Academic literature on the topic 'Test dgmp'

Purine nucleoside phosphorylase (PNP; EC 2.4.2.1) deficiency is thought to cause T-lymphocyte depletion by accumulation of dG and dGTP, resulting in feedback inhibition of ribonucleotide reductase (RR; EC 1.17.4.1) and hence DNA synthesis. To test for additional toxic mechanisms of dG, we selected a double mutant of the mouse T-lymphoma S-49 cell line, dGuo-L, which is deficient in PNP and partially resistant to dGTP feedback inhibition of RR. The effects of dG on dGuo-L cells (concn. causing 50% inhibition, IC50 = 150 microM) were compared with those on the wild-type cells (IC50 = 30 microM) and the NSU-1 mutant with PNP deficiency only (IC50 = 15 microM). Fluorescence flow cytometry showed that equitoxic dG concentrations arrested wild-type and NSU-1 cells at the G1-S interface while allowing continued DNA synthesis in the S-phase, whereas the double mutant dGuo-L cells progressed through the cell cycle normally. dGuo-L cells accumulated high levels of dGTP in G1-phase, but not in S-phase cells, because of the utilization of dGTP for DNA synthesis and limited capacity to synthesize dGTP from dG. These results support the hypothesis that dG/dGTP toxicity occurs in the G1-phase or at the G1-S interface. Failure of dG to arrest the double mutant dGuo-L cells at the G1-S interface allows these cells to escape into S-phase, with an accompanying drop in dGTP levels. Thus the partial resistance of dGuo-L cells to dG toxicity may result from their shorter residence time in G1, allowing them to sustain higher dGTP levels. Hence RR inhibition by dGuo may not be the primary toxic mechanism in S-49 cells; rather, it may serve as an accessory event in dG toxicity by keeping the cells in the sensitive phase of the cell cycle. Among the possible targets of dG toxicity is RNA synthesis, which was inhibited at an early stage in dGuo-L cells.

The performance of Global Navigation Satellite System (GNSS) and Micro-Electro-Mechanical System (MEMS)-based Inertial Navigation System (INS) integrated navigation is reduced during GNSS outages. To bridge the period during GNSS outages, a novel hybrid intelligent algorithm incorporating a Discrete Grey Predictor (DGP) and a Multilayer Perceptron (MLP) neural network (DGP-MLP) is proposed. The DGP-MLP is used to provide a pseudo-GNSS position to correct the INS errors during GNSS outages; the DGP uses the GNSS position information of the latest few moments to predict the position of future moments; in the process of DGP-MLP, the MLP is used to modify the prediction errors of DGP, and the MLP is improved by adding momentum terms and adaptively adjusting the learning rate and momentum factor. To evaluate the effectiveness of the proposed methodology, four GNSS outages in different cases over a real field test data were employed. The experimental results demonstrate that the proposed methodology can significantly improve positioning accuracy during GNSS outages.

Abstract Background Statins inhibit HMG-CoA reductase, leading to decreased production of cholesterol and isoprenoid metabolites. There is growing evidence that statins have protective effects on arterial thrombosis through pleiotropic mechanisms that may be independent of their cholesterol lowering effects. The antithrombotic effects of statins have been proposed to be related in part to diminished synthesis of geranylgeranyl pyrophosphate (GGPP). To test this hypothesis, we determined the hemostatic and thrombotic effects of atorvastatin and digeranyl bisphosphonate (DGBP), a specific inhibitor of GGPP synthase, in apolipoprotein E-deficient (ApoE-/-) mice. Methods ApoE-/- mice were treated with either vehicle, atorvastatin (50 mg/kg/d), or DGBP (0.4 mg/kg/d) subcutaneously for 7 days. Tissue levels of GGPP and its precursor farnesyl pyrophosphate (FPP) were measured by HPLC. Plasma total cholesterol was measured enzymatically. Susceptibility to thrombotic occlusion of the carotid artery was measured in response to injury with FeCl3. Platelet count, early platelet activation responses (surface expression of P-selectin and activation of integrin αIIbβ3), platelet clot retraction, and tail-transection bleeding times were also assessed. Results Compared with vehicle or atorvastatin-treated mice, DGBP- treated mice had elevated levels of FPP in heart (P<0.001) and lung (P<0.001) and decreased levels of GGPP in heart (P<0.01) and liver (P<0.01). Plasma total cholesterol was decreased in atorvastatin-treated mice (199±14 mg/dL) compared with vehicle- (284±32 mg/dL) or DGBP- treated (321±21 mg/dL) mice (P<0.05). The platelet count was decreased in DGBP-treated mice (638,000±90,000/mL) compared with vehicle-treated mice (1,208,000±72,000/mL; P<0.01). The time to stable occlusion of the carotid artery was prolonged in atorvastatin-treated mice compared with vehicle-treated mice (8.6±2.4 vs. 5.3± 0.3 minutes; P<0.05). In contrast, DGBP-treated mice were not protected from carotid artery thrombosis (6.8±0.9 minutes). Bleeding times were markedly prolonged in DGBP-treated mice (502±68 seconds) compared with atorvastatin-treated (152±66 seconds) or vehicle-treated (132±72 seconds) mice (P<0.05). Early platelet activation responses (αIIbβ3 activation and surface P-selectin expression) after stimulation with thrombin (0.01, 0.05 and 0.1 units/mL) did not differ between vehicle-, atorvastatin- and DGBP-treated mice, but platelet clot retraction was significantly delayed in DGBP-treated mice compared with atorvastatin- or vehicle-treated mice (P<0.05). Conclusions The observed changes in isoprenoid metabolites were consistent with the known inhibitory effects of atorvastatin on the isoprenoid pathway upstream of cholesterol synthesis, and of DGBP downstream of FPP synthesis. In contrast to our hypothesis, inhibition of GGPP production with DGBP did not prevent arterial thrombosis despite causing modest thrombocytopenia, decreased platelet clot retraction, and impairment of primary hemostasis in hypercholesterolemic mice. The differential effects of DGBP and atorvastatin suggest that the antithrombotic effects of statins are largely independent of geranylgeranyl-mediated processes. Disclosures: Hohl: Terpenoid Therapeutics: Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties. Lentz:Novo Nordisk: Consultancy, Research Funding.

Abstract BACKGROUND Limited progress has been made in improving therapeutic outcomes for glioblastoma (GBM) patients. Enzastaurin (enza) is an oral PKC-β inhibitor that suppresses signaling through the PKC and PI3K/AKT pathways. Although enza did not significantly improve survival in a prior Phase 1/2 study, we have identified a novel genomic biomarker, DGM1, that may predict a response to enza in GBM. PRIMARY OBJECTIVE To assess whether enza added to temozolomide and radiation therapy (RT) improves overall survival (OS) in newly diagnosed GBM patients who possess the DGM1 biomarker. POPULATION Adults with newly diagnosed GBM regardless of DGM1 status who have undergone surgical resection and are candidates for chemoradiation. Approximately 318 patients will be enrolled. DGM1 status will be determined prior to analysis. DESIGN This is a randomized, double-blinded, placebo-controlled study. Patients will be stratified by MGMT and IDH1 status and by geographic region. Treatment will be divided into 3 phases. In the Concurrent Phase (6 weeks), patients will receive RT plus temozolomide and either enzastaurin or placebo. Patients will then enter the Single-Agent Phase and receive either enza or placebo (21-35 days). Then, patients will enter the Adjuvant Phase and receive temozolomide with either enza or placebo (6-12 cycles) followed by enza or placebo alone (to 24 cycles total). ANALYSIS The primary efficacy endpoint of OS will be analyzed using stratified log-rank test for all DGM1-positive randomized patients. The study has approximately 90% power to detect a HR of 0.63 assuming 196 OS events based on a 2.5% one-sided false positive error rate. Statistical significance would be achieved with an estimated observed HR &lt; 0.76. Safety evaluation will include all patients receiving at least one dose of enza or placebo. If OS in DGM1-positive patients is statistically significant, OS in the overall population will be assessed.

Abstract Background: Some patients with celiac disease (CD) may be seronegative with the commonly used test for IgA anti–tissue transglutaminase (anti-tTG) antibodies. Our aim was to explore whether newer assays incorporating synthetic deamidated gliadin-related peptides (DGPs) or other TG isoenzymes as antigen are useful for detecting gluten sensitivity in IgA anti-tTG–seronegative patients. Methods: We assayed serum samples obtained at diagnosis from (a) anti-tTG–seronegative patients with a CD-like enteropathy (n = 12), (b) skin biopsy–proven dermatitis herpetiformis (DH) patients (n = 26), and (c) IgA anti-tTG–positive CD patients (n = 26). All patients had typical total IgA concentrations. All patients underwent intestinal biopsy and serum testing for (a) detection of IgA and IgG isotypes of both anti-DGP and anti-tTG in a single assay (tTG/DGP Screen; INOVA Diagnostics), (b) simultaneous detection of both IgA and IgG anti-DGP antibody isotypes (DGP Dual; INOVA Diagnostics), and (c) detection of antibodies to transglutaminase 3 (TG3) or transglutaminase 6 (TG6). Results: All anti-tTG–seropositive patients also tested positive in anti-DGP assays. Overall, tTG/DGP Screen detected 6 (31.6%) of the 19 anti-tTG seronegatives, and anti-DGP Dual produced positive results in 5 (26.3%) of these cases. Whereas both assays detected 2 anti-tTG–negative DH patients with partial villous atrophy, they were positive in only 2 of the 5 cases with no histologically discernible mucosal damage. Testing for antibodies to TG3 and TG6 identified 7 (36.8%) of the 19 anti-tTG–negative patients, 5 of which were also positive for anti-DGP. Conclusions: Detection of anti-DGP with tTG/DGP Screen or anti-DGP Dual, or detection of antibodies to other TG isoenzymes, enhances the sensitivity for detecting gluten sensitivity among non–IgA- deficient, anti-tTG–seronegative patients with CD-like enteropathy.

AbstractThis paper proposes a monitoring cumulative sum of squares (CUSQ)-type test for structural breaks in real time via an autoregressive (AR) approximation framework where data generating process (DGP) is a long memory process. The limiting distribution of the monitoring test follows a Brownian bridge and is free of long memory parameters under the null hypothesis of no break. The test is easy to implement and avoids the issue of spurious breaks found for some retrospective tests for long memory process. Neither does it need to use the bootstrap procedure to find the critical values. Monte Carlo simulations appear to confirm that there exists negligible size distortion and satisfactory power performances in finite samples. The procedure is then applied to monitor the real-time pattern of realized volatilities of dollar–Deutschmark and dollar–Japanese Yen.

In this paper, we will present a Dvali-Gabadadze-Porrati stable model in order to perform an observational test using $H(z)$ data and radial BAO scale in the galaxy distribution. In this vein, we study the tension between constraints on the cosmological constant $\Lambda$ and the crossover scale $r_c$, which is associated with the DGP model. Our results show that observations do not favor the DGP stable model as a possible candidate to fit to the observations of the late cosmic acceleration.

Abstract Recent data show that dried larvae of darkling beetles (Zophobas morio L., DZML) and dried larvae of wax moths (Galleria mellonella L., DGML) contains a significant amount of protein, fat, chitin, melanin, antimicrobial peptides, trace elements etc. Larva’s fat is rich in lauric and other medium-chain fatty acids. The aim of our research was to study the influence of dietary replacement of fishmeal (FM) by insect meal on growth performance and nonspecific immunity of growing pigs. Experiments were performed using crossbred [(BWxL)xD] pigs (BW1=14.39±0.19 kg, N=27, n = 9) during the growing period. Animals were allocated to 3 groups: 1 – control (standard feed (SF), including FM), 2 – experimental (SF+2.5%DZML), 3 – experimental (SF+3.0%DGML). The materials obtained in the experiment was biometrically processed using the ANOVA method (at P &gt;0.05 or P &lt; 0.05). The use of DZML&DGML in feed didn’t reduce ADG of experimental animals during the growing period (413.23&413.76 vs. 413.76 g) compared to the control group. Dried larvae supplementation didn’t reduce feed intake and nutrient digestibility. The fat digestibility increased in the 2&3-experimental group (45.0&44.36 vs 29.75%, P &lt; 0.05), due to the high level of lipids and the profile of fatty acids in the larvae. Biochemical blood test showed a higher ALB/GLB ratio (0.85&1.43 vs 0.59, P = 0.05), higher number of WBC (12.36&12.89 vs. 10.44, P = 0.19) in the blood of the experimental animals compared to the control group. Growing pigs of the experimental groups had a higher level of nonspecific immunity, which is expressed in an increase in bactericidal, lysozyme activity of blood serum and phagocytic activity of neutrophils. Consequently, it is possible to consider the prospects of using DGML&DGML as dietary supplements to diets of growing pigs. The work was supported by the GZ АААА-А18-118021590136-7 of the Ministry of Science and Higher Education of the Russian Federation.

A discontinuous Galerkin formulation of the Contrast Source Inversion algorithm (DGM-CSI) for microwave breast imaging employing a frequency-cycling reconstruction technique has been modified here to include a set of automated stopping criteria that determine a suitable time to shift imaging frequencies and to globally terminate the reconstruction. Recent studies have explored the use of tissue-dependent geometrical mapping of the well-reconstructed real part to its imaginary part as initial guesses during consecutive frequency hops. This practice was shown to improve resulting 2D images of the dielectric properties of synthetic breast models, but a fixed number of iterations was used to halt DGM-CSI inversions arbitrarily. Herein, a new set of stopping conditions is introduced based on an intelligent statistical analysis of a window of past iterations of data error using the two-sample Kolmogorov-Smirnov (K-S) test. This non-parametric goodness-of-fit test establishes a pattern in the data error distribution, indicating an appropriate time to shift frequencies, or terminate the algorithm. The proposed stopping criteria are shown to improve the efficiency of DGM-CSI while yielding images of equivalent quality to assigning an often liberally overestimated number of iterations per reconstruction.

A modified predictor-corrector scheme combining with the depth gradient method (DGM) and the weighted average flux (WAF) method has been presented to solve the one-dimensional shallow water equations with source terms. Approximate solutions in the predictor step are obtained by the DGM with piecewise-linear reconstructions in each cell volume. The source terms can then be calculated directly by these predicted values at the corresponding half-time step. In the corrector step, the TVD version of the WAF method is applied to calculate the numerical fluxes at the same half-time step for each cell face. The accuracy of numerical solutions is shown by applying the method to solve various test cases in both steady and unsteady problems with and without source terms. It shows that the numerical results are in good agreement with the existing analytical solutions as well as experimental data in some test cases.

L'obiettivo di questa tesi è stato effettuare una valutazione preliminare sull'utilizzabilità dei sensori inerziali per la valutazione del movimento fine durante attività di coordinazione manuale. Lo scopo finale è valutare la possibilità di utilizzare parametri quantitativi utilizzati in analisi del movimento per la caratterizzazione della performance dell’arto superiore durante compiti che richiedono abilità grafo-motorie. A questo scopo sono stati selezionati alcuni test che potessero fornire un quadro completo delle funzioni grafo-motorie tra quelli maggiormente utilizzati nella pratica clinica: il test DGMP (per la valutazione del livello di automatizzazione di qualità e di apprendimento della scrittura in corsivo) e i test Cycle Trail e Flower Trail, scelti fra la batteria di Test Movement ABC-2 (per la valutazione di destrezza manuale). Hanno preso parte allo studio undici soggetti adulti giovani sani e quattro bambini con sviluppo tipico. Dopo aver posizionato i sensori inerziali sui polsi è stato richiesto ai soggetti di svolgere i test sopraelencati in diverse condizioni: "migliore" e "veloce", "lenta" e "veloce", mano destra e mano sinistra. Sono stati applicati gli indici (RMS accelerazione, RMS Jerk, MIJerk, IJerk, MSE) al segnale di accelerazione dell’arto che eseguiva l’esercizio ed è stato valutato se gli indici analizzati fossero in grado di distinguere diverse condizioni di esecuzione. Da questo studio preliminare, i parametri utilizzati (RMS accelerazione, RMS Jerk, MIJerk, IJerk, MSE) hanno mostrato una specificità sufficiente nel distinguere le diverse condizione analizzate, supportando quindi sviluppi futuri per l’applicazione dei sensori inerziali per la valutazione oggettiva della coordinazione fine durante attività grafo-motorie.

L'objectif de ce travail est de construire une machine d'essai pour la prothèse. La machine doit être capable de reproduire les mêmes conditions dynamiques et cinématiques appliquées sur la prothèse pendant l'utilisation normale.Le nombre d'amputation et les causes d'amputation ont été recueillis. Différents types de prothèses ont été classés selon la prothèse de jambe par hauteur d'amputation, prothèse passive et active, différenciées par la nature de leur actionneur. La plupart des machines d'essai pour la prothèse ont été étudiées à partir de la prospective technologique et capacitaire. Déterminer toutes les limitations de la plupart des machines d'essai existantes, et les besoins de développer une nouvelle machine pour remplir complètement ces besoins ont été développés.Ensuite, nous avons étudié et analysé la dynamique de la marche et de la course humaines. Les équations du mouvement en prenant en considération les masses et les moments d'inertie des segments squelettiques. La plupart des paramètres de la démarche ont été extraits. En conclusion, nous avons les exigences cinématiques du centre de gravité humain pour générer 6 DOF que la machine d'essai devrait effectuer pour imiter la démarche humaine normale et courir.Trois conceptions ont été proposées pour implanter la machine d'essai; Bras de robot articulé, manipulateur cartésien et Stewart Platform (SP). Après la mise en œuvre des trois solutions, nous avons trouvé la solution la plus appropriée est le SP attaché avec une hanche active artificielle. Nous avons choisi la puissance hydraulique car c'est la technique d'actionnement la plus appropriée pour notre solution, connaissant les forces d'actionnement requises.Pour aider à contrôler le mouvement de SP, une nouvelle solution de modèle géométrique direct pour la planeuse et la plate-forme Stewart 6-6 a été développée en utilisant les capteurs rotatifs au lieu de capteurs de revêtement comme voulu pour les actionneurs hydrauliques. L'analyse de sensibilité a été étudiée pour cette solution, et un calcul analytique pour le calcul de l'espace de travail a également été développé.La conclusion de cette machine d'essai est que nous pouvons créer toute la dynamique du corps humain, c'est-à-dire marcher ou courir ou monter et descendre des escaliers. La solution développée peut porter des procédures d'essai pour la prothèse passive ou active
The objective of this work is to build a testing machine for prosthesis. The machine should be able to reproduce the same dynamic and kinematics conditions applied on the prosthesis during the normal use.Numbers of amputation, and causes of amputation were collected. Different types of prosthesis were classified according to the leg prosthesis per amputation height, passive and active prosthesis, differentiated by the nature of their actuator. Most of the testing machine for the prosthesis were studied form the technological and capability prospective. Determining all the limitations of most of existing testing machines, and the needs to develop a new machine to full fill these needs were developed.Then we studied and analyzed the dynamics of the human gait and run. The equations of motion by taking into consideration the masses and moments of inertia of skeletal segments. Most of the parameters of gait were extracted. In conclusion, we have the kinematic requirements of the human center of gravity to generate 6 DOF that the testing machine should carry out to emulate the normal human gait and run.Three designs were proposed to implement the testing machine; Articulated robot arm, Cartesian manipulator, and Stewart Platform (SP). After implementing the three solutions we found the most suitable solution is the SP attached with it an artificial active hip. We have chosen the hydraulic power as it is the most suitable actuation technique for our solution knowing the required actuation forces.To help in controlling the SP motion, a novel Closed-form solution of direct Geometric model for planer and 6-6 Stewart Platform using the rotary sensors instead of liner sensors as wanted to the hydraulic actuators was developed. Sensitivity analysis was studied for that solution, and analytical calculation for computing the workspace was also developed.The conclusion from this testing machine is that we can create all the dynamics of the human body, i.e. walking or running or going up and down stairs. The developed solution can carry testing procedures for either passive or active prothesis

Seafloor compliance is a non-intrusive geophysical method sensitive to the shear modulus of the sediments below the seafloor. A compliance analysis requires the computation of the frequency dependent transfer function between the vertical stress, produced at the seafloor by the ultra low frequency passive source-infra-gravity waves, and the resulting displacement, related to velocity through the frequency. The displacement of the ocean floor is dependent on the elastic structure of the sediments and the compliance function is tuned to different depths, i.e., a change in the elastic parameters at a given depth is sensed by the compliance function at a particular frequency. In a gas hydrate system, the magnitude of the stiffness is a measure of the quantity of gas hydrates present. Gas hydrates contain immense stores of greenhouse gases making them relevant to climate change science, and represent an important potential alternative source of energy. Bullseye Vent is a gas hydrate system located in an area that has been intensively studied for over 2 decades and research results suggest that this system is evolving over time. A partnership with NEPTUNE Canada allowed for the investigation of this possible evolution. This thesis describes a compliance experiment configured for NEPTUNE Canada’s seafloor observatory and its failure. It also describes the use of 203 days of simultaneously logged pressure and velocity time-series data, measured by a Scripps differential pressure gauge, and a Güralp CMG-1T broadband seismometer on NEPTUNE Canada’s seismic station, respectively, to evaluate variations in sediment stiffness near Bullseye. The evaluation resulted in a (- 4.49 x10-3± 3.52 x 10-3) % change of the transfer function of 3rd October, 2010 and represents a 2.88% decrease in the stiffness of the sediments over the period. This thesis also outlines a new algorithm for calculating the static compliance of isotropic layered sediments.

Hard rock drilling is facing increasing importance by using geothermal energy as a new energy source. Percussive drilling methods are generally well suited for drilling hard rocks. However, until now there is no drilling tool available on the market that uses percussive drilling methods and can be applied in deep boreholes in combination with common drilling muds. The aim of the DGMK project 733 is to develop a hammer drill which generates the impact energy downhole and works with conventional drilling mud. Seven different drive concepts were developed during the feasibility study. Demonstrators were manufactured for four of the seven drive concepts. The evaluation of the drive concepts showed that two of them have a high potential for the implementation in the field. These two concepts will be developed further to laboratory prototypes and were investigated at a test facility.