellulose-binding protein consisting of two cellulose-binding domains (CBDs) from Trichoderma reesei cellulases linked together in combination with monoclonal anticellulase antibodies and anti-mouse immunoglobulin fluorescein conjugate to specifically stain cellulose in the cysts of Acanthamoeba strains for fluorescence microscopy imaging. Staining was observed in ruptured cysts and frozen sections of cysts but not in intact mature cysts. No staining reaction was observed with the chitin-containing cyst walls of Giardia intestinalis, Entamoeba dispar, or Pneumocystis carinii. Thus, the recombinant CBD can be used as a marker to distinguish between cellulose and chitin. Thirteen of 25 environmental or clinical isolates of amoebae reacted in the CBD binding assay. All 13 isolates were identified as Acanthamoeba spp. Five isolates of Hartmannella and seven isolates of Naegleria tested negative in the CBD binding assay. Whether cyst wall cellulose really is a unique property of Acanthamoeba spp. among free-living amoebae, as suggested by our findings, remains to be shown in more extensive studies.