MP-Pic simulation of CFB riser with EMMS-based drag model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, F.; Song, F.; Benyahia, S.

2012-01-01

MP-PIC (multi-phase particle in cell) method combined with the EMMS (energy minimization multi- scale) drag force model was implemented with the open source program MFIX to simulate the gas–solid flows in CFB (circulatingfluidizedbed) risers. Calculated solid flux by the EMMS drag agrees well with the experimental value; while the traditional homogeneous drag over-predicts this value. EMMS drag force model can also predict the macro-and meso-scale structures. Quantitative comparison of the results by the EMMS drag force model and the experimental measurements show high accuracy of the model. The effects of the number of particles per parcel and wall conditions onmore » the simulation results have also been investigated in the paper. This work proved that MP-PIC combined with the EMMS drag model can successfully simulate the fluidized flows in CFB risers and it serves as a candidate to realize real-time simulation of industrial processes in the future.« less

Use of a novel radiometric method to assess the inhibitory effect of donepezil on acetylcholinesterase activity in minimally diluted tissue samples

PubMed Central

Kikuchi, Tatsuya; Okamura, Toshimitsu; Arai, Takuya; Obata, Takayuki; Fukushi, Kiyoshi; Irie, Toshiaki; Shiraishi, Tetsuya

2010-01-01

Background and purpose: Cholinesterase inhibitors have been widely used for the treatment of patients with dementia. Monitoring of the cholinesterase activity in the blood is used as an indicator of the effect of the cholinesterase inhibitors in the brain. The selective measurement of cholinesterase with low tissue dilution is preferred for accurate monitoring; however, the methods have not been established. Here, we investigated the effect of tissue dilution on the action of cholinesterase inhibitors using a novel radiometric method with selective substrates, N-[14C]methylpiperidin-4-yl acetate ([14C]MP4A) and (R)-N-[14C]methylpiperidin-3-yl butyrate ([14C]MP3B_R), for AChE and butyrylcholinesterase (BChE) respectively. Experimental approach: We investigated the kinetics of hydrolysis of [14C]-MP4A and [14C]-MP3B_R by cholinesterases, and evaluated the selectivity of [14C]MP4A and [14C]MP3B_R for human AChE and BChE, respectively, compared with traditional substrates. Then, IC50 values of cholinesterase inhibitors in minimally diluted and highly diluted tissues were measured with [14C]MP4A and [14C]MP3B_R. Key results: AChE and BChE activities were selectively measured as the first-order hydrolysis rates of [14C]-MP4A and [14C]MP3B_R respectively. The AChE selectivity of [14C]MP4A was an order of magnitude higher than traditional substrates used for the AChE assay. The IC50 values of specific AChE and BChE inhibitors, donepezil and ethopropazine, in 1.2-fold diluted human whole blood were much higher than those in 120-fold diluted blood. In addition, the IC50 values of donepezil in monkey brain were dramatically decreased as the tissue was diluted. Conclusions and implications: This method would effectively monitor the activity of cholinesterase inhibitors used for therapeutics, pesticides and chemical warfare agents. PMID:20401964

Uncertainty in solid precipitation and snow depth prediction for Siberia using the Noah and Noah-MP land surface models

NASA Astrophysics Data System (ADS)

Suzuki, Kazuyoshi; Zupanski, Milija

2018-01-01

In this study, we investigate the uncertainties associated with land surface processes in an ensemble predication context. Specifically, we compare the uncertainties produced by a coupled atmosphere-land modeling system with two different land surface models, the Noah- MP land surface model (LSM) and the Noah LSM, by using the Maximum Likelihood Ensemble Filter (MLEF) data assimilation system as a platform for ensemble prediction. We carried out 24-hour prediction simulations in Siberia with 32 ensemble members beginning at 00:00 UTC on 5 March 2013. We then compared the model prediction uncertainty of snow depth and solid precipitation with observation-based research products and evaluated the standard deviation of the ensemble spread. The prediction skill and ensemble spread exhibited high positive correlation for both LSMs, indicating a realistic uncertainty estimation. The inclusion of a multiple snowlayer model in the Noah-MP LSM was beneficial for reducing the uncertainties of snow depth and snow depth change compared to the Noah LSM, but the uncertainty in daily solid precipitation showed minimal difference between the two LSMs. The impact of LSM choice in reducing temperature uncertainty was limited to surface layers of the atmosphere. In summary, we found that the more sophisticated Noah-MP LSM reduces uncertainties associated with land surface processes compared to the Noah LSM. Thus, using prediction models with improved skill implies improved predictability and greater certainty of prediction.

Running ATLAS workloads within massively parallel distributed applications using Athena Multi-Process framework (AthenaMP)

NASA Astrophysics Data System (ADS)

Calafiura, Paolo; Leggett, Charles; Seuster, Rolf; Tsulaia, Vakhtang; Van Gemmeren, Peter

2015-12-01

AthenaMP is a multi-process version of the ATLAS reconstruction, simulation and data analysis framework Athena. By leveraging Linux fork and copy-on-write mechanisms, it allows for sharing of memory pages between event processors running on the same compute node with little to no change in the application code. Originally targeted to optimize the memory footprint of reconstruction jobs, AthenaMP has demonstrated that it can reduce the memory usage of certain configurations of ATLAS production jobs by a factor of 2. AthenaMP has also evolved to become the parallel event-processing core of the recently developed ATLAS infrastructure for fine-grained event processing (Event Service) which allows the running of AthenaMP inside massively parallel distributed applications on hundreds of compute nodes simultaneously. We present the architecture of AthenaMP, various strategies implemented by AthenaMP for scheduling workload to worker processes (for example: Shared Event Queue and Shared Distributor of Event Tokens) and the usage of AthenaMP in the diversity of ATLAS event processing workloads on various computing resources: Grid, opportunistic resources and HPC.

Mechanism of action of a novel recombinant peptide, MP1102, against Clostridium perfringens type C.

PubMed

Zong, Lifen; Teng, Da; Wang, Xiumin; Mao, Ruoyu; Yang, Na; Hao, Ya; Wang, Jianhua

2016-06-01

This work is the first to report the antibacterial characteristics and antibacterial mechanisms of MP1102, which is a variant of NZ2114, against pathogenic Clostridium perfringens. MP1102 exhibited strong antimicrobial activity against C. perfringens strains CVCC 61, CVCC 1163, and CVCC 2032 at a low minimal inhibitory concentration (MIC) of 0.91 μM. MP1102 showed anti-C. perfringens activity over a wide pH range of 2.0 and 10.0, high thermal stability from 20 to 80 °C, and remarkable resistance to pepsin. The fractional inhibitory concentration index (FICI) indicated an additive or synergic effect between MP1102 and bacitracin zinc, nisin, vancomycin, virginiamycin, aureomycin, and ampicillin against C. perfringens (FICI = 0.3125-1.0). To further elucidate the antibacterial mechanism of MP1102, its effect on the C. perfringens CVCC 61 cell membrane and intracellular DNA was studied. Flow cytometry and scanning electron microscopy (SEM) indicated that MP1102 treatment resulted in the release of cellular contents by damaging the membrane. A DNA gel retardation and circular dichroism analysis demonstrated that MP1102 interacted with DNA and intercalated into the DNA base pairs. A cell cycle assay demonstrated that MP1102 affected cellular functions, such as DNA synthesis. These results suggested that MP1102 exhibited potential as a new antimicrobial agent against C. perfringens infections.

Discrete sensitivity derivatives of the Navier-Stokes equations with a parallel Krylov solver

NASA Technical Reports Server (NTRS)

Ajmani, Kumud; Taylor, Arthur C., III

1994-01-01

This paper solves an 'incremental' form of the sensitivity equations derived by differentiating the discretized thin-layer Navier Stokes equations with respect to certain design variables of interest. The equations are solved with a parallel, preconditioned Generalized Minimal RESidual (GMRES) solver on a distributed-memory architecture. The 'serial' sensitivity analysis code is parallelized by using the Single Program Multiple Data (SPMD) programming model, domain decomposition techniques, and message-passing tools. Sensitivity derivatives are computed for low and high Reynolds number flows over a NACA 1406 airfoil on a 32-processor Intel Hypercube, and found to be identical to those computed on a single-processor Cray Y-MP. It is estimated that the parallel sensitivity analysis code has to be run on 40-50 processors of the Intel Hypercube in order to match the single-processor processing time of a Cray Y-MP.

Antagonistic effect of Pseudomonas graminis CPA-7 against foodborne pathogens in fresh-cut apples under simulated commercial conditions.

PubMed

Alegre, Isabel; Viñas, Inmaculada; Usall, Josep; Anguera, Marina; Altisent, Rosa; Abadias, Maribel

2013-04-01

Recently, we reported that the application of the strain CPA-7 of Pseudomonas graminis, previously isolated from apple, could reduce the population of foodborne pathogens on minimally processed (MP) apples and peaches under laboratory conditions. Therefore, the objective of the present work was to find an antioxidant treatment and a packaging atmosphere condition to improve CPA-7 efficacy in reducing a cocktail of four Salmonella and five Listeria monocytogenes strains on MP apples under simulated commercial processing. The effect of CPA-7 application on apple quality and its survival to simulated gastric stress were also evaluated. Ascorbic acid (2%, w/v) and N-acetyl-l-cysteine (1%, w/v) as antioxidant treatments reduced Salmonella, L. monocytogenes and CPA-7 recovery, meanwhile no reduction was observed with NatureSeal(®) AS1 (NS, 6%, w/v). The antagonistic strain was effective on NS-treated apple wedges stored at 10 °C with or without modified atmosphere packaging (MAP). Then, in a semi-commercial assay, efficacy of CPA-7 inoculated at 10(5) and 10(7) cfu mL(-1) against Salmonella and L. monocytogenes strains on MP apples with NS and MAP and stored at 5 and 10 °C was evaluated. Although high CPA-7 concentrations/populations avoided Salmonella growth at 10 °C and lowered L. monocytogenes population increases were observed at both temperatures, the effect was not instantaneous. No effect on apple quality was detected and CPA-7 did not survived to simulated gastric stress throughout storage. Therefore, CPA-7 could avoid pathogens growth on MP apples during storage when use as part of a hurdle technology in combination with disinfection techniques, low storage temperature and MAP. Copyright © 2012 Elsevier Ltd. All rights reserved.

Shelf-life extension of minimally processed carrots by gaseous chlorine dioxide.

PubMed

Gómez-López, V M; Devlieghere, F; Ragaert, P; Debevere, J

2007-05-10

Chlorine dioxide (ClO(2)) gas is a strong oxidizing and sanitizing agent that has a broad and high biocidal effectiveness and big penetration ability; its efficacy to prolong the shelf-life of a minimally processed (MP) vegetable, grated carrots (Daucus carota L.), was tested in this study. Carrots were sorted, their ends removed, hand peeled, cut, washed, spin dried and separated in 2 portions, one to be treated with ClO(2) gas and the other to remain untreated for comparisons. MP carrots were decontaminated in a cabinet at 91% relative humidity and 28 degrees C for up to 6 min, including 30 s of ClO(2) injection to the cabinet, then stored under equilibrium modified atmosphere (4.5% O(2), 8.9% CO(2), 86.6% N(2)) at 7 degrees C for shelf-life studies. ClO(2) concentration in the cabinet rose to 1.33 mg/l after 30 s of treatment, and then fell to nil before 6 min. The shelf-life study included: O(2) and CO(2) headspace concentrations, microbiological quality (mesophilic aerobic bacteria, psychrotrophs, lactic acid bacteria, and yeasts), sensory quality (odour, flavour, texture, overall visual quality, and white blushing), and pH. ClO(2) did not affect respiration rate of MP carrots significantly (alpha< or =0.05), and lowered the pH significantly (alpha< or =0.05). The applied packaging configuration kept O(2) headspace concentrations in treated samples in equilibrium and prevented CO(2) accumulation. After ClO(2) treatment, the decontamination levels (log CFU/g) achieved were 1.88, 1.71, 2.60, and 0.66 for mesophilic aerobic bacteria, psychrotrophs, and yeasts respectively. The initial sensory quality of MP carrots was not impaired significantly (alpha< or =0.05). A lag phase of at least 2 days was observed for mesophilic aerobic bacteria, psychrotrophs, and lactic acid bacteria in treated samples, while mesophilic aerobic bacteria and psychrotrophs increased parallelly. Odour was the only important attribute in sensory deterioration, but it reached an unacceptable score when samples were already rejected from the microbiological point of view. The shelf-life extension was limited to one day due to the restricted effect of the ClO(2) treatment on yeast counts. Nevertheless, ClO(2) seems to be a promising alternative to prolong the shelf-life of grated carrots.

Analytical gradients for tensor hyper-contracted MP2 and SOS-MP2 on graphical processing units

DOE PAGES

Song, Chenchen; Martinez, Todd J.

2017-08-29

Analytic energy gradients for tensor hyper-contraction (THC) are derived and implemented for second-order Møller-Plesset perturbation theory (MP2), with and without the scaled-opposite-spin (SOS)-MP2 approximation. By exploiting the THC factorization, the formal scaling of MP2 and SOS-MP2 gradient calculations with respect to system size is reduced to quartic and cubic, respectively. An efficient implementation has been developed that utilizes both graphics processing units and sparse tensor techniques exploiting spatial sparsity of the atomic orbitals. THC-MP2 has been applied to both geometry optimization and ab initio molecular dynamics (AIMD) simulations. Furthermore, the resulting energy conservation in micro-canonical AIMD demonstrates that the implementationmore » provides accurate nuclear gradients with respect to the THC-MP2 potential energy surfaces.« less

Analytical gradients for tensor hyper-contracted MP2 and SOS-MP2 on graphical processing units

NASA Astrophysics Data System (ADS)

Song, Chenchen; Martínez, Todd J.

2017-10-01

Analytic energy gradients for tensor hyper-contraction (THC) are derived and implemented for second-order Møller-Plesset perturbation theory (MP2), with and without the scaled-opposite-spin (SOS)-MP2 approximation. By exploiting the THC factorization, the formal scaling of MP2 and SOS-MP2 gradient calculations with respect to system size is reduced to quartic and cubic, respectively. An efficient implementation has been developed that utilizes both graphics processing units and sparse tensor techniques exploiting spatial sparsity of the atomic orbitals. THC-MP2 has been applied to both geometry optimization and ab initio molecular dynamics (AIMD) simulations. The resulting energy conservation in micro-canonical AIMD demonstrates that the implementation provides accurate nuclear gradients with respect to the THC-MP2 potential energy surfaces.

Analytical gradients for tensor hyper-contracted MP2 and SOS-MP2 on graphical processing units

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Chenchen; Martinez, Todd J.

Analytic energy gradients for tensor hyper-contraction (THC) are derived and implemented for second-order Møller-Plesset perturbation theory (MP2), with and without the scaled-opposite-spin (SOS)-MP2 approximation. By exploiting the THC factorization, the formal scaling of MP2 and SOS-MP2 gradient calculations with respect to system size is reduced to quartic and cubic, respectively. An efficient implementation has been developed that utilizes both graphics processing units and sparse tensor techniques exploiting spatial sparsity of the atomic orbitals. THC-MP2 has been applied to both geometry optimization and ab initio molecular dynamics (AIMD) simulations. Furthermore, the resulting energy conservation in micro-canonical AIMD demonstrates that the implementationmore » provides accurate nuclear gradients with respect to the THC-MP2 potential energy surfaces.« less

Daily intake of Mucuna pruriens in advanced Parkinson's disease: A 16-week, noninferiority, randomized, crossover, pilot study.

PubMed

Cilia, Roberto; Laguna, Janeth; Cassani, Erica; Cereda, Emanuele; Raspini, Benedetta; Barichella, Michela; Pezzoli, Gianni

2018-04-01

Thousands of individuals with Parkinson's disease (PD) in low-income countries have limited access to marketed levodopa preparations. Mucuna pruriens (MP), a levodopa-containing leguminous plant growing in tropical areas, may be a sustainable alternative therapy for indigent patients. Single-dose intake of MP proved noninferior to marketed levodopa preparations. Fourteen PD patients with motor fluctuations and dyskinesias received MP powder (obtained from roasted seeds) and marketed levodopa/carbidopa (LD/CD) in a randomized order and crossover design over a 16-week period. Efficacy measures were changes in quality of life, motor and non-motor symptoms, and time with good mobility without troublesome dyskinesias. Safety measures included tolerability, frequency of adverse events, changes in laboratory indices and electrocardiogram. Daily intake of MP was associated with a variable clinical response, especially in terms of tolerability. Seven patients (50%) discontinued MP prematurely due to either gastrointestinal side-effects (n = 4) or progressive worsening of motor performance (n = 3), while nobody discontinued during the LD/CD phase. In those who tolerated MP, clinical response to MP was similar to LD/CD on all efficacy outcome measures. Patients who dropped out entered a study extension using MP supernatant water (median[IQR], 16 [7-20] weeks), which was well tolerated. The overall benefit provided by MP on the clinical outcome was limited by tolerability issues, as one could expect by the relatively rapid switch from LD/CD to levodopa alone in advanced PD. Larger parallel-group studies are needed to identify appropriate MP formulation (e.g. supernatant water), titration scheme and maintenance dose to minimize side-effects in the long-term. CLINICAL TRIALS. NCT02680977. Copyright © 2018 Elsevier Ltd. All rights reserved.

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn’s disease with low rate of side effects: results of double blind Phase II clinical trial

PubMed Central

Israeli, E; Goldin, E; Fishman, S; Konikoff, F; Lavy, A; Chowers, Y; Melzer, E; Lahat, A; Mahamid, M; Shirin, H; Nussinson, E; Segol, O; Ya’acov, A Ben; Shabbat, Y; Ilan, Y

2015-01-01

Therapy for Crohn’s disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn’s Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62+ expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects. PMID:25846055

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.

PubMed

Israeli, E; Goldin, E; Fishman, S; Konikoff, F; Lavy, A; Chowers, Y; Melzer, E; Lahat, A; Mahamid, M; Shirin, H; Nussinson, E; Segol, O; Ya'acov, A Ben; Shabbat, Y; Ilan, Y

2015-08-01

Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects. © 2015 British Society for Immunology.

R-process Enrichment in Cosmological Zoom Simulation of a Milkyway Type Halo by Neutron Star Mergers; The Origin of the MP-R and CEMP-R Stars

NASA Astrophysics Data System (ADS)

Safarzadeh, Mohammadtaher; Scannapieco, Evan

2018-06-01

The history of r-process enrichment in our galaxy is modeled through a novel set of zoom cosmo- logical simulations on a MilkyWay type galaxy. r-process sources are assumed to be neutron star mergers with a distribution of natal kicks and merge time distribution. We model turbulent mixing to estimate the pristine gas fraction in each simulation cell which we use to determine the Pop III star formation with assigned Carbon rich ejecta when going off as SNe. We follow the formation of Carbon-Enhanced Metal-Poor (CEMP) stars and the statistics of different r-process enhanced class of stars. The simulation underpredict the frequency of CEMP/MP stars by a factor of 2-4. Likewise the MP-rI/MP and MP-rII/MP and CEMP-r/CEMP cumulative ratios are all under predicted by 1-2 orders of magnitude. Our results show that NS binaries by themselves fall too short to explain the observed frequency of r-process enhanced stars and other sources of r-process enrichment at high redshifts are needed to fill the gap.

Phonological Neighborhood Effects in Spoken Word Production: An fMRI Study

ERIC Educational Resources Information Center

Peramunage, Dasun; Blumstein, Sheila E.; Myers, Emily B.; Goldrick, Matthew; Baese-Berk, Melissa

2011-01-01

The current study examined the neural systems underlying lexically conditioned phonetic variation in spoken word production. Participants were asked to read aloud singly presented words, which either had a voiced minimal pair (MP) neighbor (e.g., cape) or lacked a minimal pair (NMP) neighbor (e.g., cake). The voiced neighbor never appeared in the…

A novel processed food classification system applied to Australian food composition databases.

PubMed

O'Halloran, S A; Lacy, K E; Grimes, C A; Woods, J; Campbell, K J; Nowson, C A

2017-08-01

The extent of food processing can affect the nutritional quality of foodstuffs. Categorising foods by the level of processing emphasises the differences in nutritional quality between foods within the same food group and is likely useful for determining dietary processed food consumption. The present study aimed to categorise foods within Australian food composition databases according to the level of food processing using a processed food classification system, as well as assess the variation in the levels of processing within food groups. A processed foods classification system was applied to food and beverage items contained within Australian Food and Nutrient (AUSNUT) 2007 (n = 3874) and AUSNUT 2011-13 (n = 5740). The proportion of Minimally Processed (MP), Processed Culinary Ingredients (PCI) Processed (P) and Ultra Processed (ULP) by AUSNUT food group and the overall proportion of the four processed food categories across AUSNUT 2007 and AUSNUT 2011-13 were calculated. Across the food composition databases, the overall proportions of foods classified as MP, PCI, P and ULP were 27%, 3%, 26% and 44% for AUSNUT 2007 and 38%, 2%, 24% and 36% for AUSNUT 2011-13. Although there was wide variation in the classifications of food processing within the food groups, approximately one-third of foodstuffs were classified as ULP food items across both the 2007 and 2011-13 AUSNUT databases. This Australian processed food classification system will allow researchers to easily quantify the contribution of processed foods within the Australian food supply to assist in assessing the nutritional quality of the dietary intake of population groups. © 2017 The British Dietetic Association Ltd.

Coupling of Noah-MP and the High Resolution CI-WATER ADHydro Hydrological Model

NASA Astrophysics Data System (ADS)

Moreno, H. A.; Goncalves Pureza, L.; Ogden, F. L.; Steinke, R. C.

2014-12-01

ADHydro is a physics-based, high-resolution, distributed hydrological model suitable for simulating large watersheds in a massively parallel computing environment. It simulates important processes such as: rainfall and infiltration, snowfall and snowmelt in complex terrain, vegetation and evapotranspiration, soil heat flux and freezing, overland flow, channel flow, groundwater flow and water management. For the vegetation and evapotranspiration processes, ADHydro uses the validated community land surface model (LSM) Noah-MP. Noah-MP uses multiple options for key land-surface hydrology and was developed to facilitate climate predictions with physically based ensembles. This presentation discusses the lessons learned in coupling Noah-MP to ADHydro. Noah-MP is delivered with a main driver program and not as a library with a clear interface to be called from other codes. This required some investigation to determine the correct functions to call and the appropriate parameter values. ADHydro runs Noah-MP as a point process on each mesh element and provides initialization and forcing data for each element. Modeling data are acquired from various sources including the Soil Survey Geographic Database (SSURGO), the Weather Research and Forecasting (WRF) model, and internal ADHydro simulation states. Despite these challenges in coupling Noah-MP to ADHydro, the use of Noah-MP provides the benefits of a supported community code.

High hydrostatic pressure processing reduces the glycemic index of fresh mango puree in healthy subjects.

PubMed

Elizondo-Montemayor, Leticia; Hernández-Brenes, Carmen; Ramos-Parra, Perla A; Moreno-Sánchez, Diana; Nieblas, Bianca; Rosas-Pérez, Aratza M; Lamadrid-Zertuche, Ana C

2015-04-01

Dietary guidelines recommend the daily consumption of fruits; however, healthy and type 2 diabetes mellitus (T2DM) subjects receive conflicting messages regarding ingestion of fruits, such as mango, because of its sugar content. We investigated the effects of high hydrostatic pressure (HHP) processing of fresh mango puree (MP) on the glycemic indexes (GIs) and postprandial glycemic responses of 38 healthy Mexican subjects in a randomized cross-over clinical trial. Physicochemical characterization of MP included sugar profiles by HPLC-ELSD, starch, fibers, moisture, viscosity, swelling capacity and solubility properties of alcohol insoluble residue (AIR). The mean GI for HHP-MP was significantly lower (32.7 ± 13.4) than that of unprocessed-MP (42.7 ± 19.5). A significantly higher proportion of subjects showed a low GI following the consumption of HHP-MP compared to unprocessed-MP and none of them showed a high GI for the HHP-MP, compared to a significantly higher proportion for the unprocessed-MP. The viscosity and AIR solubility values of HHP-MP samples were significantly higher, which influenced glucose peaking later (Tmax) at 45 minutes and induced 20% lower AUC values than unprocessed-MP, corresponding to greater retardation indexes. The study findings support data stating that low GI fruits are appropriate for glycemic control and that mango may be included as part of healthy subjects' diets and potentially T2DM subjects' diets. Furthermore, HHP processing of mango may offer additional benefits for glycemic control, as its performance regarding GI, AUC and Tmax was significantly better than that of the unprocessed-MP. To our knowledge, this is the first report on the impact of this commercial non-thermal pasteurization technology on glucose metabolism.

Efficacy and Safety of Medicinal Plants or Related Natural Products for Fibromyalgia: A Systematic Review

PubMed Central

de Souza Nascimento, Simone; DeSantana, Josimari Melo; Ribeiro, Êurica Adélia Nogueira; da Silva, Daniel Lira; Araújo-Júnior, João Xavier; da Silva Almeida, Jackson Roberto Guedes; Bonjardim, Leonardo Rigoldi; de Souza Araújo, Adriano Antunes; Quintans-Júnior, Lucindo José

2013-01-01

To assess the effects of medicinal plants (MPs) or related natural products (RNPs) on fibromyalgia (FM) patients, we evaluate the possible benefits and advantages of MP or RNP for the treatment of FM based on eight randomized placebo-controlled trials (RCTs) involving 475 patients. The methodological quality of all studies included was determined according to JADAD and “Risk of Bias” with the criteria in the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. Evidence suggests significant benefits of MP or RNP in sleep disruption, pain, depression, joint stiffness, anxiety, physical function, and quality of life. Our results demonstrated that MP or RNP had significant effects on improving the symptoms of FM compared to conventional drug or placebo; longer tests are required to determine the duration of the treatment and characterize the long-term safety of using MP, thus suggesting effective alternative therapies in the treatment of pain with minimized side effects. PMID:23861696

Antioxidant properties of selected Oriental non-culinary/nutraceutical herb extracts as evaluated in raw and cooked meat.

PubMed

Han, J; Rhee, K S

2005-05-01

Ethanol extracts of white peony (WP), red peony (RP), sappanwood (SW), Moutan peony (MP), rehmania (RE) or angelica (AN) were individually added to ground goat meat at 0.5-2.0% (g dry extract/100 g final meat sample), and raw and cooked samples were aerobically refrigerated for 0, 3 or 6 days. These extracts and rosemary extract (RO) were also individually added to salted or unsalted ground beef at 0.01-0.25% and refrigerated as raw or cooked patties. WP, RP, RE, SW and MP markedly reduced (P<0.05) lipid oxidation in cooked-stored goat meat. With 0.25% of WP, RP, SW, MP or RO in beef, lipid oxidation during storage was minimal in raw and cooked patties (plain or salted); raw patty redness values at day 6 were higher (P<0.05) for SW, WP, RP or MP than RO treatment or the control. At 0.01%, SW was more antioxidative (P<0.05) than the other extracts.

Friedman tongue position and cone beam computed tomography in patients with obstructive sleep apnea

PubMed Central

O'Brien, Louise; Aronovich, Sharon; Shelgikar, Anita; Hoff, Paul; Palmisano, John; Stanley, Jeffrey

2017-01-01

Objective Evaluate the correlation between Friedman Tongue Position (FTP) and airway cephalometrics in patients with obstructive sleep apnea (OSA). Study Design Retrospective review of adult patients with OSA undergoing Cone Beam Computed Tomography (CBCT). Methods Collected data included age, sex, body mass index, apnea hypopnea index, FTP, and airway cephalometric parameters. Data analyses were performed using ANOVA, dichotomous t‐testing, and linear regression. Results 203 patients were included in the analysis. (M:F 132:71). The mean posterior airway space (PAS) was inversely correlated (p = 0.001, r =.119) with higher FTP grades with means of 12.3 mm, 7.9 mm, 6.6 mm, and 4.3 mm, I‐IV respectively. Minimal cross‐sectional area for patients with FTP I‐IV was 245.7, 179.8, 137.6, and 74.2 mm, 2 respectively (p = 0.002, r = .095). Mean hyoid‐mandibular plane (H‐MP) for FTP I‐IV was 20.6 mm, 20.4 mm, 24.7 mm, and 28.9 mm respectively. No statistically significant difference between H‐MP values when comparing patients with FTP I or II (p = 0.22). There were statistically significant differences when these two groups were individually compared to FTP III and IV (p = 0.002). Linear regression analysis confirmed an independent association between FTP and PAS (β = −2.06, p < 0.001), minimal cross‐sectional area (β = −45.07, p = 0.02), and H‐MP (β = 3.03, p = 0.01) controlling for BMI, age, AHI, and sex. Conclusions Use of FTP is supported by objective CBCT cephalometric results, in particular the PAS, minimal cross‐sectional area, and H‐MP. Understanding the correlation between objective measurements of retroglossal collapse should allow Otolaryngologists to more confidently select patients who may require surgery to address the retroglossal area, particularly when the ability to perform cephalometric analysis is not possible Level of Evidence 4. PMID:29094076

Friedman tongue position and cone beam computed tomography in patients with obstructive sleep apnea.

PubMed

Harvey, Rebecca; O'Brien, Louise; Aronovich, Sharon; Shelgikar, Anita; Hoff, Paul; Palmisano, John; Stanley, Jeffrey

2017-10-01

Evaluate the correlation between Friedman Tongue Position (FTP) and airway cephalometrics in patients with obstructive sleep apnea (OSA). Retrospective review of adult patients with OSA undergoing Cone Beam Computed Tomography (CBCT). Collected data included age, sex, body mass index, apnea hypopnea index, FTP, and airway cephalometric parameters. Data analyses were performed using ANOVA, dichotomous t-testing, and linear regression. 203 patients were included in the analysis. (M:F 132:71). The mean posterior airway space (PAS) was inversely correlated ( p  = 0.001, r =.119) with higher FTP grades with means of 12.3 mm, 7.9 mm, 6.6 mm, and 4.3 mm, I-IV respectively. Minimal cross-sectional area for patients with FTP I-IV was 245.7, 179.8, 137.6, and 74.2 mm, 2 respectively ( p  = 0.002, r  = .095). Mean hyoid-mandibular plane (H-MP) for FTP I-IV was 20.6 mm, 20.4 mm, 24.7 mm, and 28.9 mm respectively. No statistically significant difference between H-MP values when comparing patients with FTP I or II ( p  = 0.22). There were statistically significant differences when these two groups were individually compared to FTP III and IV ( p  = 0.002). Linear regression analysis confirmed an independent association between FTP and PAS (β = -2.06, p  < 0.001), minimal cross-sectional area (β = -45.07, p  = 0.02), and H-MP (β = 3.03, p  = 0.01) controlling for BMI, age, AHI, and sex. Use of FTP is supported by objective CBCT cephalometric results, in particular the PAS, minimal cross-sectional area, and H-MP. Understanding the correlation between objective measurements of retroglossal collapse should allow Otolaryngologists to more confidently select patients who may require surgery to address the retroglossal area, particularly when the ability to perform cephalometric analysis is not possible. 4.

Effects of pH-Shift Processing and Microbial Transglutaminase on the Gel and Emulsion Characteristics of Porcine Myofibrillar System

PubMed Central

Hong, Geun-Pyo; Chun, Ji-Yeon; Jo, Yeon-Ji

2014-01-01

This study investigated the effects of microbial transglutaminase (MTGase) and pH-shift processing on the functional properties of porcine myofibrillar proteins (MP). The pH-shift processing was carried out by decreasing the pH of MP suspension to 3.0, followed by re-adjustment to pH 6.2. The native (CM) and pH-shifted MP (PM) was reacted with and without MTGase, and the gelling and emulsion characteristics were compared. To compare the pH-shifted MTGase-treated MP (PT), deamidation (DM) was conducted by reacting MTGase with MP at pH 3.0. Rigid thermal gel was produced by MTGase-treated native MP (CT) and PT. PM and DM showed the lowest storage modulus (G') at the end of thermal scanning. Both MTGase and pH-shifting produced harder MP gel, and the highest gel strength was obtained in PT. All treatments yielded lower than CM, and CT showed significantly higher yield than PM and DM treatments. For emulsion characteristics, pH-shifting improved the emulsifying ability of MP-stabilized emulsion, while the treatments had lower emulsion stability. PM-stabilized emulsion exhibited the lowest creaming stability among all treatments. The emulsion stability could be improved by the usage of MTGase. The results indicated that pH-shifting combined with MTGase had a potential application to modify or improve functional properties of MP in manufacturing of meat products. PMID:26760940

Hydrodynamic interactions in metachronal paddling: effects of varying stroke kinematics

NASA Astrophysics Data System (ADS)

Samaee, Milad; Kasoju, Vishwa; Lai, Hong Kuan; Santhanakrishnan, Arvind

2017-11-01

Crustaceans such as shrimp and krill use a drag-based technique for propulsion, in which multiple pairs of limbs are paddled rhythmically from the tail to the head. Each limb is phase-shifted in time relative to its neighbor. Most studies of this type of metachronal swimming have focused on the jet formed in the animal's wake. However, synergistic hydrodynamic interactions between adjacent limbs in metachrony have received minimal attention. We used a dynamically scaled robotic model to experimentally investigate how variations in stroke kinematics impact inter-paddle hydrodynamic interactions and thrust generation. Physical models of limbs were fitted to the robot and paddled with two different motion profiles (MPs)-1) MP1: metachronal power stroke (PS) and metachronal recovery stroke (RS); and 2) MP2: metachronal PS and synchronous RS. Stroke frequency and amplitude were maintained constant across both MPs. Our results show that MP2 produced faster jets in the thrust-generating direction as compared to MP1. The necessity for a pause in MP2 after completion of PS by the paddles leading the motion, prior to executing the synchronous RS, aided in further downstream flow propagation. The effect of using asymmetric stroke kinematics on thrust generated will be discussed.

Comparison of HFC-134a and the ternary blend, Suva MP39, as replacements for the refrigerant, CGC-12

NASA Astrophysics Data System (ADS)

Fletcher, Lyn E.

1993-09-01

The refrigerant gas CFC-12 has been widely used in Royal Australian Navy (RAN) equipment. With the Montreal protocol phase-out of this and other ozone depleting substances, alternative refrigerant gases must be identified. These replacements would ideally have the same efficiency as CFC-12, cause no health and safety risks and allow changeover to proceed with minimal costs. This paper reviews the attributes of two refrigerant gases, HFC-134a and Suva MP39, which are being considered by the RAN.

Western Arctic Shelf-Basin Interactions Experiment: Processing and Calibration of Moored Profiler Data from the Beaufort Shelf Edge Mooring Array

DTIC Science & Technology

2006-12-01

EM-CTD and ACM data (MMP only) were extracted from a PC flashcard on the MP controller and converted to ASCII file format. The MP reports engineering...downloaded from the flashcards of the MP instruments and unpacked, we used the processing system developed by John Toole at the Woods Hole Oceanographic

Assessment of Central Retinal Sensitivity Employing Two Types of Microperimetry Devices

PubMed Central

Liu, Hongting; Bittencourt, Millena G.; Wang, Jiangxia; Sophie, Raafay; Annam, Rachel; Ibrahim, Mohamed A.; Sepah, Yasir J.; Moradi, Ahmadreza; Scholl, Hendrik P. N.; Nguyen, Quan Dong

2014-01-01

Purpose To compare the retinal sensitivity measurements obtained with two microperimeters, the Micro-Perimeter 1 (MP-1) and the Optos optical coherence tomography (OCT)/scanning laser ophthalmoscope (SLO) in subjects with and without maculopathies. Methods Forty-five eyes with no known ocular disease and 47 eyes with maculopathies were examined using both microperimeters. A contrast-adjusted scale was applied to resolve the different stimuli and background luminance existing between the two devices. Results There was a strong ceiling effect with the MP-1 in the healthy group, with 90.1% (1136 of 1260) test points clustered at 20 dB. The mean sensitivity for the corresponding points in the OCT/SLO was 25.8 ± 1.9 dB. A floor effect was also observed with the OCT/SLO in the maculopathy group with 9.7% (128 of 1316) points clustered at 9-dB values. The corresponding mean sensitivity in the MP-1 was 1.7 ± 3.9 dB. A regression equation between the two microperimeters was established in the common 10 to19 dB intervals as: OCT/SLO = 15.6 + 0.564 × MP-1 − 0.009 × MP-12 + k (k is an individual point constant; MP-1 coefficient P < 0.001; MP-12 coefficient P = 0.006). Conclusion The OCT/SLO and the MP-1 provide two different ranges of contrasts for microperimetry examination. Broadening the dynamic range may minimize the constraint of the ceiling and floor effect. There is a significant mathematical relationship in the common interval of the contrast scale. Translational Relevance Applying a unified and broadened dynamic range in different types of microperimeters will help to generate consistent clinical reference for measurements. PMID:25237592

Behavior Models for Software Architecture

DTIC Science & Technology

2014-11-01

MP. Existing process modeling frameworks (BPEL, BPMN [Grosskopf et al. 2009], IDEF) usually follow the “single flowchart” paradigm. MP separates...Process: Business Process Modeling using BPMN , Meghan Kiffer Press. HAREL, D., 1987, A Visual Formalism for Complex Systems. Science of Computer

OpenMP 4.5 Validation and Verification Suite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pophale, Swaroop S; Bernholdt, David E; Hernandez, Oscar R

2017-12-15

OpenMP, a directive-based programming API, introduce directives for accelerator devices that programmers are starting to use more frequently in production codes. To make sure OpenMP directives work correctly across architectures, it is critical to have a mechanism that tests for an implementation's conformance to the OpenMP standard. This testing process can uncover ambiguities in the OpenMP specification, which helps compiler developers and users make a better use of the standard. We fill this gap through our validation and verification test suite that focuses on the offload directives available in OpenMP 4.5.

Automatic Generation of OpenMP Directives and Its Application to Computational Fluid Dynamics Codes

NASA Technical Reports Server (NTRS)

Yan, Jerry; Jin, Haoqiang; Frumkin, Michael; Yan, Jerry (Technical Monitor)

2000-01-01

The shared-memory programming model is a very effective way to achieve parallelism on shared memory parallel computers. As great progress was made in hardware and software technologies, performance of parallel programs with compiler directives has demonstrated large improvement. The introduction of OpenMP directives, the industrial standard for shared-memory programming, has minimized the issue of portability. In this study, we have extended CAPTools, a computer-aided parallelization toolkit, to automatically generate OpenMP-based parallel programs with nominal user assistance. We outline techniques used in the implementation of the tool and discuss the application of this tool on the NAS Parallel Benchmarks and several computational fluid dynamics codes. This work demonstrates the great potential of using the tool to quickly port parallel programs and also achieve good performance that exceeds some of the commercial tools.

Embrittlement phenomenon of Ag core MP35N cable as lead conductor in medical device.

PubMed

Wang, Ling; Li, Bernie; Zhang, Haitao

2013-02-01

Ag core MP35N (Ag/MP35N) wire has been used in lead electric conductor wires in the medical device industry for many years. Recently it was noticed that the combination of silver and MP35N restricts its wire drawing process. The annealing temperature in Ag/MP35N has to be lower than the melting temperature of pure Ag (960 °C), which cannot fully anneal MP35N. The lower annealing temperature results in a highly cold worked MP35N, which significantly reduces Ag/MP35N ductility. The embrittlement phenomenon of Ag/MP35N cable was observed in tension and bending deformation. The effect of the embrittlement on the wire flex fatigue life was evaluated using a newly developed flex fatigue testing method. The Ag/MP35N cable fatigue results was analyzed with a Coffin-Manson approach and compared to the MP35N cable fatigue results. The root causes of the Ag/Mp35N embrittlement phenomenon are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Virus-like particles in venom of Meteorus pulchricornis induce host hemocyte apoptosis.

PubMed

Suzuki, M; Tanaka, T

2006-06-01

Ultrastructural studies on the reproductive tract and venom apparatus of a female braconid, Meteorus pulchricornis, revealed that the parasitoid lacks the calyx region in its oviduct, but possesses a venom gland with two venom gland filaments and a venom reservoir filled with white and cloudy fluid. Its venom gland cell is concaved and has a lumen filled with numerous granules. Transmisson electron microscopic (TEM) observation revealed that virus-like particles (VLPs) were produced in venom gland cells. The virus-like particle observed in M. pulchricornis (MpVLP) is composed of membranous envelopes with two different parts: a high-density core and a whitish low-density part. The VLPs of M. pulchricornis is also found assembling ultimately in the lumen of venom gland cell. Microvilli were found thrusting into the lumen of the venom gland cell and seem to aid in driving the matured MpVLPs to the common duct of the venom gland filament. Injection of MpVLPs into non-parasitized Pseudaletia separata hosts induced apoptosis in hemocytes, particularly granulocytes (GRs). Rate of apoptosis induced in GRs peaked 48h after VLP injection. While a large part of the GR population collapsed due to apoptosis caused by MpVLPs, the plasmatocyte population was minimally affected. The capacity of MpVLPs to cause apoptosis in host's hemocytes was further demonstrated by a decrease ( approximately 10-fold) in ability of host hemocytes to encapsulate fluorescent latex beads when MpVLPs were present. Apparently, the reduced encapsulation ability was due to a decrease in the GR population resulting from MpVLP-induced apoptosis.

Risk analysis of inter-species reassortment through a Rift Valley fever phlebovirus MP-12 vaccine strain.

PubMed

Ly, Hoai J; Lokugamage, Nandadeva; Nishiyama, Shoko; Ikegami, Tetsuro

2017-01-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula. The causative agent, Rift Valley fever phlebovirus (RVFV), belongs to the genus Phlebovirus in the family Phenuiviridae and causes high rates of abortions in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral maintenance by mosquito vectors has led to sporadic RVF outbreaks in ruminants and humans in endemic countries, and effective vaccination of animals and humans may minimize the impact of this disease. A live-attenuated MP-12 vaccine strain is one of the best characterized RVFV strains, and was conditionally approved as a veterinary vaccine in the U.S. Live-attenuated RVF vaccines including MP-12 strain may form reassortant strains with other bunyavirus species. This study thus aimed to characterize the occurrence of genetic reassortment between the MP-12 strain and bunyavirus species closely related to RVFV. The Arumowot virus (AMTV) and Gouleako goukovirus (GOLV), are transmitted by mosquitoes in Africa. The results of this study showed that GOLV does not form detectable reassortant strains with the MP-12 strain in co-infected C6/36 cells. The AMTV also did not form any reassortant strains with MP-12 strain in co-infected C6/36 cells, due to the incompatibility among N, L, and Gn/Gc proteins. A lack of reassortant formation could be due to a functional incompatibility of N and L proteins derived from heterologous species, and due to a lack of packaging via heterologous Gn/Gc proteins. The MP-12 strain did, however, randomly exchange L-, M-, and S-segments with a genetic variant strain, rMP12-GM50, in culture cells. The MP-12 strain is thus unlikely to form any reassortant strains with AMTV or GOLV in nature.

Efficient Process Migration for Parallel Processing on Non-Dedicated Networks of Workstations

NASA Technical Reports Server (NTRS)

Chanchio, Kasidit; Sun, Xian-He

1996-01-01

This paper presents the design and preliminary implementation of MpPVM, a software system that supports process migration for PVM application programs in a non-dedicated heterogeneous computing environment. New concepts of migration point as well as migration point analysis and necessary data analysis are introduced. In MpPVM, process migrations occur only at previously inserted migration points. Migration point analysis determines appropriate locations to insert migration points; whereas, necessary data analysis provides a minimum set of variables to be transferred at each migration pint. A new methodology to perform reliable point-to-point data communications in a migration environment is also discussed. Finally, a preliminary implementation of MpPVM and its experimental results are presented, showing the correctness and promising performance of our process migration mechanism in a scalable non-dedicated heterogeneous computing environment. While MpPVM is developed on top of PVM, the process migration methodology introduced in this study is general and can be applied to any distributed software environment.

Influence of Genista tinctoria L. or methylparaben on subchronic toxicity of bisphenol A in rats.

PubMed

Popa, Daniela-Saveta; Bolfa, Pompei; Kiss, Bela; Vlase, Laurian; Păltinean, Ramona; Pop, Anca; Cătoi, Cornel; Crişan, Gianina; Loghin, Felicia

2014-02-01

To evaluate the influence of an extract of Genista tinctoria L. herba (GT) or methylparaben (MP) on histopathological changes and 2 biomarkers of oxidative stress in rats subchronicly exposed to bisphenol A (BPA). Adult female Wistar rats were orally exposed for 90 d to BPA (50 mg/kg), BPA+GT (35 mg isoflavones/kg) or BPA+MP (250 mg/kg). Plasma and tissue samples were taken from liver, kidney, thyroid, uterus, ovary, and mammary gland after 30, 60, and 90 d of exposure respectively. Lipid peroxidation and in vivo hydroxyl radical production were evaluated by histological analysis along with malondialdehyde and 2,3-dihydroxybenzoic acid detection. The severity of histopathological changes in liver and kidneys was lower after GT treatment than after BPA or BPA+MP treatment. A minimal thyroid receptor antagonist effect was only observed after BPA+MP treatment. The abnormal folliculogenesis increased in a time-dependent manner, and the number of corpus luteum decreased. No significant histological alterations were found in the uterus. The mammary gland displayed specific estrogen stimulation changes at all periods. Both MP and GT revealed antioxidant properties reducing lipid peroxidation and BPA-induced hydroxyl radical generation. GT L. extract ameliorates the toxic effects of BPA and is proved to have antioxidant potential and antitoxic effect. MP has antioxidant properties, but has either no effect or exacerbates the BPA-induced histopathological changes. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications

PubMed Central

Chan, Ka Man Carmen; Li, Randolph H.; Chapman, Joseph W.; Trac, Eric M.; Kobler, James B.; Zeitels, Steven M.; Langer, Robert; Karajanagi, Sandeep S.

2014-01-01

Particle size, stiffness and surface functionality are important in determining the injection site, safety and efficacy of injectable soft-tissue fillers. Methods to produce soft injectable biomaterials with controlled particle characteristics are therefore desirable. Here we report a method based on suspension photopolymerization and semi-interpenetrating network (semi-IPN) to synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of independently tunable size and stiffness. MP were prepared using acrylated forms of polyethylene glycol (PEG), gelatin and hyaluronic acid. Semi-IPN MP of PEG-diacrylate and PEG were used to study the effect of process parameters on particle characteristics. The process parameters were systematically varied to produce MP with size ranging from 115 to 515 μm and stiffness ranging from 190 to 1600 Pa. In vitro studies showed that the MP thus prepared were cytocompatible. The ratio and identity of the polymers used to make the semi-IPN MP were varied to control their stiffness and to introduce amine groups for potential functionalization. Slow-release polymeric particles loaded with Rhodamine or dexamethasone were incorporated in the MP as a proof-of-principle of drug incorporation and release from the MP. This work has implications in preparing injectable biomaterials of natural or synthetic polymers for applications as soft-tissue fillers. PMID:24561708

Impact of the hard-coded parameters on the hydrologic fluxes of the land surface model Noah-MP

NASA Astrophysics Data System (ADS)

Cuntz, Matthias; Mai, Juliane; Samaniego, Luis; Clark, Martyn; Wulfmeyer, Volker; Attinger, Sabine; Thober, Stephan

2016-04-01

Land surface models incorporate a large number of processes, described by physical, chemical and empirical equations. The process descriptions contain a number of parameters that can be soil or plant type dependent and are typically read from tabulated input files. Land surface models may have, however, process descriptions that contain fixed, hard-coded numbers in the computer code, which are not identified as model parameters. Here we searched for hard-coded parameters in the computer code of the land surface model Noah with multiple process options (Noah-MP) to assess the importance of the fixed values on restricting the model's agility during parameter estimation. We found 139 hard-coded values in all Noah-MP process options, which are mostly spatially constant values. This is in addition to the 71 standard parameters of Noah-MP, which mostly get distributed spatially by given vegetation and soil input maps. We performed a Sobol' global sensitivity analysis of Noah-MP to variations of the standard and hard-coded parameters for a specific set of process options. 42 standard parameters and 75 hard-coded parameters were active with the chosen process options. The sensitivities of the hydrologic output fluxes latent heat and total runoff as well as their component fluxes were evaluated. These sensitivities were evaluated at twelve catchments of the Eastern United States with very different hydro-meteorological regimes. Noah-MP's hydrologic output fluxes are sensitive to two thirds of its standard parameters. The most sensitive parameter is, however, a hard-coded value in the formulation of soil surface resistance for evaporation, which proved to be oversensitive in other land surface models as well. Surface runoff is sensitive to almost all hard-coded parameters of the snow processes and the meteorological inputs. These parameter sensitivities diminish in total runoff. Assessing these parameters in model calibration would require detailed snow observations or the calculation of hydrologic signatures of the runoff data. Latent heat and total runoff exhibit very similar sensitivities towards standard and hard-coded parameters in Noah-MP because of their tight coupling via the water balance. It should therefore be comparable to calibrate Noah-MP either against latent heat observations or against river runoff data. Latent heat and total runoff are sensitive to both, plant and soil parameters. Calibrating only a parameter sub-set of only soil parameters, for example, thus limits the ability to derive realistic model parameters. It is thus recommended to include the most sensitive hard-coded model parameters that were exposed in this study when calibrating Noah-MP.

A comparison of transfer-appropriate processing and multi-process frameworks for prospective memory performance.

PubMed

McBride, Dawn M; Abney, Drew H

2012-01-01

We examined multi-process (MP) and transfer-appropriate processing descriptions of prospective memory (PM). Three conditions were compared that varied the overlap in processing type (perceptual/conceptual) between the ongoing and PM tasks such that two conditions involved a match of perceptual processing and one condition involved a mismatch in processing (conceptual ongoing task/perceptual PM task). One of the matched processing conditions also created a focal PM task, whereas the other two conditions were considered non-focal (Einstein & McDaniel, 2005). PM task accuracy and ongoing task completion speed in baseline and PM task conditions were measured. Accuracy results indicated a higher PM task completion rate for the focal condition than the non-focal conditions, a finding that is consistent with predictions made by the MP view. However, reaction time (RT) analyses indicated that PM task cost did not differ across conditions when practice effects are considered. Thus, the PM accuracy results are consistent with a MP description of PM, but RT results did not support the MP view predictions regarding PM cost.

Distributed process manager for an engineering network computer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gait, J.

1987-08-01

MP is a manager for systems of cooperating processes in a local area network of engineering workstations. MP supports transparent continuation by maintaining multiple copies of each process on different workstations. Computational bandwidth is optimized by executing processes in parallel on different workstations. Responsiveness is high because workstations compete among themselves to respond to requests. The technique is to select a master from among a set of replicates of a process by a competitive election between the copies. Migration of the master when a fault occurs or when response slows down is effected by inducing the election of a newmore » master. Competitive response stabilizes system behavior under load, so MP exhibits realtime behaviors.« less

Preschoolers' Awareness of Television Advertising.

ERIC Educational Resources Information Center

Levin, Stephen R.; And Others

1982-01-01

The ability of 3-, 4-, and 5-year-old children to correctly identify videotaped segments as programs or commercials was examined. Results indicate that, when a task requiring minimal verbal response is used, preschoolers demonstrate an awareness of commercials as distinct from programs. (Author/MP)

Processing silicon microparticles recycled from wafer waste via Rapid Thermal Process for lithium-ion battery anode materials

NASA Astrophysics Data System (ADS)

Tan, Hui-Gee; Duh, Jenq-Gong

2016-12-01

A vast quantity of waste sludge is generated during the silicon wafers slicing process in semiconductor and photovoltaic industries. Turning the waste powder into high-value products is of strategic importance for industrial processes. The purified Si microparticles (Si-MP) are recycled by a simple and fast procedure, Rapid Thermal Process (RTP). A prominent anodic material of Si-MP/Carbon composite with porous structure is obtained via in-spaced carbonization of water-soluble binder sodium carboxymethyl cellulose during RTP. This strategy provides buffer space, which is constructed by carbon porous continuous conductive framework throughout the entire electrode, to resist local stress and intense volume variation. In addition, a sufficiently electrochemically stable solid-electrolyte interphase layer is accomplished with the coating of SiOx film and amorphous carbon on the surface of Si-MP. Under these circumstances, the enhanced electrodes achieve a first cycle efficiency of approximately 80% and a reversible charge capacity of 800 mAhg-1 over 100 cycles at 0.5 Ag-1 with good retention. Through a green and simple procedure, a remarkable Si-MP embedded carbon-matrix with porous structure is established to achieve commercially high performance Si-MP/C composite anodes and also to resolve the issues of waste disposal.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michaelides, M.; Wang, G.; Michaelides, M.

Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated imagemore » registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.« less

Autoimmune abnormality affects ovulation and oocyte-pick-up in MRL/MpJ-Fas lpr/lpr mice.

PubMed

Hosotani, M; Ichii, O; Nakamura, T; Kanazawa, S O; Elewa, Y Hosny Ali; Kon, Y

2018-01-01

Ovulation and oocyte-pick-up are essential processes in fertilization. Herein, we found associations between autoimmune disease and the aforementioned processes in mice. At three and six months, along with the evaluation of autoimmune disease indices, the ovary, mesosalpinx, and oviducts were histologically examined in C57BL/6, MRL/MpJ, and MRL/MpJ-Fas lpr/lpr mice as healthy control, mild and severe models of autoimmune disease, respectively. In superovulated mice, the number of "oocyte cumulus complexes" found in the ampulla was macroscopically counted, and that of "ovulated oocytes" was histologically evaluated, as indicated by ruptured follicles or corpora hemorrhagica in ovaries. Finally, the oocyte-pick-up rate was calculated. In MRL/MpJ-Fas lpr/lpr mice, the oocyte-pick-up rate decreased with disease-related deterioration, unlike in other mouse strains. Further, more ovulated oocytes were found in MRL/MpJ mice than in C57BL/6 mice, and this number significantly decreased with aging in MRL/MpJ-Fas lpr/lpr mice. Numerous T-cells infiltrated into the infundibulum or a part of the mesosalpinx in aged MRL/MpJ-Fas lpr/lpr mice, and their infundibulum showed swelling and fewer ciliated epithelial cells compared to that of C57BL/6 mice. In conclusion, the progression of severe autoimmune disease affected the oocyte-pick-up process through histopathological changes in the infundibulum. These results provide important insights into female infertility associated with autoimmune disease.

What Multilevel Parallel Programs do when you are not Watching: A Performance Analysis Case Study Comparing MPI/OpenMP, MLP, and Nested OpenMP

NASA Technical Reports Server (NTRS)

Jost, Gabriele; Labarta, Jesus; Gimenez, Judit

2004-01-01

With the current trend in parallel computer architectures towards clusters of shared memory symmetric multi-processors, parallel programming techniques have evolved that support parallelism beyond a single level. When comparing the performance of applications based on different programming paradigms, it is important to differentiate between the influence of the programming model itself and other factors, such as implementation specific behavior of the operating system (OS) or architectural issues. Rewriting-a large scientific application in order to employ a new programming paradigms is usually a time consuming and error prone task. Before embarking on such an endeavor it is important to determine that there is really a gain that would not be possible with the current implementation. A detailed performance analysis is crucial to clarify these issues. The multilevel programming paradigms considered in this study are hybrid MPI/OpenMP, MLP, and nested OpenMP. The hybrid MPI/OpenMP approach is based on using MPI [7] for the coarse grained parallelization and OpenMP [9] for fine grained loop level parallelism. The MPI programming paradigm assumes a private address space for each process. Data is transferred by explicitly exchanging messages via calls to the MPI library. This model was originally designed for distributed memory architectures but is also suitable for shared memory systems. The second paradigm under consideration is MLP which was developed by Taft. The approach is similar to MPi/OpenMP, using a mix of coarse grain process level parallelization and loop level OpenMP parallelization. As it is the case with MPI, a private address space is assumed for each process. The MLP approach was developed for ccNUMA architectures and explicitly takes advantage of the availability of shared memory. A shared memory arena which is accessible by all processes is required. Communication is done by reading from and writing to the shared memory.

The MP (Materialization Pattern) Model for Representing Math Educational Standards

NASA Astrophysics Data System (ADS)

Choi, Namyoun; Song, Il-Yeol; An, Yuan

Representing natural languages with UML has been an important research issue for various reasons. Little work has been done for modeling imperative mood sentences which are the sentence structure of math educational standard statements. In this paper, we propose the MP (Materialization Pattern) model that captures the semantics of English sentences used in math educational standards. The MP model is based on the Reed-Kellogg sentence diagrams and creates MP schemas with the UML notation. The MP model explicitly represents the semantics of the sentences by extracting math concepts and the cognitive process of math concepts from math educational standard statements, and simplifies modeling. This MP model is also developed to be used for aligning math educational standard statements via schema matching.

User applications driven by the community contribution framework MPContribs in the Materials Project

DOE PAGES

Huck, P.; Gunter, D.; Cholia, S.; ...

2015-10-12

This paper discusses how the MPContribs framework in the Materials Project (MP) allows user-contributed data to be shown and analyzed alongside the core MP database. The MP is a searchable database of electronic structure properties of over 65,000 bulk solid materials, which is accessible through a web-based science-gateway. We describe the motivation for enabling user contributions to the materials data and present the framework's features and challenges in the context of two real applications. These use cases illustrate how scientific collaborations can build applications with their own 'user-contributed' data using MPContribs. The Nanoporous Materials Explorer application provides a unique searchmore » interface to a novel dataset of hundreds of thousands of materials, each with tables of user-contributed values related to material adsorption and density at varying temperature and pressure. The Unified Theoretical and Experimental X-ray Spectroscopy application discusses a full workflow for the association, dissemination, and combined analyses of experimental data from the Advanced Light Source with MP's theoretical core data, using MPContribs tools for data formatting, management, and exploration. The capabilities being developed for these collaborations are serving as the model for how new materials data can be incorporated into the MP website with minimal staff overhead while giving powerful tools for data search and display to the user community.« less

The L, M, and S Segments of Rift Valley Fever Virus MP-12 Vaccine Independently Contribute to a Temperature-Sensitive Phenotype

PubMed Central

Nishiyama, Shoko; Lokugamage, Nandadeva

2016-01-01

ABSTRACT Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by “abortion storms” in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff (100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of the M or L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in the M segment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments. IMPORTANCE Rift Valley fever (RVF) is a mosquito-borne viral disease endemic to Africa, characterized by high rates of abortion in ruminants and severe diseases in humans. Vaccination is important to prevent the spread of disease, and a live-attenuated MP-12 vaccine is currently the only vaccine with a conditional license in the United States. This study determined the temperature sensitivity (ts) of MP-12 vaccine to understand virologic characteristics. Our study revealed that MP-12 vaccine contains ts mutations independently in the L, M, and S segments and that MP-12 displays a restrictive replication at 38°C. PMID:26819307

The L, M, and S Segments of Rift Valley Fever Virus MP-12 Vaccine Independently Contribute to a Temperature-Sensitive Phenotype.

PubMed

Nishiyama, Shoko; Lokugamage, Nandadeva; Ikegami, Tetsuro

2016-01-27

Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by "abortion storms" in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff (100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of the M or L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in the M segment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments. Rift Valley fever (RVF) is a mosquito-borne viral disease endemic to Africa, characterized by high rates of abortion in ruminants and severe diseases in humans. Vaccination is important to prevent the spread of disease, and a live-attenuated MP-12 vaccine is currently the only vaccine with a conditional license in the United States. This study determined the temperature sensitivity (ts) of MP-12 vaccine to understand virologic characteristics. Our study revealed that MP-12 vaccine contains ts mutations independently in the L, M, and S segments and that MP-12 displays a restrictive replication at 38°C. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Quantum Mechanics Approach to Hydration Energies and Structures of Alanine and Dialanine.

PubMed

Lanza, Giuseppe; Chiacchio, Maria A

2017-06-20

A systematic approach to the phenomena related to hydration of biomolecules is reported at the state of the art of electronic-structure methods. Large-scale CCSD(T), MP4-SDQ, MP2, and DFT(M06-2X) calculations for some hydrated complexes of alanine and dialanine (Ala⋅13 H 2 O, Ala 2 H + ⋅18 H 2 O, and Ala 2 ⋅18 H 2 O) are compared with experimental data and other elaborate modeling to assess the reliability of a simple bottom-up approach. The inclusion of a minimal number of water molecules for microhydration of the polar groups together with the polarizable continuum model is sufficient to reproduce the relative bulk thermodynamic functions of the considered biomolecules. These quantities depend on the adopted electronic-structure method, which should be chosen with great care. Nevertheless, the computationally feasible MP2 and M06-2X functionals with the aug-cc-pVTZ basis set satisfactorily reproduce values derived by high-level CCSD(T) and MP4-SDQ methods, and thus they are suitable for future developments of more elaborate and hence more biochemically significant peptides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prostate cancer: computer-aided diagnosis on multiparametric MRI

NASA Astrophysics Data System (ADS)

Marin, Laura; Racoceanu, Daniel; Renard Penna, Raphaele; Ezziane, Malek

2017-11-01

Prostate cancer (PCa) is one of the most common cancers in men, being also the second most deadly cancer after lung cancer. There is increasing interest in active surveillance and minimally invasive focal therapies in PCa to avoid morbidities associated with whole gland therapy. Tumor volume represents an essential prognostic factor of PCa and the definition of index lesion volume is critical for appropriate decision making, especially for image guide focal treatment or in case of active surveillance. Multi-parametric Magnetic Resonance Imaging (mp-MRI) is the modality of choice for the detection and the localization of PCa foci. However, little has been published on mp-MRI accuracy in determining PCa volume, especially at 3T. There is insufficient evidence and no consensus to determine which of the methods for measuring volume is optimal. The objective of this study concerns the elaboration of an algorithm for automatic interpretation of mp-MRI. We determine the accuracy of the proposed method by comparing the prostate tumor volume issued from the automated volumetric mp-MRI measurements of the tumoral region, with manual and semi-automated volumetric measurements done by and respectively with radiologists. Information issued from whole mount histopathology is used to validate the whole approach.

The application of pentaprism scanning technology on the manufacturing of M3MP

NASA Astrophysics Data System (ADS)

Qi, Erhui; Hu, Haixiang; Hu, Haifei; Cole, Glen; Luo, Xiao; Ford, Virginia; Zhang, Xuejun

2016-10-01

The PSS (pentaprism scanning system) has advantages of simple structure, needless of reference flat, be able of on-site testing, etc, it plays an important role in large flat reflective mirror's manufacturing, especially the high accuracy testing of low order aberrations. The PSS system measures directly the slope information of the tested flat surface. Aimed at the unique requirement of M3MP, which is the prototype mirror of the tertiary mirror in TMT (Thirty Meter Telescope) project, this paper analyzed the slope distribution of low order aberrations, power and astigmatism, which is very important in the manufacturing process of M3MP. Then the sample route lines of PSS are reorganized and new data process algorism is implemented. All this work is done to improve PSS's measure sensitivity of power and astigmatism, for guiding the manufacturing process of M3MP.

Low levels of microplastics (MP) in wild mussels indicate that MP ingestion by humans is minimal compared to exposure via household fibres fallout during a meal.

PubMed

Catarino, Ana I; Macchia, Valeria; Sanderson, William G; Thompson, Richard C; Henry, Theodore B

2018-06-01

Microplastics (MPs) are the most numerous debris reported in marine environments and assessment of the amounts of MPs that accumulate in wild organisms is necessary for risk assessment. Our objective was to assess MP contamination in mussels collected around the coast of Scotland (UK) to identify characteristics of MPs and to evaluate risk of human exposure to MPs via ingestion of mussels. We deployed caged mussels (Mytilus edulis) in an urbanised estuary (Edinburgh, UK) to assess seasonal changes in plastic pollution, and collected mussels (Mytilus spp and subtidal Modiolus modiolus) from eight sampling stations around Scotland to enumerate MP types at different locations. We determined the potential exposure of humans to household dust fibres during a meal to compare with amounts of MPs present in edible mussels. The mean number of MPs in M. modiolus was 0.086 ± 0.031 (SE, n = 6)/g ww (3.5 ± 1.29 (SE) per mussel). In Mytilus spp, the mean number of MPs/g ww was 3.0 ± 0.9 (SE, n = 36) (3.2 ± 0.52 (SE) per mussel), but weight dependent. The visual accuracy of plastic fibres identification was estimated to be between 48 and 50%, using Nile Red staining and FT-IR methodologies, respectively, halving the observed amounts of MPs in wild mussels. We observed an allometric relationship between the number of MPs and the mussels wet weight. Our predictions of MPs ingestion by humans via consumption of mussels is 123 MP particles/y/capita in the UK and can go up to 4620 particles/y/capita in countries with a higher shellfish consumption. By comparison, the risk of plastic ingestion via mussel consumption is minimal when compared to fibre exposure during a meal via dust fallout in a household (13,731-68,415 particles/Y/capita). Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

From the sea to the laboratory: Characterization of microplastic as prerequisite for the assessment of ecotoxicological impact.

PubMed

Potthoff, Annegret; Oelschlägel, Kathrin; Schmitt-Jansen, Mechthild; Rummel, Christoph Daniel; Kühnel, Dana

2017-05-01

The presence of microplastic (MP) in the aquatic environment is recognized as a global-scale pollution issue. Secondary MP particles result from an ongoing fragmentation process governed by various biotic and abiotic factors. For a reliable risk assessment of these MP particles, knowledge about interactions with biota is needed. However, extensive testing with standard organisms under reproducible laboratory conditions with well-characterized MP suspensions is not available yet. As MP in the environment represents a mixture of particles differing in properties (e.g., size, color, polymer type, surface characteristics), it is likely that only specific particle fractions pose a threat towards organisms. In order to assign hazardous effects to specific particle properties, these characteristics need to be analyzed. As shown by the testing of particles (e.g. nanoparticles), characteristics other than chemical properties are important for the emergence of toxicity in organisms, and parameters such as surface area or size distribution need consideration. Therefore, the use of "well-defined" particles for ecotoxicological testing (i.e., standard particles) facilitates the establishment of causal links between physical-chemical properties of MP particles and toxic effects in organisms. However, the benefits of well-defined particles under laboratory conditions are offset by the disadvantage of the unknown comparability with MP in the environment. Therefore, weathering effects caused by biological, chemical, physical or mechanical processes have to be considered. To date, the characterization of the progression of MP weathering based on powder and suspension characterization methods is in its infancy. The aim of this commentary is to illustrate the prerequisites for testing MP in the laboratory from 3 perspectives: (i) knowledge of particle properties; (ii) behavior of MP in test setups involving ecotoxicological test organisms; and (iii) accordingly, test conditions that may need adjustment. Only under those prerequisites will reliable hazard assessment of MP be feasible. Integr Environ Assess Manag 2017;13:500-504. © 2017 SETAC. © 2017 SETAC.

Incorporating DSA in multipatterning semiconductor manufacturing technologies

NASA Astrophysics Data System (ADS)

Badr, Yasmine; Torres, J. A.; Ma, Yuansheng; Mitra, Joydeep; Gupta, Puneet

2015-03-01

Multi-patterning (MP) is the process of record for many sub-10nm process technologies. The drive to higher densities has required the use of double and triple patterning for several layers; but this increases the cost of the new processes especially for low volume products in which the mask set is a large percentage of the total cost. For that reason there has been a strong incentive to develop technologies like Directed Self Assembly (DSA), EUV or E-beam direct write to reduce the total number of masks needed in a new technology node. Because of the nature of the technology, DSA cylinder graphoepitaxy only allows single-size holes in a single patterning approach. However, by integrating DSA and MP into a hybrid DSA-MP process, it is possible to come up with decomposition approaches that increase the design flexibility, allowing different size holes or bar structures by independently changing the process for every patterning step. A simple approach to integrate multi-patterning with DSA is to perform DSA grouping and MP decomposition in sequence whether it is: grouping-then-decomposition or decomposition-then-grouping; and each of the two sequences has its pros and cons. However, this paper describes why these intuitive approaches do not produce results of acceptable quality from the point of view of design compliance and we highlight the need for custom DSA-aware MP algorithms.

Systemic Exposure to Thiopurines and Risk of Relapse in Children With Acute Lymphoblastic Leukemia: A Children's Oncology Group Study.

PubMed

Bhatia, Smita; Landier, Wendy; Hageman, Lindsey; Chen, Yanjun; Kim, Heeyoung; Sun, Can-Lan; Kornegay, Nancy; Evans, William E; Angiolillo, Anne L; Bostrom, Bruce; Casillas, Jacqueline; Lew, Glen; Maloney, Kelly W; Mascarenhas, Leo; Ritchey, A Kim; Termuhlen, Amanda M; Carroll, William L; Wong, F Lennie; Relling, Mary V

2015-06-01

Variability in prescribed doses of 6-mercaptopurine (6MP) and lack of adherence to a 6MP treatment regimen could result in intra-individual variability in systemic exposure to 6MP (measured as erythrocyte thioguanine nucleotide [TGN] levels) in children with acute lymphoblastic leukemia (ALL). The effect on relapse risk of this variability is unknown. To determine the effect of high intra-individual variability of 6MP systemic exposure on relapse risk in children with ALL. We used a prospective longitudinal design (Children's Oncology Group study [COG-AALL03N1]) to monitor 6MP and disease relapse in 742 children with ALL in ambulatory care settings of 94 participating institutions from May 30, 2005, to September 9, 2011. All participants met the following eligibility criteria: (1) diagnosis of ALL at 21 years or younger; (2) first continuous remission in progress at the time of study entry; (3) receiving self-, parent-, or caregiver-administered oral 6MP during maintenance therapy; and (4) completion of at least 6 months of maintenance therapy at the time of study enrollment. The median patient age at diagnosis was 5 years; 68% were boys; and 43% had National Cancer Institute-based high-risk disease. Daily 6MP regimen adherence was measured over 68 716 person-days using an electronic system that recorded the date and time of each 6MP bottle opening; adherence rate was defined as the ratio of days that a 6MP bottle was opened to days thata 6MP bottle was prescribed. Average monthly 6MP dose intensity was measured over 120 439 person-days by dividing the number of 6MP doses actually prescribed by the number of planned protocol doses (75 mg/m2/d). Monthly erythrocyte TGN levels (pmol/8 × 108 erythrocytes) were measured over 6 consecutive months per patient (n = 3944 measurements). Using intra-individual coefficients of variation (CV%), patients were classified as having stable (CV% <85th percentile) vs varying (CV% ≥85th percentile) indices. Median follow-up time was 6.7 years from the time of diagnosis. Adjusting for clinical prognosticators, we found that patients with 6MP nonadherence (mean adherence rate <95%) were at a 2.7-fold increased risk of relapse (95% CI, 1.3-5.6; P = .01) compared with patients with a mean adherence rate of 95% or greater. Among adherers, high intra-individual variability in TGN levels contributed to increased relapse risk (hazard ratio, 4.4; 95% CI, 1.2-15.7; P = .02). Furthermore, adherers with varying TGN levels had varying 6MP dose intensity (odds ratio [OR], 4.5; 95% CI, 1.5-13.4; P = .01) and 6MP drug interruptions (OR, 10.2; 95% CI, 2.2-48.3; P = .003). These findings emphasize the need to maximize 6MP regimen adherence and maintain steady thiopurine exposure to minimize relapse in children with ALL.

Breaking down barriers in cooperative fault management: Temporal and functional information displays

NASA Technical Reports Server (NTRS)

Potter, Scott S.; Woods, David D.

1994-01-01

At the highest level, the fundamental question addressed by this research is how to aid human operators engaged in dynamic fault management. In dynamic fault management there is some underlying dynamic process (an engineered or physiological process referred to as the monitored process - MP) whose state changes over time and whose behavior must be monitored and controlled. In these types of applications (dynamic, real-time systems), a vast array of sensor data is available to provide information on the state of the MP. Faults disturb the MP and diagnosis must be performed in parallel with responses to maintain process integrity and to correct the underlying problem. These situations frequently involve time pressure, multiple interacting goals, high consequences of failure, and multiple interleaved tasks.

Emission and Structure-Varying ZnO and Carbon Nanocrystal Composite in Mechanical Processing

NASA Astrophysics Data System (ADS)

Torchynska, T.; Perez Millan, B.; Polupan, G.; Kakazey, M.

2018-03-01

Morphology, photoluminescence (PL), and Raman scattering spectra have been investigated for mixtures of ZnO+0.1%C nanocrystals (NCs) at different stages of mechanical processing (MP). The transformation of graphite into graphene monolayers covering the ZnO NC surface is revealed for the first MP stage. The interaction with oxygen has been detected in the second MP stage which leads to the dissolution of oxygen interstitials in the ZnO NCs and to the formation of graphene (graphite) oxides. Increasing the concentration of the oxygen interstitials in ZnO NCs also enhances the intensity stimulation of the orange PL band (2.18eV). Simultaneously, the PL band peaking at 2.82-2.90 eV is detected in the PL spectra of the ZnO+0.1%C NC mixture after MP for 9-90 min. Then, the variation of the ZnO NC shape, agglomeration of ZnO NCs, modification of ZnO defects and decreasing PL intensity have been detected after prolonged MP for 390 min. It is expected that short stages of MP can be useful for ZnO NC surface covering by graphene layers or graphene (graphite) oxides.

[Effect of Corynebacterium non diphtheriae on functional activity and apoptosis of macrophages].

PubMed

Kharseeva, G G; Voronina, N A; Tiukavkina, S Iu

2014-01-01

Determine the ability of Corynebacterium non diphtheriae to induce phagocytosis and apoptosis of macrophages and evaluate regulatory effect of nuetrophilokines (NPK) induced by Corynebacterium non diphtheriae on these processes. The ability of Corynebacterium non diphtheriae, isolated from upper respiratory tract, skin and urogenital tract (UGT) were studied for the ability to induce phagocytosis and apoptosis of mice macrophages (MP; in vitro during staining by May-Grunwald with additional staining by Romanowsky-Giemsa) before and after the addition of NPK induced by Corynebacterium non diphtheriae. Phagocytic index (PI) was the same for all the Corynebacterium non diphtheriae species, phagocytic number (PN) and index of phagocytosis completion (IPC)--were minimal relative to corynebacteria isolated from UGT. All the studied corynebacteria species induced MP apoptosis; the most pronounced apoptogenic effect was detected in Corynebacterium pseudotuberculosis isolated from UGT. NPK increased PN against corynebacteria isolated from the studied biotopes, IPC--only during studies of corynebacteria isolated from skin. The effect of NPK resulted in a reduction of apoptogenic effect for almost all the Corynebacterium non diphtheriae, regardless of the isolation location. A pronounced apoptogenic effect and insufficiency of phagocytosis processes induced by corynebacteria are the means of realization of Corynebacterium non diphtheriae pathogenic effect. NPK use is possible for immune correction of immune deficiency conditions developing against the background of diseases determined by Corynebacterium non diphtheriae.

Research study on materials processing in space, experiment M512

NASA Technical Reports Server (NTRS)

Rubenstein, M.; Hopkins, R. H.; Kim, H. B.

1973-01-01

Gallium arsenide, a commercially valuable semiconductor, has been prepared from the melt (M.P. 1237C), by vapor growth, and by growth from metallic solutions. It has been established that growth from metallic solution can produce material with high, and perhaps with the highest possible, chemical homogeneity and crystalline perfection. Growth of GaAs from metallic solution can be performed at relatively low temperatures (about 600C) and is relatively insensitive to temperature fluctuations. However, this type of crystal growth is subject to the decided disadvantage that density induced convection currents may produce variations in rates of growth at a growing surface. This problem would be minimized under reduced gravity conditions.

The Pariser-Parr-Pople model for trans-polyenes. I. Ab initio and semiempirical study of the bond alternation in trans-butadiene

NASA Astrophysics Data System (ADS)

Förner, Wolfgang

1992-03-01

Ab initio investigations of the bond alternation in butadiene are presented. The atomic basis sets applied range from minimal to split valence plus polarization quality. With the latter one the Hartree-Fock limit for the bond alternation is reached. Correlation is considered on Møller-Plesset many-body perturbation theory of second order (MP2), linear coupled cluster doubles (L-CCD) and coupled cluster doubles (CCD) level. For the smaller basis sets it is shown that for the bond alternation π-π correlations are essential while the effects of σ-σ and σ-π correlations are, though large, nearly independent of bond alternation. On MP2 level the variation of σ-π correlation with bond alternation is surprisingly large. This is discussed as an artefact of MP2. Comparative Su-Schrieffer-Heeger (SSH) and Pariser-Parr-Pople (PPP) calculations show that these models in their usual parametrizations cannot reproduce the ab initio results.

A general range-separated double-hybrid density-functional theory

NASA Astrophysics Data System (ADS)

Kalai, Cairedine; Toulouse, Julien

2018-04-01

A range-separated double-hybrid (RSDH) scheme which generalizes the usual range-separated hybrids and double hybrids is developed. This scheme consistently uses a two-parameter Coulomb-attenuating-method (CAM)-like decomposition of the electron-electron interaction for both exchange and correlation in order to combine Hartree-Fock exchange and second-order Møller-Plesset (MP2) correlation with a density functional. The RSDH scheme relies on an exact theory which is presented in some detail. Several semi-local approximations are developed for the short-range exchange-correlation density functional involved in this scheme. After finding optimal values for the two parameters of the CAM-like decomposition, the RSDH scheme is shown to have a relatively small basis dependence and to provide atomization energies, reaction barrier heights, and weak intermolecular interactions globally more accurate or comparable to range-separated MP2 or standard MP2. The RSDH scheme represents a new family of double hybrids with minimal empiricism which could be useful for general chemical applications.

Atomic orbital-based SOS-MP2 with tensor hypercontraction. II. Local tensor hypercontraction

NASA Astrophysics Data System (ADS)

Song, Chenchen; Martínez, Todd J.

2017-01-01

In the first paper of the series [Paper I, C. Song and T. J. Martinez, J. Chem. Phys. 144, 174111 (2016)], we showed how tensor-hypercontracted (THC) SOS-MP2 could be accelerated by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs). This reduced the formal scaling of the SOS-MP2 energy calculation to cubic with respect to system size. The computational bottleneck then becomes the THC metric matrix inversion, which scales cubically with a large prefactor. In this work, the local THC approximation is proposed to reduce the computational cost of inverting the THC metric matrix to linear scaling with respect to molecular size. By doing so, we have removed the primary bottleneck to THC-SOS-MP2 calculations on large molecules with O(1000) atoms. The errors introduced by the local THC approximation are less than 0.6 kcal/mol for molecules with up to 200 atoms and 3300 basis functions. Together with the graphical processing unit techniques and locality-exploiting approaches introduced in previous work, the scaled opposite spin MP2 (SOS-MP2) calculations exhibit O(N2.5) scaling in practice up to 10 000 basis functions. The new algorithms make it feasible to carry out SOS-MP2 calculations on small proteins like ubiquitin (1231 atoms/10 294 atomic basis functions) on a single node in less than a day.

Atomic orbital-based SOS-MP2 with tensor hypercontraction. II. Local tensor hypercontraction.

PubMed

Song, Chenchen; Martínez, Todd J

2017-01-21

In the first paper of the series [Paper I, C. Song and T. J. Martinez, J. Chem. Phys. 144, 174111 (2016)], we showed how tensor-hypercontracted (THC) SOS-MP2 could be accelerated by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs). This reduced the formal scaling of the SOS-MP2 energy calculation to cubic with respect to system size. The computational bottleneck then becomes the THC metric matrix inversion, which scales cubically with a large prefactor. In this work, the local THC approximation is proposed to reduce the computational cost of inverting the THC metric matrix to linear scaling with respect to molecular size. By doing so, we have removed the primary bottleneck to THC-SOS-MP2 calculations on large molecules with O(1000) atoms. The errors introduced by the local THC approximation are less than 0.6 kcal/mol for molecules with up to 200 atoms and 3300 basis functions. Together with the graphical processing unit techniques and locality-exploiting approaches introduced in previous work, the scaled opposite spin MP2 (SOS-MP2) calculations exhibit O(N 2.5 ) scaling in practice up to 10 000 basis functions. The new algorithms make it feasible to carry out SOS-MP2 calculations on small proteins like ubiquitin (1231 atoms/10 294 atomic basis functions) on a single node in less than a day.

Ultra-low dose quantitative CT myocardial perfusion imaging with sparse-view dynamic acquisition and image reconstruction: A feasibility study.

PubMed

Enjilela, Esmaeil; Lee, Ting-Yim; Hsieh, Jiang; Wisenberg, Gerald; Teefy, Patrick; Yadegari, Andrew; Bagur, Rodrigo; Islam, Ali; Branch, Kelley; So, Aaron

2018-03-01

We implemented and validated a compressed sensing (CS) based algorithm for reconstructing dynamic contrast-enhanced (DCE) CT images of the heart from sparsely sampled X-ray projections. DCE CT imaging of the heart was performed on five normal and ischemic pigs after contrast injection. DCE images were reconstructed with filtered backprojection (FBP) and CS from all projections (984-view) and 1/3 of all projections (328-view), and with CS from 1/4 of all projections (246-view). Myocardial perfusion (MP) measurements with each protocol were compared to those with the reference 984-view FBP protocol. Both the 984-view CS and 328-view CS protocols were in good agreements with the reference protocol. The Pearson correlation coefficients of 984-view CS and 328-view CS determined from linear regression analyses were 0.98 and 0.99 respectively. The corresponding mean biases of MP measurement determined from Bland-Altman analyses were 2.7 and 1.2ml/min/100g. When only 328 projections were used for image reconstruction, CS was more accurate than FBP for MP measurement with respect to 984-view FBP. However, CS failed to generate MP maps comparable to those with 984-view FBP when only 246 projections were used for image reconstruction. DCE heart images reconstructed from one-third of a full projection set with CS were minimally affected by aliasing artifacts, leading to accurate MP measurements with the effective dose reduced to just 33% of conventional full-view FBP method. The proposed CS sparse-view image reconstruction method could facilitate the implementation of sparse-view dynamic acquisition for ultra-low dose CT MP imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

Attenuation and protective efficacy of Rift Valley fever phlebovirus rMP12-GM50 strain.

PubMed

Ly, Hoai J; Nishiyama, Shoko; Lokugamage, Nandadeva; Smith, Jennifer K; Zhang, Lihong; Perez, David; Juelich, Terry L; Freiberg, Alexander N; Ikegami, Tetsuro

2017-12-04

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula that affects sheep, cattle, goats, camels, and humans. Effective vaccination of susceptible ruminants is important for the prevention of RVF outbreaks. Live-attenuated RVF vaccines are in general highly immunogenic in ruminants, whereas residual virulence might be a concern for vulnerable populations. It is also important for live-attenuated strains to encode unique genetic markers for the differentiation from wild-type RVFV strains. In this study, we aimed to strengthen the attenuation profile of the MP-12 vaccine strain via the introduction of 584 silent mutations. To minimize the impact on protective efficacy, codon usage and codon pair bias were not de-optimized. The resulting rMP12-GM50 strain showed 100% protective efficacy with a single intramuscular dose, raising a 1:853 mean titer of plaque reduction neutralization test. Moreover, outbred mice infected with one of three pathogenic reassortant ZH501 strains, which encoded rMP12-GM50 L-, M-, or S-segments, showed 90%, 50%, or 30% survival, respectively. These results indicate that attenuation of the rMP12-GM50 strain is significantly attenuated via the L-, M-, and S-segments. Recombinant RVFV vaccine strains encoding similar silent mutations will be also useful for the surveillance of reassortant strains derived from vaccine strains in endemic countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fabrication of biodegradable micelles with reduction-triggered release of 6-mercaptopurine profile based on disulfide-linked graft copolymer conjugate.

PubMed

Zhang, Xuzhu; Du, Fang; Huang, Jin; Lu, Wei; Liu, Shiyuan; Yu, Jiahui

2012-12-01

This research is aimed to develop a biodegradable micelle delivery system with sheddable poly (ethylene glycol) shell to achieve the reduction-triggered intracellular sustained release of 6-mercaptopurine (6-MP) and decreased toxicity. Firstly, the amino-disulfide linked poly (ethylene glycol) monomethyl ether (mPEG-SS-NH(2)) was synthesized by the amidation reaction between cystamine and active ester of mPEG and p-nitrophenyl chloroformate (p-NPC) (mPEG-NPC). And then, the five-member rings in poly (l-succinimide) (PSI) were successively opened by mPEG-SS-NH(2) and 2-(pyridyldithio)-ethylamine (PDA) to produce the graft copolymer of mPEG-SS-NH-graft-PAsp-PDA. To avoid the drug initial burst, 6-MP was covalently conjugated with mPEG-SS-NH-graft-PAsp-PDA by thoil-disulfide exchange reaction to give the resultant product mPEG-SS-NH-graft-PAsp-MP. The product was found to form spherical micelles in aqueous media because of its amphiphilic nature with average particle size of 160 nm measured by dynamic light scattering (DLS). It was found that the mPEG-SS-NH-graft-PAsp-MP micelles, though stable in phosphate buffer solution (PBS), were prone to aggregation in the presence of dithiothreitol (DTT). The in vitro drug release studies revealed the release of 6-MP were distinct from the conventional micelles whose drugs loaded by physical encapsulation. Sustained release profile of 6-MP over 85 h was found in the presence of DTT (40 mM) simulating the intracellular condition while minimal drug release was observed within 24h at the level of DTT corresponding to extracellular environment. Remarkably, the cell viability results showed there was essential decrease of cytotoxicity to HL-60 cell line compared to free 6-MP. Copyright © 2012 Elsevier B.V. All rights reserved.

Neural integration of speech and gesture in schizophrenia: evidence for differential processing of metaphoric gestures.

PubMed

Straube, Benjamin; Green, Antonia; Sass, Katharina; Kirner-Veselinovic, André; Kircher, Tilo

2013-07-01

Gestures are an important component of interpersonal communication. Especially, complex multimodal communication is assumed to be disrupted in patients with schizophrenia. In healthy subjects, differential neural integration processes for gestures in the context of concrete [iconic (IC) gestures] and abstract sentence contents [metaphoric (MP) gestures] had been demonstrated. With this study we wanted to investigate neural integration processes for both gesture types in patients with schizophrenia. During functional magnetic resonance imaging-data acquisition, 16 patients with schizophrenia (P) and a healthy control group (C) were shown videos of an actor performing IC and MP gestures and associated sentences. An isolated gesture (G) and isolated sentence condition (S) were included to separate unimodal from bimodal effects at the neural level. During IC conditions (IC > G ∩ IC > S) we found increased activity in the left posterior middle temporal gyrus (pMTG) in both groups. Whereas in the control group the left pMTG and the inferior frontal gyrus (IFG) were activated for the MP conditions (MP > G ∩ MP > S), no significant activation was found for the identical contrast in patients. The interaction of group (P/C) and gesture condition (MP/IC) revealed activation in the bilateral hippocampus, the left middle/superior temporal and IFG. Activation of the pMTG for the IC condition in both groups indicates intact neural integration of IC gestures in schizophrenia. However, failure to activate the left pMTG and IFG for MP co-verbal gestures suggests a disturbed integration of gestures embedded in an abstract sentence context. This study provides new insight into the neural integration of co-verbal gestures in patients with schizophrenia. Copyright © 2012 Wiley Periodicals, Inc.

Safety and immunogenicity of a modified process hepatitis B vaccine in healthy neonates.

PubMed

Minervini, Gianmaria; McCarson, Barbara J; Reisinger, Keith S; Martin, Jason C; Stek, Jon E; Atkins, Barbara M; Nadig, Karin B; Liska, Vladimir; Schödel, Florian P; Bhuyan, Prakash K

2012-02-14

A manufacturing process using a modified adjuvant was developed to optimize the consistency and immunogenicity for recombinant hepatitis B vaccine (control: RECOMBIVAX-HB™). This modified process hepatitis B vaccine (mpHBV), which was previously shown to have an acceptable safety and immunogenicity profile in young adults, has now been studied in newborn infants. Healthy 1-10-day-old neonates (N=566) received 3 intramuscular doses (5μg hepatitis B surface antigen [HBsAg] per dose) of either mpHBV or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed at Month 7 (1 month Postdose 3). Anti-HBs geometric mean titers (GMTs) and seroprotection rates (SPRs) (% of subjects with an anti-HBs titer ≥10mIU/mL) were compared at Month 7. After each dose, injection-site adverse experiences (AEs) and axillary temperatures were recorded for 5 days; systemic AEs were recorded for Days 1-14. Month 7 SPR was 97.9% for the mpHBV group and 98.9% for the control. The GMT was 843.7mIU/mL for the mpHBV group and 670.1mIU/mL for the control. The GMT ratio (mpHBV/control) was 1.26 (95% confidence interval [CI]: 0.94, 1.69), meeting the prespecified non-inferiority criteria. The percentages of subjects reporting any AE, injection-site AEs, or systemic AEs were similar across the 2 vaccination groups. There were no serious AEs. The safety profile of mpHBV was comparable to that of the control vaccine. The geometric mean antibody titer for mpHBV was higher than control vaccine in this infant population, but the difference did not meet the predefined statistical criterion for superiority. Copyright © 2012 Elsevier Ltd. All rights reserved.

Multiparametric Magnetic Resonance Imaging for Active Surveillance of Prostate Cancer.

PubMed

An, Julie Y; Sidana, Abhinav; Choyke, Peter L; Wood, Bradford J.; Pinto, Peter A; Türkbey, İsmail Barış

2017-09-29

Active surveillance has gained popularity as an acceptable management option for men with low-risk prostate cancer. Successful utilization of this strategy can delay or prevent unnecessary interventions - thereby reducing morbidity associated with overtreatment. The usefulness of active surveillance primarily depends on correct identification of patients with low-risk disease. However, current population-wide algorithms and tools do not adequately exclude high-risk disease, thereby limiting the confidence of clinicians and patients to go on active surveillance. Novel imaging tools such as mpMRI provide information about the size and location of potential cancers enabling more informed treatment decisions. The term "multiparametric" in prostate mpMRI refers to the summation of several MRI series into one examination whose initial goal is to identify potential clinically-significant lesions suitable for targeted biopsy. The main advantages of MRI are its superior anatomic resolution and the lack of ionizing radiation. Recently, the Prostate Imaging-Reporting and Data System has been instituted as an international standard for unifying mpMRI results. The imaging sequences in mpMRI defined by Prostate Imaging Reporting and Data System version 2 includes: T2-weighted MRI, diffusion-weighted MRI, derived apparent-diffusion coefficient from diffusion-weighted MRI, and dynamic contrast-enhanced MRI. The use of mpMRI prior to starting active surveillance could prevent those with missed, high-grade lesions from going on active surveillance, and reassure those with minimal disease who may be hesitant to take part in active surveillance. Although larger validation studies are still necessary, preliminary results suggest mpMRI has a role in selecting patients for active surveillance. Less certain is the role of mpMRI in monitoring patients on active surveillance, as data on this will take a long time to mature. The biggest obstacles to routine use of prostate MRI are quality control, cost, reproducibility, and access. Nevertheless, there is great a potential for mpMRI to improve outcomes and quality of treatment. The major roles of MRI will continue to expand and its emerging use in standard of care approaches becomes more clearly defined and supported by increasing levels of data.

The fourth space surgery: endoscopic subserosal dissection for upper gastrointestinal subepithelial tumors originating from the muscularis propria layer.

PubMed

Liu, Fei; Zhang, Song; Ren, Wei; Yang, Tian; Lv, Ying; Ling, Tingsheng; Zou, Xiaoping; Wang, Lei

2018-05-01

We developed a novel method of endoscopic subserosal dissection (ESSD) for removal of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the upper gastrointestinal (GI) tract. The aim of this study was to evaluate the efficacy, safety, and clinical outcome of this method. Eleven patients with upper GI SETs originating from the MP layer were treated by ESSD between October 2016 and March 2017. ESSD technique consists of six major procedures: (1) incising the mucosal and submucosal layer around the lesion and exposing MP layer; (2) continuous injection was performed while the injection needle slowly moved from the MP layer toward the subserosal layer; (3) incising MP layer; (4) subserosal injection was performed to further separate the serosa from the MP layer; (5) the mucosa, submucosa, and MP layer including SET were carefully dissected en bloc; and (6) closure of the gastric-wall defect with endoscopic techniques. Primary outcome including clinical procedural success and procedure-related adverse events were documented. ESSD was successfully performed in 11 patients. The complete resection rate was 100%, and the mean operation time was 51 (range 22-76) min. The mean resected lesion size was 27 (range 15-40) mm. Pathological diagnosis of these lesions included gastrointestinal stromal tumors (8/11), heterotopic pancreas (1/11), hamartoma (1/11), and leiomyoma (1/11). The small perforations occurred in two patients (4 × 4 and 5 × 5 mm, respectively) during the operation. All perforations and defects were closed successfully by endoscopic techniques. No GI bleeding, peritonitis, abdominal abscess, and other adverse events were observed. No lesion residual or recurrence was found during the follow-up period (mean 18 weeks; range 10-29 weeks). ESSD seems to be an efficacious, safe, and minimally invasive treatment for patients with upper GI SETs originating from the MP layer, making it possible to resect deep lesions, provide precise pathological diagnosis, and maintain the integrity of serosa.

Mucuna pruriens in Parkinson disease

PubMed Central

Laguna, Janeth; Cassani, Erica; Cereda, Emanuele; Pozzi, Nicolò G.; Isaias, Ioannis U.; Contin, Manuela; Barichella, Michela; Pezzoli, Gianni

2017-01-01

Objective: To investigate whether Mucuna pruriens (MP), a levodopa-containing leguminous plant growing in all tropical areas worldwide, may be used as alternative source of levodopa for indigent individuals with Parkinson disease (PD) who cannot afford long-term therapy with marketed levodopa preparations. Methods: We investigated efficacy and safety of single-dose intake of MP powder from roasted seeds obtained without any pharmacologic processing. Eighteen patients with advanced PD received the following treatments, whose sequence was randomized: (1) dispersible levodopa at 3.5 mg/kg combined with the dopa-decarboxylase inhibitor benserazide (LD+DDCI; the reference treatment); (2) high-dose MP (MP-Hd; 17.5 mg/kg); (3) low-dose MP (MP-Ld; 12.5 mg/kg); (4) pharmaceutical preparation of LD without DDCI (LD−DDCI; 17.5 mg/kg); (5) MP plus benserazide (MP+DDCI; 3.5 mg/kg); (6) placebo. Efficacy outcomes were the change in motor response at 90 and 180 minutes and the duration of on state. Safety measures included any adverse event (AE), changes in blood pressure and heart rate, and the severity of dyskinesias. Results: When compared to LD+DDCI, MP-Ld showed similar motor response with fewer dyskinesias and AEs, while MP-Hd induced greater motor improvement at 90 and 180 minutes, longer ON duration, and fewer dyskinesias. MP-Hd induced less AEs than LD+DDCI and LD−DDCI. No differences in cardiovascular response were recorded. Conclusion: Single-dose MP intake met all noninferiority efficacy and safety outcome measures in comparison to dispersible levodopa/benserazide. Clinical effects of high-dose MP were similar to levodopa alone at the same dose, with a more favorable tolerability profile. ClinicalTrials.gov identifier: NCT02680977. PMID:28679598

Mucuna pruriens in Parkinson disease: A double-blind, randomized, controlled, crossover study.

PubMed

Cilia, Roberto; Laguna, Janeth; Cassani, Erica; Cereda, Emanuele; Pozzi, Nicolò G; Isaias, Ioannis U; Contin, Manuela; Barichella, Michela; Pezzoli, Gianni

2017-08-01

To investigate whether Mucuna pruriens (MP), a levodopa-containing leguminous plant growing in all tropical areas worldwide, may be used as alternative source of levodopa for indigent individuals with Parkinson disease (PD) who cannot afford long-term therapy with marketed levodopa preparations. We investigated efficacy and safety of single-dose intake of MP powder from roasted seeds obtained without any pharmacologic processing. Eighteen patients with advanced PD received the following treatments, whose sequence was randomized: (1) dispersible levodopa at 3.5 mg/kg combined with the dopa-decarboxylase inhibitor benserazide (LD+DDCI; the reference treatment); (2) high-dose MP (MP-Hd; 17.5 mg/kg); (3) low-dose MP (MP-Ld; 12.5 mg/kg); (4) pharmaceutical preparation of LD without DDCI (LD-DDCI; 17.5 mg/kg); (5) MP plus benserazide (MP+DDCI; 3.5 mg/kg); (6) placebo. Efficacy outcomes were the change in motor response at 90 and 180 minutes and the duration of on state. Safety measures included any adverse event (AE), changes in blood pressure and heart rate, and the severity of dyskinesias. When compared to LD+DDCI, MP-Ld showed similar motor response with fewer dyskinesias and AEs, while MP-Hd induced greater motor improvement at 90 and 180 minutes, longer ON duration, and fewer dyskinesias. MP-Hd induced less AEs than LD+DDCI and LD-DDCI. No differences in cardiovascular response were recorded. Single-dose MP intake met all noninferiority efficacy and safety outcome measures in comparison to dispersible levodopa/benserazide. Clinical effects of high-dose MP were similar to levodopa alone at the same dose, with a more favorable tolerability profile. NCT02680977. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Interaction of the Tobacco mosaic virus movement protein with microtubules during the cell cycle in tobacco BY-2 cells.

PubMed

Boutant, Emmanuel; Fitterer, Chantal; Ritzenthaler, Christophe; Heinlein, Manfred

2009-10-01

Cell-to-cell movement of Tobacco mosaic virus (TMV) involves the interaction of virus-encoded 30-kDa movement protein (MP) with microtubules. In cells behind the infection front that accumulate high levels of MP, this activity is reflected by the formation of stabilized MP/microtubule complexes. The ability of MP to bind along and stabilize microtubules is conserved upon expression in mammalian cells. In mammalian cells, the protein also leads to inhibition of mitosis and cell division through a microtubule-independent process correlated with the loss of centrosomal gamma-tubulin and of centrosomal microtubule-nucleation activity. Since MP has the capacity to interact with plant factors involved in microtubule nucleation and dynamics, we used inducible expression in BY-2 cells to test whether MP expression inhibits mitosis and cell division also in plants. We demonstrate that MP:GFP associates with all plant microtubule arrays and, unlike in mammalian cells, does not interfere with mitosis. Thus, MP function and the interaction of MP with factors of the cytoskeleton do not entail an inhibition of mitosis in plants. We also report that the protein targets primary plasmodesmata in BY-2 cells immediately upon or during cytokinesis and that the accumulation of MP in plasmodesmata occurs in the presence of inhibitors of the cytoskeleton and the secretory pathway.

Functional diversification of cerato-platanins in Moniliophthora perniciosa as seen by differential expression and protein function specialization.

PubMed

de O Barsottini, Mario R; de Oliveira, Juliana F; Adamoski, Douglas; Teixeira, Paulo J P L; do Prado, Paula F V; Tiezzi, Henrique O; Sforça, Mauricio L; Cassago, Alexandre; Portugal, Rodrigo V; de Oliveira, Paulo S L; de M Zeri, Ana C; Dias, Sandra M G; Pereira, Gonçalo A G; Ambrosio, Andre L B

2013-11-01

Cerato-platanins (CP) are small, cysteine-rich fungal-secreted proteins involved in the various stages of the host-fungus interaction process, acting as phytotoxins, elicitors, and allergens. We identified 12 CP genes (MpCP1 to MpCP12) in the genome of Moniliophthora perniciosa, the causal agent of witches' broom disease in cacao, and showed that they present distinct expression profiles throughout fungal development and infection. We determined the X-ray crystal structures of MpCP1, MpCP2, MpCP3, and MpCP5, representative of different branches of a phylogenetic tree and expressed at different stages of the disease. Structure-based biochemistry, in combination with nuclear magnetic resonance and mass spectrometry, allowed us to define specialized capabilities regarding self-assembling and the direct binding to chitin and N-acetylglucosamine (NAG) tetramers, a fungal cell wall building block, and to map a previously unknown binding region in MpCP5. Moreover, fibers of MpCP2 were shown to act as expansin and facilitate basidiospore germination whereas soluble MpCP5 blocked NAG6-induced defense response. The correlation between these roles, the fungus life cycle, and its tug-of-war interaction with cacao plants is discussed.

Effect of thermal processing on estimated metabolizable protein supply to dairy cattle from camelina seeds: relationship with protein molecular structural changes.

PubMed

Peng, Quanhui; Khan, Nazir A; Wang, Zhisheng; Zhang, Xuewei; Yu, Peiqiang

2014-08-20

This study evaluated the effect of thermal processing on the estimated metabolizable protein (MP) supply to dairy cattle from camelina seeds (Camelina sativa L. Crantz) and determined the relationship between heat-induced changes in protein molecular structural characteristics and the MP supply. Seeds from two camelina varieties were sampled in two consecutive years and were either kept raw or were heated in an autoclave (moist heating) or in an air-draft oven (dry heating) at 120 °C for 1 h. The MP supply to dairy cattle was modeled by three commonly used protein evaluation systems. The protein molecular structures were analyzed by Fourier transform/infrared-attenuated total reflectance molecular spectroscopy. The results showed that both the dry and moist heating increased the contents of truly absorbable rumen-undegraded protein (ARUP) and total MP and decreased the degraded protein balance (DPB). However, the moist-heated camelina seeds had a significantly higher (P < 0.05) content of ARUP and total MP and a significantly lower (P < 0.05) content of DPB than did the dry-heated camelina seeds. The regression equations showed that intensities of the protein molecular structural bands can be used to estimate the contents of ARUP, MP, and DPB with high accuracy (R(2) > 0.70). These results show that protein molecular structural characteristics can be used to rapidly assess the MP supply to dairy cattle from raw and heat-treated camelina seeds.

40 CFR 158.2120 - Microbial pesticides product analysis data requirements table.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Product Chemistry and Composition 885.1100 Product Identity R MP EP -- 885.1200 Manufacturing process R... Certification of limits R MP EP -- Physical and Chemical Characteristics 830.6302 Color R TGAI TGAI -- 830.6303...

40 CFR 158.2120 - Microbial pesticides product analysis data requirements table.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Product Chemistry and Composition 885.1100 Product Identity R MP EP -- 885.1200 Manufacturing process R... Certification of limits R MP EP -- Physical and Chemical Characteristics 830.6302 Color R TGAI TGAI -- 830.6303...

High-throughput NIR spectroscopic (NIRS) detection of microplastics in soil.

PubMed

Paul, Andrea; Wander, Lukas; Becker, Roland; Goedecke, Caroline; Braun, Ulrike

2018-05-12

The increasing pollution of terrestrial and aquatic ecosystems with plastic debris leads to the accumulation of microscopic plastic particles of still unknown amount. To monitor the degree of contamination, analytical methods are urgently needed, which help to quantify microplastics (MP). Currently, time-costly purified materials enriched on filters are investigated both by micro-infrared spectroscopy and/or micro-Raman. Although yielding precise results, these techniques are time consuming, and are restricted to the analysis of a small part of the sample in the order of few micrograms. To overcome these problems, we tested a macroscopic dimensioned near-infrared (NIR) process-spectroscopic method in combination with chemometrics. For calibration, artificial MP/ soil mixtures containing defined ratios of polyethylene, polyethylene terephthalate, polypropylene, and polystyrene with diameters < 125 μm were prepared and measured by a process FT-NIR spectrometer equipped with a fiber-optic reflection probe. The resulting spectra were processed by chemometric models including support vector machine regression (SVR), and partial least squares discriminant analysis (PLS-DA). Validation of models by MP mixtures, MP-free soils, and real-world samples, e.g., fermenter residue, suggests a reliable detection and a possible classification of MP at levels above 0.5 to 1.0 mass% depending on the polymer. The benefit of the combined NIRS chemometric approach lies in the rapid assessment whether soil contains MP, without any chemical pretreatment. The method can be used with larger sample volumes and even allows for an online prediction and thus meets the demand of a high-throughput method.

Comparison of MP AES and ICP-MS for analysis of principal and selected trace elements in nitric acid digests of sunflower (Helianthus annuus).

PubMed

Karlsson, Stefan; Sjöberg, Viktor; Ogar, Anna

2015-04-01

The use of nitrogen as plasma gas for microwave plasma atomic emission spectroscopy (MP AES) is an interesting development in analytical science since the running cost can be significantly reduced in comparison to the inductively coupled argon plasma. Here, we evaluate the performance of the Agilent 4100 MP AES instrument for the analysis of principal metals (Ca, K, Mg, and Na), lithogenic metals (Al, Fe, and Mn) and selected trace metals (As, Ba, Cd, Co, Cr, Cu, Mo, Ni, Pb, V, and Zn) in nitric acid plant digests. The digests were prepared by microwave-assisted dissolution of dry plant material from sunflower (Helianthus annuus) in concentrated nitric acid. Comparisons are made with analysis of the same solutions with ICP-MS (Agilent 7500cx) using the octopole reaction system (ORS) in the collision mode for As, Fe, and V. The limits of detection were usually in the low µg L(-1) range and all principal and lithogenic metals were successfully determined with the MP AES and provided almost identical results with the ICP-MS. The same applies for the selected trace metals except for As, Co and Mo where the concentrations were below the detection limit with the MP AES. For successful analysis we recommend that (i) only atom lines are used, (ii) ionization is minimized (e.g. addition of CsNO3) and (iii) the use of internal standards should be considered to resolve spectral interferences. Copyright © 2014 Elsevier B.V. All rights reserved.

40 CFR 158.2171 - Experimental use permit microbial pesticides product analysis data requirements table.

Code of Federal Regulations, 2014 CFR

2014-07-01

... notes Product Chemistry and Composition 885.1100 Product identity R MP EP 885.1200 Manufacturing process....1500 Certification of limits R MP EP Physical and Chemical Characteristics 830.6302 Color R TGAI TGAI...

40 CFR 158.2171 - Experimental use permit microbial pesticides product analysis data requirements table.

Code of Federal Regulations, 2013 CFR

2013-07-01

... notes Product Chemistry and Composition 885.1100 Product identity R MP EP 885.1200 Manufacturing process....1500 Certification of limits R MP EP Physical and Chemical Characteristics 830.6302 Color R TGAI TGAI...

Mycelial development preceding basidioma formation in Moniliophthora perniciosa is associated to chitin, sugar and nutrient metabolism alterations involving autophagy.

PubMed

Gomes, Dayane Santos; Lopes, Maíza Alves; Menezes, Sara Pereira; Ribeiro, Lidiane Figueredo; Dias, Cristiano Villela; Andrade, Bruno Silva; de Jesus, Raildo Mota; Pires, Acassia Benjamin Leal; Goes-Neto, Aristóteles; Micheli, Fabienne

2016-01-01

We identified and characterized two chitinases, named MpCHIT1 and MpCHIT2, from the fungus Moniliophthora perniciosa - the etiologic agent of witches' broom disease in cacao tree (Theobroma cacao L.) - during its development, mainly in the mycelia phases preceding the basidioma formation. The expression of MpCHIT1 and MpCHIT2, together with MpCHS and MpATG8 (chitin synthase and autophagy genes, respectively), was analyzed during the M. perniciosa growth and development on bran-based solid medium as well as in liquid medium containing H2O2 or rapamycin (oxidative and nutritional related-autophagy stress agents, respectively). In order to link the expression of chitin metabolism-related genes to nutritional composition influencing fungus development, we also quantified total and reduced sugars, as well as macro- and micronutrients in the bran-based solid medium. The expression analysis showed that the MpCHS expression increased through mycelial development and then decreased in the primordium and basidioma phases, while the expression of MpCHIT1 and MpCHIT2 was higher in basidioma and primordium phases, respectively. Moreover, the expression pattern of MpCHIT1 and MpCHIT2 is distinct, the second correlated with the MpATG8 expression pattern and possibly with autophagy process, while the first may be related to the basidioma formation. The quantification of total and reduced sugars, as well as macro- and micronutrients supported the idea that the cell wall restructuration due to MpCHS, MpCHIT1 and MpCHIT2 is related to stress and fungal nutrient reallocation, allowing the formation and development of the basidioma. Experiments involving M. perniciosa growth on liquid medium containing H2O2 or rapamycin showed that MpCHIT1 and MpCHIT2 were over-expressed in response to oxidative but also to nutritional related-autophagy stresses. Interestingly, the expression level of MpCHS, MpCHIT1 and MpCHIT2 in presence of rapamycin is similar to the one observed in the primordium and basidioma from bran-based solid medium. The analysis of the overall data allowed designing a general scheme of chitin metabolism and autophagy during M. perniciosa development, focusing on the mycelium phases as crucial and environmentally influenced steps preceding the primordium and basidioma formation. These data support the idea that the nutritional environment of M. perniciosa influences its development and life cycle. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of Neuromorphic Sift Operator with Application to High Speed Image Matching

NASA Astrophysics Data System (ADS)

Shankayi, M.; Saadatseresht, M.; Bitetto, M. A. V.

2015-12-01

There was always a speed/accuracy challenge in photogrammetric mapping process, including feature detection and matching. Most of the researches have improved algorithm's speed with simplifications or software modifications which increase the accuracy of the image matching process. This research tries to improve speed without enhancing the accuracy of the same algorithm using Neuromorphic techniques. In this research we have developed a general design of a Neuromorphic ASIC to handle algorithms such as SIFT. We also have investigated neural assignment in each step of the SIFT algorithm. With a rough estimation based on delay of the used elements including MAC and comparator, we have estimated the resulting chip's performance for 3 scenarios, Full HD movie (Videogrammetry), 24 MP (UAV photogrammetry), and 88 MP image sequence. Our estimations led to approximate 3000 fps for Full HD movie, 250 fps for 24 MP image sequence and 68 fps for 88MP Ultracam image sequence which can be a huge improvement for current photogrammetric processing systems. We also estimated the power consumption of less than10 watts which is not comparable to current workflows.

Conformations of organophosphine oxides

DOE PAGES

De Silva, Nuwan; Zahariev, Federico; Hay, Benjamin P.; ...

2015-07-17

The conformations of a series of organophosphine oxides, OP(CH 3) 2R, where R = methyl, ethyl, isopropyl, tert-butyl, vinyl, and phenyl, are predicted using the MP2/cc-pVTZ level of theory. Comparison of potential energy surfaces for rotation about P–C bonds with crystal structure data reveals a strong correlation between predicted location and energetics of minima and histograms of dihedral angle distributions observed in the solid state. In addition, the most stable conformers are those that minimize the extent of steric repulsion between adjacent rotor substituents, and the torsional barriers tend to increase with the steric bulk of the rotating alkyl group.more » MM3 force field parameters were adjusted to fit the MP2 results, providing a fast and accurate model for predicting organophosphine oxides shapes—an essential part of understanding the chemistry of these compounds. As a result, the predictive power of the modified MM3 model was tested against MP2/cc-pVTZ conformations for triethylphosphine oxide, OP(CH 2CH 3) 3, and triphenylphosphine oxide, OP(Ph) 3.« less

Exploring the Effects of Subfreezing Temperature and Salt Concentration on Ice Growth Inhibition of Antarctic Gram-Negative Bacterium Marinomonas Primoryensis Using Coarse-Grained Simulation.

PubMed

Nguyen, Hung; Dac Van, Thanh; Tran, Nhut; Le, Ly

2016-04-01

The aim of this work is to study the freezing process of water molecules surrounding Antarctic Gram-negative bacterium Marinomonas primoryensis antifreeze protein (MpAFP) and the MpAFP interactions to the surface of ice crystals under various marine environments (at different NaCl concentrations of 0.3, 0.6, and 0.8 mol/l). Our result indicates that activating temperature region of MpAFPs reduced as NaCl concentration increased. Specifically, MpAFP was activated and functioned at 0.6 mol/l with temperatures equal or larger 278 K, and at 0.8 mol/l with temperatures equal or larger 270 K. Additionally, MpAFP was inhibited by ice crystal network from 268 to 274 K and solid-liquid hybrid from 276 to 282 K at 0.3 mol/l concentration. Our results shed lights on structural dynamics of MpAFP among different marine environments.

Atomic orbital-based SOS-MP2 with tensor hypercontraction. I. GPU-based tensor construction and exploiting sparsity

NASA Astrophysics Data System (ADS)

Song, Chenchen; Martínez, Todd J.

2016-05-01

We present a tensor hypercontracted (THC) scaled opposite spin second order Møller-Plesset perturbation theory (SOS-MP2) method. By using THC, we reduce the formal scaling of SOS-MP2 with respect to molecular size from quartic to cubic. We achieve further efficiency by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs) to accelerate integral construction and matrix multiplication. The practical scaling of GPU-accelerated atomic orbital-based THC-SOS-MP2 calculations is found to be N2.6 for reference data sets of water clusters and alanine polypeptides containing up to 1600 basis functions. The errors in correlation energy with respect to density-fitting-SOS-MP2 are less than 0.5 kcal/mol for all systems tested (up to 162 atoms).

Atomic orbital-based SOS-MP2 with tensor hypercontraction. I. GPU-based tensor construction and exploiting sparsity.

PubMed

Song, Chenchen; Martínez, Todd J

2016-05-07

We present a tensor hypercontracted (THC) scaled opposite spin second order Møller-Plesset perturbation theory (SOS-MP2) method. By using THC, we reduce the formal scaling of SOS-MP2 with respect to molecular size from quartic to cubic. We achieve further efficiency by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs) to accelerate integral construction and matrix multiplication. The practical scaling of GPU-accelerated atomic orbital-based THC-SOS-MP2 calculations is found to be N(2.6) for reference data sets of water clusters and alanine polypeptides containing up to 1600 basis functions. The errors in correlation energy with respect to density-fitting-SOS-MP2 are less than 0.5 kcal/mol for all systems tested (up to 162 atoms).

Mathematical Modeling of Protein Misfolding Mechanisms in Neurological Diseases: A Historical Overview.

PubMed

Carbonell, Felix; Iturria-Medina, Yasser; Evans, Alan C

2018-01-01

Protein misfolding refers to a process where proteins become structurally abnormal and lose their specific 3-dimensional spatial configuration. The histopathological presence of misfolded protein (MP) aggregates has been associated as the primary evidence of multiple neurological diseases, including Prion diseases, Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob disease. However, the exact mechanisms of MP aggregation and propagation, as well as their impact in the long-term patient's clinical condition are still not well understood. With this aim, a variety of mathematical models has been proposed for a better insight into the kinetic rate laws that govern the microscopic processes of protein aggregation. Complementary, another class of large-scale models rely on modern molecular imaging techniques for describing the phenomenological effects of MP propagation over the whole brain. Unfortunately, those neuroimaging-based studies do not take full advantage of the tremendous capabilities offered by the chemical kinetics modeling approach. Actually, it has been barely acknowledged that the vast majority of large-scale models have foundations on previous mathematical approaches that describe the chemical kinetics of protein replication and propagation. The purpose of the current manuscript is to present a historical review about the development of mathematical models for describing both microscopic processes that occur during the MP aggregation and large-scale events that characterize the progression of neurodegenerative MP-mediated diseases.

Research on sub-surface damage and its stress deformation in the process of large aperture and high diameter-to-thickness ratio TMT M3MP

NASA Astrophysics Data System (ADS)

Hu, Hai-xiang; Qi, Erhui; Cole, Glen; Hu, Hai-fei; Luo, Xiao; Zhang, Xue-jun

2016-10-01

Large flat mirrors play important roles in large aperture telescopes. However, they also introduce unpredictable problems. The surface errors created during manufacturing, testing, and supporting are all combined during measurement, thus making understanding difficult for diagnosis and treatment. Examining a high diameter-to-thickness ratio flat mirror, TMT M3MP, and its unexpected deformation during processing, we proposed a strain model of subsurface damage to explain the observed phenomenon. We designed a set of experiment, and checked the validity of our diagnosis. On that basis, we theoretical predicted the trend of this strain and its scale effect on Zerodur®, and checked the validity on another piece experimentally. This work guided the grinding-polishing process of M3MP, and will be used as reference for M3M processing as well.

Monte Carlo MP2 on Many Graphical Processing Units.

PubMed

Doran, Alexander E; Hirata, So

2016-10-11

In the Monte Carlo second-order many-body perturbation (MC-MP2) method, the long sum-of-product matrix expression of the MP2 energy, whose literal evaluation may be poorly scalable, is recast into a single high-dimensional integral of functions of electron pair coordinates, which is evaluated by the scalable method of Monte Carlo integration. The sampling efficiency is further accelerated by the redundant-walker algorithm, which allows a maximal reuse of electron pairs. Here, a multitude of graphical processing units (GPUs) offers a uniquely ideal platform to expose multilevel parallelism: fine-grain data-parallelism for the redundant-walker algorithm in which millions of threads compute and share orbital amplitudes on each GPU; coarse-grain instruction-parallelism for near-independent Monte Carlo integrations on many GPUs with few and infrequent interprocessor communications. While the efficiency boost by the redundant-walker algorithm on central processing units (CPUs) grows linearly with the number of electron pairs and tends to saturate when the latter exceeds the number of orbitals, on a GPU it grows quadratically before it increases linearly and then eventually saturates at a much larger number of pairs. This is because the orbital constructions are nearly perfectly parallelized on a GPU and thus completed in a near-constant time regardless of the number of pairs. In consequence, an MC-MP2/cc-pVDZ calculation of a benzene dimer is 2700 times faster on 256 GPUs (using 2048 electron pairs) than on two CPUs, each with 8 cores (which can use only up to 256 pairs effectively). We also numerically determine that the cost to achieve a given relative statistical uncertainty in an MC-MP2 energy increases as O(n 3 ) or better with system size n, which may be compared with the O(n 5 ) scaling of the conventional implementation of deterministic MP2. We thus establish the scalability of MC-MP2 with both system and computer sizes.

Improving students’ mathematical representational ability through RME-based progressive mathematization

NASA Astrophysics Data System (ADS)

Warsito; Darhim; Herman, T.

2018-01-01

This study aims to determine the differences in the improving of mathematical representation ability based on progressive mathematization with realistic mathematics education (PMR-MP) with conventional learning approach (PB). The method of research is quasi-experiments with non-equivalent control group designs. The study population is all students of class VIII SMPN 2 Tangerang consisting of 6 classes, while the sample was taken two classes with purposive sampling technique. The experimental class is treated with PMR-MP while the control class is treated with PB. The instruments used are test of mathematical representation ability. Data analysis was done by t-test, ANOVA test, post hoc test, and descriptive analysis. The result of analysis can be concluded that: 1) there are differences of mathematical representation ability improvement between students treated by PMR-MP and PB, 2) no interaction between learning approach (PMR-MP, PB) and prior mathematics knowledge (PAM) to improve students’ mathematical representation; 3) Students’ mathematical representation improvement in the level of higher PAM is better than medium, and low PAM students. Thus, based on the process of mathematization, it is very important when the learning direction of PMR-MP emphasizes on the process of building mathematics through a mathematical model.

Establishment of dsDNA/GNs/chit/GCE biosensor and electrochemical study on interaction between 6-mercaptopurine and DNA.

PubMed

Tang, Wenwei; Zhang, Min; Zeng, Xinping

2014-01-01

In this paper, the anti-cancer drug 6-mercaptopurine (6-MP) was taken as the detection object. The biosensor of dsDNA/GNs/chit/GCE was established using the grapheme (GNs) and chitosan (chit) as the compound modified material. The electrochemical behavior of 6-MP on the sensor was discussed, and the damage and its mechanism of 6-MP on DNA were studied. The experimental result showed that, after the modification of GNs-chit, the electrode activation area of GNs/chit/GCE increased remarkably, which was improved from 1.76cm2 to 8.64 cm2, and the responsive oxidation peak current of GNs/chit/GCE to K3[Fe(CN)6] also increased remarkably. At the meantime, it was demonstrated that DNA was effectively fixed on the GNs/chit/GCE electrode;6-MP caused obvious damage to dsDNA, and the damage degree on the adenine was bigger than that on the guanine; the interaction between 6-MP and dsDNA was preliminarily deduced as the intercalation, and its electrochemical oxidation process was an irreversible process controlled by the adsorption.

We Could Have Loved and Lost. Or We Never Could Have Love at All: Syntactic Misanalysis in L2 Sentence Processing

ERIC Educational Resources Information Center

Conroy, Mark A.; Cupples, Linda

2011-01-01

This study investigated sentence-processing strategies adopted by advanced nonnative speakers (NNSs) and native speakers (NSs) of English in the context of an English structure with which NNSs reportedly have an acquisition difficulty (e.g., Swan & Smith, 2001)--namely, modal perfect (MP). Participants read MP sentences such as "He could have…

Breast-feeding during maternal use of azathioprine.

PubMed

Moretti, Myla E; Verjee, Zul; Ito, Shinya; Koren, Gideon

2006-12-01

To report the clinical outcome of infants whose mothers were taking azathioprine while nursing and to quantify the transfer of 6-mercaptopurine (6-MP), its active metabolite, into breast milk. We report on a series of 4 patients treated with azathioprine while lactating. Breast milk samples were analyzed for 6-MP in 2 of the mothers. Several milk samples per patient were analyzed; levels of 6-MP were undetectable by high performance liquid chromatography (limit of detection 5 ng/mL). Therefore, the absolute relative infant dose would have been less than 0.09% of the maternal weight-adjusted dose. No adverse effects were encountered in any of the 4 infants. A large number of women of reproductive age are treated with azathioprine for a range of chronic conditions that require immunosuppression, such as systemic lupus erythematosus or solid organ transplants. Similar to other antimetabolites, the drug has generally been contraindicated for use during breast-feeding because of the theoretical concern for toxicity in the nursing infant. The available literature in this area is sparse and dated. The data presented here confirm published reports of minimal 6-MP excretion into milk, suggesting that significant systemic adverse effects in the infant are unlikely. Maternal azathioprine use during lactation does not appear to pose a significant immediate clinical risk to the suckling infant. Continued monitoring and long-term assessment of these infants are warranted.

Sparse maps—A systematic infrastructure for reduced-scaling electronic structure methods. I. An efficient and simple linear scaling local MP2 method that uses an intermediate basis of pair natural orbitals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinski, Peter; Riplinger, Christoph; Neese, Frank, E-mail: evaleev@vt.edu, E-mail: frank.neese@cec.mpg.de

2015-07-21

In this work, a systematic infrastructure is described that formalizes concepts implicit in previous work and greatly simplifies computer implementation of reduced-scaling electronic structure methods. The key concept is sparse representation of tensors using chains of sparse maps between two index sets. Sparse map representation can be viewed as a generalization of compressed sparse row, a common representation of a sparse matrix, to tensor data. By combining few elementary operations on sparse maps (inversion, chaining, intersection, etc.), complex algorithms can be developed, illustrated here by a linear-scaling transformation of three-center Coulomb integrals based on our compact code library that implementsmore » sparse maps and operations on them. The sparsity of the three-center integrals arises from spatial locality of the basis functions and domain density fitting approximation. A novel feature of our approach is the use of differential overlap integrals computed in linear-scaling fashion for screening products of basis functions. Finally, a robust linear scaling domain based local pair natural orbital second-order Möller-Plesset (DLPNO-MP2) method is described based on the sparse map infrastructure that only depends on a minimal number of cutoff parameters that can be systematically tightened to approach 100% of the canonical MP2 correlation energy. With default truncation thresholds, DLPNO-MP2 recovers more than 99.9% of the canonical resolution of the identity MP2 (RI-MP2) energy while still showing a very early crossover with respect to the computational effort. Based on extensive benchmark calculations, relative energies are reproduced with an error of typically <0.2 kcal/mol. The efficiency of the local MP2 (LMP2) method can be drastically improved by carrying out the LMP2 iterations in a basis of pair natural orbitals. While the present work focuses on local electron correlation, it is of much broader applicability to computation with sparse tensors in quantum chemistry and beyond.« less

Comparison of outcomes for single-incision laparoscopic inguinal herniorrhaphy and traditional three-port laparoscopic herniorrhaphy at a single institution.

PubMed

Buckley, F Paul; Vassaur, Hannah; Monsivais, Sharon; Sharp, Nicole E; Jupiter, Daniel; Watson, Rob; Eckford, John

2014-01-01

Evidence in the literature regarding the potential of single-incision laparoscopic (SILS) inguinal herniorrhaphy currently is limited. A retrospective comparison of SILS and traditional multiport laparoscopic (MP) inguinal hernia repair was conducted to assess the safety and feasibility of the minimally invasive laparoscopic technique. All laparoscopic inguinal hernia repairs performed by three surgeons at a single institution during 4 years were reviewed. Statistical evaluation included descriptive analysis of demographics including age, gender, body mass index (BMI), and hernia location (uni- or bilateral), in addition to bivariate and multivariate analyses of surgical technique and outcomes including operative times, conversions, and complications. The study compared 129 patients who underwent SILS inguinal hernia repair and 76 patients who underwent MP inguinal hernia repair. The cases included 190 men (92.68 %) with a mean age of 55.36 ± 18.01 years (range, 8-86 years) and a mean BMI of 26.49 ± 4.33 kg/m(2) (range, 17.3-41.7 kg/m(2)). These variables did not differ significantly between the SILS and MP cohorts. The average operative times for the SILS and MP unilateral cases were respectively 57.51 and 66.96 min. For the bilateral cases, the average operative times were 81.07 min for SILS and 81.38 min for MP. A multivariate analysis using surgical approach, BMI, case complexity, and laterality as the covariates demonstrated noninferiority of the SILS technique in terms of operative time (p = 0.031). No conversions from SILS to MP occurred, and the rates of conversion to open procedure did not differ significantly between the cohorts (p = 1.00, Fisher's exact test), nor did the complication rates (p = 0.65, χ (2)). As shown by the findings, SILS inguinal herniorrhaphy is a safe and feasible alternative to traditional MP inguinal hernia repair and can be performed successfully with similar operative times, conversion rates, and complication rates. Prospective trials are essential to confirm equivalence in these areas and to detect differences in patient-centered outcomes.

Sparse maps—A systematic infrastructure for reduced-scaling electronic structure methods. I. An efficient and simple linear scaling local MP2 method that uses an intermediate basis of pair natural orbitals.

PubMed

Pinski, Peter; Riplinger, Christoph; Valeev, Edward F; Neese, Frank

2015-07-21

In this work, a systematic infrastructure is described that formalizes concepts implicit in previous work and greatly simplifies computer implementation of reduced-scaling electronic structure methods. The key concept is sparse representation of tensors using chains of sparse maps between two index sets. Sparse map representation can be viewed as a generalization of compressed sparse row, a common representation of a sparse matrix, to tensor data. By combining few elementary operations on sparse maps (inversion, chaining, intersection, etc.), complex algorithms can be developed, illustrated here by a linear-scaling transformation of three-center Coulomb integrals based on our compact code library that implements sparse maps and operations on them. The sparsity of the three-center integrals arises from spatial locality of the basis functions and domain density fitting approximation. A novel feature of our approach is the use of differential overlap integrals computed in linear-scaling fashion for screening products of basis functions. Finally, a robust linear scaling domain based local pair natural orbital second-order Möller-Plesset (DLPNO-MP2) method is described based on the sparse map infrastructure that only depends on a minimal number of cutoff parameters that can be systematically tightened to approach 100% of the canonical MP2 correlation energy. With default truncation thresholds, DLPNO-MP2 recovers more than 99.9% of the canonical resolution of the identity MP2 (RI-MP2) energy while still showing a very early crossover with respect to the computational effort. Based on extensive benchmark calculations, relative energies are reproduced with an error of typically <0.2 kcal/mol. The efficiency of the local MP2 (LMP2) method can be drastically improved by carrying out the LMP2 iterations in a basis of pair natural orbitals. While the present work focuses on local electron correlation, it is of much broader applicability to computation with sparse tensors in quantum chemistry and beyond.

Characterization of the programmed cell death induced by metabolic products of Alternaria alternata in tobacco BY-2 cells.

PubMed

Cheng, Dan-Dan; Jia, Yu-Jiao; Gao, Hui-Yuan; Zhang, Li-Tao; Zhang, Zi-Shan; Xue, Zhong-Cai; Meng, Qing-Wei

2011-02-01

Alternaria alternata has received considerable attention in current literature and most of the studies are focused on its pathogenic effects on plant chloroplasts, but little is known about the characteristics of programmed cell death (PCD) induced by metabolic products (MP) of A. alternata, the effects of the MP on mitochondrial respiration and its relation to PCD. The purpose of this study was to explore the mechanism of MP-induced PCD in non-green tobacco BY-2 cells and to explore the role of mitochondrial inhibitory processes in the PCD of tobacco BY-2 cells. MP treatment led to significant cell death that was proven to be PCD by the concurrent cytoplasm shrinkage, chromatin condensation and DNA laddering observed in the cells. Moreover, MP treatment resulted in the overproduction of reactive oxygen species (ROS), rapid ATP depletion and a respiratory decline in the tobacco BY-2 cells. It was concluded that the direct inhibition of the mitochondrial electron transport chain (ETC), alternative pathway (AOX) capacity and catalase (CAT) activity by the MP might be the main contributors to the MP-induced ROS burst observed in tobacco BY-2 cells. The addition of adenosine together with the MP significantly inhibited ATP depletion without preventing PCD; however, when the cells were treated with the MP plus CAT, ROS overproduction was blocked and PCD did not occur. The data presented here demonstrate that the ROS burst played an important role in MP-induced PCD in the tobacco BY-2 cells.

Superior Temporal Sulcus Disconnectivity During Processing of Metaphoric Gestures in Schizophrenia

PubMed Central

Straube, Benjamin; Green, Antonia; Sass, Katharina; Kircher, Tilo

2014-01-01

The left superior temporal sulcus (STS) plays an important role in integrating audiovisual information and is functionally connected to disparate regions of the brain. For the integration of gesture information in an abstract sentence context (metaphoric gestures), intact connectivity between the left STS and the inferior frontal gyrus (IFG) should be important. Patients with schizophrenia have problems with the processing of metaphors (concretism) and show aberrant structural connectivity of long fiber bundles. Thus, we tested the hypothesis that patients with schizophrenia differ in the functional connectivity of the left STS to the IFG for the processing of metaphoric gestures. During functional magnetic resonance imaging data acquisition, 16 patients with schizophrenia (P) and a healthy control group (C) were shown videos of an actor performing gestures in a concrete (iconic, IC) and abstract (metaphoric, MP) sentence context. A psychophysiological interaction analysis based on the seed region from a previous analysis in the left STS was performed. In both groups we found common positive connectivity for IC and MP of the STS seed region to the left middle temporal gyrus (MTG) and left ventral IFG. The interaction of group (C>P) and gesture condition (MP>IC) revealed effects in the connectivity to the bilateral IFG and the left MTG with patients exhibiting lower connectivity for the MP condition. In schizophrenia the left STS is misconnected to the IFG, particularly during the processing of MP gestures. Dysfunctional integration of gestures in an abstract sentence context might be the basis of certain interpersonal communication problems in the patients. PMID:23956120

Cyanide binding to ferrous and ferric microperoxidase-11.

PubMed

Ascenzi, Paolo; Sbardella, Diego; Santucci, Roberto; Coletta, Massimo

2016-07-01

Microperoxidase-11 (MP11) is an undecapeptide derived from horse heart cytochrome c (cytc). MP11 is characterized by a covalently linked solvent-exposed heme group, the heme-Fe atom being axially coordinated by a histidyl residue. Here, the reactions of ferrous and ferric MP11 (MP11-Fe(II) and MP11-Fe(III), respectively) with cyanide have been investigated from the kinetic and thermodynamic viewpoints, at pH 7.0 and 20.0 °C. Values of the second-order rate constant for cyanide binding to MP11-Fe(II) and MP11-Fe(III) are 4.5 M(-1) s(-1) and 8.9 × 10(3) M(-1) s(-1), respectively. Values of the first-order rate constant for cyanide dissociation from ligated MP11-Fe(II) and MP11-Fe(III) are 1.8 × 10(-1) s(-1) and 1.5 × 10(-3) s(-1), respectively. Values of the dissociation equilibrium constant for cyanide binding to MP11-Fe(II) and MP11-Fe(III) are 3.7 × 10(-2) and 1.7 × 10(-7) M, respectively, matching very well with those calculated from kinetic parameters so that no intermediate species seem to be involved in the ligand-binding process. The pH-dependence of cyanide binding to MP11-Fe(III) indicates that CN(-) is the only binding species. Present results have been analyzed in parallel with those of several heme-proteins, suggesting that (1) the ligand accessibility to the metal center and cyanide ionization may modulate the formation of heme-Fe-cyanide complexes, and (2) the general polarity of the heme pocket and/or hydrogen bonding of the heme-bound ligand may affect cyanide exit from the protein matrix. Microperoxidase-11 (MP11) is an undecapeptide derived from horse heart cytochrome c. Penta-coordinated MP11 displays a very high reactivity towards cyanide, whereas the reactivity of hexa-coordinated horse heart cytochrome c is very low.

The impact of standard and hard-coded parameters on the hydrologic fluxes in the Noah-MP land surface model

NASA Astrophysics Data System (ADS)

Cuntz, Matthias; Mai, Juliane; Samaniego, Luis; Clark, Martyn; Wulfmeyer, Volker; Branch, Oliver; Attinger, Sabine; Thober, Stephan

2016-09-01

Land surface models incorporate a large number of process descriptions, containing a multitude of parameters. These parameters are typically read from tabulated input files. Some of these parameters might be fixed numbers in the computer code though, which hinder model agility during calibration. Here we identified 139 hard-coded parameters in the model code of the Noah land surface model with multiple process options (Noah-MP). We performed a Sobol' global sensitivity analysis of Noah-MP for a specific set of process options, which includes 42 out of the 71 standard parameters and 75 out of the 139 hard-coded parameters. The sensitivities of the hydrologic output fluxes latent heat and total runoff as well as their component fluxes were evaluated at 12 catchments within the United States with very different hydrometeorological regimes. Noah-MP's hydrologic output fluxes are sensitive to two thirds of its applicable standard parameters (i.e., Sobol' indexes above 1%). The most sensitive parameter is, however, a hard-coded value in the formulation of soil surface resistance for direct evaporation, which proved to be oversensitive in other land surface models as well. Surface runoff is sensitive to almost all hard-coded parameters of the snow processes and the meteorological inputs. These parameter sensitivities diminish in total runoff. Assessing these parameters in model calibration would require detailed snow observations or the calculation of hydrologic signatures of the runoff data. Latent heat and total runoff exhibit very similar sensitivities because of their tight coupling via the water balance. A calibration of Noah-MP against either of these fluxes should therefore give comparable results. Moreover, these fluxes are sensitive to both plant and soil parameters. Calibrating, for example, only soil parameters hence limit the ability to derive realistic model parameters. It is thus recommended to include the most sensitive hard-coded model parameters that were exposed in this study when calibrating Noah-MP.

6-mercaptopurine transport in human lymphocytes: Correlation with drug-induced cytotoxicity

PubMed Central

CONKLIN, Laurie S.; CUFFARI, Carmen; OKAZAKI, Toshihiko; MIAO, Yinglei; SAATIAN, Bahman; CHEN, Tian-E.; TSE, Ming; BRANT, Steven R.; LI, Xuhang

2013-01-01

OBJECTIVE 6-mercaptopurine (6-MP) is efficacious in the treatment of inflammatory bowel disease (IBD). However, about one-third of patients respond poorly to therapy. This study aimed to characterize the inherent differences in 6-MP transport that may contribute to the differences in treatment responses. METHODS Intracellular 6-MP accumulation was assayed in Epstein–Barr virus (EBV)-transformed lymphocytes from IBD patients, using 14C-radiolabeled 6-MP. Cell proliferation was determined by methyl thiazolyl tetrazolium (MTT) assay. Apoptosis was assayed based on the activation of caspase 3. The expressions of 15 potential 6-MP transporters were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS Intracellular 6-MP accumulation, varying significantly among patients, was carrier-dependent and partially sodium-dependent. 6-MP cytotoxicity was, at least in part, due to apoptosis and correlated with intracellular drug accumulation. The efflux transporters did not appear to contribute to the variability of intracellular drug accumulation between patients, since none correlated with drug accumulation or cyto-toxicity. Rather, differential expression of five influx/uptake transporters might be a key contributor to the difference in the accumulation of and susceptibility to the drug. CONCLUSIONS The heterogeneity of the drug transporters may be the reason for the therapeutic sensitivity of 6-MP in IBD patients. As the 6-MP uptake is a carrier-mediated and partially sodium-dependent process, future studies are necessary to evaluate the role of the putative transporters and their correlation with drug sensitivity in patients. PMID:22257476

Multi-processing control system for the SEL 840MP (MPCS/1) users guide. Volume 2: Operations guide

NASA Technical Reports Server (NTRS)

1972-01-01

The generation and operational use of the SEL 840MP multiprocessing control system (MPCS) are considered. System initialization, job task table generation, the MPCS command language, display library generation, and system error summary are reviewed.

Communication: A reduced scaling J-engine based reformulation of SOS-MP2 using graphics processing units.

PubMed

Maurer, S A; Kussmann, J; Ochsenfeld, C

2014-08-07

We present a low-prefactor, cubically scaling scaled-opposite-spin second-order Møller-Plesset perturbation theory (SOS-MP2) method which is highly suitable for massively parallel architectures like graphics processing units (GPU). The scaling is reduced from O(N⁵) to O(N³) by a reformulation of the MP2-expression in the atomic orbital basis via Laplace transformation and the resolution-of-the-identity (RI) approximation of the integrals in combination with efficient sparse algebra for the 3-center integral transformation. In contrast to previous works that employ GPUs for post Hartree-Fock calculations, we do not simply employ GPU-based linear algebra libraries to accelerate the conventional algorithm. Instead, our reformulation allows to replace the rate-determining contraction step with a modified J-engine algorithm, that has been proven to be highly efficient on GPUs. Thus, our SOS-MP2 scheme enables us to treat large molecular systems in an accurate and efficient manner on a single GPU-server.

Atomic orbital-based SOS-MP2 with tensor hypercontraction. I. GPU-based tensor construction and exploiting sparsity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Chenchen; Martínez, Todd J.; SLAC National Accelerator Laboratory, Menlo Park, California 94025

We present a tensor hypercontracted (THC) scaled opposite spin second order Møller-Plesset perturbation theory (SOS-MP2) method. By using THC, we reduce the formal scaling of SOS-MP2 with respect to molecular size from quartic to cubic. We achieve further efficiency by exploiting sparsity in the atomic orbitals and using graphical processing units (GPUs) to accelerate integral construction and matrix multiplication. The practical scaling of GPU-accelerated atomic orbital-based THC-SOS-MP2 calculations is found to be N{sup 2.6} for reference data sets of water clusters and alanine polypeptides containing up to 1600 basis functions. The errors in correlation energy with respect to density-fitting-SOS-MP2 aremore » less than 0.5 kcal/mol for all systems tested (up to 162 atoms).« less

USHPRR FUEL FABRICATION PILLAR: FABRICATION STATUS, PROCESS OPTIMIZATIONS, AND FUTURE PLANS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wight, Jared M.; Joshi, Vineet V.; Lavender, Curt A.

The Fuel Fabrication (FF) Pillar, a project within the U.S. High Performance Research Reactor Conversion program of the National Nuclear Security Administration’s Office of Material Management and Minimization, is tasked with the scale-up and commercialization of high-density monolithic U-Mo fuel for the conversion of appropriate research reactors to use of low-enriched fuel. The FF Pillar has made significant steps to demonstrate and optimize the baseline co-rolling process using commercial-scale equipment at both the Y-12 National Security Complex (Y-12) and BWX Technologies (BWXT). These demonstrations include the fabrication of the next irradiation experiment, Mini-Plate 1 (MP-1), and casting optimizations at Y-12.more » The FF Pillar uses a detailed process flow diagram to identify potential gaps in processing knowledge or demonstration, which helps direct the strategic research agenda of the FF Pillar. This paper describes the significant progress made toward understanding the fuel characteristics, and models developed to make informed decisions, increase process yield, and decrease lifecycle waste and costs.« less

A lifestyle intervention program for successfully addressing major cardiometabolic risks in persons with SCI: a three-subject case series.

PubMed

Bigford, Gregory E; Mendez, Armando J; Betancourt, Luisa; Burns-Drecq, Patricia; Backus, Deborah; Nash, Mark S

2017-01-01

This study is a prospective case series analyzing the effects of a comprehensive lifestyle intervention program in three patients with chronic paraplegia having major risks for the cardiometabolic syndrome (CMS). Individuals underwent an intense 6-month program of circuit resistance exercise, nutrition using a Mediterranean diet and behavioral support, followed by a 6-month extension (maintenance) phase involving minimal support. The primary goal was a 7% reduction of body mass. Other outcomes analyzed insulin resistance using the HOMA-IR model, and plasma levels of fasting triglycerides and high-density lipoprotein cholesterol. All participants achieved the goal for 7% reduction of body mass and maintained the loss after the MP. Improvements were observed in 2/3 subjects for HOMA-IR and high-density lipoprotein cholesterol. All participants improved their risk for plasma triglycerides. We conclude, in a three-person case series of persons with chronic paraplegia, a lifestyle intervention program involving circuit resistance training, a calorie-restrictive Mediterranean-style diet and behavioral support, results in clinically significant loss of body mass and effectively reduced component risks for CMS and diabetes. These results were for the most part maintained after a 6-month MP involving minimal supervision.

Explicit hydration of ammonium ion by correlated methods employing molecular tailoring approach

NASA Astrophysics Data System (ADS)

Singh, Gurmeet; Verma, Rahul; Wagle, Swapnil; Gadre, Shridhar R.

2017-11-01

Explicit hydration studies of ions require accurate estimation of interaction energies. This work explores the explicit hydration of the ammonium ion (NH4+) employing Møller-Plesset second order (MP2) perturbation theory, an accurate yet relatively less expensive correlated method. Several initial geometries of NH4+(H2O)n (n = 4 to 13) clusters are subjected to MP2 level geometry optimisation with correlation consistent aug-cc-pVDZ (aVDZ) basis set. For large clusters (viz. n > 8), molecular tailoring approach (MTA) is used for single point energy evaluation at MP2/aVTZ level for the estimation of MP2 level binding energies (BEs) at complete basis set (CBS) limit. The minimal nature of the clusters upto n ≤ 8 is confirmed by performing vibrational frequency calculations at MP2/aVDZ level of theory, whereas for larger clusters (9 ≤ n ≤ 13) such calculations are effected via grafted MTA (GMTA) method. The zero point energy (ZPE) corrections are done for all the isomers lying within 1 kcal/mol of the lowest energy one. The resulting frequencies in N-H region (2900-3500 cm-1) and in O-H stretching region (3300-3900 cm-1) are in found to be in excellent agreement with the available experimental findings for 4 ≤ n ≤ 13. Furthermore, GMTA is also applied for calculating the BEs of these clusters at coupled cluster singles and doubles with perturbative triples (CCSD(T)) level of theory with aVDZ basis set. This work thus represents an art of the possible on contemporary multi-core computers for studying explicit molecular hydration at correlated level theories.

The difference in spatiotemporal dynamics between modus ponens and modus tollens in the Wason selection task: an event-related potential study.

PubMed

Li, Bingbing; Zhang, Meng; Luo, Junlong; Qiu, Jiang; Liu, Yijun

2014-06-13

High-density, event-related brain potentials (ERPs) were recorded to explore differences in spatiotemporal dynamics between modus ponens (MP) and modus tollens (MT) in the Wason selection task. Results showed that MP elicits a more positive P3b-like component than MT from 400 to 800 ms. MP appeared to occur earlier than MT in various stages of proposition testing, such as stimulus processing and response selection. ERP results showed that MT has a longer duration and more negative later negative component (LNC) than MP at 2,000 ms. This result suggests that MT occupies more cognitive resources than MP in the final stages of proposition testing. The short and small left frontal LNC obtained by MP implies examination of the expectable conclusion, whereas the long and large left frontal LNC elicited by MT may be involved in the retention operation of the card in working memory from the monitoring and inspecting putative conclusion in the later stages of proposition testing. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

An Alternative Mechanism for the Dimerization of Formic Acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brinkman, Nicole R.; Tschumper, Gregory; Yan, Ge

Gas-phase formic acid exists primarily as a cyclic dimer. The mechanism of dimerization has been traditionally considered to be a synchronous process; however, recent experimental findings suggest a possible alternative mechanism by which two formic acid monomers proceed through an acyclic dimer to the cyclic dimer in a stepwise process. To investigate this newly proposed process of dimerization in formic acid, density functional theory and second-order Moeller-Plesset perturbation theory (MP2) have been used to optimize cis and trans monomers of formic acid, the acyclic and cyclic dimers, and the acyclic and cyclic transition states between minima. Single-point energies of themore » trans monomer, dimer minima, and transition states at the MP2/TZ2P+diff optimized geometries were computed at the coupled-cluster level of theory including singles and doubles with perturbatively applied triple excitations [CCSD(T)] with an aug-cc-pVTZ basis set to obtain an accurate determination of energy barriers and dissociation energies. A counterpoise correction was performed to determine an estimate of the basis set superposition error in computing relative energies. The explicitly correlated MP2 method of Kutzelnigg and Klopper (MP2-R12) was used to provide an independent means for obtaining the MP2 one-particle limit. The cyclic minimum is predicted to be 6.3 kcal/mol more stable than the acyclic minimum, and the barrier to double proton transfer is 7.1 kcal/mol.« less

A Simple Auxin Transcriptional Response System Regulates Multiple Morphogenetic Processes in the Liverwort Marchantia polymorpha

PubMed Central

Flores-Sandoval, Eduardo; Eklund, D. Magnus; Bowman, John L.

2015-01-01

In land plants comparative genomics has revealed that members of basal lineages share a common set of transcription factors with the derived flowering plants, despite sharing few homologous structures. The plant hormone auxin has been implicated in many facets of development in both basal and derived lineages of land plants. We functionally characterized the auxin transcriptional response machinery in the liverwort Marchantia polymorpha, a member of the basal lineage of extant land plants. All components known from flowering plant systems are present in M. polymorpha, but they exist as single orthologs: a single MpTOPLESS (TPL) corepressor, a single MpTRANSPORT INHIBITOR RESPONSE 1 auxin receptor, single orthologs of each class of AUXIN RESPONSE FACTOR (ARF; MpARF1, MpARF2, MpARF3), and a single negative regulator AUXIN/INDOLE-3-ACETIC ACID (MpIAA). Phylogenetic analyses suggest this simple system is the ancestral condition for land plants. We experimentally demonstrate that these genes act in an auxin response pathway — chimeric fusions of the MpTPL corepressor with heterodimerization domains of MpARF1, MpARF2, or their negative regulator, MpIAA, generate auxin insensitive plants that lack the capacity to pattern and transition into mature stages of development. Our results indicate auxin mediated transcriptional regulation acts as a facilitator of branching, differentiation and growth, rather than acting to determine or specify tissues during the haploid stage of the M. polymorpha life cycle. We hypothesize that the ancestral role of auxin is to modulate a balance of differentiated and pluri- or totipotent cell states, whose fates are determined by interactions with combinations of unrelated transcription factors. PMID:26020649

Unraveling Synaptic GCaMP Signals: Differential Excitability and Clearance Mechanisms Underlying Distinct Ca2+ Dynamics in Tonic and Phasic Excitatory, and Aminergic Modulatory Motor Terminals in Drosophila

PubMed Central

Xing, Xiaomin

2018-01-01

Abstract GCaMP is an optogenetic Ca2+ sensor widely used for monitoring neuronal activities but the precise physiological implications of GCaMP signals remain to be further delineated among functionally distinct synapses. The Drosophila neuromuscular junction (NMJ), a powerful genetic system for studying synaptic function and plasticity, consists of tonic and phasic glutamatergic and modulatory aminergic motor terminals of distinct properties. We report a first simultaneous imaging and electric recording study to directly contrast the frequency characteristics of GCaMP signals of the three synapses for physiological implications. Different GCaMP variants were applied in genetic and pharmacological perturbation experiments to examine the Ca2+ influx and clearance processes underlying the GCaMP signal. Distinct mutational and drug effects on GCaMP signals indicate differential roles of Na+ and K+ channels, encoded by genes including paralytic (para), Shaker (Sh), Shab, and ether-a-go-go (eag), in excitability control of different motor terminals. Moreover, the Ca2+ handling properties reflected by the characteristic frequency dependence of the synaptic GCaMP signals were determined to a large extent by differential capacity of mitochondria-powered Ca2+ clearance mechanisms. Simultaneous focal recordings of synaptic activities further revealed that GCaMPs were ineffective in tracking the rapid dynamics of Ca2+ influx that triggers transmitter release, especially during low-frequency activities, but more adequately reflected cytosolic residual Ca2+ accumulation, a major factor governing activity-dependent synaptic plasticity. These results highlight the vast range of GCaMP response patterns in functionally distinct synaptic types and provide relevant information for establishing basic guidelines for the physiological interpretations of presynaptic GCaMP signals from in situ imaging studies. PMID:29464198

6-Mercaptopurine attenuates tumor necrosis factor-α production in microglia through Nur77-mediated transrepression and PI3K/Akt/mTOR signaling-mediated translational regulation.

PubMed

Huang, Hsin-Yi; Chang, Hui-Fen; Tsai, Ming-Jen; Chen, Jhih-Si; Wang, Mei-Jen

2016-04-13

The pathogenesis of several neurodegenerative diseases often involves the microglial activation and associated inflammatory processes. Activated microglia release pro-inflammatory factors that may be neurotoxic. 6-Mercaptopurine (6-MP) is a well-established immunosuppressive drug. Common understanding of their immunosuppressive properties is largely limited to peripheral immune cells. However, the effect of 6-MP in the central nervous system, especially in microglia in the context of neuroinflammation is, as yet, unclear. Tumor necrosis factor-α (TNF-α) is a key cytokine of the immune system that initiates and promotes neuroinflammation. The present study aimed to investigate the effect of 6-MP on TNF-α production by microglia to discern the molecular mechanisms of this modulation. Lipopolysaccharide (LPS) was used to induce an inflammatory response in cultured primary microglia or murine BV-2 microglial cells. Released TNF-α was measured by enzyme-linked immunosorbent assay (ELISA). Gene expression was determined by real-time reverse transcription polymerase chain reaction (RT-PCR). Signaling molecules were analyzed by western blotting, and activation of NF-κB was measured by ELISA-based DNA binding analysis and luciferase reporter assay. Chromatin immunoprecipitation (ChIP) analysis was performed to examine NF-κB p65 and coactivator p300 enrichments and histone modifications at the endogenous TNF-α promoter. Treatment of LPS-activated microglia with 6-MP significantly attenuated TNF-α production. In 6-MP pretreated microglia, LPS-induced MAPK signaling, IκB-α degradation, NF-κB p65 nuclear translocation, and in vitro p65 DNA binding activity were not impaired. However, 6-MP suppressed transactivation activity of NF-κB and TNF-α promoter by inhibiting phosphorylation and acetylation of p65 on Ser276 and Lys310, respectively. ChIP analyses revealed that 6-MP dampened LPS-induced histone H3 acetylation of chromatin surrounding the TNF-α promoter, ultimately leading to a decrease in p65/coactivator-mediated transcription of TNF-α gene. Furthermore, 6-MP enhanced orphan nuclear receptor Nur77 expression. Using RNA interference approach, we further demonstrated that Nur77 upregulation contribute to 6-MP-mediated inhibitory effect on TNF-α production. Additionally, 6-MP also impeded TNF-α mRNA translation through prevention of LPS-activated PI3K/Akt/mTOR signaling cascades. These results suggest that 6-MP might have a therapeutic potential in neuroinflammation-related neurodegenerative disorders through downregulation of microglia-mediated inflammatory processes.

Improving the accuracy of Møller-Plesset perturbation theory with neural networks

NASA Astrophysics Data System (ADS)

McGibbon, Robert T.; Taube, Andrew G.; Donchev, Alexander G.; Siva, Karthik; Hernández, Felipe; Hargus, Cory; Law, Ka-Hei; Klepeis, John L.; Shaw, David E.

2017-10-01

Noncovalent interactions are of fundamental importance across the disciplines of chemistry, materials science, and biology. Quantum chemical calculations on noncovalently bound complexes, which allow for the quantification of properties such as binding energies and geometries, play an essential role in advancing our understanding of, and building models for, a vast array of complex processes involving molecular association or self-assembly. Because of its relatively modest computational cost, second-order Møller-Plesset perturbation (MP2) theory is one of the most widely used methods in quantum chemistry for studying noncovalent interactions. MP2 is, however, plagued by serious errors due to its incomplete treatment of electron correlation, especially when modeling van der Waals interactions and π-stacked complexes. Here we present spin-network-scaled MP2 (SNS-MP2), a new semi-empirical MP2-based method for dimer interaction-energy calculations. To correct for errors in MP2, SNS-MP2 uses quantum chemical features of the complex under study in conjunction with a neural network to reweight terms appearing in the total MP2 interaction energy. The method has been trained on a new data set consisting of over 200 000 complete basis set (CBS)-extrapolated coupled-cluster interaction energies, which are considered the gold standard for chemical accuracy. SNS-MP2 predicts gold-standard binding energies of unseen test compounds with a mean absolute error of 0.04 kcal mol-1 (root-mean-square error 0.09 kcal mol-1), a 6- to 7-fold improvement over MP2. To the best of our knowledge, its accuracy exceeds that of all extant density functional theory- and wavefunction-based methods of similar computational cost, and is very close to the intrinsic accuracy of our benchmark coupled-cluster methodology itself. Furthermore, SNS-MP2 provides reliable per-conformation confidence intervals on the predicted interaction energies, a feature not available from any alternative method.

Improving the accuracy of Møller-Plesset perturbation theory with neural networks.

PubMed

McGibbon, Robert T; Taube, Andrew G; Donchev, Alexander G; Siva, Karthik; Hernández, Felipe; Hargus, Cory; Law, Ka-Hei; Klepeis, John L; Shaw, David E

2017-10-28

Noncovalent interactions are of fundamental importance across the disciplines of chemistry, materials science, and biology. Quantum chemical calculations on noncovalently bound complexes, which allow for the quantification of properties such as binding energies and geometries, play an essential role in advancing our understanding of, and building models for, a vast array of complex processes involving molecular association or self-assembly. Because of its relatively modest computational cost, second-order Møller-Plesset perturbation (MP2) theory is one of the most widely used methods in quantum chemistry for studying noncovalent interactions. MP2 is, however, plagued by serious errors due to its incomplete treatment of electron correlation, especially when modeling van der Waals interactions and π-stacked complexes. Here we present spin-network-scaled MP2 (SNS-MP2), a new semi-empirical MP2-based method for dimer interaction-energy calculations. To correct for errors in MP2, SNS-MP2 uses quantum chemical features of the complex under study in conjunction with a neural network to reweight terms appearing in the total MP2 interaction energy. The method has been trained on a new data set consisting of over 200 000 complete basis set (CBS)-extrapolated coupled-cluster interaction energies, which are considered the gold standard for chemical accuracy. SNS-MP2 predicts gold-standard binding energies of unseen test compounds with a mean absolute error of 0.04 kcal mol -1 (root-mean-square error 0.09 kcal mol -1 ), a 6- to 7-fold improvement over MP2. To the best of our knowledge, its accuracy exceeds that of all extant density functional theory- and wavefunction-based methods of similar computational cost, and is very close to the intrinsic accuracy of our benchmark coupled-cluster methodology itself. Furthermore, SNS-MP2 provides reliable per-conformation confidence intervals on the predicted interaction energies, a feature not available from any alternative method.

NASA-STD-(I)-6016, Standard Materials and Processes Requirements for Spacecraft

NASA Technical Reports Server (NTRS)

Pedley, Michael; Griffin, Dennis

2006-01-01

This document is directed toward Materials and Processes (M&P) used in the design, fabrication, and testing of flight components for all NASA manned, unmanned, robotic, launch vehicle, lander, in-space and surface systems, and spacecraft program/project hardware elements. All flight hardware is covered by the M&P requirements of this document, including vendor designed, off-the-shelf, and vendor furnished items. Materials and processes used in interfacing ground support equipment (GSE); test equipment; hardware processing equipment; hardware packaging; and hardware shipment shall be controlled to prevent damage to or contamination of flight hardware.

Mobile phone use for 5 minutes can cause significant memory impairment in humans.

PubMed

Kalafatakis, F; Bekiaridis-Moschou, D; Gkioka, Eirini; Tsolaki, Magda

2017-01-01

Concerns about the possible adverse health effects of mobile phones (MP) have increased along with the expansion of their use. A number of research papers have tried to address this issue. Although many investigations concluded that MP use does have negative consequences, in terms of cognitive function of the human brain, the results so far have been divisive. A number of studies reported impairment of cognitive function after exposure to mobile phone electromagnetic field (MP EMF), while others observed no effect or improved performance. The variance in the results may be attributed to methodological issues. The present article focuses on possible effects of MP use on cognitive function and more specifically on working memory processes. An emphasis is placed in the lack of a validated tool, a cognitive task, that can produce MP EMF effects on human cognition in a repeatable fashion. Sixty four (64) healthy participants as well as 20 with Mild Cognitive Impairment (MCI) were the experimental group, while 36 healthy individuals were the control group. A computerized list of 10 words was presented and the participants were asked to reproduce it. The words were presented very briefly in order to increase the difficulty and hence the sensitivity of the task. Three measurements were taken for the experimental group: a) before using the MP, b) immediately after using the MP for a duration of 5 minutes, c) 5 minutes after the second measurement with no usage of the MP in between. Three measurements of the memory task were also taken for the control group in the same time intervals with no usage of a MP. The effect of age and gender in the performance of the task was taken into account. Healthy participants of the experimental group performed worst in the memory task after using the MP. While the third measurement (5 minutes after the 2nd measurement) was better than the second (after using the MP), but worse than the first (before using the MP). In contrast for the control group the second measurement was better than the first and the third even better than both previous ones. All differences were statistically significant. The reduction of the performance in the task after using the MP was even higher for the age group of 60-80 years old in comparison with younger age groups, as well as for the individuals with MCI in comparison to healthy participants. Age was significantly negative correlated with performance in the task, while gender showed no significant correlation. MP use has a significant negative impact on working memory performance of human participants. The effect is apparent even for a 5 minute use of the MP. Working memory deficits are greater not only for the 60 years old and above participants but also for individuals with Mild Cognitive Impairment. These results are in agreement with previous studies on animals as well as humans on the effects of MP use on the brain. It is argued that low sensitivity of some of the cognitive tasks used until now and the lack of a validated tool in the form of a cognitive task may account for some of the variability in the literature so far. It is suggested that the experimental paradigm that was used in this study for an increased sensitivity measurement of cognitive function and working memory processes in particular may be used for the display of the effects of MP use on cognitive function and for the development of other tasks sensitive to it. Overall, it is concluded that the development of certain restrictions on MP use is necessary for the protection of the brain health of the users.

Wetland dynamics influence mid-continent duck recruitment

USGS Publications Warehouse

Anteau, Michael J.; Pearse, Aaron T.; Szymankski, Michael L.

2013-01-01

Recruitment is a key factor influencing duck population dynamics. Understanding what regulates recruitment of ducks is a prerequisite to informed habitat and harvest management. Quantity of May ponds (MP) has been linked to recruitment and population size (Kaminski and Gluesing 1987, Raveling and Heitmeyer 1989). However, wetland productivity (quality) is driven by inter-annual hydrological fluctuations. Periodic drying of wetlands due to wet-dry climate cycles releases nutrients and increases invertebrate populations when wet conditions return (Euliss et al. 1999). Wetlands may also become wet or dry within a breeding season. Accordingly, inter-annual and intra-seasonal hydrologic variation potentially influence duck recruitment. Here, we examined influences of wetland quantity, quality, and intra-seasonal dynamics on recruitment of ducks. We indexed duck recruitment by vulnerability-corrected age ratios (juveniles/adult females) for mid-continent Gadwall (Anas strepera). We chose Gadwall because the majority of the continental population breeds in the Prairie Pothole Region (PPR), where annual estimates of MP exist since 1974. We indexed wetland quality by calculating change in MP (?MP) over the past two years (?MP = 0.6[MPt – MPt-1] + 0.4[MPt – MPt-2]). We indexed intra-seasonal change in number of ponds by dividing the PPR mean standardized precipitation index for July by MP (hereafter summer index). MP and ?MP were positively correlated (r = 0.65); therefore, we calculated residual ?MP (?MPr) with a simple linear regression using MP, creating orthogonal variables. Finally, we conducted a multiple regression to examine how MP, ?MPr, and summer index explained variation in recruitment of Gadwall from 1976–2010. Our model explained 67% of the variation in mid-continent Gadwall recruitment and all three hydrologic indices were positively correlated with recruitment (Figure 1). Type II semi-partial R2 estimates indicated that MP accounted for 41%, ?MPr accounted for an additional 22%, and summer index accounted for the remaining 4% of the variation in recruitment. Our results are consistent with previous findings that quantity of MP was important for explaining variation in recruitment of ducks. However, our results also indicated that considering hydrologic dynamics was important for explaining recruitment. Additionally, the index for retention of MP within breeding year also was important, despite its coarse resolution as an average of precipitation events that can vary greatly spatially and in intensity within the PPR. Our results support the idea that wetland ecosystems in the PPR are ultimately regulated through bottom-up process driven by inter- and intra-annual hydrological dynamics. However from the ducks' perspective, hydrological dynamics could influence recruitment proximately through both bottom-up and top-down processes. Specifically, hydrological fluctuations may influence predator populations, prey switching by predators, or duckling vulnerability to predators (Cox et al. 1998). We will propose a conceptual model for understanding the potential role of bottom-up and top-down regulation of duck recruitment based on different hydrological contexts. Clearly, a better understanding of ultimate and proximate factors regulating duck recruitment would improve the effectiveness and efficiency of habitat conservation for ducks. Lastly, our findings could be used to improve models that predict fall flights for the purposes of informing harvest regulations.

Inhibition of GTPase Rac1 in endothelium by 6-mercaptopurine results in immunosuppression in nonimmune cells: new target for an old drug.

PubMed

Marinković, Goran; Kroon, Jeffrey; Hoogenboezem, Mark; Hoeben, Kees A; Ruiter, Matthijs S; Kurakula, Kondababu; Otermin Rubio, Iker; Vos, Mariska; de Vries, Carlie J M; van Buul, Jaap D; de Waard, Vivian

2014-05-01

Azathioprine and its metabolite 6-mercaptopurine (6-MP) are well established immunosuppressive drugs. Common understanding of their immunosuppressive properties is largely limited to immune cells. However, in this study, the mechanism underlying the protective role of 6-MP in endothelial cell activation is investigated. Because 6-MP and its derivative 6-thioguanosine-5'-triphosphate (6-T-GTP) were shown to block activation of GTPase Rac1 in T lymphocytes, we focused on Rac1-mediated processes in endothelial cells. Indeed, 6-MP and 6-T-GTP decreased Rac1 activation in endothelial cells. As a result, the compounds inhibited TNF-α-induced downstream signaling via JNK and reduced activation of transcription factors c-Jun, activating transcription factor-2 and, in addition, NF κ-light-chain-enhancer of activated B cells (NF-κB), which led to decreased transcription of proinflammatory cytokines. Moreover, 6-MP and 6-T-GTP selectively decreased TNF-α-induced VCAM-1 but not ICAM-1 protein levels. Rac1-mediated generation of cell membrane protrusions, which form docking structures to capture leukocytes, also was reduced by 6-MP/6-T-GTP. Consequently, leukocyte transmigration was inhibited after 6-MP/6-T-GTP treatment. These data underscore the anti-inflammatory effect of 6-MP and 6-T-GTP on endothelial cells by blocking Rac1 activation. Our data provide mechanistic insight that supports development of novel Rac1-specific therapeutic approaches against chronic inflammatory diseases.

Checkout/demonstration application program for the SEL 840MP Multi-Processing Control System: Version 1 (MPCS/1)

NASA Technical Reports Server (NTRS)

Anderson, W. F.; Conway, J. R.; Keller, L. C.

1972-01-01

The characteristics of the application program were developed to verify and demonstrate the SEL 840MP Multi-Processing Control System - Version I (MPCS/1). The application program emphasizes the display support and task control capabilities. The application program is further intended to be used as an aid to familization with MPCS/1. It complements the information provided in the MPCS/1 Users Guide, Volume I and II.

Microplastics in Sewage Sludge: Effects of Treatment.

PubMed

Mahon, A M; O'Connell, B; Healy, M G; O'Connor, I; Officer, R; Nash, R; Morrison, L

2017-01-17

Waste water treatment plants (WWTPs) are receptors for the cumulative loading of microplastics (MPs) derived from industry, landfill, domestic wastewater and stormwater. The partitioning of MPs through the settlement processes of wastewater treatment results in the majority becoming entrained in the sewage sludge. This study characterized MPs in sludge samples from seven WWTPs in Ireland which use anaerobic digestion (AD), thermal drying (TD), or lime stabilization (LS) treatment processes. Abundances ranged from 4196 to 15 385 particles kg -1 (dry weight). Results of a general linear mixed model (GLMM) showed significantly higher abundances of MPs in smaller size classes in the LS samples, suggesting that the treatment process of LS shears MP particles. In contrast, lower abundances of MPs found in the AD samples suggests that this process may reduce MP abundances. Surface morphologies examined using scanning electron microscopy (SEM) showed characteristics of melting and blistering of TD MPs and shredding and flaking of LS MPs. This study highlights the potential for sewage sludge treatment processes to affect the risk of MP pollution prior to land spreading and may have implications for legislation governing the application of biosolids to agricultural land.

Preparation of porous magnesium oxide foam and study on its enrichment of uranium

NASA Astrophysics Data System (ADS)

Wang, Yunsheng; Chen, Yuantao; Liu, Chen; Yu, Fang

2018-06-01

Herein, we prepared porous magnesium oxide (MP-MgO) by in situ carbonization and using Mg(NO3)2 as precursor along with P123 as soft template. The BET surface area, and total pore volume of MP-MgO were found to be 14.76 m2 g, 0.15 cm3 g-1, respectively. The adsorption behavior of U (Ⅵ) by the porous MgO was studied by static adsorption experiments, and also the effects of adsorption time, pH of wastewater and U (Ⅵ) concentration were discussed. The results indicated that the optimum pH for MP-MgO was 3.0-4.5, the removal of uranium in this case was mainly due to surface complexation. Through the study, we found that the adsorption capacity of MP-MgO for uranium was more than 2500 mg g-1, the adsorption equilibrium time was about 150 min. Moreover, the kinetic study showed that the process followed the pseudo-first-order model, and the adsorption process was spontaneous and endothermic.

Communication: A reduced scaling J-engine based reformulation of SOS-MP2 using graphics processing units

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maurer, S. A.; Kussmann, J.; Ochsenfeld, C., E-mail: Christian.Ochsenfeld@cup.uni-muenchen.de

2014-08-07

We present a low-prefactor, cubically scaling scaled-opposite-spin second-order Møller-Plesset perturbation theory (SOS-MP2) method which is highly suitable for massively parallel architectures like graphics processing units (GPU). The scaling is reduced from O(N{sup 5}) to O(N{sup 3}) by a reformulation of the MP2-expression in the atomic orbital basis via Laplace transformation and the resolution-of-the-identity (RI) approximation of the integrals in combination with efficient sparse algebra for the 3-center integral transformation. In contrast to previous works that employ GPUs for post Hartree-Fock calculations, we do not simply employ GPU-based linear algebra libraries to accelerate the conventional algorithm. Instead, our reformulation allows tomore » replace the rate-determining contraction step with a modified J-engine algorithm, that has been proven to be highly efficient on GPUs. Thus, our SOS-MP2 scheme enables us to treat large molecular systems in an accurate and efficient manner on a single GPU-server.« less

Large-scale FMO-MP3 calculations on the surface proteins of influenza virus, hemagglutinin (HA) and neuraminidase (NA)

NASA Astrophysics Data System (ADS)

Mochizuki, Yuji; Yamashita, Katsumi; Fukuzawa, Kaori; Takematsu, Kazutomo; Watanabe, Hirofumi; Taguchi, Naoki; Okiyama, Yoshio; Tsuboi, Misako; Nakano, Tatsuya; Tanaka, Shigenori

2010-06-01

Two proteins on the influenza virus surface have been well known. One is hemagglutinin (HA) associated with the infection to cells. The fragment molecular orbital (FMO) calculations were performed on a complex consisting of HA trimer and two Fab-fragments at the third-order Møller-Plesset perturbation (MP3) level. The numbers of residues and 6-31G basis functions were 2351 and 201276, and thus a massively parallel-vector computer was utilized to accelerate the processing. This FMO-MP3 job was completed in 5.8 h with 1024 processors. Another protein is neuraminidase (NA) involved in the escape from infected cells. The FMO-MP3 calculation was also applied to analyze the interactions between oseltamivir and surrounding residues in pharmacophore.

Harmful Effects of the Azathioprine Metabolite 6-Mercaptopurine in Vascular Cells: Induction of Mineralization

PubMed Central

Tölle, Markus; Prüfer, Nicole; Höhne, Matthias; Zidek, Walter; van der Giet, Markus

2014-01-01

Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteo-chondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis. PMID:25029363

Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: induction of mineralization.

PubMed

Prüfer, Jasmin; Schuchardt, Mirjam; Tölle, Markus; Prüfer, Nicole; Höhne, Matthias; Zidek, Walter; van der Giet, Markus

2014-01-01

Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteo-chondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis.

Evaluate dry deposition velocity of the nitrogen oxides using Noah-MP physics ensemble simulations for the Dinghushan Forest, Southern China

NASA Astrophysics Data System (ADS)

Zhang, Qi; Chang, Ming; Zhou, Shengzhen; Chen, Weihua; Wang, Xuemei; Liao, Wenhui; Dai, Jianing; Wu, ZhiYong

2017-11-01

There has been a rapid growth of reactive nitrogen (Nr) deposition over the world in the past decades. The Pearl River Delta region is one of the areas with high loading of nitrogen deposition. But there are still large uncertainties in the study of dry deposition because of its complex processes of physical chemistry and vegetation physiology. At present, the forest canopy parameterization scheme used in WRF-Chem model is a single-layer "big leaf" model, and the simulation of radiation transmission and energy balance in forest canopy is not detailed and accurate. Noah-MP land surface model (Noah-MP) is based on the Noah land surface model (Noah LSM) and has multiple parametric options to simulate the energy, momentum, and material interactions of the vegetation-soil-atmosphere system. Therefore, to investigate the improvement of the simulation results of WRF-Chem on the nitrogen deposition in forest area after coupled with Noah-MP model and to reduce the influence of meteorological simulation biases on the dry deposition velocity simulation, a dry deposition single-point model coupled by Noah- MP and the WRF-Chem dry deposition module (WDDM) was used to simulate the deposition velocity (Vd). The model was driven by the micro-meteorological observation of the Dinghushan Forest Ecosystem Location Station. And a series of numerical experiments were carried out to identify the key processes influencing the calculation of dry deposition velocity, and the effects of various surface physical and plant physiological processes on dry deposition were discussed. The model captured the observed Vd well, but still underestimated the Vd. The self-defect of Wesely scheme applied by WDDM, and the inaccuracy of built-in parameters in WDDM and input data for Noah-MP (e.g. LAI) were the key factors that cause the underestimation of Vd. Therefore, future work is needed to improve model mechanisms and parameterization.

Modelling the fate of organic micropollutants in stormwater ponds.

PubMed

Vezzaro, Luca; Eriksson, Eva; Ledin, Anna; Mikkelsen, Peter S

2011-06-01

Urban water managers need to estimate the potential removal of organic micropollutants (MP) in stormwater treatment systems to support MP pollution control strategies. This study documents how the potential removal of organic MP in stormwater treatment systems can be quantified by using multimedia models. The fate of four different MP in a stormwater retention pond was simulated by applying two steady-state multimedia fate models (EPI Suite and SimpleBox) commonly applied in chemical risk assessment and a dynamic multimedia fate model (Stormwater Treatment Unit Model for Micro Pollutants--STUMP). The four simulated organic stormwater MP (iodopropynyl butylcarbamate--IPBC, benzene, glyphosate and pyrene) were selected according to their different urban sources and environmental fate. This ensures that the results can be extended to other relevant stormwater pollutants. All three models use substance inherent properties to calculate MP fate but differ in their ability to represent the small physical scale and high temporal variability of stormwater treatment systems. Therefore the three models generate different results. A Global Sensitivity Analysis (GSA) highlighted that settling/resuspension of particulate matter was the most sensitive process for the dynamic model. The uncertainty of the estimated MP fluxes can be reduced by calibrating the dynamic model against total suspended solids data. This reduction in uncertainty was more significant for the substances with strong tendency to sorb, i.e. glyphosate and pyrene and less significant for substances with a smaller tendency to sorb, i.e. IPBC and benzene. The results provide support to the elaboration of MP pollution control strategies by limiting the need for extensive and complex monitoring campaigns targeting the wide range of specific organic MP found in stormwater runoff. Copyright © 2011 Elsevier B.V. All rights reserved.

6-Mercaptopurine transport in human lymphocytes: correlation with drug-induced cytotoxicity.

PubMed

Conklin, Laurie S; Cuffari, Carmen; Okazaki, Toshihiko; Miao, Yinglei; Saatian, Bahman; Chen, Tian-E; Tse, Ming; Brant, Steven R; Li, Xuhang

2012-02-01

  6-mercaptopurine (6-MP) is efficacious in the treatment of inflammatory bowel disease (IBD). However, about one-third of patients respond poorly to therapy. This study aimed to characterize the inherent differences in 6-MP transport that may cotribute to the differences in treatment responses.   Intracellular 6-MP accumulation was assayed in Epstein-Barr virus (EBV)-transformed lymphocytes from IBD patients, using (14) C-radiolabeled 6-MP. Cell proliferation was determined by methyl thiazolyl tetrazolium (MTT) assay. Apoptosis was assayed based on the activation of caspase 3. The expressions of 15 potential 6-MP transporters were evaluated by reverse transcription-polymerase chain reaction (RT-PCR).   Intracellular 6-MP accumulation, varying significantly among patients, was carrier-dependent and partially sodium-dependent. 6-MP cytotoxicity was, at least in part, due to apoptosis and correlated with intracellular drug accumulation. The efflux transporters did not appear to contribute to the variability of intracellular drug accumulation between patients, since none correlated with drug accumulation or cytotoxicity. Rather, differential expression of five influx/uptake transporters might be a key contributor to the difference in the accumulation of and susceptibility to the drug.   The heterogeneity of the drug transporters may be the reason for the therapeutic sensitivity of 6-MP in IBD patients. As the 6-MP uptake is a carrier-mediated and partially sodium-dependent process, future studies are necessary to evaluate the role of the putative transporters and their correlation with drug sensitivity in patients. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Neuroprotection and Acute Spinal Cord Injury: A Reappraisal

PubMed Central

Hall, Edward D.; Springer, Joe E.

2004-01-01

Summary: It has long been recognized that much of the post-traumatic degeneration of the spinal cord following injury is caused by a multi-factorial secondary injury process that occurs during the first minutes, hours, and days after spinal cord injury (SCI). A key biochemical event in that process is reactive oxygen-induced lipid peroxidation (LP). In 1990 the results of the Second National Acute Spinal Cord Injury Study (NASCIS II) were published, which showed that the administration of a high-dose regimen of the glucocorticoid steroid methylprednisolone (MP), which had been previously shown to inhibit post-traumatic LP in animal models of SCI, could improve neurological recovery in spinal-cord-injured humans. This resulted in the registration of high-dose MP for acute SCI in several countries, although not in the U.S. Nevertheless, this treatment quickly became the standard of care for acute SCI since the drug was already on the U.S. market for many other indications. Subsequently, it was demonstrated that the non-glucocorticoid 21-aminosteroid tirilazad could duplicate the antioxidant neuroprotective efficacy of MP in SCI models, and evidence of human efficacy was obtained in a third NASCIS trial (NASCIS III). In recent years, the use of high-dose MP in acute SCI has become controversial largely on the basis of the risk of serious adverse effects versus what is perceived to be on average a modest neurological benefit. The opiate receptor antagonist naloxone was also tested in NASCIS II based upon the demonstration of its beneficial effects in SCI models. Although it did not a significant overall effect, some evidence of efficacy was seen in incomplete (i.e., paretic) patients. The monosialoganglioside GM1 has also been examined in a recently completed clinical trial in which the patients first received high-dose MP treatment. However, GM1 failed to show any evidence of a significant enhancement in the extent of neurological recovery over the level afforded by MP therapy alone. The present paper reviews the past development of MP, naloxone, tirilazad, and GM1 for acute SCI, the ongoing MP-SCI controversy, identifies the regulatory complications involved in future SCI drug development, and suggests some promising neuroprotective approaches that could either replace or be used in combination with high-dose MP. PMID:15717009

Influence of chemical and mechanical polishing on water sorption and solubility of denture base acrylic resins.

PubMed

Rahal, Juliana Saab; Mesquita, Marcelo Ferraz; Henriques, Guilherme Elias Pessanha; Nóbilo, Mauro Antonio Arruda

2004-01-01

Influence of polishing methods on water sorption and solubility of denture base acrylic resins was studied. Eighty samples were divided into groups: Classico (CL), and QC 20 (QC) - hot water bath cured; Acron MC (AC), and Onda Cryl (ON) - microwave cured; and submitted to mechanical polishing (MP) - pumice slurry, chalk powder, soft brush and felt cone in a bench vise; or chemical polishing (CP) - heated monomer fluid in a chemical polisher. The first desiccation process was followed by storage in distilled water at 37 +/- 1 degrees C for 1 h, 1 day, 1, 2, 3 and 4 weeks. Concluding each period, water sorption was measured. After the fourth week, a second desiccation process was done to calculate solubility. Data were submitted to analysis of variance, followed by Tukey test (p

[Alteration of Microparticle Levels in Early Complications During Hematopoietic Stem Cell Transplantation].

PubMed

Zhou, Li-Li; Han, Yue; Zhu, Qian; Zhao, Shi-Xiang; Wang, Qian; Zhu, Ming-Qing; Dai, Lan; Shen, Wen-Hong; Wu, De-Pei

2015-12-01

To investigate the alteration of microparticles (MP) in the recipients following hematopoietic stem cell transplantation (HSCT) and its significance, and to search the early diagnostic indicators of thrombotic complications after transplantation. According to the occurrence of transplantation-associated complications, 94 allo-HSCT patients were divided into 4 groups: thrombotic group (VOD n = 7, TMA n = 2), acute graft-versus-host disease (aGVHD) group (n = 27), infection group (n = 41) and non-complication group (n = 17). Alterations of serum concentration of tissue factor positive microparticles (TF(+) MP) and endothelial microparticles (EMP) were analyzed by flow cytometry during the process of conditioning treatment and the early stage after transplantation. The relation of these 2 kinds of MP with complications was analysed. (1) The levels of TF(+) MP and EMP of patients undogoing allo-HSCT before conditioning treatment were obviously higher than those in normal controls, and showed some elevation during different times, but there was no significant statistical difference. Although the levels of TF(+) MP and EMP at the end of conditioning treatment were some higher than those before conditioning treatment, but there was no statistical difference between them. (2)The levels of TF(+) MP and EMP in thrombotic group were obviously higher than those in aGVHD group and infection group (P < 0.05). (3)The levels of TF(+) MP and EMP in thrombotic group at different times were significant differences from those in other groups (P < 0.05), and the levels of TF(+) MP and EMP were no significant difference from those in non-complication group. The increase of the TF(+) MP and EMP levels may be associated with occurrence of thrombosis after transplantation, indicating occurrence of the thrombotic complications, like hepatic vein occulusive disease (HVOD). The dynamically monitoring levels of TF(+) MP and EMP contributes to early discovery of thrombotic complications.

A Vision for Future Virtual Training

DTIC Science & Technology

2006-06-15

Future Virtual Training. In Virtual Media for Military Applications (pp. KN2-1 – KN2-12). Meeting Proceedings RTO-MP-HFM-136, Keynote 2. Neuilly-sur...Spin Out. By 2017 , the FCS program will meet Full Operation Capability (FOC). The force structure of the Army at this time will include two BCTs...training environment, allowing them to meet preparatory training proficiency objectives virtually while minimizing the use of costly live ammunition. In

Mathematizing Process of Junior High School Students to Improve Mathematics Literacy Refers PISA on RCP Learning

NASA Astrophysics Data System (ADS)

Wardono; Mariani, S.; Hendikawati, P.; Ikayani

2017-04-01

Mathematizing process (MP) is the process of modeling a phenomenon mathematically or establish the concept of a phenomenon. There are two mathematizing that is Mathematizing Horizontal (MH) and Mathematizing Vertical (MV). MH as events changes contextual problems into mathematical problems, while MV is the process of formulation of the problem into a variety of settlement mathematics by using some appropriate rules. Mathematics Literacy (ML) is the ability to formulate, implement and interpret mathematics in various contexts, including the capacity to perform reasoning mathematically and using the concepts, procedures, and facts to describe, explain or predict phenomena incident. If junior high school students are conditioned continuously to conduct mathematizing activities on RCP (RME-Card Problem) learning, it will be able to improve ML that refers PISA. The purpose of this research is to know the capability of the MP grade VIII on ML content shape and space with the matter of the cube and beams with RCP learning better than the scientific learning, upgrade MP grade VIII in the issue of the cube and beams with RCP learning better than the scientific learning in terms of cognitive styles reflective and impulsive the MP grade VIII with the approach of the RCP learning in terms of cognitive styles reflective and impulsive This research is the mixed methods model concurrent embedded. The population in this study, i.e., class VIII SMPN 1 Batang with sample two class. Data were taken with the observation, interviews, and tests and analyzed with a different test average of one party the right qualitative and descriptive. The results of this study demonstrate the capability of the MP student with RCP learning better than the scientific learning, upgrade MP with RCP learning better compare with scientific learning in term cognitive style of reflective and impulsive. The subject of the reflective group top, middle, and bottom can meet all the process of MH indicators are then the subject of the reflective upper and intermediate group can meet all the MV indicators but to lower groups can only fulfill some MV indicators. The subject is impulsive upper and middle group can meet all the MH indicators but to lower groups can only meet some MH indicator, then the subject is impulsive group can meet all the MV indicators but for middle and the bottom group can only fulfill some MV indicators.

A lifestyle intervention program for successfully addressing major cardiometabolic risks in persons with SCI: a three-subject case series

PubMed Central

Bigford, Gregory E; Mendez, Armando J; Betancourt, Luisa; Burns-Drecq, Patricia; Backus, Deborah; Nash, Mark S

2017-01-01

Introduction This study is a prospective case series analyzing the effects of a comprehensive lifestyle intervention program in three patients with chronic paraplegia having major risks for the cardiometabolic syndrome (CMS). Case presentation: Individuals underwent an intense 6-month program of circuit resistance exercise, nutrition using a Mediterranean diet and behavioral support, followed by a 6-month extension (maintenance) phase involving minimal support. The primary goal was a 7% reduction of body mass. Other outcomes analyzed insulin resistance using the HOMA-IR model, and plasma levels of fasting triglycerides and high-density lipoprotein cholesterol. All participants achieved the goal for 7% reduction of body mass and maintained the loss after the MP. Improvements were observed in 2/3 subjects for HOMA-IR and high-density lipoprotein cholesterol. All participants improved their risk for plasma triglycerides. Discussion: We conclude, in a three-person case series of persons with chronic paraplegia, a lifestyle intervention program involving circuit resistance training, a calorie-restrictive Mediterranean-style diet and behavioral support, results in clinically significant loss of body mass and effectively reduced component risks for CMS and diabetes. These results were for the most part maintained after a 6-month MP involving minimal supervision. PMID:28382218

Parallel k-means++

DOE Office of Scientific and Technical Information (OSTI.GOV)

A parallelization of the k-means++ seed selection algorithm on three distinct hardware platforms: GPU, multicore CPU, and multithreaded architecture. K-means++ was developed by David Arthur and Sergei Vassilvitskii in 2007 as an extension of the k-means data clustering technique. These algorithms allow people to cluster multidimensional data, by attempting to minimize the mean distance of data points within a cluster. K-means++ improved upon traditional k-means by using a more intelligent approach to selecting the initial seeds for the clustering process. While k-means++ has become a popular alternative to traditional k-means clustering, little work has been done to parallelize this technique.more » We have developed original C++ code for parallelizing the algorithm on three unique hardware architectures: GPU using NVidia's CUDA/Thrust framework, multicore CPU using OpenMP, and the Cray XMT multithreaded architecture. By parallelizing the process for these platforms, we are able to perform k-means++ clustering much more quickly than it could be done before.« less

Emergence Processes up to Consciousness Using the Multiplicity Principle and Quantum Physics

NASA Astrophysics Data System (ADS)

Ehresmann, Andrée C.; Vanbremeersch, Jean-Paul

2002-09-01

Evolution is marked by the emergence of new objects and interactions. Pursuing our preceding work on Memory Evolutive Systems (MES; cf. our Internet site), we propose a general mathematical model for this process, based on Category Theory. Its main characteristics is the Multiplicity Principle (MP) which asserts the existence of complex objects with several possible configurations. The MP entails the emergence of non-reducible more and more complex objects (emergentist reductionism). From the laws of Quantum Physics, it follows that the MP is valid for the category of particles and atoms, hence, by complexification, for any natural autonomous anticipatory complex system, such as biological systems up to neural systems, or social systems. Applying the model to the MES of neurons, we describe the emergence of higher and higher cognitive processes and of a semantic memory. Consciousness is characterized by the development of a permanent `personal' memory, the archetypal core, which allows the formation of extended landscapes with an integration of the temporal dimensions.

On the accuracy of density-functional theory exchange-correlation functionals for H bonds in small water clusters: Benchmarks approaching the complete basis set limit

NASA Astrophysics Data System (ADS)

Santra, Biswajit; Michaelides, Angelos; Scheffler, Matthias

2007-11-01

The ability of several density-functional theory (DFT) exchange-correlation functionals to describe hydrogen bonds in small water clusters (dimer to pentamer) in their global minimum energy structures is evaluated with reference to second order Møller-Plesset perturbation theory (MP2). Errors from basis set incompleteness have been minimized in both the MP2 reference data and the DFT calculations, thus enabling a consistent systematic evaluation of the true performance of the tested functionals. Among all the functionals considered, the hybrid X3LYP and PBE0 functionals offer the best performance and among the nonhybrid generalized gradient approximation functionals, mPWLYP and PBE1W perform best. The popular BLYP and B3LYP functionals consistently underbind and PBE and PW91 display rather variable performance with cluster size.

On the accuracy of density-functional theory exchange-correlation functionals for H bonds in small water clusters: benchmarks approaching the complete basis set limit.

PubMed

Santra, Biswajit; Michaelides, Angelos; Scheffler, Matthias

2007-11-14

The ability of several density-functional theory (DFT) exchange-correlation functionals to describe hydrogen bonds in small water clusters (dimer to pentamer) in their global minimum energy structures is evaluated with reference to second order Moller-Plesset perturbation theory (MP2). Errors from basis set incompleteness have been minimized in both the MP2 reference data and the DFT calculations, thus enabling a consistent systematic evaluation of the true performance of the tested functionals. Among all the functionals considered, the hybrid X3LYP and PBE0 functionals offer the best performance and among the nonhybrid generalized gradient approximation functionals, mPWLYP and PBE1W perform best. The popular BLYP and B3LYP functionals consistently underbind and PBE and PW91 display rather variable performance with cluster size.

Automatic Generation of Directive-Based Parallel Programs for Shared Memory Parallel Systems

NASA Technical Reports Server (NTRS)

Jin, Hao-Qiang; Yan, Jerry; Frumkin, Michael

2000-01-01

The shared-memory programming model is a very effective way to achieve parallelism on shared memory parallel computers. As great progress was made in hardware and software technologies, performance of parallel programs with compiler directives has demonstrated large improvement. The introduction of OpenMP directives, the industrial standard for shared-memory programming, has minimized the issue of portability. Due to its ease of programming and its good performance, the technique has become very popular. In this study, we have extended CAPTools, a computer-aided parallelization toolkit, to automatically generate directive-based, OpenMP, parallel programs. We outline techniques used in the implementation of the tool and present test results on the NAS parallel benchmarks and ARC3D, a CFD application. This work demonstrates the great potential of using computer-aided tools to quickly port parallel programs and also achieve good performance.

Serum of patients with oral pemphigus vulgaris impairs keratinocyte wound repair in vitro: a time-lapse study on the efficacy of methylprednisolone and pyridostigmine bromide.

PubMed

Lanza, A; Stellavato, A; Heulfe, I; Landi, C; Gombos, F; Cirillo, N

2009-10-01

Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting primarily oral mucosa and skin. Among the drugs used for the therapy of pemphigus, both methylprednisolone (MP) and pyridostigmine bromide (PBr) can prevent acantholysis in vitro. However, their putative therapeutic properties in regenerating PV-like lesions and promoting the healing process still remain to be demonstrated. To address this issue, here we have developed a model for studying the process of epithelial cleft regeneration in PV by artificially wounding keratinocyte monolayers. The experimental model was established by scratching confluent monolayers to simulate the epithelial cleft; then, wound regeneration in the presence of submaximal concentrations of PV sera was studied by time-lapse microscopy, with or without the addition of MP and PBr in the culture medium. Pemphigus vulgaris serum inhibited epithelial cleft repair of wounded monolayers. Indeed, in the presence of 10% (v/v) PV serum, keratinocytes reached only 2% confluence within 72 h vs an almost complete healing of controls. When administered together with PV sera, MP significantly (P < 0.01) enhanced wound fill by 30% after 72 h. PV-associated wound repair was significantly (P < 0.05) ameliorated by PBr by 24 h and keratinocytes reached 20% confluence after 72 h. Interestingly, neither MP nor PBr could accelerate wound healing when compared with untreated control monolayers. In PV, MP and PBr exert their curative effects in part by enhancing the regeneration properties of keratinocytes. Indeed, our data suggest that both drugs can specifically counterbalance the detrimental effects of PV serum on keratinocyte wound healing. These findings provide an explanation for the efficacy of MP and PBr in the treatment of PV lesions in human skin and oral mucosa.

Alterations in pain response are partially reversed by methylphenidate (Ritalin) in adults with attention deficit hyperactivity disorder (ADHD).

PubMed

Treister, Roi; Eisenberg, Elon; Demeter, Naor; Pud, Dorit

2015-01-01

Attention deficit hyperactivity disorder (ADHD) is characterized by dysregulation of sensory processing and neurobiology of dopamine. Although cumulative evidence suggests that dopamine is involved in pain processing, pain perception in ADHD subjects and the effect of dopamine agonists such as methylphenidate (MP, Ritalin) on it have rarely been studied. The aims of this study were to (1) psychophysically assess sensitivity to pain in ADHD subjects as compared to controls and (2) examine the effects of MP on pain response in ADHD subjects. Thirty subjects with ADHD and 30 age- and gender-matched controls participated in a preliminary trial. Pain threshold, intensity, and tolerance in response to cold pain stimulation were measured for both groups (ADHD with no treatment). In addition, the ADHD group was reassessed following a single dose of MP treatment. The ADHD subjects "without MP" in comparison with controls displayed significantly shorter cold pain threshold (2.8 ± 2.1 vs. 5.8 ± 2.5 seconds, respectively, P < 0.001) and cold tolerance (21.8 ± 22.3 vs. 62.8 ± 59.8 seconds, respectively P < 0.001). No differences in pain intensities between the groups were found. Following MP treatment, both cold threshold and tolerance in the ADHD subjects increased significantly compared to those with no treatment (3.6 ± 2.5 seconds, P = 0.011, and 46.4 ± 53.3 seconds, P < 0.001, respectively). These results suggest that adults with ADHD are more sensitive to pain compared with controls and that MP may exert antinociceptive properties in these subjects. Randomized, controlled trials are warranted to verify these findings. © 2013 World Institute of Pain.

Assessment of MagNA pure LC extraction system for detection of human papillomavirus (HPV) DNA in PreservCyt samples by the Roche AMPLICOR and LINEAR ARRAY HPV tests.

PubMed

Stevens, Matthew P; Rudland, Elice; Garland, Suzanne M; Tabrizi, Sepehr N

2006-07-01

Roche Molecular Systems recently released two PCR-based assays, AMPLICOR and LINEAR ARRAY (LA), for the detection and genotyping, respectively, of human papillomaviruses (HPVs). The manual specimen processing method recommended for use with both assays, AmpliLute, can be time-consuming and labor-intensive and is open to potential specimen cross-contamination. We evaluated the Roche MagNA Pure LC (MP) as an alternative for specimen processing prior to use with either assay. DNA was extracted from cervical brushings, collected in PreservCyt media, by AmpliLute and MP using DNA-I and Total Nucleic Acid (TNA) kits, from 150 patients with histologically confirmed cervical abnormalities. DNA was amplified and detected by AMPLICOR and the LA HPV test. Concordances of 96.5% (139 of 144) (kappa=0.93) and 95.1% (135 of 142) (kappa=0.90) were generated by AMPLICOR when we compared DNA extracts from AmpliLute to MP DNA-I and TNA, respectively. The HPV genotype profiles were identical in 78.7 and 74.7% of samples between AmpliLute and DNA-I or TNA, respectively. To improve LA concordance, all 150 specimens were extracted by MP DNA-I protocol after the centrifugation of 1-ml PreservCyt samples. This modified approach improved HPV genotype concordance levels between AmpliLute and MP DNA-I to 88.0% (P=0.043) without affecting AMPLICOR sensitivity. Laboratories that have an automated MP extraction system would find this procedure more feasible and easier to handle than the recommended manual extraction method and could substitute such extractions for AMPLICOR and LA HPV tests once internally validated.

Fast evaluation of scaled opposite spin second-order Møller-Plesset correlation energies using auxiliary basis expansions and exploiting sparsity.

PubMed

Jung, Yousung; Shao, Yihan; Head-Gordon, Martin

2007-09-01

The scaled opposite spin Møller-Plesset method (SOS-MP2) is an economical way of obtaining correlation energies that are computationally cheaper, and yet, in a statistical sense, of higher quality than standard MP2 theory, by introducing one empirical parameter. But SOS-MP2 still has a fourth-order scaling step that makes the method inapplicable to very large molecular systems. We reduce the scaling of SOS-MP2 by exploiting the sparsity of expansion coefficients and local integral matrices, by performing local auxiliary basis expansions for the occupied-virtual product distributions. To exploit sparsity of 3-index local quantities, we use a blocking scheme in which entire zero-rows and columns, for a given third global index, are deleted by comparison against a numerical threshold. This approach minimizes sparse matrix book-keeping overhead, and also provides sufficiently large submatrices after blocking, to allow efficient matrix-matrix multiplies. The resulting algorithm is formally cubic scaling, and requires only moderate computational resources (quadratic memory and disk space) and, in favorable cases, is shown to yield effective quadratic scaling behavior in the size regime we can apply it to. Errors associated with local fitting using the attenuated Coulomb metric and numerical thresholds in the blocking procedure are found to be insignificant in terms of the predicted relative energies. A diverse set of test calculations shows that the size of system where significant computational savings can be achieved depends strongly on the dimensionality of the system, and the extent of localizability of the molecular orbitals. Copyright 2007 Wiley Periodicals, Inc.

Protecting the ozone layer.

PubMed

Munasinghe, M; King, K

1992-06-01

Stratospheric ozone layer depletion has been recognized as a problem by the Vienna Convention for the Protection of the Ozone Layer and the 1987 Montreal Protocol (MP). The ozone layer shields the earth from harmful ultraviolet radiation (UV-B), which is more pronounced at the poles and around the equator. Industrialized countries have contributed significantly to the problem by releasing chlorofluorocarbons (CFCs) and halons into the atmosphere. The effect of these chemicals, which were known for their inertness, nonflammability, and nontoxicity, was discovered in 1874. Action to deal with the effects of CFCs and halons was initiated in 1985 in a 49-nation UN meeting. 21 nations signed a protocol limiting ozone depleting substances (ODS): CFCs and halons. Schedules were set based on each country's use in 1986; the target phaseout was set for the year 2000. The MP restricts trade in ODSs and weights the impact of substances to reflect the extent of damage; i.e., halons are 10 times more damaging than CFCs. ODS requirements for developing countries were eased to accommodate scarce resources and the small fraction of ODS emissions. An Interim Multilateral Fund under the Montreal Protocol (IMFMP) was established to provide loans to finance the costs to developing countries in meeting global environmental requirements. The IMFMP is administered by the World Bank, the UN Environmental Program, and the UN Development Program. Financing is available to eligible countries who use .3 kg of ODS/person/year. Rapid phaseout in developed countries has occurred due to strong support from industry and a lower than expected cost. Although there are clear advantages to rapid phaseout, there were no incentives included in the MP for rapid phaseout. Some of the difficulties occur because the schedules set minimum targets at the lowest possible cost. Also, costs cannot be minimized by a country-specific and ODS-specific process. The ways to improve implementation in scheduling and incremental costs are indicated.

A conceptual framework for Lake Michigan coastal/nearshore ecosystems, with application to Lake Michigan Lakewide Management Plan (LaMP) objectives

USGS Publications Warehouse

Seelbach, Paul W.; Fogarty, Lisa R.; Bunnell, David Bo; Haack, Sheridan K.; Rogers, Mark W.

2013-01-01

The Lakewide Management Plans (LaMPs) within the Great Lakes region are examples of broad-scale, collaborative resource-management efforts that require a sound ecosystems approach. Yet, the LaMP process is lacking a holistic framework that allows these individual actions to be planned and understood within the broader context of the Great Lakes ecosystem. In this paper we (1) introduce a conceptual framework that unifies ideas and language among Great Lakes managers and scientists, whose focus areas range from tributary watersheds to open-lake waters, and (2) illustrate how the framework can be used to outline the geomorphic, hydrologic biological, and societal processes that underlie several goals of the Lake Michigan LaMP, thus providing a holistic and fairly comprehensive roadmap for tackling these challenges. For each selected goal, we developed a matrix that identifies the key ecosystem processes within the cell for each lake zone and each discipline; we then provide one example where a process is poorly understood and a second where a process is understood, but its impact or importance is unclear. Implicit in these objectives was our intention to highlight the importance of the Great Lakes coastal/nearshore zone. Although the coastal/nearshore zone is the important linkage zone between the watershed and open-lake zones—and is the zone where most LaMP issues are focused--scientists and managers have a relatively poor understanding of how the coastal/nearshore zone functions. We envision follow-up steps including (1) collaborative development of a more detailed and more complete conceptual model of how (and where) identified processes are thought to function, and (2) a subsequent gap analysis of science and monitoring priorities.

Hydromorphone transfer into breast milk after intranasal administration.

PubMed

Edwards, Jeffrey E; Rudy, Anita C; Wermeling, Daniel P; Desai, Nirmala; McNamara, Patrick J

2003-02-01

To determine the distribution of hydromorphone into breast milk and the potential exposure of the suckling infant, and whether the distribution of hydromorphone into milk can be predicted accurately by a passive diffusion model. Single-dose, pharmacokinetic study. University clinical research unit. Eight lactating, nonsmoking, healthy women aged 24-32 years. Hydromorphone HCl 2 mg was given intranasally to the women to characterize its pharmacokinetics and extent of its transfer into breast milk. Plasma and milk samples were analyzed using liquid chromatography with tandem mass spectrometry detection. The milk:plasma ratio (M:P) was calculated as the total area under the concentration-time curve (AUC) of the milk divided by the total AUC of the plasma. Predicted in vitro M:P ratios were calculated using a diffusion model. Protein binding in milk and plasma, partitioning into milk fat (whole milk:skim milk ratios), as well as pH partitioning between plasma and milk were incorporated in the model. Protein binding was determined by equilibrium dialysis. Protein binding was minimal in both milk and plasma, with unbound fractions of 1 and 0.84, respectively There was little partitioning into milk fat, as demonstrated by the whole milk:skim milk ratio of 0.98. The observed and predicted M:P ratios +/- SD for hydromorphone were 2.57 +/- 0.47 and 1.11 +/- 0.28, respectively. The 95% confidence interval for the observed M:P ratio overlapped the confidence interval of the predicted M:P ratio, a finding that supports a role for both passive diffusion and active transport as mechanisms of hydromorphone transfer into milk. Hydromorphone distributes rapidly from plasma into breast milk; however, the drug does not partition into fat. The suckling infant would receive approximately 0.67% of the maternal dose of hydromorphone (adjusted for body weight). As this is a limited exposure, further studies are needed to determine any potential impact to an infant who is fed breast milk from a mother treated with hydromorphone.

Induced structural changes of humic acid by exposure of polystyrene microplastics: A spectroscopic insight.

PubMed

Chen, Wei; Ouyang, Zhen-Yu; Qian, Chen; Yu, Han-Qing

2018-02-01

The occurrence of microplastics (MPs) as emerging contaminants in the environment may cause changes in water or sediment characteristics, and further affect their biogeochemical cycles. Thus, insights into the interactions between dissolved organic matter (DOM) and MPs are essential for the assessment of environmental impacts of MPs in ecosystems. Integrating spectroscopic methods with chemometric analyses, this work explored the chemical and microstructural changes of DOM-MP complex to reveal the mechanism of DOM-MP interaction at a molecular level. MPs were found to interact with the aromatic structure of DOM via π-π conjugation, then be entrapped in the DOM polymers by the carboxyl groups and C=O bonds, constituting a highly conjugated co-polymer with increased electron density. This induced the fluorescence intensity increase in DOM. The interaction affinity of DOM-MP was highly dependent on the MP size and solution pH. This work offers a new insight into the impact of MP discharge on environment and may provide an analytical framework for evaluating MP hetero-aggregation and the roles of MPs in the transportation of other contaminants. Furthermore, the integrated methods used in this work exhibit potential applications in exploring the fragmentation processes of MPs and formation of secondary MPs under natural conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bromate formation from the oxidation of bromide in the UV/chlorine process with low pressure and medium pressure UV lamps.

PubMed

Fang, Jingyun; Zhao, Quan; Fan, Chihhao; Shang, Chii; Fu, Yun; Zhang, Xiangru

2017-09-01

When a bromide-containing water is treated by the ultraviolet (UV)/chlorine process, hydroxyl radicals (HO) and halogen radicals such as Cl or Br are formed due to the UV photolysis of free halogens. These reactive species may induce the formation of bromate, which is a probable human carcinogen. Bromate formation in the UV/chlorine process using low pressure (LP) and medium pressure (MP) lamps in the presence of bromide was investigated in the present study. The UV/chlorine process significantly enhanced bromate formation as compared to dark chlorination. The bromate formation was elevated with increasing UV fluence, bromide concentration, and pH values under both LP and MP UV irradiations. It was significantly enhanced at pH 9 compared to those at pH 6 and 7 with MP UV irradiation, while it was slightly enhanced at pH 9 with LP UV. The formation by UV/chlorine process started with the formation of free bromine (HOBr/OBr - ) through the reaction of chlorine and bromide, followed by a subsequent oxidation of free bromine and formation of BrO and bromate by reacting with radicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spray-dried mucoadhesives for intravesical drug delivery using N-acetylcysteine- and glutathione-glycol chitosan conjugates.

PubMed

Denora, Nunzio; Lopedota, Angela; Perrone, Mara; Laquintana, Valentino; Iacobazzi, Rosa M; Milella, Antonella; Fanizza, Elisabetta; Depalo, Nicoletta; Cutrignelli, Annalisa; Lopalco, Antonio; Franco, Massimo

2016-10-01

This work describes N-acetylcysteine (NAC)- and glutathione (GSH)-glycol chitosan (GC) polymer conjugates engineered as potential platform useful to formulate micro-(MP) and nano-(NP) particles via spray-drying techniques. These conjugates are mucoadhesive over the range of urine pH, 5.0-7.0, which makes them advantageous for intravesical drug delivery and treatment of local bladder diseases. NAC- and GSH-GC conjugates were generated with a synthetic approach optimizing reaction times and purification in order to minimize the oxidation of thiol groups. In this way, the resulting amount of free thiol groups immobilized per gram of NAC- and GSH-GC conjugates was 6.3 and 3.6mmol, respectively. These polymers were completely characterized by molecular weight, surface sulfur content, solubility at different pH values, substitution and swelling degree. Mucoadhesion properties were evaluated in artificial urine by turbidimetric and zeta (ζ)-potential measurements demonstrating good mucoadhesion properties, in particular for NAC-GC at pH 5.0. Starting from the thiolated polymers, MP and NP were prepared using both the Büchi B-191 and Nano Büchi B-90 spray dryers, respectively. The resulting two formulations were evaluated for yield, size, oxidation of thiol groups and ex-vivo mucoadhesion. The new spray drying technique provided NP of suitable size (<1μm) for catheter administration, low degree of oxidation, and sufficient mucoadhesion property with 9% and 18% of GSH- and NAC-GC based NP retained on pig mucosa bladder after 3h of exposure, respectively. The aim of the present study was first to optimize the synthesis of NAC-GC and GSH-GC, and preserve the oxidation state of the thiol moieties by introducing several optimizations of the already reported synthetic procedures that increase the mucoadhesive properties and avoid pH-dependent aggregation. Second, starting from these optimized thiomers, we studied the feasibility of manufacturing MP and NP by spray-drying techniques. The aim of this second step was to produce mucoadhesive drug delivery systems of adequate size for vesical administration by catheter, and comparable mucoadhesive properties with respect to the processed polymers, avoiding thiolic oxidation during the formulation. MP with acceptable size produced by spray-dryer Büchi B-191 were compared with NP made with the apparatus Nano Büchi B-90. Copyright © 2016 Acta Materialia Inc. All rights reserved.

Interexaminer reliability of the electromagnetic radiation receiver for determining lumbar spinal joint dysfunction in subjects with low back pain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gemmell, H.A.; Jacobson, B.H.; Edwards, S.W.

Twenty subjects (6 male, 14 female) with low back pain were examined by two experienced and licensed chiropractic doctors (E1 and E2). Both examiners examined the patients using a Toftness Electromagnetic Radiation Receiver (EMRR) and by manual palpation (MP) of the spinous processes. Interexaminer reliability was calculated at three sites (L3, L4, L5) for the following combinations: (a) E1,MP--E2,MP; (b) E1,EMRR--E2,EMRR; (c) E1,MP--E2,EMRR; and (d) E2,MP--E1,EMRR, and intraexaminer reliability was calculated for the following variables: (e) E1,MP--E1,EMRR; and (f) E2,MP--E2,EMRR. Results of a Kappa coefficient analysis for interexaminer reliability of the stated combinations and at the specific sites were: (a)more » -0.071, 0.400, 0.200; (b) -0.013, 0.100, -0.120; (c) 0.286, 0.300, 0.200; (d) -0.081, 0.000, 0.048. These results predominantly indicate a poor to fair interexaminer reliability. The results of a Kappa coefficient analysis for intraexaminer reliability of the stated combinations were: (e) 0.111, 0.400, 0.737; (f) 0.000, 0.100, 0.368. These results indicate a poor to fair reliability. It was concluded that in subjects with low back pain the EMRR may not be a reliable indicator of spinal joint dysfunction.« less

Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD.

PubMed

Amin, Jaimin; Huang, Brian; Yoon, Jessica; Shih, David Q

2015-02-01

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine (AZA), remain as a mainstay therapy in inflammatory bowel disease (IBD). Differences in metabolism of these drugs lead to individual variation in thiopurine metabolite levels that can determine its therapeutic efficacy and development of adverse reactions. In this update, we will review thiopurine metabolic pathway along with the up-to-date approaches in administering thiopurine medications based on the current literature. A search of the PubMed database by 2 independent reviewers identifying 98 articles evaluating thiopurine metabolism and IBD management. Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD. Based on the currently available literature, various dosing strategies to improve therapeutic response and reduce adverse reactions can be considered, including use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of thiopurine.

Multiple products monitoring as a robust approach for peptide quantification.

PubMed

Baek, Je-Hyun; Kim, Hokeun; Shin, Byunghee; Yu, Myeong-Hee

2009-07-01

Quantification of target peptides and proteins is crucial for biomarker discovery. Approaches such as selected reaction monitoring (SRM) and multiple reaction monitoring (MRM) rely on liquid chromatography and mass spectrometric analysis of defined peptide product ions. These methods are not very widespread because the determination of quantifiable product ion using either SRM or MRM is a very time-consuming process. We developed a novel approach for quantifying target peptides without such an arduous process of ion selection. This method is based on monitoring multiple product ions (multiple products monitoring: MpM) from full-range MS2 spectra of a target precursor. The MpM method uses a scoring system that considers both the absolute intensities of product ions and the similarities between the query MS2 spectrum and the reference MS2 spectrum of the target peptide. Compared with conventional approaches, MpM greatly improves sensitivity and selectivity of peptide quantification using an ion-trap mass spectrometer.

Biocompatibility of metal injection molded versus wrought ASTM F562 (MP35N) and ASTM F1537 (CCM) cobalt alloys.

PubMed

Chen, Hao; Sago, Alan; West, Shari; Farina, Jeff; Eckert, John; Broadley, Mark

2011-01-01

We present a comparative analysis between biocompatibility test results of wrought and Metal Injection Molded (MIM) ASTM F562-02 UNS R30035 (MP35N) and F1537 UNS R31538 (CCM) alloy samples that have undergone the same generic orthopedic implant's mechanical, chemical surface pre-treatment, and a designed pre-testing sample preparation method. Because the biocompatibility properties resulting from this new MIM cobalt alloy process are not well understood, we conducted tests to evaluate cytotoxicity (in vitro), hemolysis (in vitro), toxicity effects (in vivo), tissue irritation level (in vivo), and pyrogenicity count (in vitro) on such samples. We show that our developed MIM MP35N and CCM materials and treatment processes are biocompatible, and that both the MIM and wrought samples, although somewhat different in microstructure and surface, do not show significant differences in biocompatibility.

Approaching the theoretical limit in periodic local MP2 calculations with atomic-orbital basis sets: the case of LiH.

PubMed

Usvyat, Denis; Civalleri, Bartolomeo; Maschio, Lorenzo; Dovesi, Roberto; Pisani, Cesare; Schütz, Martin

2011-06-07

The atomic orbital basis set limit is approached in periodic correlated calculations for solid LiH. The valence correlation energy is evaluated at the level of the local periodic second order Møller-Plesset perturbation theory (MP2), using basis sets of progressively increasing size, and also employing "bond"-centered basis functions in addition to the standard atom-centered ones. Extended basis sets, which contain linear dependencies, are processed only at the MP2 stage via a dual basis set scheme. The local approximation (domain) error has been consistently eliminated by expanding the orbital excitation domains. As a final result, it is demonstrated that the complete basis set limit can be reached for both HF and local MP2 periodic calculations, and a general scheme is outlined for the definition of high-quality atomic-orbital basis sets for solids. © 2011 American Institute of Physics

Using a multimedia presentation to improve patient understanding and satisfaction with informed consent for minimally invasive vascular procedures.

PubMed

Bowers, N; Eisenberg, E; Montbriand, J; Jaskolka, J; Roche-Nagle, G

2017-02-01

As vascular procedures become more complex, patient understanding of their treatment(s) can become more difficult. We wished to evaluate the utility of multimedia presentations (MPs) to improve patient understanding of their vascular interventions. Patients undergoing endovascular aneurysm repair (EVAR), peripheral angioplasty, Hickman catheter and peripherally inserted central catheter (PICC) insertion were randomized into a control group receiving traditional verbal consent, and a MP group that were shown a two minute simplified video of their procedure on an iPad™ computer in addition to the traditional verbal consent. After obtaining consent, all patients completed a questionnaire assessing their comprehension of the procedure, and satisfaction with the consent process. Satisfaction was rated on a 5 point Likert scale with 5 being 'very helpful' in understanding the procedure. Ninety-three patients were recruited for this study, 62% of which were male. The intervention significantly increased total comprehension in all procedure types controlling for procedure type (multimedia vs. control; F = 9.14, P = .003). A second ANOVA showed there was a significant main effect by intervention (F = 44.06, p < .000) with those in the intervention group showing higher overall satisfaction scores after controlling for surgery type. This study suggests that patients find the use of MP during the consent process to be helpful in patient understanding and that there is improved satisfaction. Given the rapid rate of innovation in vascular interventions, increased regular use of MPs to help patients understand their procedures would be beneficial in the care of patients undergoing vascular interventions. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Design and evaluation of multi-indicator profiles for targeted-selective treatment against gastrointestinal nematodes at housing in adult dairy cows.

PubMed

Ravinet, Nadine; Lehebel, Anne; Bareille, Nathalie; Lopez, Carlos; Chartier, Christophe; Chauvin, Alain; Madouasse, Aurélien

2017-04-15

Targeted-selective treatments against gastrointestinal nematode (GIN) in adult dairy cows require the identification of "cows to treat", i.e. cows whose milk production (MP) would increase after treatment. This study aimed at quantifying the ability of multi-indicator profiles to identify such cows. A randomized controlled clinical trial was conducted at housing in 25 French pasturing dairy herds. In each herd, treated cows received fenbendazole orally, control cows remained untreated. Daily MP was recorded and the MP variation between the pre- and post-visit periods was calculated (ΔMP) for each cow. ΔMP was modelled with control cows data (n=412) (piecewise linear mixed model). Estimated parameters were applied to treated cows data (n=414) to predict the expected ΔMP in treated cows if they had not been treated. Treated cows with an observed ΔMP (with treatment) higher than the expected ΔMP (without treatment) were labelled as "cows to treat". Herds where at least 50% of the young cows were "cows to treat" were qualified as "herds to target". To characterize such cows and herds, the available candidate indicators were (i) at the cow-level: parity, stage of lactation and production level, faecal egg count (FEC), serum pepsinogen level and anti-Ostertagia antibody level (expressed as ODR); (ii) at the herd-level: bulk tank milk (BTM) Ostertagia ODR, Time of Effective Contact (TEC, in months) with GIN infective larvae before the first calving, and percentage of positive FEC. These indicators were tested one-by-one or in combination to assess their ability to characterize "herds to target" and "cows to treat" (Chi-square tests). 115 out of 414 treated cows (27.8%) were considered as "cows to treat", and 9 out of 22 herds were qualified as "herds to target". The indicators retained to profile such cows and herds were the parity, the production level, the BTM Ostertagia ODR and the TEC. Multi-indicator profiles were much more specific than single indicator profiles, induced lower treatment rates, thereby minimizing the selection pressure on parasite populations. Particularly, to target a herd, the specificity was better with the profile "high BTM Ostertagia ODR and low-TEC" than with the BTM ODR value taken into account alone. The targeted-selective treatment of "young cows, belonging to herds with a high BTM ODR at housing and a low TEC" appeared as a pertinent solution, enabling a global approach for the control of GIN infection in which GIN control in heifers is connected to GIN control in adult cows. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of the solution pH in the 6-mercaptopurine self-assembled monolayer (6MP-SAM) on a Au(111) single-crystal electrode.

PubMed

Madueño, Rafael; García-Raya, Daniel; Viudez, Alfonso J; Sevilla, José M; Pineda, Teresa; Blázquez, Manuel

2007-10-23

Self-assembled monolayers (SAMs) of 6-mercaptopurine (6MP) have been prepared on a Au(111) single-crystal electrode by immersion of the metal surface in a 100 microM 6MP and 0.01 M HClO4 solution. The 6MP-SAM Au(111) single-crystal electrodes were transferred to the cell and allowed to equilibrate with the different aqueous working solutions before the electrochemical experiments. The influence of the solution pH was studied by cyclic voltammetry, double layer capacitance curves, and electrochemical impedance spectroscopy. The electrochemical behavior of the 6MP-SAM in acetic acid at pH 4 presents important differences in comparison to that obtained in 0.1 M KOH solutions. Cyclic voltammograms for the reductive desorption process in acid medium are broad and show some features that can be explained by a phase transition between a chemisorbed and a physisorbed state of the 6MP molecules. The low solubility of these molecules in acid medium could explain this phenomenon and the readsorption of the complete monolayer when the potential is scanned in the positive direction. The variation of the double-layer capacitance values in the potential range of monolayer stability with the pH suggests that the acid-base chemistry of the 6MP molecules is playing a role. This fact has been studied by following the variations of the electron-transfer rate constant of the highly charged redox probes as are Fe(CN)(6)-3/-4 and Ru(NH3)(6)+3/+2 as a function of solution pH. The apparent surface pKa value for the 6MP-SAM (pKa approximately 8) is explained by the total conversion of the different 6MP tautomers that exist in solution to the thiol species in the adsorbed state.

Zinc Mesoporphyrin Induces Rapid Proteasomal Degradation of Hepatitis C Nonstructural 5A Protein in Human Hepatoma Cells

PubMed Central

Hou, Weihong; Tian, Qing; Zheng, Jianyu; Bonkovsky, Herbert L.

2009-01-01

Background & Aims The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV), plays a critical role in HCV replication and is an attractive target for the therapy of HCV infection. So far, little is known about the post-translational regulation of NS5A protein and its precise role in HCV RNA replication. Our objectives were to elucidate the down-regulation of NS5A protein and HCV RNA replication by zinc mesoporphyrin (ZnMP), and the mechanism by which this process occurs. Methods Human hepatoma cells expressing HCV proteins were used to investigate the post-translational regulation of ZnMP on NS5A protein by Western blots (WB) and immunoprecipitation (IP). Quantitative RT-PCR (qRT-PCR) was used to determine the effects of ZnMP on HCV RNA replication. Results ZnMP selectively and markedly down-regulated NS5A protein levels by increasing degradation of NS5A protein [half life fell from 18.7 h to 2.7 h]. The proteasome inhibitors, epoxomicin and MG132, significantly abrogated degradation of NS5A protein by ZnMP without affecting levels of NS5A in the absence of ZnMP. Analysis of immunoprecipitates with an anti-ubiquitin antibody revealed polyubiquitination of NS5A, suggesting that ZnMP induces ubiquitination of NS5A protein. In addition, 10 μM of ZnMP reduced HCV replication by ~63% in the Con1 replicon cells, ~70% in J6/JFH1 HCV transfected cells, and ~90% in J6/JFH1 HCV infected cells without affecting cell viability. Conclusions ZnMP produces a rapid and profound down-regulation of the NS5A protein by enhancing its polyubiquitination and proteasome-dependent catabolism. Zinc mesoporphyrin may hold promise as a novel agent to treat HCV infection. PMID:19909748

Improvement and speed optimization of numerical tsunami modelling program using OpenMP technology

NASA Astrophysics Data System (ADS)

Chernov, A.; Zaytsev, A.; Yalciner, A.; Kurkin, A.

2009-04-01

Currently, the basic problem of tsunami modeling is low speed of calculations which is unacceptable for services of the operative notification. Existing algorithms of numerical modeling of hydrodynamic processes of tsunami waves are developed without taking the opportunities of modern computer facilities. There is an opportunity to have considerable acceleration of process of calculations by using parallel algorithms. We discuss here new approach to parallelization tsunami modeling code using OpenMP Technology (for multiprocessing systems with the general memory). Nowadays, multiprocessing systems are easily accessible for everyone. The cost of the use of such systems becomes much lower comparing to the costs of clusters. This opportunity also benefits all programmers to apply multithreading algorithms on desktop computers of researchers. Other important advantage of the given approach is the mechanism of the general memory - there is no necessity to send data on slow networks (for example Ethernet). All memory is the common for all computing processes; it causes almost linear scalability of the program and processes. In the new version of NAMI DANCE using OpenMP technology and multi-threading algorithm provide 80% gain in speed in comparison with the one-thread version for dual-processor unit. The speed increased and 320% gain was attained for four core processor unit of PCs. Thus, it was possible to reduce considerably time of performance of calculations on the scientific workstations (desktops) without complete change of the program and user interfaces. The further modernization of algorithms of preparation of initial data and processing of results using OpenMP looks reasonable. The final version of NAMI DANCE with the increased computational speed can be used not only for research purposes but also in real time Tsunami Warning Systems.

Columnar Segregation of Magnocellular and Parvocellular Streams in Human Extrastriate Cortex

PubMed Central

2017-01-01

Magnocellular versus parvocellular (M-P) streams are fundamental to the organization of macaque visual cortex. Segregated, paired M-P streams extend from retina through LGN into V1. The M stream extends further into area V5/MT, and parts of V2. However, elsewhere in visual cortex, it remains unclear whether M-P-derived information (1) becomes intermixed or (2) remains segregated in M-P-dominated columns and neurons. Here we tested whether M-P streams exist in extrastriate cortical columns, in 8 human subjects (4 female). We acquired high-resolution fMRI at high field (7T), testing for M- and P-influenced columns within each of four cortical areas (V2, V3, V3A, and V4), based on known functional distinctions in M-P streams in macaque: (1) color versus luminance, (2) binocular disparity, (3) luminance contrast sensitivity, (4) peak spatial frequency, and (5) color/spatial interactions. Additional measurements of resting state activity (eyes closed) tested for segregated functional connections between these columns. We found M- and P-like functions and connections within and between segregated cortical columns in V2, V3, and (in most experiments) area V4. Area V3A was dominated by the M stream, without significant influence from the P stream. These results suggest that M-P streams exist, and extend through, specific columns in early/middle stages of human extrastriate cortex. SIGNIFICANCE STATEMENT The magnocellular and parvocellular (M-P) streams are fundamental components of primate visual cortical organization. These streams segregate both anatomical and functional properties in parallel, from retina through primary visual cortex. However, in most higher-order cortical sites, it is unknown whether such M-P streams exist and/or what form those streams would take. Moreover, it is unknown whether M-P streams exist in human cortex. Here, fMRI evidence measured at high field (7T) and high resolution revealed segregated M-P streams in four areas of human extrastriate cortex. These results suggest that M-P information is processed in segregated parallel channels throughout much of human visual cortex; the M-P streams are more than a convenient sorting property in earlier stages of the visual system. PMID:28724749

6-mercaptopurine (6-MP) entrapped stealth liposomes for improvement of leukemic treatment without hepatotoxicity and nephrotoxicity.

PubMed

Umrethia, Manish; Ghosh, Pradip Kumar; Majithya, Rita; Murthy, R S R

2007-03-01

6-mercaptopurine (6-MP) is a purine analogue used in childhood leukemia. Because of the oral bioavailability of 6-MP is low and highly variable, the aim of this study was to develop a new parenteral formulation that can prolong the biological half-life of the drug, improve its therapeutic efficacy, and its associated reduce side effects. Conventional and stealth 6-MP liposomes were prepared by a thin film hydration technique followed by a high-pressure homogenization process and characterized for percent entrapment efficiency (%EE), particle size, and stability in human plasma. Pharmacokinetic, tissue distribution, and biochemical analysis were performed after intravenous (IV) administration of all formulations of 6-MP on rats. The conventional liposomes were found less stable than stealth liposomes in human plasma at 37 degrees C. Stealth liposomes exhibited high peak plasma concentration (C(max)), and long circulating capacity in blood and biological half-life. The uptake of stealth liposomes by the liver and spleen and accumulation in the kidney were significantly less than that of conventional liposomes and the free drug. Serum urea, creatinine, GOT (Glutamic Oxaloacetic Transaminase), and GPT (Glutamic Pyruvic Transaminase) increased significantly in rats given an IV injection of conventional liposomes and the free drug, but not in those administered with the same dose of stealth liposomes. Stealth liposomes may help to increase therapeutic efficacy of 6-MP and to reduce total amount of dose as well as frequency of the dose. It also may reduce the possibility of the risk of toxicity to the liver and kidney generally associated with free 6-MP.

Remediation mechanisms of mercapto-grafted palygorskite for cadmium pollutant in paddy soil.

PubMed

Liang, Xuefeng; Qin, Xu; Huang, Qingqing; Huang, Rong; Yin, Xiuling; Cai, Yanming; Wang, Lin; Sun, Yuebing; Xu, Yingming

2017-10-01

The immobilization agent was the key factor that determined the success of remediation of heavy metal polluted soil. In this study, mercapto-grafted palygorskite (MP) as a novel and efficient immobilization agent was utilized for the remediation of Cd-polluted paddy soil in pot trials, and the remediation mechanisms were investigated in the aspect of soil chemistry and plant physiology with different rice cultivars as model plants. Mercapto-grafted palygorskite at applied doses of 0.1-0.3% could reduce Cd contents of brown rice and straws of different cultivars significantly. Both reduced DTPA-extractable Cd contents in rhizosphere and non-rhizosphere soil and decreasing Cd contents in iron plaques on rice root surfaces confirmed that MP was an efficient immobilization agent for Cd pollutant in paddy soil. In the aspect of soil chemistry, the pH values of rhizosphere and non-rhizosphere soils had no statistical changes in the MP treatment groups, but their zeta potentials decreased obviously, indicating that MP could enhance the fixation or sorption of Cd on soil compositions. In the aspect of antioxidant system, MP could increase POD activity of rice roots significantly to alleviate the stress of Cd to roots, and resulted in the decrease of T-AOC, SOD, and CAT activities of rice roots of the selected cultivars. MP had no inhabitation or enhancement effects on TSH of rice roots but enhance the contents of MTs and NPT to binding Cd to complete detoxification process. MP as a novel and efficient immobilization agent could complete the remediation effects through soil chemistry and plant physiological mechanisms.

Zeolite-Templated Mesoporous Silicon Particles for Advanced Lithium-Ion Battery Anodes.

PubMed

Kim, Nahyeon; Park, Hyejeong; Yoon, Naeun; Lee, Jung Kyoo

2018-04-24

For the practical use of high-capacity silicon anodes in high-energy lithium-based batteries, key issues arising from the large volume change of silicon during cycling must be addressed by the facile structural design of silicon. Herein, we discuss the zeolite-templated magnesiothermic reduction synthesis of mesoporous silicon (mpSi) (mpSi-Y, -B, and -Z derived from commercial zeolite Y, Beta, and ZSM-5, respectively) microparticles having large pore volume (0.4-0.5 cm 3 /g), wide open pore size (19-31 nm), and small primary silicon particles (20-35 nm). With these appealing mpSi particle structural features, a series of mpSi/C composites exhibit outstanding performance including excellent cycling stabilities for 500 cycles, high specific and volumetric capacities (1100-1700 mAh g -1 and 640-1000 mAh cm -3 at 100 mA g -1 ), high Coulombic efficiencies (approximately 100%), and remarkable rate capabilities, whereas conventional silicon nanoparticles (SiNP)/C demonstrate limited cycle life. These enhanced electrochemical responses of mpSi/C composites are further manifested by low impedance build-up, high Li ion diffusion rate, and small electrode thickness changes after cycling compared with those of SiNP/C composite. In addition to the outstanding electrochemical properties, the low-cost materials and high-yield processing make the mpSi/C composites attractive candidates for high-performance and high-energy Li-ion battery anodes.

Hemoglobin extravasation in the brain of rats exchange-transfused with hemoglobin-based oxygen carriers.

PubMed

Terraneo, Laura; Bianciardi, Paola; Malavalli, Ashok; Mkrtchyan, Gnel; Spann, Stephanie N; Lohman, Jeff; Samaja, Michele; Vandegriff, Kim D

2017-06-01

Haemoglobin (Hb)-based oxygen carriers are under consideration as oxygen therapeutics. Their effect on apoptosis is critical, because the onset of pro-apoptotic pathways may lead to tissue damage. MP4OX, a polyethylene glycol-conjugated human Hb preserves the baseline level of neuron apoptosis with respect to sham. Here we develop a method for measuring Hb extravasation in brain. We exchange transfused rats by haemorrhaging 50% of their blood with simultaneous, isovolemic replacement with Hextend (negative control), MP4OX, or αα-cross-linked Hb. Animals were sacrificed 2 h after transfusion, brain tissue was harvested and processed for double-staining immunofluorescence, whereby Hb ? chain and NeuN (a neuron protein) were stained and quantitated. Whereas Hextend did not induce Hb extravasation, in both MP4OX and ??Hb brains Hb molecules were detected outside neurons. The level of extravasated Hb chains was > 3-fold higher in Hb compared to MP4OX. Western blot analysis revealed that the expression levels of protein related to redox imbalance (e.g., Nrf2, iNOS and ERK phosphorylation) were higher in ααHb than MP4OX. In conclusions, higher Hb extravasation in ααHb than MP4OX induces redox imbalance, which causes higher anti-oxidant response. Whereas Nrf2 response may be considered protective, iNOS response appears damaging.

Seawater Corrosion of Fasteners in Various Structural Materials

DTIC Science & Technology

1976-04-01

17 - 4PH stainless steel. The seven bolt materials were: 2024 aluminum, anodized ASTM grade 5 steel, 304 and 316 stainless steels, A286 stain- less...performed well in titanium structures. Use of MP35N, A286, and 304 stainless steel fasteners for constantly immersed 17 - 4PH stainless steel structures...would have been satisfactory only if sealant was not used and if protection had been provided to the 17 - 4PH to minimize crevice corrosion. Additional

Electrical Neural Stimulation and Simultaneous in Vivo Monitoring with Transparent Graphene Electrode Arrays Implanted in GCaMP6f Mice.

PubMed

Park, Dong-Wook; Ness, Jared P; Brodnick, Sarah K; Esquibel, Corinne; Novello, Joseph; Atry, Farid; Baek, Dong-Hyun; Kim, Hyungsoo; Bong, Jihye; Swanson, Kyle I; Suminski, Aaron J; Otto, Kevin J; Pashaie, Ramin; Williams, Justin C; Ma, Zhenqiang

2018-01-23

Electrical stimulation using implantable electrodes is widely used to treat various neuronal disorders such as Parkinson's disease and epilepsy and is a widely used research tool in neuroscience studies. However, to date, devices that help better understand the mechanisms of electrical stimulation in neural tissues have been limited to opaque neural electrodes. Imaging spatiotemporal neural responses to electrical stimulation with minimal artifact could allow for various studies that are impossible with existing opaque electrodes. Here, we demonstrate electrical brain stimulation and simultaneous optical monitoring of the underlying neural tissues using carbon-based, fully transparent graphene electrodes implanted in GCaMP6f mice. Fluorescence imaging of neural activity for varying electrical stimulation parameters was conducted with minimal image artifact through transparent graphene electrodes. In addition, full-field imaging of electrical stimulation verified more efficient neural activation with cathode leading stimulation compared to anode leading stimulation. We have characterized the charge density limitation of capacitive four-layer graphene electrodes as 116.07-174.10 μC/cm 2 based on electrochemical impedance spectroscopy, cyclic voltammetry, failure bench testing, and in vivo testing. This study demonstrates the transparent ability of graphene neural electrodes and provides a method to further increase understanding and potentially improve therapeutic electrical stimulation in the central and peripheral nervous systems.

Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization

PubMed Central

Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

2015-01-01

6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP’s widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient’s ability to metabolize the drug instead of the traditional standard-dose-for-all approach. PMID:26226448

Flexible piezoelectric nanogenerators based on a transferred ZnO nanorod/Si micro-pillar array

NASA Astrophysics Data System (ADS)

Baek, Seong-Ho; Park, Il-Kyu

2017-03-01

Flexible piezoelectric nanogenerators (PNGs) based on a composite of ZnO nanorods (NRs) and an array of Si micro-pillars (MPs) are demonstrated by a transfer process. The flexible composite structure was fabricated by hydrothermal growth of ZnO NRs on an electrochemically etched Si MP array with various lengths followed by mechanically delaminating the Si MP arrays from the Si substrate after embedding them in a polydimethylsiloxane matrix. Because the Si MP arrays act as a supporter to connect the ZnO NRs electrically and mechanically, verified by capacitance measurement, the output voltage from the flexible PNGs increased systematically with the increased density ZnO NRs depending on the length of the Si MPs. The flexible PNGs showed 3.2 times higher output voltage with a small change in current with increasing Si MP length from 5 to 20 μm. The enhancement of the output voltage is due to the increased number of series-connected ZnO NRs and the beneficial effect of a ZnO NR/Si MP heterojunction on reducing free charge screening effects. The flexible PNGs can be attached on fingers as a wearable electrical power source or motion sensor.

The mechanism of action of lymphokines. IX. The enzymatic basis of hydrogen peroxide production by lymphokine-activated macrophages.

PubMed

Freund, M; Pick, E

1986-08-15

The purpose of this study was to elucidate the biochemical basis of the enhanced hydrogen peroxide (H2O2) production by guinea pig peritoneal macrophages (MP) cultured in lymphokine (LK)-containing medium. The markedly augmented H2O2 generation by these cells, demonstrable by the horseradish peroxidase (HRP)-catalyzed oxidation of phenol red, is distinguished by its lack of dependence on a second stimulus. We demonstrate that H2O2 production is truly spontaneous and is not caused by a stimulant present among the H2O2 assay reagents. The principal candidate for such a role was HRP type II (a mixture of five isoenzymes) that was reported to be capable of eliciting an oxidative burst in MP. Four distinct HRP isoenzymes that were found incapable of provoking an oxidative response were nevertheless adequate for demonstrating H2O2 production by LK-activated MP. Blocking the MP receptor for mannose by the addition of mannan to the assay system resulted in enhanced detection of H2O2 by low concentrations of HRP type II and by three out of four HRP isoenzymes. Treatment of MP with LK-containing medium for 72 hr did not result in a significant change in the activity of cellular superoxide dismutase (SOD) compared with MP cultured for the same length of time in control medium. By using the specific inhibitor of copper, zinc-containing SOD, sodium diethyldithiocarbamate (DDC), and the universal SOD inhibitor, sodium nitroprusside, we found that the predominant enzyme in guinea pig peritoneal MP is probably manganese-containing SOD. Incubation of LK-activated MP with nitroprusside resulted in almost total inhibition of H2O2 production and a simultaneous switch to superoxide (O2-) liberation. Similar exposure to DDC had no effect. These data indicate that H2O2 produced by LK-activated MP is derived exclusively by enzymatic dismutation of O2- mediated by a manganese-containing SOD. The increase in spontaneous H2O2 production induced by LK is therefore secondary to augmented O2- production that occurs at a cellular location where O2- is accessible to SOD. The enzymatic basis of the enhanced oxygen radical production was investigated by determining the kinetic parameters of the O2- -forming NADPH oxidase of resting LK-treated MP in a cellfree system in which O-2 production was induced by sodium dodecyl sulfate. The Km for NADPH and the Vmax of the enzyme of LK-treated MP were not different from those of the enzyme of MP incubated in control medium. We conclude that LK treatment of MP does not modulate the NADPH oxidase itself but, most likely, a process related to activation of the enzyme.

A high-throughput microparticle microarray platform for dendritic cell-targeting vaccines.

PubMed

Acharya, Abhinav P; Clare-Salzler, Michael J; Keselowsky, Benjamin G

2009-09-01

Immunogenomic approaches combined with advances in adjuvant immunology are guiding progress toward rational design of vaccines. Furthermore, drug delivery platforms (e.g., synthetic particles) are demonstrating promise for increasing vaccine efficacy. Currently there are scores of known antigenic epitopes and adjuvants, and numerous synthetic delivery systems accessible for formulation of vaccines for various applications. However, the lack of an efficient means to test immune cell responses to the abundant combinations available represents a significant blockade on the development of new vaccines. In order to overcome this barrier, we report fabrication of a new class of microarray consisting of antigen/adjuvant-loadable poly(D,L lactide-co-glycolide) microparticles (PLGA MPs), identified as a promising carrier for immunotherapeutics, which are co-localized with dendritic cells (DCs), key regulators of the immune system and prime targets for vaccines. The intention is to utilize this high-throughput platform to optimize particle-based vaccines designed to target DCs in vivo for immune system-related disorders, such as autoimmune diseases, cancer and infection. Fabrication of DC/MP arrays leverages the use of standard contact printing miniarraying equipment in conjunction with surface modification to achieve co-localization of particles/cells on isolated islands while providing background non-adhesive surfaces to prevent off-island cell migration. We optimized MP overspotting pin diameter, accounting for alignment error, to allow construction of large, high-fidelity arrays. Reproducible, quantitative delivery of as few as 16+/-2 MPs per spot was demonstrated and two-component MP dosing arrays were constructed, achieving MP delivery which was independent of formulation, with minimal cross-contamination. Furthermore, quantification of spotted, surface-adsorbed MP degradation was demonstrated, potentially useful for optimizing MP release properties. Finally, we demonstrate DC co-localization with PLGA MPs on isolated islands and that DCs do not migrate between islands for up to 24 h. Using this platform, we intend to analyze modulation of DC function by providing multi-parameter combinatorial cues in the form of proteins, peptides and other immuno-modulatory molecules encapsulated in or tethered on MPs. Critically, the miniaturization attained enables high-throughput investigation of rare cell populations by reducing the requirement for cells and reagents by many-fold, facilitating advances in personalized vaccines which target DCs in vivo.

Gaps in aquatic toxicological studies of microplastics.

PubMed

Karami, Ali

2017-10-01

The contamination of aquatic environments with microplastics (MPs) has spurred an unprecedented interest among scientific communities to investigate their impacts on biota. Despite the rapid growth in the number of studies on the aquatic toxicology of MPs, controversy over the fate and biological impacts of MPs is increasingly growing mainly due to the absence of standardized laboratory bioassays. Given the complex features of MPs, such as the diversity of constituent polymers, additives, shapes and sizes, as well as continuous changes in the particle buoyancy as a result of fouling and defouling processes, it is necessary to modify conventional bioassay protocols before employing them for MP toxicity testings. Moreover, several considerations including quantification of chemicals on/in the MP particles, choice of test organisms, approaches for renewing the test solution, aggregation prevention, stock solution preparation, and units used to report MP concentration in the test solution should be taken into account. This critical review suggests some important strategies to help conduct environmentally-relevant MP bioassays. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age-related changes in event-cued visual and auditory prospective memory proper.

PubMed

Uttl, Bob

2006-06-01

We rely upon prospective memory proper (ProMP) to bring back to awareness previously formed plans and intentions at the right place and time, and to enable us to act upon those plans and intentions. To examine age-related changes in ProMP, younger and older participants made decisions about simple stimuli (ongoing task) and at the same time were required to respond to a ProM cue, either a picture (visually cued ProM test) or a sound (auditorily cued ProM test), embedded in a simultaneously presented series of similar stimuli (either pictures or sounds). The cue display size or loudness increased across trials until a response was made. The cue size and cue loudness at the time of response indexed ProMP. The main results showed that both visual and auditory ProMP declined with age, and that such declines were mediated by age declines in sensory functions (visual acuity and hearing level), processing resources, working memory, intelligence, and ongoing task resource allocation.

Saving time and energy with oversubscription and semi-direct Møller-Plesset second order perturbation methods.

PubMed

Fought, Ellie L; Sundriyal, Vaibhav; Sosonkina, Masha; Windus, Theresa L

2017-04-30

In this work, the effect of oversubscription is evaluated, via calling 2n, 3n, or 4n processes for n physical cores, on semi-direct MP2 energy and gradient calculations and RI-MP2 energy calculations with the cc-pVTZ basis using NWChem. Results indicate that on both Intel and AMD platforms, oversubscription reduces total time to solution on average for semi-direct MP2 energy calculations by 25-45% and reduces total energy consumed by the CPU and DRAM on average by 10-15% on the Intel platform. Semi-direct gradient time to solution is shortened on average by 8-15% and energy consumption is decreased by 5-10%. Linear regression analysis shows a strong correlation between time to solution and total energy consumed. Oversubscribing during RI-MP2 calculations results in performance degradations of 30-50% at the 4n level. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Potential Biomarker of Myofibrillar Protein Oxidation in Raw and Cooked Ham: 3-Nitrotyrosine Formed by Nitrosation.

PubMed

Feng, Xianchao; Li, Chenyi; Ullah, Niamat; Hackman, Robert M; Chen, Lin; Zhou, Guanghong

2015-12-30

The stability of cured meat products is increased by the protection of its proteins from oxidation by sodium nitrite (NaNO2) during processing. This study investigated the effects of NaNO2 (0, 50, 100, 200, and 400 mg/kg) on the physiochemical and structural characteristics of myofibrillar protein (MP) in raw and cooked ham. The NaNO2 showed a dose-dependent antioxidant effect, by inhibiting carbonyl formation, dityrosine formation, and denaturation of MP, and a nitrosative effect, through the formation of 3-Nitrotyrosine (3-NT). The 3-NT content within MP of raw ham had distinct negative correlations with sulfhydryl content and surface hydrophobicity. The 3-NT content within MP of cooked ham had significantly negative correlations with carbonyl, sulfhydryl content and turbidity and had significantly positive correlations with disulfide content. These results indicated that 3-NT may be a potential marker for protein oxidation in raw and cooked cured meat products.

Physicochemical properties of beta-glucan in differently processed oat foods influence glycemic response.

PubMed

Regand, Alejandra; Tosh, Susan M; Wolever, Thomas M S; Wood, Peter J

2009-10-14

To assess the effect of food processing on the capacity of oat beta-glucan to attenuate postprandial glycemia, isocaloric crisp bread, granola, porridge, and pasta containing 4 g of beta-glucan as well as control products with low beta-glucan content were prepared. The physicochemical properties (viscosity, peak molecular weight (M(p)), and concentration (C)) of beta-glucan in in-vitro-digestion extracts were evaluated, and fasting and postprandial blood glucose concentrations were measured in human subjects. Porridge and granola had the highest efficacy in attenuating the peak blood glucose response (PBGR) because of their high M(p) and viscosity. beta-Glucan depolymerization in bread and pasta reduced beta-glucan bioactivity. Pastas, known to have low glycemic responses, showed the lowest PBGR. The analyses of these products with previously reported data indicated that 73% of the bioactivity in reducing PBGR can be explained by M(p) x C. Characterizing the physicochemical properties of beta-glucan in bioactive foods aids functional food development.

Hydroxyl radical and ferryl-generating systems promote gel network formation of myofibrillar protein.

PubMed

Xiong, Youling L; Blanchard, Suzanne P; Ooizumi, Tooru; Ma, Yuanyuan

2010-03-01

The objective of the study was to examine how oxidatively induced protein cross-linking would influence the gelation properties of myofibrillar protein (MP) under meat processing conditions. MP suspensions in 0.6 M NaCl at pH 6 were treated with an iron-catalyzed oxidizing system (IOS: 10 microM FeCl(3), 0.1 mM ascorbic acid, 0.05 to 5 mM H(2)O(2)) or a H(2)O(2)-activated metmyoglobin oxidizing system (MOS: 0.01 to 0.1 mM metmyoglobin/H(2)O(2)) that produced hydroxyl radical and ferryl species, respectively. Both oxidizing systems promoted MP thermal gelation, which was evidenced by rapid protein-protein interaction and the enhancement in storage modulus (elasticity) of the gel network as revealed by dynamic rheological testing in the 20 to 74 degrees C temperature range. This gelation-enhancing effect was attributed to the shift of myosin aggregation in the early stage of heating from predominantly head-head association (nonoxidized control samples) to prevalently tail-tail cross-linking through disulfide bonds. However, both hardness and water-holding capacity of chilled gels tended to decline when MP was exposed to >or=1 mM H(2)O(2) in IOS and to all concentrations of metmyoglobin in MOS. Microscopic examination confirmed a more porous structure in oxidized gels when compared with nonoxidized protein gels. The results demonstrated that mild oxidation altered the mode of myosin aggregation in favor of an elastic gel network formation, but it did not improve or had a negative effect on water-binding properties of MP gels. Mild oxidation promotes protein network formation and enhances gelation of myofibrillar protein under normal salt and pH conditions used in meat processing. This oxidative effect, which involves disulfide linkages, is somewhat similar to that in bakery product processing where oxidants are used to improve dough performance through gluten protein interaction.

The impact of standard and hard-coded parameters on the hydrologic fluxes in the Noah-MP land surface model

NASA Astrophysics Data System (ADS)

Thober, S.; Cuntz, M.; Mai, J.; Samaniego, L. E.; Clark, M. P.; Branch, O.; Wulfmeyer, V.; Attinger, S.

2016-12-01

Land surface models incorporate a large number of processes, described by physical, chemical and empirical equations. The agility of the models to react to different meteorological conditions is artificially constrained by having hard-coded parameters in their equations. Here we searched for hard-coded parameters in the computer code of the land surface model Noah with multiple process options (Noah-MP) to assess the model's agility during parameter estimation. We found 139 hard-coded values in all Noah-MP process options in addition to the 71 standard parameters. We performed a Sobol' global sensitivity analysis to variations of the standard and hard-coded parameters. The sensitivities of the hydrologic output fluxes latent heat and total runoff, their component fluxes, as well as photosynthesis and sensible heat were evaluated at twelve catchments of the Eastern United States with very different hydro-meteorological regimes. Noah-MP's output fluxes are sensitive to two thirds of its standard parameters. The most sensitive parameter is, however, a hard-coded value in the formulation of soil surface resistance for evaporation, which proved to be oversensitive in other land surface models as well. Latent heat and total runoff show very similar sensitivities towards standard and hard-coded parameters. They are sensitive to both soil and plant parameters, which means that model calibrations of hydrologic or land surface models should take both soil and plant parameters into account. Sensible and latent heat exhibit almost the same sensitivities so that calibration or sensitivity analysis can be performed with either of the two. Photosynthesis has almost the same sensitivities as transpiration, which are different from the sensitivities of latent heat. Including photosynthesis and latent heat in model calibration might therefore be beneficial. Surface runoff is sensitive to almost all hard-coded snow parameters. These sensitivities get, however, diminished in total runoff. It is thus recommended to include the most sensitive hard-coded model parameters that were exposed in this study when calibrating Noah-MP.

A novel regulation mechanism of the T7 RNA polymerase based expression system improves overproduction and folding of membrane proteins.

PubMed

Angius, Federica; Ilioaia, Oana; Amrani, Amira; Suisse, Annabelle; Rosset, Lindsay; Legrand, Amélie; Abou-Hamdan, Abbas; Uzan, Marc; Zito, Francesca; Miroux, Bruno

2018-06-05

Membrane protein (MP) overproduction is one of the major bottlenecks in structural genomics and biotechnology. Despite the emergence of eukaryotic expression systems, bacteria remain a cost effective and powerful tool for protein production. The T7 RNA polymerase (T7RNAP)-based expression system is a successful and efficient expression system, which achieves high-level production of proteins. However some foreign MPs require a fine-tuning of their expression to minimize the toxicity associated with their production. Here we report a novel regulation mechanism for the T7 expression system. We have isolated two bacterial hosts, namely C44(DE3) and C45(DE3), harboring a stop codon in the T7RNAP gene, whose translation is under the control of the basal nonsense suppressive activity of the BL21(DE3) host. Evaluation of hosts with superfolder green fluorescent protein (sfGFP) revealed an unprecedented tighter control of transgene expression with a marked accumulation of the recombinant protein during stationary phase. Analysis of a collection of twenty MP fused to GFP showed an improved production yield and quality of several bacterial MPs and of one human monotopic MP. These mutant hosts are complementary to the other existing T7 hosts and will increase the versatility of the T7 expression system.

40 CFR 86.145-82 - Calculations; particulate emissions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... final reported test results for the mass particulate (Mp) in grams/mile shall be computed as follows. Mp = 0.43(Mp1 + Mp2)/(Dct + Ds) + 0.57(Mp3 + Mp2)/(Dht = Ds) where: (1) Mp1 = Mass of particulate...) for determination.) (2) Mp2 = Mass of particulate determined from the “stabilized” phase of the cold...

40 CFR 86.145-82 - Calculations; particulate emissions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... final reported test results for the mass particulate (Mp) in grams/mile shall be computed as follows. Mp = 0.43(Mp1 + Mp2)/(Dct + Ds) + 0.57(Mp3 + Mp2)/(Dht = Ds) where: (1) Mp1 = Mass of particulate...) for determination.) (2) Mp2 = Mass of particulate determined from the “stabilized” phase of the cold...

Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease

PubMed Central

Bradford, Kara; Shih, David Q

2011-01-01

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as well as in developing adverse reactions. Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects. In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine; co-administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor α; 6-TGN administration; desensitization trials; and split dosing of 6-MP. PMID:22072847

Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease.

PubMed

Bradford, Kara; Shih, David Q

2011-10-07

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as well as in developing adverse reactions. Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects. In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine; co-administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor α; 6-TGN administration; desensitization trials; and split dosing of 6-MP.

Mastoparan-induced programmed cell death in the unicellular alga Chlamydomonas reinhardtii

PubMed Central

Yordanova, Zhenya P.; Woltering, Ernst J.; Kapchina-Toteva, Veneta M.; Iakimova, Elena T.

2013-01-01

Background and Aims Under stress-promoting conditions unicellular algae can undergo programmed cell death (PCD) but the mechanisms of algal cellular suicide are still poorly understood. In this work, the involvement of caspase-like proteases, DNA cleavage and the morphological occurrence of cell death in wasp venom mastoparan (MP)-treated Chlamydomonas reinhardtii were studied. Methods Algal cells were exposed to MP and cell death was analysed over time. Specific caspase inhibitors were employed to elucidate the possible role of caspase-like proteases. YVADase activity (presumably a vacuolar processing enzyme) was assayed by using a fluorogenic caspase-1 substrate. DNA breakdown was evaluated by DNA laddering and Comet analysis. Cellular morphology was examined by confocal laser scanning microscopy. Key Results MP-treated C. reinhardtii cells expressed several features of necrosis (protoplast shrinkage) and vacuolar cell death (lytic vesicles, vacuolization, empty cell-walled corpse-containing remains of digested protoplast) sometimes within one single cell and in different individual cells. Nucleus compaction and DNA fragmentation were detected. YVADase activity was rapidly stimulated in response to MP but the early cell death was not inhibited by caspase inhibitors. At later time points, however, the caspase inhibitors were effective in cell-death suppression. Conditioned medium from MP-treated cells offered protection against MP-induced cell death. Conclusions In C. reinhardtii MP triggered PCD of atypical phenotype comprising features of vacuolar and necrotic cell deaths, reminiscent of the modality of hypersensitive response. It was assumed that depending on the physiological state and sensitivity of the cells to MP, the early cell-death phase might be not mediated by caspase-like enzymes, whereas later cell death may involve caspase-like-dependent proteolysis. The findings substantiate the hypothesis that, depending on the mode of induction and sensitivity of the cells, algal PCD may take different forms and proceed through different pathways. PMID:23250917

UAV Swarm Behavior Modeling for Early Exposure of Failure Modes

DTIC Science & Technology

2016-09-01

Systems Center Atlantic, for his patience with me through this two-year process. He worked with my schedule and was very understanding of the...emergence of new failure modes? The MP modeling environment provides a breakdown of all potential event traces. Given that the research questions call...for the revelation of potential failure modes, MP was selected as the modeling environment because it provides a substantial set of results and data

Towards the integration of mental practice in rehabilitation programs. A critical review

PubMed Central

Malouin, Francine; Jackson, Philip L.; Richards, Carol L.

2013-01-01

Many clinical studies have investigated the use of mental practice (MP) through motor imagery (MI) to enhance functional recovery of patients with diverse physical disabilities. Although beneficial effects have been generally reported for training motor functions in persons with chronic stroke (e.g., reaching, writing, walking), attempts to integrate MP within rehabilitation programs have been met with mitigated results. These findings have stirred further questioning about the value of MP in neurological rehabilitation. In fact, despite abundant systematic reviews, which customarily focused on the methodological merits of selected studies, several questions about factors underlying observed effects remain to be addressed. This review discusses these issues in an attempt to identify factors likely to hamper the integration of MP within rehabilitation programs. First, the rationale underlying the use of MP for training motor function is briefly reviewed. Second, three modes of MI delivery are proposed based on the analysis of the research protocols from 27 studies in persons with stroke and Parkinson's disease. Third, for each mode of MI delivery, a general description of MI training is provided. Fourth, the review discusses factors influencing MI training outcomes such as: the adherence to MI training, the amount of training and the interaction between physical and mental rehearsal; the use of relaxation, the selection of reliable, valid and sensitive outcome measures, the heterogeneity of the patient groups, the selection of patients and the mental rehearsal procedures. To conclude, the review proposes a framework for integrating MP in rehabilitation programs and suggests research targets for steering the implementation of MP in the early stages of the rehabilitation process. The challenge has now shifted towards the demonstration that MI training can enhance the effects of regular therapy in persons with subacute stroke during the period of spontaneous recovery. PMID:24065903

User's guide of TOUGH2-EGS-MP: A Massively Parallel Simulator with Coupled Geomechanics for Fluid and Heat Flow in Enhanced Geothermal Systems VERSION 1.0

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiong, Yi; Fakcharoenphol, Perapon; Wang, Shihao

2013-12-01

TOUGH2-EGS-MP is a parallel numerical simulation program coupling geomechanics with fluid and heat flow in fractured and porous media, and is applicable for simulation of enhanced geothermal systems (EGS). TOUGH2-EGS-MP is based on the TOUGH2-MP code, the massively parallel version of TOUGH2. In TOUGH2-EGS-MP, the fully-coupled flow-geomechanics model is developed from linear elastic theory for thermo-poro-elastic systems and is formulated in terms of mean normal stress as well as pore pressure and temperature. Reservoir rock properties such as porosity and permeability depend on rock deformation, and the relationships between these two, obtained from poro-elasticity theories and empirical correlations, are incorporatedmore » into the simulation. This report provides the user with detailed information on the TOUGH2-EGS-MP mathematical model and instructions for using it for Thermal-Hydrological-Mechanical (THM) simulations. The mathematical model includes the fluid and heat flow equations, geomechanical equation, and discretization of those equations. In addition, the parallel aspects of the code, such as domain partitioning and communication between processors, are also included. Although TOUGH2-EGS-MP has the capability for simulating fluid and heat flows coupled with geomechanical effects, it is up to the user to select the specific coupling process, such as THM or only TH, in a simulation. There are several example problems illustrating applications of this program. These example problems are described in detail and their input data are presented. Their results demonstrate that this program can be used for field-scale geothermal reservoir simulation in porous and fractured media with fluid and heat flow coupled with geomechanical effects.« less

Measurement of circulating cell-derived microparticles by flow cytometry: sources of variability within the assay.

PubMed

Ayers, Lisa; Kohler, Malcolm; Harrison, Paul; Sargent, Ian; Dragovic, Rebecca; Schaap, Marianne; Nieuwland, Rienk; Brooks, Susan A; Ferry, Berne

2011-04-01

Circulating cell-derived microparticles (MPs) have been implicated in several disease processes and elevated levels are found in many pathological conditions. The detection and accurate measurement of MPs, although attracting widespread interest, is hampered by a lack of standardisation. The aim of this study was to establish a reliable flow cytometric assay to measure distinct subtypes of MPs in disease and to identify any significant causes of variability in MP quantification. Circulating MPs within plasma were identified by their phenotype (platelet, endothelial, leukocyte and annexin-V positivity (AnnV+). The influence of key variables (i.e. time between venepuncture and centrifugation, washing steps, the number of centrifugation steps, freezing/long-term storage and temperature of thawing) on MP measurement were investigated. Increasing time between venepuncture and centrifugation leads to increased MP levels. Washing samples results in decreased AnnV+MPs (P=0.002) and platelet-derived MPs (PMPs) (P=0.002). Double centrifugation of MPs prior to freezing decreases numbers of AnnV+MPs (P=0.0004) and PMPs (P=0.0004). A single freeze thaw cycle of samples led to an increase in AnnV+MPs (P=0.0020) and PMPs (P=0.0039). Long-term storage of MP samples at -80° resulted in decreased MP levels. This study found that minor protocol changes significantly affected MP levels. This is one of the first studies attempting to standardise a method for obtaining and measuring circulating MPs. Standardisation will be essential for successful development of MP technologies, allowing direct comparison of results between studies and leading to a greater understanding of MPs in disease. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Sensor-Based Vibration Signal Feature Extraction Using an Improved Composite Dictionary Matching Pursuit Algorithm

PubMed Central

Cui, Lingli; Wu, Na; Wang, Wenjing; Kang, Chenhui

2014-01-01

This paper presents a new method for a composite dictionary matching pursuit algorithm, which is applied to vibration sensor signal feature extraction and fault diagnosis of a gearbox. Three advantages are highlighted in the new method. First, the composite dictionary in the algorithm has been changed from multi-atom matching to single-atom matching. Compared to non-composite dictionary single-atom matching, the original composite dictionary multi-atom matching pursuit (CD-MaMP) algorithm can achieve noise reduction in the reconstruction stage, but it cannot dramatically reduce the computational cost and improve the efficiency in the decomposition stage. Therefore, the optimized composite dictionary single-atom matching algorithm (CD-SaMP) is proposed. Second, the termination condition of iteration based on the attenuation coefficient is put forward to improve the sparsity and efficiency of the algorithm, which adjusts the parameters of the termination condition constantly in the process of decomposition to avoid noise. Third, composite dictionaries are enriched with the modulation dictionary, which is one of the important structural characteristics of gear fault signals. Meanwhile, the termination condition of iteration settings, sub-feature dictionary selections and operation efficiency between CD-MaMP and CD-SaMP are discussed, aiming at gear simulation vibration signals with noise. The simulation sensor-based vibration signal results show that the termination condition of iteration based on the attenuation coefficient enhances decomposition sparsity greatly and achieves a good effect of noise reduction. Furthermore, the modulation dictionary achieves a better matching effect compared to the Fourier dictionary, and CD-SaMP has a great advantage of sparsity and efficiency compared with the CD-MaMP. The sensor-based vibration signals measured from practical engineering gearbox analyses have further shown that the CD-SaMP decomposition and reconstruction algorithm is feasible and effective. PMID:25207870

Sensor-based vibration signal feature extraction using an improved composite dictionary matching pursuit algorithm.

PubMed

Cui, Lingli; Wu, Na; Wang, Wenjing; Kang, Chenhui

2014-09-09

This paper presents a new method for a composite dictionary matching pursuit algorithm, which is applied to vibration sensor signal feature extraction and fault diagnosis of a gearbox. Three advantages are highlighted in the new method. First, the composite dictionary in the algorithm has been changed from multi-atom matching to single-atom matching. Compared to non-composite dictionary single-atom matching, the original composite dictionary multi-atom matching pursuit (CD-MaMP) algorithm can achieve noise reduction in the reconstruction stage, but it cannot dramatically reduce the computational cost and improve the efficiency in the decomposition stage. Therefore, the optimized composite dictionary single-atom matching algorithm (CD-SaMP) is proposed. Second, the termination condition of iteration based on the attenuation coefficient is put forward to improve the sparsity and efficiency of the algorithm, which adjusts the parameters of the termination condition constantly in the process of decomposition to avoid noise. Third, composite dictionaries are enriched with the modulation dictionary, which is one of the important structural characteristics of gear fault signals. Meanwhile, the termination condition of iteration settings, sub-feature dictionary selections and operation efficiency between CD-MaMP and CD-SaMP are discussed, aiming at gear simulation vibration signals with noise. The simulation sensor-based vibration signal results show that the termination condition of iteration based on the attenuation coefficient enhances decomposition sparsity greatly and achieves a good effect of noise reduction. Furthermore, the modulation dictionary achieves a better matching effect compared to the Fourier dictionary, and CD-SaMP has a great advantage of sparsity and efficiency compared with the CD-MaMP. The sensor-based vibration signals measured from practical engineering gearbox analyses have further shown that the CD-SaMP decomposition and reconstruction algorithm is feasible and effective.

Rambrain - a library for virtually extending physical memory

NASA Astrophysics Data System (ADS)

Imgrund, Maximilian; Arth, Alexander

2017-08-01

We introduce Rambrain, a user space library that manages memory consumption of your code. Using Rambrain you can overcommit memory over the size of physical memory present in the system. Rambrain takes care of temporarily swapping out data to disk and can handle multiples of the physical memory size present. Rambrain is thread-safe, OpenMP and MPI compatible and supports Asynchronous IO. The library was designed to require minimal changes to existing programs and to be easy to use.

A novel broadband impedance method for detection of cell-derived microparticles

PubMed Central

Lvovich, Vadim; Srikanthan, Sowmya; Silverstein, Roy L.

2010-01-01

A novel label-free method is presented to detect and quantify cell-derived microparticles (MPs) by the electrochemical potential-modulated electrochemical impedance spectroscopy (EIS). MPs are present in elevated concentrations during pathological conditions and play a major role in the establishment and pathogenesis of many diseases. Considering this, accurate detection and quantification of MPs is very important in clinical diagnostics and therapeutics. A combination of bulk solution electrokinetic sorting and interfacial impedance responses allows achieving detection limits as low as several MPs per µL. By fitting resulting EIS spectra with an equivalent electrical circuit, the bulk solution electrokinetic and interfacial impedance responses were characterized. In the bulk solution two major relaxations were prominent - β-relaxation in low MHz region due to the MP capacitive membrane bridging, and α-relaxation at ∼ 10 kHz due to counter ions diffusion. At low frequencies (10-0.1 Hz) at electrochemical potentials exceeding −100 mV, a facile interfacial Faradaic process of oxidation in MPs coupled with diffusion and non Faradaic double layer charging dominate, probably due to oxidation of phospholipids and/or proteins on the MP surface and MP lysis. Buffer influence on the MP detection demonstrated that that a relatively low conductivity Tyrode’s buffer background solution is preferential for the MP electrokinetic separation and characterization. This study also demonstrated that standard laboratory methods such as flow cytometry underestimate MP concentrations, especially those with smaller average sizes, by as much as a factor of 2 to 40. PMID:20729061

Occurrence, identification and removal of microplastic particles and fibers in conventional activated sludge process and advanced MBR technology.

PubMed

Lares, Mirka; Ncibi, Mohamed Chaker; Sillanpää, Markus; Sillanpää, Mika

2018-04-15

Wastewater treatment plants (WWTPs) are acting as routes of microplastics (MPs) to the environment, hence the urgent need to examine MPs in wastewaters and different types of sludge through sampling campaigns covering extended periods of time. In this study, the efficiency of a municipal WWTP to remove MPs from wastewater was studied by collecting wastewater and sludge samples once in every two weeks during a 3-month sampling campaign. The WWTP was operated based on the conventional activated sludge (CAS) process and a pilot-scale membrane bioreactor (MBR). The microplastic particles and fibers from both water and sludge samples were identified by using an optical microscope, Fourier Transform Infrared (FTIR) microscope and Raman microscope. Overall, the retention capacity of microplastics in the studied WWTP was found to be 98.3%. Most of the MP fraction was removed before the activated sludge process. The efficiency of an advanced membrane bioreactor (MBR) technology was also examined. The main related finding is that MBR permeate contained 0.4 MP/L in comparison with the final effluent of the CAS process (1.0 MP/L). According to this study, both microplastic fibers and particles are discharged from the WWTP to the aquatic environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Emotional conflict processing in adolescent chronic fatigue syndrome: A pilot study using functional magnetic resonance imaging.

PubMed

Wortinger, Laura Anne; Endestad, Tor; Melinder, Annika Maria D; Øie, Merete Glenne; Sulheim, Dag; Fagermoen, Even; Wyller, Vegard Bruun

2017-05-01

Studies of neurocognition suggest that abnormalities in cognitive control contribute to the pathophysiology of chronic fatigue syndrome (CFS) in adolescents, yet these abnormalities remain poorly understood at the neurobiological level. Reports indicate that adolescents with CFS are significantly impaired in conflict processing, a primary element of cognitive control. In this study, we examine whether emotional conflict processing is altered on behavioral and neural levels in adolescents with CFS and a healthy comparison group. Fifteen adolescent patients with CFS and 24 healthy adolescent participants underwent functional magnetic resonance imaging (fMRI) while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect labeled words. Adolescent CFS patients were less able to engage the left amygdala and left midposterior insula (mpINS) in response to conflict than the healthy comparison group. An association between accuracy interference and conflict-related reactivity in the amygdala was observed in CFS patients. A relationship between response time interference and conflict-related reactivity in the mpINS was also reported. Neural responses in the amygdala and mpINS were specific to fatigue severity. These data demonstrate that adolescent CFS patients displayed deficits in emotional conflict processing. Our results suggest abnormalities in affective and cognitive functioning of the salience network, which might underlie the pathophysiology of adolescent CFS.

Preparation, characterization and binding behaviors of host-guest inclusion complexes of metoclopramide hydrochloride with α- and β-cyclodextrin molecules

NASA Astrophysics Data System (ADS)

Barman, Siti; Barman, Biraj Kumar; Roy, Mahendra Nath

2018-03-01

The supramolecular interaction of metoclopramide hydrochloride (MP) with α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) has been inspected by ultraviolet-visible (UV-vis) light, infra-red (IR) light, fluorescence and 1H NMR spectroscopy. The formation of an inclusion complex greatly affects the physical-chemical properties of the guest molecules, such as solubility, chemical reactivity and the spectroscopic and electrochemical properties. Thus the changes in the spectral properties and physico-chemical properties confirm the inclusion complex formation. Surface tension, conductivity studies and Job's plot indicate a 1: 1 stoichiometry of the MP:CD host-guest inclusion complexes. The binding/association constants have been evaluated by both UV-Vis and fluorescence spectroscopic study indicating a higher degree of encapsulation for β-cyclodextrin (β-CD). Furthermore, the negative value of thermodynamic parameter (ΔG°) of the host-guest system suggests that the inclusion process proceeded spontaneously at 298.15 K. Based on the NMR data, the plausible mode of interaction of MP:α-CD and MP:β-CD complexes were proposed, which suggested that lipophilic aromatic ring of the MP entered into the cavity of CDs from the wider side, with the amide (sbnd CONH) and methoxy (-OMe) residues inside the CD cavity.

Anatomical consideration of the occipital cutaneous nerves and artery for the safe treatment of occipital neuralgia.

PubMed

Shin, Kang-Jae; Kim, Hong-San; O, Jehoon; Kwon, Hyun-Jin; Yang, Hun-Mu

2018-05-12

There is no standardized approach to the greater occipital nerve (GON) block technique for treating occipital neuralgia. The aim of the present study was to validate the previously-suggested guidelines for conventional injection techniques and to provide navigational guidelines for safe GON block. The GON, lesser occipital nerve (LON) and occipital artery (OA) were carefully dissected in the occipital region of embalmed cadavers. Using a 3D digitizer, the GON, LON, and OA were observed on the two reference lines. The distances between the landmarks were recorded and statistically analyzed. On the superior nuchal line, the mean distances between the external occipital protuberance (EOP) and the most medial branch of the GON was 33.5 mm. The mean distance between the EOP and the most medial branch of the OA was 37.4 mm. On the EOP-mastoid process (MP) line, the GON was on the medial third and the LON the lateral third of the EOP-MP line. The safe injection points on the EOP-MP line are about 3 cm from the EOP, 1 cm inferior parallel to the EOP-MP line, and about 3 cm away from the MP. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Combination treatment with 6-mercaptopurine and allopurinol in HepG2 and HEK293 cells - Effects on gene expression levels and thiopurine metabolism.

PubMed

Haglund, Sofie; Vikingsson, Svante; Almer, Sven; Söderman, Jan

2017-01-01

Combination treatment with low-dose thiopurine and allopurinol (AP) has successfully been used in patients with inflammatory bowel disease with a so called skewed thiopurine metabolite profile. In red blood cells in vivo, it reduces the concentration of methylated metabolites and increases the concentration of the phosphorylated ones, which is associated with improved therapeutic efficacy. This study aimed to investigate the largely unknown mechanism of AP on thiopurine metabolism in cells with an active thiopurine metabolic pathway using HepG2 and HEK293 cells. Cells were treated with 6-mercaptopurine (6MP) and AP or its metabolite oxypurinol. The expression of genes known to be associated with thiopurine metabolism, and the concentration of thiopurine metabolites were analyzed. Gene expression levels were only affected by AP in the presence of 6MP. The addition of AP to 6MP affected the expression of in total 19 genes in the two cell lines. In both cell lines the expression of the transporter SLC29A2 was reduced by the combined treatment. Six regulated genes in HepG2 cells and 8 regulated genes in HEK293 cells were connected to networks with 18 and 35 genes, respectively, present at known susceptibility loci for inflammatory bowel disease, when analyzed using a protein-protein interaction database. The genes identified as regulated as well as the disease associated interacting genes represent new candidates for further investigation in the context of combination therapy with thiopurines and AP. However, no differences in absolute metabolite concentrations were observed between 6MP+AP or 6MP+oxypurinol vs. 6MP alone in either of the two cell lines. In conclusion; the effect of AP on gene expression levels requires the presence of 6MP, at least in vitro. Previously described AP-effects on metabolite concentrations observed in red blood cells in vivo could not be reproduced in our cell lines in vitro. AP's effects in relation to thiopurine metabolism are complex. The network-identified susceptibility genes represented biological processes mainly associated with purine nucleotide biosynthetic processes, lymphocyte proliferation, NF-KB activation, JAK-STAT signaling, and apoptotic signaling at oxidative stress.

Combination treatment with 6-mercaptopurine and allopurinol in HepG2 and HEK293 cells – Effects on gene expression levels and thiopurine metabolism

PubMed Central

Haglund, Sofie; Vikingsson, Svante; Almer, Sven; Söderman, Jan

2017-01-01

Combination treatment with low-dose thiopurine and allopurinol (AP) has successfully been used in patients with inflammatory bowel disease with a so called skewed thiopurine metabolite profile. In red blood cells in vivo, it reduces the concentration of methylated metabolites and increases the concentration of the phosphorylated ones, which is associated with improved therapeutic efficacy. This study aimed to investigate the largely unknown mechanism of AP on thiopurine metabolism in cells with an active thiopurine metabolic pathway using HepG2 and HEK293 cells. Cells were treated with 6-mercaptopurine (6MP) and AP or its metabolite oxypurinol. The expression of genes known to be associated with thiopurine metabolism, and the concentration of thiopurine metabolites were analyzed. Gene expression levels were only affected by AP in the presence of 6MP. The addition of AP to 6MP affected the expression of in total 19 genes in the two cell lines. In both cell lines the expression of the transporter SLC29A2 was reduced by the combined treatment. Six regulated genes in HepG2 cells and 8 regulated genes in HEK293 cells were connected to networks with 18 and 35 genes, respectively, present at known susceptibility loci for inflammatory bowel disease, when analyzed using a protein-protein interaction database. The genes identified as regulated as well as the disease associated interacting genes represent new candidates for further investigation in the context of combination therapy with thiopurines and AP. However, no differences in absolute metabolite concentrations were observed between 6MP+AP or 6MP+oxypurinol vs. 6MP alone in either of the two cell lines. In conclusion; the effect of AP on gene expression levels requires the presence of 6MP, at least in vitro. Previously described AP-effects on metabolite concentrations observed in red blood cells in vivo could not be reproduced in our cell lines in vitro. AP’s effects in relation to thiopurine metabolism are complex. The network-identified susceptibility genes represented biological processes mainly associated with purine nucleotide biosynthetic processes, lymphocyte proliferation, NF-KB activation, JAK-STAT signaling, and apoptotic signaling at oxidative stress. PMID:28278299

Streamflow response to future land-cover change at a headwaters catchment spanning the alpine-subalpine transition on the Colorado Front Range

NASA Astrophysics Data System (ADS)

Barnhart, T. B.; Vukomanovic, J.; Bourgeron, P.; Molotch, N. P.

2017-12-01

Land-cover change at the alpine-subalpine interface has the potential to change the water balance of mountainous, snow-dominated catchments due to the influence of vegetation on blowing snow, effective precipitation, evapotranspiration, and other processes. Understanding how land-cover change will impact water resources in snow-dominated regions is of critical importance as these locations produce a disproportionate amount of runoff relative to their land area. We coupled the LANdscape DIsturbance and Succession (LANDIS-II) model with a spatially explicit, physics-based, watershed process model, the Regional Hydro-Ecologic Simulation System (RHESSys), to simulate land-cover change and its impact on the water balance in a 6.6 km­2 headwater catchment that spans the alpine-subalpine transition on the Colorado Front Range. We simulated two potential futures of air temperature warming (+4 °C/century) to 2100: a) increased precipitation (+15%, MP) and b) decreased precipitation (-15%, LP). As the LANDIS-II model simulates forest succession in a stochastic manner, we use three LANDIS-II model runs each for the MP and LP future forcing conditions. For both MP and LP, the RHESSys forcing data set was updated to reflect the changes in precipitation and temperature used to generate the land-cover futures. Forest cover in the catchment increased from 72% in 2000 to 84% and 83% in 2050 and to 95% and 92% in 2100 for MP and LP, respectively. Somewhat surprisingly, this increase in forest cover led to mean increases in streamflow production of 9% for MP and 3% for LP in 2050. In 2100, mean streamflow production increased by 15% and 6% for the MP and LP scenarios, respectively. This is likely due to increases in effective precipitation as the catchment forested and blowing snow decreased. Indeed, catchment effective precipitation increased from 94% in 2000 to 97% and 99% in 2050 and 2100, respectively, for both MP and LP conditions. This result counters previous work as runoff production increased with forested area, highlighting the need to better understand the impacts of forest expansion on blowing snow and effective precipitation. Identifying the hydrologic response of mountainous areas to climate warming induced land-cover change is of critical importance due to the potential water resources impacts in downstream regions.

Effect of borojo (Borojoa patinoi Cuatrecasas) three-phase composition and gum arabic on the glass transition temperature.

PubMed

Rodríguez-Bernal, Jenny M; Tello, Edisson; Flores-Andrade, Enrique; Perea-Flores, Maria de Jesús; Vallejo-Cardona, Alba A; Gutiérrez-López, Gustavo F; Quintanilla-Carvajal, Maria X

2016-02-01

The search for natural, novel, high-quality, stable food ingredients is an ongoing practice in the food industry. Pulp of borojo (Borojoa patinoi Cuatrecasas), which is a fruit of the Colombian Pacific region, can be separated into three phases: liquid (LP), medium (MP) and solid (SP) phases. The objective of this work was to evaluate the effect of the three-phase composition and gum arabic on their glass transitions temperatures (T(g)). The best mixture, LP-MP, MP-SP and LP-SP and gum arabic (GA) was identified by response surface methodology. When adding GA to SP borojo phase in a 1:1 proportion, the resulting T(g) of the mixture was 132.27 °C whereas Tg for GA and SP-phase were 154.89 °C and 79.86 °C respectively, which supported this combination as attractive from a processing perspective and supports an industrial advantage of using borojo as food ingredient. Phases were characterized by high-performance liquid chromatography, Fourier transform infrared spectroscopy, confocal laser scanning microscopy and mass spectrometry. Low molecular weight compounds such as fructose for MP lowered T(g) whereas the presence of lignin increased T(g) of the mixtures as with the SP. The addition of GA significantly increased T(g) of borojo phases so leading to propose them as novel food processing materials. © 2015 Society of Chemical Industry.

TMVOC-MP: a parallel numerical simulator for Three-PhaseNon-isothermal Flows of Multicomponent Hydrocarbon Mixtures inporous/fractured media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Keni; Yamamoto, Hajime; Pruess, Karsten

2008-02-15

TMVOC-MP is a massively parallel version of the TMVOC code (Pruess and Battistelli, 2002), a numerical simulator for three-phase non-isothermal flow of water, gas, and a multicomponent mixture of volatile organic chemicals (VOCs) in multidimensional heterogeneous porous/fractured media. TMVOC-MP was developed by introducing massively parallel computing techniques into TMVOC. It retains the physical process model of TMVOC, designed for applications to contamination problems that involve hydrocarbon fuels or organic solvents in saturated and unsaturated zones. TMVOC-MP can model contaminant behavior under 'natural' environmental conditions, as well as for engineered systems, such as soil vapor extraction, groundwater pumping, or steam-assisted sourcemore » remediation. With its sophisticated parallel computing techniques, TMVOC-MP can handle much larger problems than TMVOC, and can be much more computationally efficient. TMVOC-MP models multiphase fluid systems containing variable proportions of water, non-condensible gases (NCGs), and water-soluble volatile organic chemicals (VOCs). The user can specify the number and nature of NCGs and VOCs. There are no intrinsic limitations to the number of NCGs or VOCs, although the arrays for fluid components are currently dimensioned as 20, accommodating water plus 19 components that may be either NCGs or VOCs. Among them, NCG arrays are dimensioned as 10. The user may select NCGs from a data bank provided in the software. The currently available choices include O{sub 2}, N{sub 2}, CO{sub 2}, CH{sub 4}, ethane, ethylene, acetylene, and air (a pseudo-component treated with properties averaged from N{sub 2} and O{sub 2}). Thermophysical property data of VOCs can be selected from a chemical data bank, included with TMVOC-MP, that provides parameters for 26 commonly encountered chemicals. Users also can input their own data for other fluids. The fluid components may partition (volatilize and/or dissolve) among gas, aqueous, and NAPL phases. Any combination of the three phases may present, and phases may appear and disappear in the course of a simulation. In addition, VOCs may be adsorbed by the porous medium, and may biodegrade according to a simple half-life model. Detailed discussion of physical processes, assumptions, and fluid properties used in TMVOC-MP can be found in the TMVOC user's guide (Pruess and Battistelli, 2002). TMVOC-MP was developed based on the parallel framework of the TOUGH2-MP code (Zhang et al. 2001, Wu et al. 2002). It uses the MPI (Message Passing Forum, 1994) for parallel implementation. A domain decomposition approach is adopted for the parallelization. The code partitions a simulation domain, defined by an unstructured grid, using partitioning algorithm from the METIS software package (Karypsis and Kumar, 1998). In parallel simulation, each processor is in charge of one part of the simulation domain for assembling mass and energy balance equations, solving linear equation systems, updating thermophysical properties, and performing other local computations. The local linear-equation systems are solved in parallel by multiple processors with the Aztec linear solver package (Tuminaro et al., 1999). Although each processor solves the linearized equations of subdomains independently, the entire linear equation system is solved together by all processors collaboratively via communication between neighboring processors during each iteration. Detailed discussion of the prototype of the data-exchange scheme can be found in Elmroth et al. (2001). In addition, FORTRAN 90 features are introduced to TMVOC-MP, such as dynamic memory allocation, array operation, matrix manipulation, and replacing 'common blocks' (used in the original TMVOC) with modules. All new subroutines are written in FORTRAN 90. Program units imported from the original TMVOC remain in standard FORTRAN 77. This report provides a quick starting guide for using the TMVOC-MP program. We suppose that the users have basic knowledge of using the original TMVOC code. The users can find the detailed technical description of the physical processes modeled, and the mathematical and numerical methods in the user's guide for TMVOC (Pruess and Battistelli, 2002).« less

Preparation and Evaluation of a Modified Mohs Paste Mixed with Zinc Oxide 10% Topical Oil-Based Ointment.

PubMed

Tsuruta, Minako; Miyoshi, Takanori; Tsuruyama, Moeko; Matsumoto, Saori; Yamashina, Takuya; Irie, Kenji; Matsuo, Naomi; Itonaga, Tomomi; Hiraki, Yoichi; Kawamata, Yosei

2018-05-01

The skin fixative used in Mohs chemosurgery contains zinc chloride and is referred to as Mohs paste (MP). However, MP shows a remarkable change in rheological characteristics after its preparation. To prepare an MP with stable rheological characteristics, we prepared a modified MP (mMP) using zinc oxide 10% single ointment (Zn _ointment ), which is an oil-based ointment. We evaluated mMP by determining its rheological characteristics, depth of tissue fixation, and observation of the tissue surface after treatment. The viscosity of mMP increased after three months. However, the treatment-dependent viscosity of mMP could be obtained by mixing with glycerin. The viscosity and spreadability of mMP _3mth , which was three months after preparation, were 1992.0 ± 376.5 Pa·s and 2.1 ± 0.1 cm, respectively. In contrast, the viscosity and spreadability of MP mixed with glycerin were 436.9 ± 0.0 Pa·s and 2.8 ± 0.0 cm, respectively. The fixed invasion depth of MP was significantly higher than that of mMP (p < 0.05). This study of a mixture of MP and Zn _ointment showed that the viscosity of mMP could be adjusted with glycerin. Also, the tissue fixation of mMP progressed slowly compared with that of MP. This finding suggests that mMP is effective and safe for Mohs treatment.

Novel derivatives of 6-mercaptopurine: synthesis, characterization and antiproliferative activities of S-allylthio-mercaptopurines.

PubMed

Miron, T; Arditti, F; Konstantinovski, L; Rabinkov, A; Mirelman, D; Berrebi, A; Wilchek, M

2009-02-01

Biologically active S-allylthio derivatives of 6-mercaptopurine (6-MP) and 6-mercaptopurine riboside (6-MPR) were synthesized. The products, S-allylthio-6-mercaptopurine (SA-6MP) and S-allylthio-6-mercaptopurine riboside (SA-6MPR) were characterized. The antiproliferative activity of the new prodrugs was tested on human leukemia and monolayer cell lines, and compared to that of their parent reactants. The new prodrugs acted by a concentration-dependent mechanism. They inhibited cell proliferation and induced-apoptosis more efficiently than the parent molecules. Leukemia cell lines were more sensitive to the new prodrugs than monolayer cell lines. Higher hydrophobicity of the derivatives improves their penetration into cells, where upon reaction with glutathione, S-allylthioglutathione (GSSA) is formed, and 6-MP or 6-MPR is released for further processing.

Penetrating adolescents' mental models of mp3 with ZMET.

PubMed

Ling, I-Ling; Yang, Chun-Ming; Liu, Yi-Fen; Tsai, Yu-Hsuan

2009-01-01

This article demonstrates the application of the Zaltman metaphor-elicitation technique (ZMET) to help adolescent consumers delve into their unconscious thoughts and provide them with insights into the use of mp3. An analysis of interview transcripts and images revealed that the ZMET process provides a description of how the knowledge structures of adolescent consumers are subdivided and grouped around important themes that frame and motivate their involvement with a product. The findings reveal that there are 33 themes of consumer knowledge structure toward mp3. Furthermore, among these themes, there are four major concepts: size/form, convenience, relaxation, comfort, and appearance. The respondents' minds include not only rational components but emotional ingredients. Notably, the results also show that music can be an effective metaphor in the application of the ZMET method.

Low-Yellowing Phosphor-in-Glass for High-Power Chip-on-board White LEDs by Optimizing a Low-Melting Sn-P-F-O Glass Matrix.

PubMed

Yoon, Hee Chang; Yoshihiro, Kouhara; Yoo, Heeyeon; Lee, Seung Woo; Oh, Ji Hye; Do, Young Rag

2018-05-09

We introduce a low-melting-point (MP) Sn-P-F-O glass ceramic material into the phosphor-in-glass (PIG) material to realize an 'on-chip' chip-on-board (COB) type of phosphor-converted (pc) white light-emitting diode (WLED) with green (BaSr) 2 SiO 4 :Eu 2+ and red (SrCa)AlSiN 3 :Eu 2+ (SCASN) phosphors. The optimum Sn-P-F-O-based ceramic components can be sintered into the glass phase with a facile one-step heating process at 285 °C for 1 min. Specifically, these soft-fabrication conditions can be optimized to minimize the degradation of the luminescent properties of the red SCASN phosphor as well as the green silicate phosphor in PIG-based white COB-type pc-LEDs owing to the low thermal loss of the phosphors at low fabrication temperatures below 300 °C. Moreover, the constituents of the COB package, in this case the wire bonding and plastic exterior, can be preserved simultaneously from thermal damage. That is, the low sintering temperature of the glass ceramic encapsulant is a very important factor to realize excellent optical qualities of white COB LEDs. The optical performances of low-MP Sn-P-F-O-based PIG on-chip COB-type pc-WLEDs exhibit low yellowing phenomena, good luminous efficacy of 70.9-86.0 lm/W, excellent color rendering index of 94-97 with correlated color temperatures from 2700 to 10000 K, and good long-term stability.

Effects of vehicles and prodrug properties and their interactions on the delivery of 6-mercaptopurine through skin: S6-acyloxymethyl-6-mercaptopurine prodrugs.

PubMed

Waranis, R P; Sloan, K B

1988-03-01

A homologous series of S6-acyloxymethyl-6-mercaptopurine (6-mono-6-MP) and two 9-acyloxymethyl-6-mercaptopurine (9-mono-6-MP) prodrugs have been synthesized and characterized. The ability of the 6-mono-6-MP prodrugs to deliver 6-mercaptopurine (6-MP) through hairless mouse skin from isopropyl myristate (IPM) and propylene glycol (PG) has been evaluated. There was a good correlation between the log experimental permeability coefficients from the diffusion data and calculated solubility parameters of the prodrugs. Although there was no statistical difference between the rates of delivery of 6-MP by the acetyl through valeryl 6-mono-6-MP prodrugs from IPM, the butyryl and valeryl prodrugs were significantly better at delivering 6-MP from PG. For a given solubility parameter value, the 6-mono-6-MP prodrugs were less soluble in water and IPM, and more soluble in PG than the previously studied S6,9-bisacyloxymethyl-6-MP (6,9-bis-6-MP) prodrugs. On the other hand, for a given solubility parameter, the 6,9-bis-6-MP prodrugs were generally more effective at delivering 6-MP from IPM and PG. The single 9-mono-6-MP prodrug that was evaluated was much less effective at delivering 6-MP than either the 6-mono- or 6,9-bis-6-MP prodrugs. Thus, it is much less important to mask the imidazole than the thionamide functional group in 6-MP to enhance the topical delivery of 6-MP using a prodrug approach.

Modifying mesoporous silica nanoparticles to avoid the metabolic deactivation of 6-mercaptopurine and methotrexate in combinatorial chemotherapy

NASA Astrophysics Data System (ADS)

Wang, Wenjing; Fang, Chenjie; Wang, Xiaozhu; Chen, Yuxi; Wang, Yaonan; Feng, Wei; Yan, Chunhua; Zhao, Ming; Peng, Shiqi

2013-06-01

Mesoporous silica nanoparticles with amino and thiol groups (MSNSN) were prepared and covalently modified with methotrexate and 6-mercaptopurine to form 6-MP-MSNSN-MTX. In the presence of DTT, 6-MP-MSNSN-MTX gradually releases 6-MP. In rat plasma, 6-MP-MSNSN-MTX effectively inhibits the metabolic deactivation of 6-MP and MTX. 6-MP-MSNSN-MTX could be an agent for long-acting chemotherapy.Mesoporous silica nanoparticles with amino and thiol groups (MSNSN) were prepared and covalently modified with methotrexate and 6-mercaptopurine to form 6-MP-MSNSN-MTX. In the presence of DTT, 6-MP-MSNSN-MTX gradually releases 6-MP. In rat plasma, 6-MP-MSNSN-MTX effectively inhibits the metabolic deactivation of 6-MP and MTX. 6-MP-MSNSN-MTX could be an agent for long-acting chemotherapy. Electronic supplementary information (ESI) available: Experimental details of the synthesis and in vitro and in vivo assays. See DOI: 10.1039/c3nr00227f

A novel broadband impedance method for detection of cell-derived microparticles.

PubMed

Lvovich, Vadim; Srikanthan, Sowmya; Silverstein, Roy L

2010-10-15

A novel label-free method is presented to detect and quantify cell-derived microparticles (MPs) by the electrochemical potential-modulated electrochemical impedance spectroscopy (EIS). MPs are present in elevated concentrations during pathological conditions and play a major role in the establishment and pathogenesis of many diseases. Considering this, accurate detection and quantification of MPs is very important in clinical diagnostics and therapeutics. A combination of bulk solution electrokinetic sorting and interfacial impedance responses allows achieving detection limits as low as several MPs per μL. By fitting resulting EIS spectra with an equivalent electrical circuit, the bulk solution electrokinetic and interfacial impedance responses were characterized. In the bulk solution two major relaxations were prominent-β-relaxation in low MHz region due to the MP capacitive membrane bridging, and α-relaxation at ∼10 kHz due to counter ions diffusion. At low frequencies (10-0.1 Hz) at electrochemical potentials exceeding -100 mV, a facile interfacial Faradaic process of oxidation in MPs coupled with diffusion and non-Faradaic double layer charging dominate, probably due to oxidation of phospholipids and/or proteins on the MP surface and MP lysis. Buffer influence on the MP detection demonstrated that a relatively low conductivity Tyrode's buffer background solution is preferential for the MP electrokinetic separation and characterization. This study also demonstrated that standard laboratory methods such as flow cytometry underestimate MP concentrations, especially those with smaller average sizes, by as much as a factor of 2-40. Copyright © 2010 Elsevier B.V. All rights reserved.

Hierarchical ZnO Nanowires-loaded Sb-doped SnO2-ZnO Micrograting Pattern via Direct Imprinting-assisted Hydrothermal Growth and Its Selective Detection of Acetone Molecules

NASA Astrophysics Data System (ADS)

Choi, Hak-Jong; Choi, Seon-Jin; Choo, Soyoung; Kim, Il-Doo; Lee, Heon

2016-01-01

We propose a novel synthetic route by combining imprinting transfer of a Sb-doped SnO2 (ATO)-ZnO composite micrograting pattern (MP), i.e., microstrip lines, on a sensor substrate and subsequent hydrothermal growth of ZnO nanowires (NWs) for producing a hierarchical ZnO NW-loaded ATO-ZnO MP as an improved chemo-resistive sensing layer. Here, ATO-ZnO MP structure with 3-μm line width, 9-μm pitch, and 6-μm height was fabricated by direct transfer of mixed ATO and ZnO nanoparticle (NP)-dispersed resists, which are pre-patterned on a polydimethylsiloxane (PDMS) mold. ZnO NWs with an average diameter of less than 50 nm and a height of 250 nm were quasi-vertically grown on the ATO-ZnO MP, leading to markedly enhanced surface area and heterojunction composites between each ATO NP, ZnO NP, and ZnO NW. A ZnO NW-loaded MP sensor with a relative ratio of 1:9 between ATO and ZnO (1:9 ATO-ZnO), exhibited highly sensitive and selective acetone sensing performance with 2.84-fold higher response (Rair/Rgas = 12.8) compared to that (Rair/Rgas = 4.5) of pristine 1:9 ATO-ZnO MP sensor at 5 ppm. Our results demonstrate the processing advantages of direct imprinting-assisted hydrothermal growth for large-scale homogeneous coating of hierarchical oxide layers, particularly for applications in highly sensitive and selective chemical sensors.

Hierarchical ZnO Nanowires-loaded Sb-doped SnO2-ZnO Micrograting Pattern via Direct Imprinting-assisted Hydrothermal Growth and Its Selective Detection of Acetone Molecules.

PubMed

Choi, Hak-Jong; Choi, Seon-Jin; Choo, Soyoung; Kim, Il-Doo; Lee, Heon

2016-01-08

We propose a novel synthetic route by combining imprinting transfer of a Sb-doped SnO2 (ATO)-ZnO composite micrograting pattern (MP), i.e., microstrip lines, on a sensor substrate and subsequent hydrothermal growth of ZnO nanowires (NWs) for producing a hierarchical ZnO NW-loaded ATO-ZnO MP as an improved chemo-resistive sensing layer. Here, ATO-ZnO MP structure with 3-μm line width, 9-μm pitch, and 6-μm height was fabricated by direct transfer of mixed ATO and ZnO nanoparticle (NP)-dispersed resists, which are pre-patterned on a polydimethylsiloxane (PDMS) mold. ZnO NWs with an average diameter of less than 50 nm and a height of 250 nm were quasi-vertically grown on the ATO-ZnO MP, leading to markedly enhanced surface area and heterojunction composites between each ATO NP, ZnO NP, and ZnO NW. A ZnO NW-loaded MP sensor with a relative ratio of 1:9 between ATO and ZnO (1:9 ATO-ZnO), exhibited highly sensitive and selective acetone sensing performance with 2.84-fold higher response (R air/R gas = 12.8) compared to that (R air/R gas = 4.5) of pristine 1:9 ATO-ZnO MP sensor at 5 ppm. Our results demonstrate the processing advantages of direct imprinting-assisted hydrothermal growth for large-scale homogeneous coating of hierarchical oxide layers, particularly for applications in highly sensitive and selective chemical sensors.

Hierarchical ZnO Nanowires-loaded Sb-doped SnO2-ZnO Micrograting Pattern via Direct Imprinting-assisted Hydrothermal Growth and Its Selective Detection of Acetone Molecules

PubMed Central

Choi, Hak-Jong; Choi, Seon-Jin; Choo, Soyoung; Kim, Il-Doo; Lee, Heon

2016-01-01

We propose a novel synthetic route by combining imprinting transfer of a Sb-doped SnO2 (ATO)-ZnO composite micrograting pattern (MP), i.e., microstrip lines, on a sensor substrate and subsequent hydrothermal growth of ZnO nanowires (NWs) for producing a hierarchical ZnO NW-loaded ATO-ZnO MP as an improved chemo-resistive sensing layer. Here, ATO-ZnO MP structure with 3-μm line width, 9-μm pitch, and 6-μm height was fabricated by direct transfer of mixed ATO and ZnO nanoparticle (NP)-dispersed resists, which are pre-patterned on a polydimethylsiloxane (PDMS) mold. ZnO NWs with an average diameter of less than 50 nm and a height of 250 nm were quasi-vertically grown on the ATO-ZnO MP, leading to markedly enhanced surface area and heterojunction composites between each ATO NP, ZnO NP, and ZnO NW. A ZnO NW-loaded MP sensor with a relative ratio of 1:9 between ATO and ZnO (1:9 ATO-ZnO), exhibited highly sensitive and selective acetone sensing performance with 2.84-fold higher response (Rair/Rgas = 12.8) compared to that (Rair/Rgas = 4.5) of pristine 1:9 ATO-ZnO MP sensor at 5 ppm. Our results demonstrate the processing advantages of direct imprinting-assisted hydrothermal growth for large-scale homogeneous coating of hierarchical oxide layers, particularly for applications in highly sensitive and selective chemical sensors. PMID:26743814

Pyrolysis of Lantana camara and Mimosa pigra: Influences of temperature, other process parameters and incondensable gas evolution on char yield and higher heating value.

PubMed

Mundike, Jhonnah; Collard, François-Xavier; Görgens, Johann F

2017-11-01

Pyrolysis of invasive non-indigenous plants, Lantana camara (LC) and Mimosa pigra (MP) was conducted at milligram-scale for optimisation of temperature, heating rate and hold time on char yield and higher heating value (HHV). The impact of scaling-up to gram-scale was also studied, with chromatography used to correlate gas composition with HHV evolution. Statistically significant effects of temperature on char yield and HHV were obtained, while heating rate and hold time effects were insignificant. Milligram-scale maximised HHVs were 30.03MJkg -1 (525°C) and 31.01MJkg -1 (580°C) for LC and MP, respectively. Higher char yields and HHVs for MP were attributed to increased lignin content. Scaling-up promoted secondary char formation thereby increasing HHVs, 30.82MJkg -1 for LC and 31.61MJkg -1 for MP. Incondensable gas analysis showed that temperature increase beyond preferred values caused dehydrogenation that decreased HHV. Similarly, CO evolution profile explained differences in optimal HHV temperatures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Experiencing meditation - Evidence for differential effects of three contemplative mental practices in micro-phenomenological interviews.

PubMed

Przyrembel, Marisa; Singer, Tania

2018-07-01

Despite increasing interest in effects of meditation, systematic in-depth research on how it qualitatively feels to engage in different kinds of contemplative practices is still missing. To fill this gap, we explore the validity of Micro-phenomenological Interviews (MpI) to assess experiences during breathing meditation (BM), observing-thought meditation (OTM), and loving-kindness meditation (LKM). We performed psycholinguistic analyses, quantitative ratings and qualitative explorations of 104 MpI (N = 57). All results reveal differential affective, bodily and sensorial fingerprints: BM-transcripts contain the most body-related vocabulary, specifically sensations in nose and abdomen. OTM-transcripts contain the most cognition-related vocabulary. OTM is experienced in head and face. LKM-transcripts contain the most vocabulary related to socio-affective processes. LKM is associated to love, sensations around the heart, and warmth. The LKM-outcomes were replicated with another independent set of MpI. These findings verify the merit of MpI as a scientific tool to gain reliable first-person data beyond questionnaires or rating scales. Copyright © 2018 Elsevier Inc. All rights reserved.

The rate and character of spontaneous mutation in an RNA virus.

PubMed Central

Malpica, José M; Fraile, Aurora; Moreno, Ignacio; Obies, Clara I; Drake, John W; García-Arenal, Fernando

2002-01-01

Estimates of spontaneous mutation rates for RNA viruses are few and uncertain, most notably due to their dependence on tiny mutation reporter sequences that may not well represent the whole genome. We report here an estimate of the spontaneous mutation rate of tobacco mosaic virus using an 804-base cognate mutational target, the viral MP gene that encodes the movement protein (MP). Selection against newly arising mutants was countered by providing MP function from a transgene. The estimated genomic mutation rate was on the lower side of the range previously estimated for lytic animal riboviruses. We also present the first unbiased riboviral mutational spectrum. The proportion of base substitutions is the same as that in a retrovirus but is lower than that in most DNA-based organisms. Although the MP mutant frequency was 0.02-0.05, 35% of the sequenced mutants contained two or more mutations. Therefore, the mutation process in populations of TMV and perhaps of riboviruses generally differs profoundly from that in populations of DNA-based microbes and may be strongly influenced by a subpopulation of mutator polymerases. PMID:12524327

Joint Coordination and Muscle Activities of Ballet Dancers During Tiptoe Standing.

PubMed

Tanabe, Hiroko; Fujii, Keisuke; Kouzaki, Motoki

2017-01-01

We aimed to investigate joint coordination of lower limbs in dancers during tiptoe standing and the relationship between joint coordination and muscle coactivation. Seven female ballet dancers performed tiptoe standing with six leg positions (fi e classical dance positions and one modern dance position) for 10 s. The kinematic data of the metatarsophalangeal (MP), ankle, knee, and hip joints was collected, and surface electromyography (EMG) of over 13 lower limb muscles was conducted. Principal component analysis was performed to determine joint coordination. MP-ankle and ankle-knee had in-phase coordination, whereas knee-hip showed anti-phase coordination in the sagittal plane. In addition, most EMG-EMG coherence around the MP and ankle joints was significant up to 50 Hz when these two joints swayed with in-phase. This suggests that different joint coordination patterns are associated with neural processing related to different muscle coactivation patterns. In conclusion, ballet dancers showed in-phase coordination from the MP to knee joints, which was associated with muscle coactivation to a higher frequency domain (up to 50 Hz) in comparison with anti-phase coordination.

The Corrosion Control of Fastening Systems for Aircraft Carrier Steam Catapults

DTIC Science & Technology

1976-03-31

mixture AT Aluminum powder and titanium powder 1:1 mixture MP Multiphase MP35N (powder) NA Nickel Aluminide base coat and aluminum top coat T Titanium ...Subsequent lifting or peeling was also accomplished by the use of a knife blade on areas not in contact with the "Fette Head". The densification process "s...75 of big bolt. White Titanium corrosion products elsewhere. After 552 hr. 57 salt spray AT .002 Aluminum/ Red rust in recess bottom around Titanium

Characterization of microparticles in patients with venous malformations of the head and neck.

PubMed

Zhu, J-Y; Ren, J-G; Zhang, W; Wang, F-Q; Cai, Y; Zhao, J-H; Chen, G; Zhao, Y-F

2017-01-01

To determine the basic biochemical features of microparticles (MP) in patients with venous malformation (VM) of the head and neck. Microparticles were isolated from peripheral venous blood of VM patients or healthy subjects and from lesional fluid of VM patients. Flow cytometry and real-time polymerase chain reaction were employed to determine the concentration, cellular origin, and RNA expression of obtained MP. A functional coagulation test was applied to measure the coagulant activity of MP. Circulating levels of total MP, platelet-derived MP, and endothelial MP were significantly elevated in VM patients and were consistently increased in VM patients with more extensive lesions. Lesional MP (MP from lesional fluid of VM) in VM patients were more abundant than circulating MP from VM patients or healthy subjects. Moreover, MP from VM patients displayed markedly distinct mRNA and microRNA expression compared with healthy subjects. Furthermore, MP from VM patients exhibited enhanced procoagulant activity, as evidenced by significantly shorter coagulation time. This study demonstrates for the first time that patients with VM have an altered MP profile and MP may be associated with VM-associated thrombogenesis. Further studies are required to explore the precise pathophysiological roles of MP in VM. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reliability assessment of ballistic jump squats and bench throws.

PubMed

Alemany, Joseph A; Pandorf, Clay E; Montain, Scott J; Castellani, John W; Tuckow, Alexander P; Nindl, Bradley C

2005-02-01

The purpose of this investigation was to determine the test-retest reliability and coefficient of variation of 2 novel physical performance tests. Ten healthy men (22.0 +/- 3.0 years, 87.0 +/- 8.0 kg, 20.0 +/- 5.0% body fat) performed 30 continuous and dynamic jump squats (JS) and bench throws (BT) on 4 separate occasions. The movements were performed under loaded conditions utilizing 30% of subject's predetermined 1 repetition maximum in the back squat and bench press. Mean power (MP; W), peak power (PP; W), mean velocity (MV; m.s(-1)), peak velocity (PV; m.s(-1)), and total work (TW; J) were assessed using a ballistic measurement system (Innervations Inc., Muncie, IN). Data were analyzed using repeated measures analysis of variance with Duncan's post hoc test when mean differences were p < or = 0.05. Intraclass correlation coefficient (ICC) and within-subject coefficient of variation (CV%) were also calculated. All values are presented as mean +/- SE. BT variables were statistically similar across the 4 sessions: MP (350.0 +/- 13.9 W), PP (431.4 +/- 18.5 W) MV (1.6 +/- 0.03 m.s(-1)), PV (2.0 +/- 0.03 m.s(-1)), and TW (199.1 +/- 7.2 J). For JS, session 3 PP (1,669.8 +/- 111.2 W) was significantly greater vs. sessions 1, 2, and 4 (1,601.2 +/- 58.4 W). Session 4 MP (1,403.2 +/- 88.6 W) and MV (1.9 +/- 0.1 m.s(-1)) for JS were significantly lower during sessions 1, 2, and 3 (MP: 1,479.4.5 +/- 44.8 W, MV: 2.0 +/- 0.05 m.s(-1)). TW (834.7 +/- 24.3 J) and PV (2.2 +/- 0.04 m.s(-1)) were statistically similar during all sessions for JS. The CVs ranged from 3.0 to 7.6% for the BT and 3.2 to 5.7% for the JS. ICCs for MP, PP, MV, PV, and TW were 0.92, 0.95, 0.94, 0.91, and 0.95, respectively, during BT. ICCs during JS for MP, PP, MV, PV, and TW were 0.96, 0.98, 0.94, 0.94, and 0.89, respectively. The results of the current study support the use of a 30 continuous and dynamic BT protocol as a reliable upper-body physical performance test, which can be administered with minimal practice. Slightly greater variability for JS was observed, although the test had high reliability.

Pharmacokinetic and pharmacodynamic assessment of bioavailability for two prodrugs of methylprednisolone

PubMed Central

Daley-Yates, P. T.; Gregory, A. J.; Brooks, C. D.

1997-01-01

Aims The aim of this study was to establish whether pharmacokinetic differences between two pro-drugs of methylprednisolone (MP) are likely to be of clinical significance. Methods This study was a single-blind, randomized, crossover design comparing the bioequivalence of MP released from the pro-drugs Promedrol (MP suleptanate) and Solu-Medrol (MP succinate) after a single 250 mg (MP equivalent) intramuscular injection to 20 healthy male volunteers. Bioequivalence was assessed by conventional pharmacokinetic analysis, by measuring pharmacodynamic responses plus a novel approach using pharmacokinetic/pharmacodynamic modeling. The main measure of pharmacodynamic response was whole blood histamine (WBH), a measure of basophil numbers. Results The MP Cmax was less for MP suleptanate due to a longer absorption half-life of the prodrug from the intramuscular injection site. The bioavailability of MP was equivalent when based on AUC with a MP suleptanate median 108% of the MP succinate value (90% CI: 102–114%). For Cmax the MP suleptanate median was 81% of the MP succinate value (90% CI: 75–88%). The tmax for MP from MP suleptanate was delayed relative to MP succinate. The median difference was 200% (90% non-parametric CI: 141–283%). The area under the WBH effect-time curve (AUEC) and the maximum response (Emax ) were found to be equivalent (90% CI: 98–113% and 93–109% respectively). The maximum changes in other white blood cell counts, blood glucose concentration and the parameters of the pharmacodynamic sigmoid Emax model (EC50, Emax and γ) were also not significantly different between prodrugs. Conclusions MP suleptanate is an acceptable pharmaceutical alternative to MP succinate. The use of both pharmacokinetic and pharmacodynamic response data together gives greater confidence in the conclusions compared with those based only on conventional pharmacokinetic bioequivalence analysis. PMID:9205819

PARALLELISATION OF THE MODEL-BASED ITERATIVE RECONSTRUCTION ALGORITHM DIRA.

PubMed

Örtenberg, A; Magnusson, M; Sandborg, M; Alm Carlsson, G; Malusek, A

2016-06-01

New paradigms for parallel programming have been devised to simplify software development on multi-core processors and many-core graphical processing units (GPU). Despite their obvious benefits, the parallelisation of existing computer programs is not an easy task. In this work, the use of the Open Multiprocessing (OpenMP) and Open Computing Language (OpenCL) frameworks is considered for the parallelisation of the model-based iterative reconstruction algorithm DIRA with the aim to significantly shorten the code's execution time. Selected routines were parallelised using OpenMP and OpenCL libraries; some routines were converted from MATLAB to C and optimised. Parallelisation of the code with the OpenMP was easy and resulted in an overall speedup of 15 on a 16-core computer. Parallelisation with OpenCL was more difficult owing to differences between the central processing unit and GPU architectures. The resulting speedup was substantially lower than the theoretical peak performance of the GPU; the cause was explained. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Microplastics as vectors for environmental contaminants: Exploring sorption, desorption, and transfer to biota.

PubMed

Hartmann, Nanna B; Rist, Sinja; Bodin, Julia; Jensen, Louise Hs; Schmidt, Stine N; Mayer, Philipp; Meibom, Anders; Baun, Anders

2017-05-01

The occurrence and effects of microplastics (MPs) in the aquatic environment are receiving increasing attention. In addition to their possible direct adverse effects on biota, the potential role of MPs as vectors for hydrophobic organic chemicals (HOCs), compared to natural pathways, is a topic of much debate. It is evident, however, that temporal and spatial variations of MP occurrence do (and will) occur. To further improve the estimations of the role of MPs as vectors for HOC transfer into biota under varying MP concentrations and environmental conditions, it is important to identify and understand the governing processes. Here, we explore HOC sorption to and desorption from MPs and the underlying principles for their interactions. We discuss intrinsic and extrinsic parameters influencing these processes and focus on the importance of the exposure route for diffusive mass transfer. Also, we outline research needed to fill knowledge gaps and improve model-based calculations of MP-facilitated HOC transfer in the environment. Integr Environ Assess Manag 2017;13:488-493. © 2017 SETAC. © 2017 SETAC.

Pupillary Response to Negative Emotional Stimuli Is Differentially Affected in Meditation Practitioners

PubMed Central

Vasquez-Rosati, Alejandra; Brunetti, Enzo P.; Cordero, Carmen; Maldonado, Pedro E.

2017-01-01

Clinically, meditative practices have become increasingly relevant, decreasing anxiety in patients and increasing antibody production. However, few studies have examined the physiological correlates, or effects of the incorporation of meditative practices. Because pupillary reactivity is a marker for autonomic changes and emotional processing, we hypothesized that the pupillary responses of mindfulness meditation practitioners (MP) and subjects without such practices (non-meditators (NM)) differ, reflecting different emotional processing. In a group of 11 MP and 9 NM, we recorded the pupil diameter using video-oculography while subjects explored images with emotional contents. Although both groups showed a similar pupillary response for positive and neutral images, negative images evoked a greater pupillary contraction and a weaker dilation in the MP group. Also, this group had faster physiological recovery to baseline levels. These results suggest that mindfulness meditation practices modulate the response of the autonomic nervous system, reflected in the pupillary response to negative images and faster physiological recovery to baseline levels, suggesting that pupillometry could be used to assess the potential health benefits of these practices in patients. PMID:28515685

[Preliminary results of noncontact temperature measuring using an infrared thermometer on the tarsus pf swine with osteoarthrosis tarsi deformans].

PubMed

Sabec, D; Lazar, P

1990-01-01

The surface temperature on tarsus of 54 performance tested boars of about 60 kg of Swedish Landrace was measured by means of infra-red thermometer at three measuring points (MP1, MP2 and MP3). MP1 was situated above the tuberculum of os metatarsale III or, as visualised in 21 slaughtered boars, above pathoanatomical alterations of osteoarthrosis tarsi deformans (OATD). MP2 was located directly medially and MP3 laterally from MP1. A clear palpatory symptom was found only with 10 boars, while all 21 slaughtered boars showed different morphological lesions of OATD. The average temperature at MP1 was 35.69 degrees C and was significantly higher (P = .01) than at MP2 (35.34) and MP3 (35.30). The temperature differences between MP1 and MP2 or MP3 were statistically reliable. Boars, who had a clear palpatory symptoms at tuberculum, showed an average temperature at MT1 of 36.27 degrees C, which was higher (P = .0114) than of those with an unclear palpatory symptom (35.64 degrees C). The results show that the temperature differences are the consequence of OATD.

Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus

PubMed Central

Lihoradova, Olga A.; Indran, Sabarish V.; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A.; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L.; Freiberg, Alexander N.; Ikegami, Tetsuro

2013-01-01

Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever. PMID:23638202

Characterization of Rift Valley fever virus MP-12 strain encoding NSs of Punta Toro virus or sandfly fever Sicilian virus.

PubMed

Lihoradova, Olga A; Indran, Sabarish V; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L; Freiberg, Alexander N; Ikegami, Tetsuro

2013-01-01

Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are important for vaccine development for Rift Valley fever.

Parallel processing implementation for the coupled transport of photons and electrons using OpenMP

NASA Astrophysics Data System (ADS)

Doerner, Edgardo

2016-05-01

In this work the use of OpenMP to implement the parallel processing of the Monte Carlo (MC) simulation of the coupled transport for photons and electrons is presented. This implementation was carried out using a modified EGSnrc platform which enables the use of the Microsoft Visual Studio 2013 (VS2013) environment, together with the developing tools available in the Intel Parallel Studio XE 2015 (XE2015). The performance study of this new implementation was carried out in a desktop PC with a multi-core CPU, taking as a reference the performance of the original platform. The results were satisfactory, both in terms of scalability as parallelization efficiency.

Evaluating BC and NOx emission inventories for the Paris region from MEGAPOLI aircraft measurements

NASA Astrophysics Data System (ADS)

Petetin, H.; Beekmann, M.; Colomb, A.; Denier van der Gon, H. A. C.; Dupont, J.-C.; Honoré, C.; Michoud, V.; Morille, Y.; Perrussel, O.; Schwarzenboeck, A.; Sciare, J.; Wiedensohler, A.; Zhang, Q. J.

2015-09-01

High uncertainties affect black carbon (BC) emissions, and, despite its important impact on air pollution and climate, very few BC emissions evaluations are found in the literature. This paper presents a novel approach, based on airborne measurements across the Paris, France, plume, developed in order to evaluate BC and NOx emissions at the scale of a whole agglomeration. The methodology consists in integrating, for each transect, across the plume observed and simulated concentrations above background. This allows for several error sources (e.g., representativeness, chemistry, plume lateral dispersion) to be minimized in the model used. The procedure is applied with the CHIMERE chemistry-transport model to three inventories - the EMEP inventory and the so-called TNO and TNO-MP inventories - over the month of July 2009. Various systematic uncertainty sources both in the model (e.g., boundary layer height, vertical mixing, deposition) and in observations (e.g., BC nature) are discussed and quantified, notably through sensitivity tests. Large uncertainty values are determined in our results, which limits the usefulness of the method to rather strongly erroneous emission inventories. A statistically significant (but moderate) overestimation is obtained for the TNO BC emissions and the EMEP and TNO-MP NOx emissions, as well as for the BC / NOx emission ratio in TNO-MP. The benefit of the airborne approach is discussed through a comparison with the BC / NOx ratio at a ground site in Paris, which additionally suggests a spatially heterogeneous error in BC emissions over the agglomeration.

In vivo neuronal calcium imaging in C. elegans.

PubMed

Chung, Samuel H; Sun, Lin; Gabel, Christopher V

2013-04-10

The nematode worm C. elegans is an ideal model organism for relatively simple, low cost neuronal imaging in vivo. Its small transparent body and simple, well-characterized nervous system allows identification and fluorescence imaging of any neuron within the intact animal. Simple immobilization techniques with minimal impact on the animal's physiology allow extended time-lapse imaging. The development of genetically-encoded calcium sensitive fluorophores such as cameleon and GCaMP allow in vivo imaging of neuronal calcium relating both cell physiology and neuronal activity. Numerous transgenic strains expressing these fluorophores in specific neurons are readily available or can be constructed using well-established techniques. Here, we describe detailed procedures for measuring calcium dynamics within a single neuron in vivo using both GCaMP and cameleon. We discuss advantages and disadvantages of both as well as various methods of sample preparation (animal immobilization) and image analysis. Finally, we present results from two experiments: 1) Using GCaMP to measure the sensory response of a specific neuron to an external electrical field and 2) Using cameleon to measure the physiological calcium response of a neuron to traumatic laser damage. Calcium imaging techniques such as these are used extensively in C. elegans and have been extended to measurements in freely moving animals, multiple neurons simultaneously and comparison across genetic backgrounds. C. elegans presents a robust and flexible system for in vivo neuronal imaging with advantages over other model systems in technical simplicity and cost.

Focal application of low-dose-rate brachytherapy for prostate cancer: a pilot study

PubMed Central

Spadinger, Ingrid T.; Salcudean, Septimiu E.; Kozlowski, Piotr; Chang, Silvia D.; Ng, Tony; Lobo, Julio; Nir, Guy; Moradi, Hamid; Peacock, Michael; Morris, W. James

2017-01-01

Purpose To evaluate the feasibility and to report the early outcomes of focal treatment of prostate cancer using low-dose-rate brachytherapy (LDR-PB). Material and methods Seventeen patients were screened with multi-parametric magnetic resonance imaging (mpMRI), 14 of whom proceeded to receive trans-perineal template mapping biopsy (TTMB). Focal LDR-PB was performed on five eligible patients using dual air kerma strength treatment plans based on planning target volumes derived from cancer locations and determined by TTMB. Patient follow-up includes prostate specific antigen (PSA) measurements, urinary and sexual function questionnaires, repeated imaging and TTMB at specific intervals post-treatment. Results Feasibility of focal LDR-PB was shown and short-term outcomes are promising. While the detection rate of tumors, a majority of which were low grade GS 3 + 3, was found to be low on mpMRI (sensitivity of 37.5%), our results suggest the potential of mpMRI in detecting the presence of higher grade (GS ≥ 3 + 4), and bilateral disease indicating its usefulness as a screening tool for focal LDR-PB. Conclusions Low-dose-rate brachytherapy is a favorable ablation option for focal treatment of prostate cancer, requiring minimal modification to the standard (whole gland) LDR-PB treatment, and appears to have a more favorable side effect profile. Further investigation, in the form of a larger study, is needed to assess the methods used and the long-term outcomes of focal LDR-PB. PMID:28725242

GPU acceleration of a petascale application for turbulent mixing at high Schmidt number using OpenMP 4.5

NASA Astrophysics Data System (ADS)

Clay, M. P.; Buaria, D.; Yeung, P. K.; Gotoh, T.

2018-07-01

This paper reports on the successful implementation of a massively parallel GPU-accelerated algorithm for the direct numerical simulation of turbulent mixing at high Schmidt number. The work stems from a recent development (Comput. Phys. Commun., vol. 219, 2017, 313-328), in which a low-communication algorithm was shown to attain high degrees of scalability on the Cray XE6 architecture when overlapping communication and computation via dedicated communication threads. An even higher level of performance has now been achieved using OpenMP 4.5 on the Cray XK7 architecture, where on each node the 16 integer cores of an AMD Interlagos processor share a single Nvidia K20X GPU accelerator. In the new algorithm, data movements are minimized by performing virtually all of the intensive scalar field computations in the form of combined compact finite difference (CCD) operations on the GPUs. A memory layout in departure from usual practices is found to provide much better performance for a specific kernel required to apply the CCD scheme. Asynchronous execution enabled by adding the OpenMP 4.5 NOWAIT clause to TARGET constructs improves scalability when used to overlap computation on the GPUs with computation and communication on the CPUs. On the 27-petaflops supercomputer Titan at Oak Ridge National Laboratory, USA, a GPU-to-CPU speedup factor of approximately 5 is consistently observed at the largest problem size of 81923 grid points for the scalar field computed with 8192 XK7 nodes.

Estimation and application of the thermodynamic properties of aqueous phenanthrene and isomers of methylphenanthrene at high temperature

NASA Astrophysics Data System (ADS)

Dick, Jeffrey M.; Evans, Katy A.; Holman, Alex I.; Jaraula, Caroline M. B.; Grice, Kliti

2013-12-01

Estimates of standard molal Gibbs energy (ΔGf°) and enthalpy (ΔHf°) of formation, entropy (S°), heat capacity (CP°) and volume (V°) at 25 °C and 1 bar of aqueous phenanthrene (P) and 1-, 2-, 3-, 4- and 9-methylphenanthrene (1-MP, 2-MP, 3-MP, 4-MP, 9-MP) were made by combining reported standard-state properties of the crystalline compounds, solubilities and enthalpies of phenanthrene and 1-MP, and relative Gibbs energies, enthalpies and entropies of aqueous MP isomers from published quantum chemical simulations. The calculated properties are consistent with greater stabilities of the β isomers (2-MP and 3-MP) relative to the α isomers (1-MP and 9-MP) at 25 °C. However, the metastable equilibrium values of the abundance ratios 2-MP/1-MP (MPR) and (2-MP + 3-MP)/(1-MP + 9-MP) (MPI-3) decrease with temperature, becoming <1 at ∼375-455 °C. The thermodynamic model is consistent with observations of reversals of these organic maturity parameters at high temperature in hydrothermal and metamorphic settings. Application of the model to data reported for the Paleoproterozoic Here’s Your Chance (HYC) Pb-Zn-Ag ore deposit (McArthur River, Northern Territory, Australia) indicates a likely effect of high-temperature equilibration on reported values of MPR and MPI-3, but this finding is contingent on the location within the deposit. If metastable equilibrium holds, a third aromatic maturity ratio, 1.5 × (2-MP + 3-MP)/(P + 1-MP + 9-MP) (MPI-1), can be used as a proxy for oxidation potential. Values of logaH2aq determined from data reported for HYC and for a sequence of deeply buried source rocks are indicative of more reducing conditions at a given temperature than those inferred from data reported for two sets of samples exposed to contact or regional metamorphism. These results are limiting-case scenarios for the modeled systems that do not account for effects of non-ideal mixing or kinetics, or external sources or transport of the organic matter. Nevertheless, quantifying the temperature dependence of equilibrium constants of organic reactions enables the utilization of organic maturity parameters as relative geothermometers at temperatures higher than the nominal limits of the oil window.

Assessing and mitigating uncertainties in the Noah-MP land-model simulations over the Tibet Plateau region

NASA Astrophysics Data System (ADS)

Zhang, G.; Chen, F.; Gan, Y.

2017-12-01

Assessing and mitigating uncertainties in the Noah-MP land-model simulations over the Tibet Plateau region Guo Zhang1, Fei Chen1,2, Yanjun Gan11State Key Laboratory of Severe Weather, Chinese Academy of Meteorological Sciences, Beijing, China 2National Center for Atmospheric Research, Boulder, Colorado, USA Uncertainties in the Noah with multiparameterization (Noah-MP) land surface model were assessed through physics ensemble simulations for four sparsely-vegetated sites located in the Tibetan Plateau region. Those simulations were evaluated using observations at the four sites during the third Tibetan Plateau Experiment (TIPEX III).The impacts of uncertainties in precipitation data used as forcing conditions, parameterizations of sub-processes such as soil organic matter and rhizosphere on physics-ensemble simulations are identified using two different methods: the natural selection and Tukey's test. This study attempts to answer the following questions: 1) what is the relative contribution of precipitation-forcing uncertainty to the overall uncertainty range of Noah-MP simulations at those sites as compared to that at a more moisture and densely vegetated site; 2) what are the most sensitive physical parameterization for those sites; 3) can we identify the parameterizations that need to be improved? The investigation was conducted by evaluating simulated seasonal evolution of soil temperature, soilmoisture, surface heat fluxes through a number of Noah-MP ensemble simulations.

Development of novel indole-3-aldehyde loaded gastro-resistant spray-dried microparticles for post-biotic small intestine local delivery.

PubMed

Puccetti, Matteo; Giovagnoli, Stefano; Zelante, Teresa; Romani, Luigina; Ricci, Maurizio

2018-04-28

Considering the recent evidences on the therapeutic potential of post-biotics, this study was focused on two mains goals: i) to develop an enteric microparticle (MP) formulation for intestinal localized delivery of Indole-3-aldehyde (3-IAld) (a microbial-derived metabolite produced by the host's lactobacilli during the catabolic pathway of tryptophan); ii) to provide support to the employment of spray-drying as innovative one-step manufacturing technique for enteric products. For this purpose, special attention was taken in the knowledge of the influence of equipment setup and feedstock properties on MP enteric behaviour. Eudragit® S100 and L100 and ethyl cellulose were used as wall materials and NaOH and ethanol solutions as solvent systems. 3-IAld loading was maintained at 10% w/w. As postulated, feedstock properties influenced spray-drying regime. In addition, they prevailed over other spray-drying process factors in determining MP enteric behavior. Albeit the high buckling regime that produced crumped particles, gastro-resistance was obtained by spray-drying 2:1 Eudragit® S100:L100 with 30% w/w ethyl cellulose (EC) in ethanol solution. These results support the use of spray-drying as a method for manufacturing gastro-resistant MP. The obtained 3-IAld loaded enteric MP will be useful to investigate novel post-biotic-based treatments in different therapeutic areas. Copyright © 2018. Published by Elsevier Inc.

Myosin phosphatase and RhoA-activated kinase modulate neurotransmitter release by regulating SNAP-25 of SNARE complex

PubMed Central

Sipos, Adrienn; Darula, Zsuzsanna; Bécsi, Bálint; Nagy, Dénes; Iván, Judit; Erdődi, Ferenc

2017-01-01

Reversible phosphorylation of neuronal proteins plays an important role in the regulation of neurotransmitter release. Myosin phosphatase holoenzyme (MP) consists of a protein phosphatase-1 (PP1) catalytic subunit (PP1c) and a regulatory subunit, termed myosin phosphatase targeting subunit (MYPT1). The primary function of MP is to regulate the phosphorylation level of contractile proteins; however, recent studies have shown that MP is localized to neurons, and is also involved in the mediation of neuronal processes. Our goal was to investigate the effect of RhoA-activated kinase (ROK) and MP on the phosphorylation of one potential neuronal substrate, the synaptosomal-associated protein of 25 kDa (SNAP-25). SNAP-25 is a member of the SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) complex, along with synaptobrevin and syntaxin, and the primary role of SNAP25 is to mediate vesicle fusion. We showed that MYPT1 interacts with SNAP-25, as revealed by immunoprecipitation and surface plasmon resonance based binding studies. Mass spectrometry analysis and in vitro phosphorylation/dephosphorylation assays demonstrated that ROK phosphorylates, while MP dephosphorylates, SNAP-25 at Thr138. Silencing MYPT1 in B50 neuroblastoma cells increased phosphorylation of SNAP-25 at Thr138. Inhibition of PP1 with tautomycetin increased, whereas inhibition of ROK by H1152, decreased the phosphorylation of SNAP-25 at Thr138 in B50 cells, in cortical synaptosomes, and in brain slices. In response to the transduction of the MP inhibitor, kinase-enhanced PP1 inhibitor (KEPI), into synaptosomes, an increase in phosphorylation of SNAP-25 and a decrease in the extent of neurotransmitter release were detected. The interaction between SNAP-25 and syntaxin increased with decreasing phosphorylation of SNAP-25 at Thr138, upon inhibition of ROK. Our data suggest that ROK/MP play a crucial role in vesicle trafficking, fusion, and neurotransmitter release by oppositely regulating the phosphorylation of SNAP-25 at Thr138. PMID:28486561

Alkylation of 6-mercaptopurine (6-MP) with N-alkyl-N-alkoxycarbonylaminomethyl chlorides: S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP prodrug structure effect on the dermal delivery of 6-MP.

PubMed

Siver, K G; Sloan, K B

1990-01-01

The S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP (6-CARB-6-MP) prodrugs 5-20 were synthesized from the reaction of 6-MP with N-alkyl-N-alkyoxycarbonylaminomethyl chlorides (4) in dimethyl sulfoxide in overall yields of 5-62%, depending on the N-alkyl and the alkoxy groups involved. The derivatives were fully characterized by spectral and microanalyses. The assignment of the substitution pattern as S6-alkyl was based on comparisons of the UV, 1H NMR and 13C NMR spectra with model compounds. A S6, 9-bis-alkyl derivative was obtained from the reaction of 2 equivalents of 4 with 6-MP but the product was unstable and decomposed on standing to a 9-alkyl derivative. The 6-CARB-6-MP prodrugs reverted to 6-MP in water by an SN1-type mechanism involving unimolecular charge separation in the transition state of the rate determining step. There was no effect of dermal enzymes on the rate of hydrolysis. The solubilities in isopropyl myristate (IPM) for all of the 6-CARB-6-MP prodrugs were significantly greater than the solubility of 6-MP in IPM but only one prodrug (5) was apparently even as soluble as 6-MP in water. Selected 6-CARB-6-MP prodrugs were examined in diffusion cell experiments. Only the N-methyl-N-methoxycarbonyl derivative 5 gave a steady-state rate of delivery of 6-MP from IPM that was significantly greater than the steady-state rate of delivery of 6-MP from 6-MP in IPM. All the other derivatives gave steady-state rates of delivery of 6-MP from IPM that were either not significantly different, or were significantly lower than the rate obtained from 6-MP in IPM. In all cases, the effect of the 6-CARB-6-MP:IPM suspensions on the permeability of the skin, as determined by the second application flux of theophylline:propylene glycol, was of the same magnitude as the effect of IPM alone.

Methylphenidate side effects in advanced cancer: a retrospective analysis.

PubMed

Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Davis, Mellar P; Rivera, Nilo; Khoshknabi, Dilara Seyidova

2010-02-01

Methylphenidate (MP) is often recommended for symptom control in advanced cancer. Little is known about its side effects in frail adults. To evaluate MP-associated symptoms or side effects (S/E). Data was collected from 2 published prospective cohort series and a phase 2 study of MP for symptom control in advanced cancer. All 3 reports had identical dosing schedules and symptom assessments. Initial MP doses were 10 mg/d (5 mg at 8 AM and at 12 noon) titrated up to a maximum of 30 mg/d. Depression, fatigue, and symptoms identified as possible MP S/E were evaluated for presence (prevalence) and for severity (using categorical scales) before MP (day 0) and on days 3, 5, and 7 thereafter. The categorical scale used was none, mild, moderate, and severe. 62 patients were enrolled. Fifty completed 7 days of MP with a median age of 69 (range 30-90) years. Thirty-five received MP 10 mg/day. Most (96%) had improvement in depression and/or fatigue. Among the 62 patients, new symptom prevalence throughout the study was agitation (16%), insomnia (16%), dry mouth (15%), nausea (10%), tremors (6%), anorexia (5%), headache (3%), palpitations (2%), and vomiting (2%). Patients could have more than 1 symptom simultaneously. Seven (11%) withdrew due to MP S/E. Some symptoms present before MP showed significant improvement during MP therapy. (1) Treatment with MP (10-20 mg/d) in advanced cancer is well tolerated. (2) S/E symptoms with MP appeared to improve spontaneously despite continued MP therapy. (3) Depression and fatigue improved at doses lower than those recommended in other clinical conditions. (4) MP improved depression and fatigue, and some secondary symptoms associated with them. Methylphenidate (MP) appears safe when used in the treatment of depression and fatigue in advanced cancer.

Thinking About Better Speech: Mental Practice for Stroke-Induced Motor Speech Impairments

PubMed Central

Page, Stephen J.; Harnish, Stacy

2012-01-01

Background Mental practice (MP) is a mind-body technique in which physical movements are cognitively rehearsed. It has shown efficacy in reducing the severity of a number of neurological impairments. Aims In the present review, we highlight recent developments in MP research, and the basis for MP use after stroke-induced motor speech disorders. Main Contribution In this review, we: (a) propose a novel conceptual model regarding the development of learned nonuse in people with motor speech impairments; (b) review the rationale and efficacy of MP for reducing the severity of stroke-induced impairments; (c) review evidence demonstrating muscular and neural activations during and following MP use; (d) review evidence showing that MP increases skill acquisition, use, and function in stroke; (e) review literature regarding neuroplasticity after stroke, including MP-induced neuroplasticity and the neural substrates underlying motor and language reacquisition; and (f) based on the above, review the rationale and clinical application of MP for stroke-induced motor speech impairments. Conclusions Support for MP use includes decades of MP neurobiological and behavioral efficacy data in a number of populations. Most recently, these data have expanded to the application of MP in neurological populations. Given increasingly demanding managed care environments, efficacious strategies that can be easily administered are needed. We also encounter clinicians who aspire to use MP, but their protocols do not contain several of the elements shown to be fundamental to effective MP implementation. Given shortfalls of some conventional aphasia and motor speech rehabilitative techniques, and uncertainty regarding optimal MP implementation, this paper introduces the neurophysiologic bases for MP, the evidence for MP use in stroke rehabilitation, and discusses its applications and considerations in patients with stroke-induced motor speech impairments. PMID:22308050

Tycho 2: A Proxy Application for Kinetic Transport Sweeps

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garrett, Charles Kristopher; Warsa, James S.

2016-09-14

Tycho 2 is a proxy application that implements discrete ordinates (SN) kinetic transport sweeps on unstructured, 3D, tetrahedral meshes. It has been designed to be small and require minimal dependencies to make collaboration and experimentation as easy as possible. Tycho 2 has been released as open source software. The software is currently in a beta release with plans for a stable release (version 1.0) before the end of the year. The code is parallelized via MPI across spatial cells and OpenMP across angles. Currently, several parallelization algorithms are implemented.

A Block-LU Update for Large-Scale Linear Programming

DTIC Science & Technology

1990-01-01

linear programming problems. Results are given from runs on the Cray Y -MP. 1. Introduction We wish to use the simplex method [Dan63] to solve the...standard linear program, minimize cTx subject to Ax = b 1< x <U, where A is an m by n matrix and c, x, 1, u, and b are of appropriate dimension. The simplex...the identity matrix. The basis is used to solve for the search direction y and the dual variables 7r in the following linear systems: Bky = aq (1.2) and

Survey of college students' MP3 listening: Habits, safety issues, attitudes, and education.

PubMed

Hoover, Alicia; Krishnamurti, Sridhar

2010-06-01

To survey listening habits and attitudes of typical college students who use MP3 players and to investigate possible safety issues related to MP3 player listening. College students who were frequent MP3 player users (N = 428) filled out a 30-item online survey. Specific areas probed by the present survey included frequency and duration of MP3 player use, MP3 player volume levels used, types of earphones used, typical environments in which MP3 player was worn, specific activities related to safety while listening to MP3 players, and attitudes toward MP3 player use. The majority of listeners wore MP3 players for less than 2 hr daily at safe volume levels. About one third of respondents reported being distracted while wearing an MP3 player, and more than one third of listeners experienced soreness in their ears after a listening session. About one third of respondents reported occasionally using their MP3 players at maximum volume levels. Listeners indicated willingness to (a) reduce volume levels, (b) decrease listening duration, and (c) buy specialized earphones to conserve their hearing. The study found concerns regarding the occasional use of MP3 players at full volume and reduced environmental awareness among some college student users.

Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system : appendix online 10 : OR\\0x2010217 NB ramp flow & ML speed-flow plots.

DOT National Transportation Integrated Search

2008-12-01

The appendix includes various ramp flow and ML speed-flow plots: OR-217 NB, 72nd MP 6.61; OR-217 NB, 99W-EB MP 5.9; OR-217 NB, 99W-WB MP 5.85; OR-217 NB, Greenburg MP 4.65; OR-217 NB, Scholls MP 3.85; OR-217 NB, Denney MP 2.68; OR-217 NB, Allen MP 2....

Comparing Noah-MP simulations of energy and water fluxes in the soil-vegetation-atmosphere continuum with plot scale measurements

NASA Astrophysics Data System (ADS)

Gayler, Sebastian; Wöhling, Thomas; Högy, Petra; Ingwersen, Joachim; Wizemann, Hans-Dieter; Wulfmeyer, Volker; Streck, Thilo

2013-04-01

During the last years, land-surface models have proven to perform well in several studies that compared simulated fluxes of water and energy from the land surface to the atmosphere against measured fluxes at the plot-scale. In contrast, considerable deficits of land-surface models have been identified to simulate soil water fluxes and vertical soil moisture distribution. For example, Gayler et al. (2013) showed that simplifications in the representation of root water uptake can result in insufficient simulations of the vertical distribution of soil moisture and its dynamics. However, in coupled simulations of the terrestrial water cycle, both sub-systems, the atmosphere and the subsurface hydrogeo-system, must fit together and models are needed, which are able to adequately simulate soil moisture, latent heat flux, and their interrelationship. Consequently, land-surface models must be further improved, e.g. by incorporation of advanced biogeophysics models. To improve the conceptual realism in biophysical and hydrological processes in the community land surface model Noah, this model was recently enhanced to Noah-MP by a multi-options framework to parameterize individual processes (Niu et al., 2011). Thus, in Noah-MP the user can choose from several alternative models for vegetation and hydrology processes that can be applied in different combinations. In this study, we evaluate the performance of different Noah-MP model settings to simulate water and energy fluxes across the land surface at two contrasting field sites in South-West Germany. The evaluation is done in 1D offline-mode, i.e. without coupling to an atmospheric model. The atmospheric forcing is provided by measured time series of the relevant variables. Simulation results are compared with eddy covariance measurements of turbulent fluxes and measured time series of soil moisture at different depths. The aims of the study are i) to carve out the most appropriate combination of process parameterizations in Noah-MP to simultaneously match the different components of the water and energy cycle at the field sites under consideration, and ii) to estimate the uncertainty in model structure. We further investigate the potential to improve simulation results by incorporating concepts of more advanced root water uptake models from agricultural field scale models into the land-surface-scheme. Gayler S, Ingwersen J, Priesack E, Wöhling T, Wulfmeyer V, Streck T (2013): Assessing the relevance of sub surface processes for the simulation of evapotranspiration and soil moisture dynamics with CLM3.5: Comparison with field data and crop model simulations. Environ. Earth Sci., 69(2), under revision. Niu G-Y, Yang Z-L, Mitchell KE, Chen F, Ek MB, Barlage M, Kumar A, Manning K, Niyogi D, Rosero E, Tewari M and Xia Y (2011): The community Noah land surface model with multiparameterization options (Noah-MP): 1. Model description and evaluation with local-scale measurements. Journal of Geophysical Research 116(D12109).

Altering Work to Rest Ratios Differentially Influences Fatigue Indices During Repeated Sprint Ability Testing.

PubMed

La Monica, Michael B; Fukuda, David H; Beyer, Kyle S; Hoffman, Mattan W; Miramonti, Amelia A; Riffe, Josh J; Baker, Kayla M; Fragala, Maren S; Hoffman, Jay R; Stout, Jeffrey R

2016-02-01

This study examined the influence of recovery time on fatigue indices, performance (total work [TW], peak power [PP], and mean power [MP]), and oxygen consumption during repeated sprint ability (RSA) on a cycle ergometer. Eight recreationally-trained men performed 3 RSA protocols consisting of 10 × 6 s sprints with 12 s, 18 s, and 24 s rest intervals between each sprint. Fatigue indices were determined as percent decrement (%Dec) and rate of decline using either a log transform method or standard slope approach for TW, PP, and MP during respective RSA protocols. The maximal VO2 value in response to given sprint intervals and the minimal VO2 value in response to given rest periods (VO2 work and VO2 rest, respectively) were recorded. A repeated measures analysis of variance was used to analyze all variables. Average VO2 work was not different among rest interval trials. Average VO2 rest with 12 s rest was greater than 18 s and 24 s (2.16 ± 0.17 L · min(-1), 1.91 ± 0.18 L · min(-1), 1.72 ± 0.15 L · min(-1), respectively), while 18 s was greater than 24 s. Average TW and MP were greater with 24 s rest than 12 s (4,604.44 ± 915.98 J vs. 4,305.46 ± 727.17 J, respectively), with no differences between RSA protocols for PP. No differences in %Dec were observed. Both methods of calculating rates of decline per sprint for PP and TW were greater during 12 s than 18 s or 24 s. Since changes were only noted between the 12 s and 24 s protocols, a 6 s differential in rest intervals may not be enough to elicit alterations in TW, PP, MP, or %Dec in RSA performance. Rate of decline may be a more sensitive measure of fatigue than %Dec.

Prevention and synergistic control of Ph(+) ALL by a DNA vaccine and 6-mercaptopurine.

PubMed

Köchling, Joachim; Rott, Yvonne; Arndt, Stefanie; Marschke, Christina; Schmidt, Manuel; Wittig, Burghardt; Kalies, Katrin; Westermann, Jürgen; Henze, Günter

2012-09-07

Although the outcome of patients with acute lymphoblastic leukemia (ALL) has been improved continuously by chemotherapy and tyrosine kinase inhibitors, prognosis of patients with Philadelphia chromosome positive (Ph(+)) ALL still remains poor. Since further intensification of chemotherapy is limited by toxic side effects and patients with high risk of transplant-related mortality are not eligible for allogeneic stem cell transplantation new treatment strategies are urgently needed for the prevention of Ph(+) ALL relapse. There is increasing evidence that the immune system plays an essential role for the eradication or immunologic control of remaining leukemia cells. We developed several DNA-based vaccines encoding a BCR-ABL(p185) specific peptide and GM-CSF, and CD40-L, IL-27 or IL-12 and evaluated the preventive and therapeutic efficacy against a lethal challenge of syngeneic Ph(+) ALL in Balb/c mice. In vivo cell depletion assays and cytokine expression studies were performed and the efficacy of the DNA vaccine was compared with 6-mercaptopurine (6-MP) alone and the combination of the DNA vaccine and 6-MP. Preventive immunization with the vaccine BCR-ABL/GM-CSF/IL-12 and the TLR-9 agonist dSLIM induced an innate and adaptive immune response mediated by NK-cells, CD4(+) T-cells and CD8(+) T-cells leading to a survival rate of 80%. Therapeutic vaccination resulted in a significantly longer leukemia-free survival (40.7 days vs. 20.4 days) and a higher survival rate (56% vs. 10%) compared to chemotherapy with 6-MP. Remarkably, in combination with the vaccine 6-MP acted synergistically and led to 100% survival. These results demonstrate that minimal residual disease of Ph(+) ALL can be significantly better controlled by a combined treatment approach of immunotherapy and chemotherapy. This provides a rationale for improving maintenance therapy in order to reduce the relapse rate in patients with Ph(+) ALL. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Hybrid MPI/OpenMP Approach for Parallel Groundwater Model Calibration on Multicore Computers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Guoping; D'Azevedo, Ed F; Zhang, Fan

2010-01-01

Groundwater model calibration is becoming increasingly computationally time intensive. We describe a hybrid MPI/OpenMP approach to exploit two levels of parallelism in software and hardware to reduce calibration time on multicore computers with minimal parallelization effort. At first, HydroGeoChem 5.0 (HGC5) is parallelized using OpenMP for a uranium transport model with over a hundred species involving nearly a hundred reactions, and a field scale coupled flow and transport model. In the first application, a single parallelizable loop is identified to consume over 97% of the total computational time. With a few lines of OpenMP compiler directives inserted into the code,more » the computational time reduces about ten times on a compute node with 16 cores. The performance is further improved by selectively parallelizing a few more loops. For the field scale application, parallelizable loops in 15 of the 174 subroutines in HGC5 are identified to take more than 99% of the execution time. By adding the preconditioned conjugate gradient solver and BICGSTAB, and using a coloring scheme to separate the elements, nodes, and boundary sides, the subroutines for finite element assembly, soil property update, and boundary condition application are parallelized, resulting in a speedup of about 10 on a 16-core compute node. The Levenberg-Marquardt (LM) algorithm is added into HGC5 with the Jacobian calculation and lambda search parallelized using MPI. With this hybrid approach, compute nodes at the number of adjustable parameters (when the forward difference is used for Jacobian approximation), or twice that number (if the center difference is used), are used to reduce the calibration time from days and weeks to a few hours for the two applications. This approach can be extended to global optimization scheme and Monte Carol analysis where thousands of compute nodes can be efficiently utilized.« less

Control of Suspect/Counterfeit and Defective Items

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheriff, Marnelle L.

2013-09-03

This procedure implements portions of the requirements of MSC-MP-599, Quality Assurance Program Description. It establishes the Mission Support Alliance (MSA) practices for minimizing the introduction of and identifying, documenting, dispositioning, reporting, controlling, and disposing of suspect/counterfeit and defective items (S/CIs). employees whose work scope relates to Safety Systems (i.e., Safety Class [SC] or Safety Significant [SS] items), non-safety systems and other applications (i.e., General Service [GS]) where engineering has determined that their use could result in a potential safety hazard. MSA implements an effective Quality Assurance (QA) Program providing a comprehensive network of controls and verification providing defense-in-depth by preventingmore » the introduction of S/CIs through the design, procurement, construction, operation, maintenance, and modification of processes. This procedure focuses on those safety systems, and other systems, including critical load paths of lifting equipment, where the introduction of S/CIs would have the greatest potential for creating unsafe conditions.« less

MP Resulting in Autophagic Cell Death of Microglia through Zinc Changes against Spinal Cord Injury

PubMed Central

Li, Dingding; Wang, Guannan; Han, Donghe; Bi, Jing; Li, Chenyuan; Wang, Hongyu; Liu, Zhiyuan; Gao, Wei; Gao, Kai; Yao, Tianchen; Wan, Zhanghui; Li, Haihong; Mei, Xifan

2016-01-01

Methylprednisolone pulse therapy (MPPT), as a public recognized therapy of spinal cord injury (SCI), is doubted recently, and the exact mechanism of MP on SCI is unclear. This study sought to investigate the exact effect of MP on SCI. We examined the effect of MP in a model of SCI in vivo and an LPS induced model in vitro. We found that administration of MP produced an increase in the Basso, Beattie, and Bresnahan scores and motor neurons counts of injured rats. Besides the number of activated microglia was apparently reduced by MP in vivo, and Beclin-1 dependent autophagic cell death of microglia was induced by MP in LPS induced model. At the same time, MP increases cellular zinc concentration and level of ZIP8, and TPEN could revert effect of MP on autophagic cell death of microglia. Finally, we have found that MP could inhibit NF-κβ in LPS induced model. These results show that the MP could result in autophagic cell death of microglia, which mainly depends on increasing cellular labile zinc, and may be associated with inhibition of NF-κβ, and that MP can produce neuroprotective effect in SCI. PMID:27057544

Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration.

PubMed

Ding, Yu-Shin; Gatley, S John; Thanos, Panayotis K; Shea, Colleen; Garza, Victor; Xu, Youwen; Carter, Pauline; King, Payton; Warner, Don; Taintor, Nicholas B; Park, Daniel J; Pyatt, Bea; Fowler, Joanna S; Volkow, Nora D

2004-09-01

Methylphenidate (MP) (Ritalin) is widely used for the treatment of attention deficit hyperactivity disorder (ADHD). It is a chiral drug, marketed as the racemic mixture of d- and l-threo enantiomers. Our previous studies (PET and microdialysis) in humans, baboons, and rats confirm the notion that pharmacological specificity of MP resides predominantly in the d-isomer. A recent report that intraperitoneally (i.p.) administered l-threo-MP displayed potent, dose-dependent inhibition of cocaine- or apomorphine-induced locomotion in rats, raises the question of whether l-threo-MP has a similar effect when given orally. It has been speculated that l-threo-MP is poorly absorbed in humans when it is given orally because of rapid presystemic metabolism. To investigate whether l-threo-MP or its metabolites can be delivered to the brain when it is given orally, and whether l-threo-MP is pharmacologically active. PET and MicroPET studies were carried out in baboons and rats using orally delivered C-11-labeled d- and l-threo-MP ([methyl-(11)C]d-threo-MP and [methyl-(11)C]l-threo-MP). In addition, we assessed the effects of i.p. l-threo-MP on spontaneous and cocaine-stimulated locomotor activity in mice. There was a higher global uptake of carbon-11 in both baboon and rat brain for oral [(11)C]l-threo-MP than for oral [(11)C]d-threo-MP. Analysis of the chemical form of radioactivity in rat brain after [(11)C]d-threo-MP indicated mainly unchanged tracer, whereas with [(11)C]l-threo-MP, it was mainly a labeled metabolite. The possibility that this labeled metabolite might be [(11)C]methanol or [(11)C]CO(2), derived from demethylation, was excluded by ex vivo studies in rats. When l-threo-MP was given i.p. to mice at a dose of 3 mg/kg, it neither stimulated locomotor activity nor inhibited the increased locomotor activity due to cocaine administration. These results suggest that, in animal models, l-threo-MP or its metabolite(s) is (are) absorbed from the gastrointestinal tract and enters the brain after oral administration, but that l-threo-MP may not be pharmacologically active. These results are pertinent to the question of whether l-threo-MP contributes to the behavioral and side effect profile of MP during treatment of ADHD. Copyright 2004 Wiley-Liss, Inc.

Synthesis and characterization of a series of Group 4 phenoxy-thiol derivatives

DOE PAGES

Boyle, Timothy J.; Neville, Michael L.; Parkes, Marie V.

2016-02-11

In this study, a series of Group 4 phenoxy-thiols were developed from the reaction products of a series of metal tert-butoxides ([M(OBu t) 4]) with four equivalents of 4-mercaptophenol (H-4MP). The products were found by single crystal X-ray diffraction to adopt the general structure [(HOBu t)(4MP) 3M(μ-4MP)] 2 [where M = Ti (1), Zr (2), Hf (3)] from toluene and [(py) 2M(4MP)] where M = Ti (4), Zr (5) and [(py)(4MP) 3Hf(μ-4MP)] 2 (6) from pyridine (py). Varying the [Ti(OR) 4] precursors (OR = iso-propoxide (OPr i) or neo-pentoxide (ONep)) in toluene led to [(HOR)(4MP) 3Ti(μ-4MP)] 2 (OR = OPrmore » i (7), ONep (8)), which were structurally similar to 1. Lower stoichiometric reactions in toluene led to partial substitution by the 4MP ligands yielding [H][Ti(μ-4MP)(4MP)(ONep) 3] 2 (9). Independent of the stoichiometry, all of the Ti derivatives were found to be red in color, whereas the heavier congeners were colorless. Attempts to understand this phenomenon led to investigation with a series of varied –SH substituted phenols. From the reaction of H-2MP and H-3MP (2-mercaptophenol and 3-mercaptophenol, respectively), the isolated products had identical arrangements: [(ONep) 2(2MP)Ti(μ,η2-2MP)] 2 (10) and [(HOR)(3MP)M(μ-3MP)] 2 (M/OR = Ti/ONep (11); Zr/OBu t (12)) with a similar red color. Based on the simulated and observed UV–Vis spectra, it was reasoned that the color was generated due to a ligand-to-metal charge transfer for Ti that was not available for the larger congeners.« less

Microchip-Based Organophosphorus Detection Using Bienzyme Bioelectrocatalysis

NASA Astrophysics Data System (ADS)

Han, Yong Duk; Jeong, Chi Yong; Lee, Jun Hee; Lee, Dae-Sik; Yoon, Hyun C.

2012-06-01

We have developed a microsystem for the detection of organophosphorus (OP) compounds using acetylcholine esterase (AchE) and choline oxidase (ChOx) bienzyme bioelectrocatalysis. Because AchE is irreversibly inhibited by OP pesticides, the change in AchE activity with OP treatment can be traced to determine OP concentration. Polymer-associated ChOx immobilization on the working electrode surface and magnetic microparticle (MP)-assisted AchE deposition methods were employed to create an AchE-ChOx bienzyme-modified biosensing system. ChOx was immobilized on the micropatterned electrodes using poly(L-lysine), glutaraldehyde, and amine-rich interfacial surface. AchE was immobilized on the MP surface via Schiff's base formation, and the enzyme-modified MPs were deposited on the working electrode using a magnet under the microfluidic channel. The bioelectrocatalytic reaction between AchE-ChOx bienzyme cascade and the ferrocenyl electron shuttle was successfully used to detect OP with the developed microchip. This provides a self-contained and relatively easy method for OP detection. It requires minimal time and a small sample size, and has potential analytic applications in pesticides and chemical warfare agents.

A model of irreversible jam formation in dense traffic

NASA Astrophysics Data System (ADS)

Brankov, J. G.; Bunzarova, N. Zh.; Pesheva, N. C.; Priezzhev, V. B.

2018-03-01

We study an one-dimensional stochastic model of vehicular traffic on open segments of a single-lane road of finite size L. The vehicles obey a stochastic discrete-time dynamics which is a limiting case of the generalized Totally Asymmetric Simple Exclusion Process. This dynamics has been previously used by Bunzarova and Pesheva (2017) for an one-dimensional model of irreversible aggregation. The model was shown to have three stationary phases: a many-particle one, MP, a phase with completely filled configuration, CF, and a boundary perturbed MP+CF phase, depending on the values of the particle injection (α), ejection (β) and hopping (p) probabilities. Here we extend the results for the stationary properties of the MP+CF phase, by deriving exact expressions for the local density at the first site of the chain and the probability P(1) of a completely jammed configuration. The unusual phase transition, characterized by jumps in both the bulk density and the current (in the thermodynamic limit), as α crosses the boundary α = p from the MP to the CF phase, is explained by the finite-size behavior of P(1). By using a random walk theory, we find that, when α approaches from below the boundary α = p, three different regimes appear, as the size L → ∞: (i) the lifetime of the gap between the rightmost clusters is of the order O(L) in the MP phase; (ii) small jams, separated by gaps with lifetime O(1) , exist in the MP+CF phase close to the left chain boundary; and (iii) when β = p, the jams are divided by gaps with lifetime of the order O(L 1 / 2) . These results are supported by extensive Monte Carlo calculations.

Macroparticle separation and plasma collimation in positively biased ducts in filtered vacuum arc deposition systems

NASA Astrophysics Data System (ADS)

Beilis, I. I.; Keidar, M.; Boxman, R. L.; Goldsmith, S.

1999-02-01

The objective of the present work was to determine the influence of positive bias on plasma and macroparticle (MP) flow in curved magnetized plasma ducts. The plasma bulk and sheath regions were analyzed. In the plasma bulk, the current density and electrical field component normal to the wall were obtained and used as boundary conditions for the near wall sheath region. In the sheath, a nonstationary model for MP charging and motion was developed. The solution of the hydrodynamic equations in the plasma when a positive bias is applied to the wall result in a radial electrical current. The electric field in the plasma bulk is generated by the separation between the magnetically confined electrons, and the ions, which are thrown outwards by the centrifugal force. The field increases with increasing positive bias. It was shown that MPs traveling in the sheath accumulate a charge which depends on the potential distribution, in contrast to MP charging in the quasineutral plasma where the charge depends on plasma density and electron temperature. MP trapping in the near-wall sheath was found. MPs may move in the sheath region along the wall by a repetitive process of electrostatic attraction to the wall, mechanical reflection and neutralization, followed by MP charging and attraction, etc. For example, titanium MPs with a radius less than 0.4 μm and with a velocity component normal to the wall of about 20 m/s are trapped if the sheath potential drop exceeds 20 V. It was obtained that the MP transmission fraction through filter decreases by more than few orders of magnitude due to the trapping effect when a bias potential of +100 V is applied between the wall and the plasma.

Monitoring of the data processing and simulated production at CMS with a web-based service: the Production Monitoring Platform (pMp)

NASA Astrophysics Data System (ADS)

Franzoni, G.; Norkus, A.; Pol, A. A.; Srimanobhas, N.; Walker, J.

2017-10-01

Physics analysis at the Compact Muon Solenoid requires both the production of simulated events and processing of the data collected by the experiment. Since the end of the LHC Run-I in 2012, CMS has produced over 20 billion simulated events, from 75 thousand processing requests organised in one hundred different campaigns. These campaigns emulate different configurations of collision events, the detector, and LHC running conditions. In the same time span, sixteen data processing campaigns have taken place to reconstruct different portions of the Run-I and Run-II data with ever improving algorithms and calibrations. The scale and complexity of the events simulation and processing, and the requirement that multiple campaigns must proceed in parallel, demand that a comprehensive, frequently updated and easily accessible monitoring be made available. The monitoring must serve both the analysts, who want to know which and when datasets will become available, and the central production teams in charge of submitting, prioritizing, and running the requests across the distributed computing infrastructure. The Production Monitoring Platform (pMp) web-based service, has been developed in 2015 to address those needs. It aggregates information from multiple services used to define, organize, and run the processing requests. Information is updated hourly using a dedicated elastic database and the monitoring provides multiple configurable views to assess the status of single datasets as well as entire production campaigns. This contribution will describe the pMp development, the evolution of its functionalities, and one and half year of operational experience.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saeed, Noha M.; El-Demerdash, Ebtehal; Abdel-Rahman, Hanaa M.

Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). MP and EP decreased NF-κB expression in liver and lung tissues and ameliorated histopathological changes caused by LPS.more » Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models. -- Highlights: ► Efficacy of MP and EP in combating inflammation was displayed in several models. ► MP and EP reduced carrageenan-induced rat paw edema and prostaglandin E2 level. ► MP and EP decreased TNF-α and IL-6 levels in experimental endotoxemia. ► MP and EP reduced NF-κB expression and histological changes in rat liver and lung. ► MP and EP reduced croton oil-induced ear edema and neutrophil infiltration.« less

Analytic energy gradients for orbital-optimized MP3 and MP2.5 with the density-fitting approximation: An efficient implementation.

PubMed

Bozkaya, Uğur

2018-03-15

Efficient implementations of analytic gradients for the orbital-optimized MP3 and MP2.5 and their standard versions with the density-fitting approximation, which are denoted as DF-MP3, DF-MP2.5, DF-OMP3, and DF-OMP2.5, are presented. The DF-MP3, DF-MP2.5, DF-OMP3, and DF-OMP2.5 methods are applied to a set of alkanes and noncovalent interaction complexes to compare the computational cost with the conventional MP3, MP2.5, OMP3, and OMP2.5. Our results demonstrate that density-fitted perturbation theory (DF-MP) methods considered substantially reduce the computational cost compared to conventional MP methods. The efficiency of our DF-MP methods arise from the reduced input/output (I/O) time and the acceleration of gradient related terms, such as computations of particle density and generalized Fock matrices (PDMs and GFM), solution of the Z-vector equation, back-transformations of PDMs and GFM, and evaluation of analytic gradients in the atomic orbital basis. Further, application results show that errors introduced by the DF approach are negligible. Mean absolute errors for bond lengths of a molecular set, with the cc-pCVQZ basis set, is 0.0001-0.0002 Å. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system : appendix online 8 : OR\\0x2010217 NB ML speed\\0x2010occupancy plots.

DOT National Transportation Integrated Search

2008-12-01

The appendix includes various ML speed-occupancy plots: OR-217 NB, 72nd MP 6.61; OR-217 NB, 99W-EB MP 5.9; OR-217 NB, 99W-WB MP 5.85; OR-217 NB, Greenburg MP 4.65; OR-217 NB, Scholls MP 3.85; OR-217 NB, Denney MP 2.68; OR-217 NB, Allen MP 2.16; OR-21...

Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system : appendix online 7 : OR\\0x2010217 NB ML speed\\0x2010flow plots.

DOT National Transportation Integrated Search

2008-12-01

The appendix includes various ML speed-flow plots: OR-217 NB, 72nd MP 6.61; OR-217 NB, 99W-EB MP 5.9; OR-217 NB, 99W-WB MP 5.85; OR-217 NB, Greenburg MP 4.65; OR-217 NB, Scholls MP 3.85; OR-217 NB, Denney MP 2.68; OR-217 NB, Allen MP 2.16; OR-217 NB,...

Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system : appendix online 9 : OR\\0x2010217 NB ML flow\\0x2010occupancy plots.

DOT National Transportation Integrated Search

2008-12-01

The appendix includes various ML flow occupancy plots: OR-217 NB, 72nd MP 6.61; OR-217 NB, 99W-EB MP 5.9; OR-217 NB, 99W-WB MP 5.85; OR-217 NB, Greenburg MP 4.65; OR-217 NB, Scholls MP 3.85; OR-217 NB, Denney MP 2.68; OR-217 NB, Allen MP 2.16; OR-217...

Detectability of BI-RADS category 3 or higher breast lesions and reading time on mammography: comparison between 5-MP and 8-MP LCD monitors.

PubMed

Yabuuchi, Hidetake; Kawanami, Satoshi; Kamitani, Takeshi; Matsumura, Tomomi; Yamasaki, Yuzo; Morishita, Junji; Honda, Hiroshi

2017-04-01

Background Five-megapixel (MP) displays are recommended as soft copy devices for digital mammogram. An 8-MP liquid crystal display (LCD) (two 4-MP displays within one display) might offer the advantage of being able to view biplane mammography more easily than the dual planes of 5-MP LCDs. Purpose To compare detectability of Breast Imaging Reporting and Data System (BI-RADS) category 3 or higher lesions and reading time on mammography between 5- MP and 8-MP LCDs. Material and Methods The mammograms of 240 breasts of 120 patients including 60 breasts with BI-RADS category 3 or higher lesions and 180 breasts with normal or category 2 lesions were enrolled. All bilateral mammograms were displayed on bifacial 5-MP LCDs or an 8-MP LCD (two 4-MP displays within one display). Six radiologists assessed 240 breasts on each display. The observations were analyzed using receiver operating characteristic (ROC) analysis. A jack-knife method was used for statistical analysis. We employed a paired t-test to determine whether any significant differences existed in the reading time between two different displays. A P value < 0.05 was considered significant. Results The mean areas under the ROC curve obtained using 5-MP and 8-MP LCDs were 0.925 and 0.915, respectively, and there was no significant difference ( P = 0.46). There was also no significant difference in the reading time between two types of displays (57.8 min. vs. 51.5 min, P = 0.39). Conclusion The detectability of BI-RADS category 3 or higher lesions and reading time using an 8-MP LCD were comparable to those using a 5-MP LCD.

Increased endothelial microparticles and oxidative stress at extreme altitude.

PubMed

Pichler Hefti, Jacqueline; Leichtle, Alexander; Stutz, Monika; Hefti, Urs; Geiser, Thomas; Huber, Andreas R; Merz, Tobias M

2016-04-01

Hypoxia and oxidative stress affect endothelial function. Endothelial microparticles (MP) are established measures of endothelial dysfunction and influence vascular reactivity. To evaluate the effects of hypoxia and antioxidant supplementation on endothelial MP profiles, a double-blind, placebo-controlled trial, during a high altitude expedition was performed. 29 participants were randomly assigned to a treatment group (n = 14), receiving vitamin E, C, A, and N-acetylcysteine daily, and a control group (n = 15), receiving placebo. Blood samples were obtained at 490 m (baseline), 3530, 4590, and 6210 m. A sensitive tandem mass spectrometry method was used to measure 8-iso-prostaglandin F2α and hydroxyoctadecadienoic acids as markers of oxidative stress. Assessment of MP profiles including endothelial activation markers (CD62+MP and CD144+MP) and cell apoptosis markers (phosphatidylserine+MP and CD31+MP) was performed using a standardized flow cytometry-based protocol. 15 subjects reached all altitudes and were included in the final analysis. Oxidative stress increased significantly at altitude. No statistically significant changes were observed comparing baseline to altitude measurements of phosphatidylserine expressing MP (p = 0.1718) and CD31+MP (p = 0.1305). Compared to baseline measurements, a significant increase in CD62+MP (p = 0.0079) and of CD144+MP was detected (p = 0.0315) at high altitudes. No significant difference in any MP level or oxidative stress markers were found between the treatment and the control group. Hypobaric hypoxia is associated with increased oxidative stress and induces a significant increase in CD62+ and CD144+MP, whereas phosphatidylserine+MP and CD31+MP remain unchanged. This indicates that endothelial activation rather than an apoptosis is the primary factor of hypoxia induced endothelial dysfunction.

The Caterer's Problem.

ERIC Educational Resources Information Center

Krause, Eugene F.

1983-01-01

An approach to teaching problem solving to preservice and in-service middle school teachers is described. They examined an unsolved question as a class research project. The process of developing the solution is detailed, and difficulties contained within the process are noted. (MP)

Scaled MP3 non-covalent interaction energies agree closely with accurate CCSD(T) benchmark data.

PubMed

Pitonák, Michal; Neogrády, Pavel; Cerný, Jirí; Grimme, Stefan; Hobza, Pavel

2009-01-12

Scaled MP3 interaction energies calculated as a sum of MP2/CBS (complete basis set limit) interaction energies and scaled third-order energy contributions obtained in small or medium size basis sets agree very closely with the estimated CCSD(T)/CBS interaction energies for the 22 H-bonded, dispersion-controlled and mixed non-covalent complexes from the S22 data set. Performance of this so-called MP2.5 (third-order scaling factor of 0.5) method has also been tested for 33 nucleic acid base pairs and two stacked conformers of porphine dimer. In all the test cases, performance of the MP2.5 method was shown to be superior to the scaled spin-component MP2 based methods, e.g. SCS-MP2, SCSN-MP2 and SCS(MI)-MP2. In particular, a very balanced treatment of hydrogen-bonded compared to stacked complexes is achieved with MP2.5. The main advantage of the approach is that it employs only a single empirical parameter and is thus biased by two rigorously defined, asymptotically correct ab-initio methods, MP2 and MP3. The method is proposed as an accurate but computationally feasible alternative to CCSD(T) for the computation of the properties of various kinds of non-covalently bound systems.

77 FR 55268 - Union Pacific Railroad Company-Acquisition and Operation Exemption-San Pedro Railroad Operating...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-07

....15 at Curtiss, Ariz., and MP 1041.32 near Curtiss (Parcel 1), and between MP 1071.16 and MP 1084 at... operating easement, in a line segment between MP 1041.32 and MP 1071.16 (Parcel 3),\\1\\ whose underlying...

Heroin - Multiple Languages

MedlinePlus

... Spanish) PDF The basics - Opioids, part 1 - English MP3 The basics - Opioids, part 1 - español (Spanish) MP3 The basics - Opioids, part 1 - English MP4 The ... Spanish) PDF Heroin - Opioid addiction, part 7 - English MP3 Heroin - Opioid addiction, part 7 - español (Spanish) MP3 ...

Toward Prostate Cancer Contouring Guidelines on Magnetic Resonance Imaging: Dominant Lesion Gross and Clinical Target Volume Coverage Via Accurate Histology Fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gibson, Eli; Biomedical Engineering, University of Western Ontario, London, Ontario; Centre for Medical Image Computing, University College London, London

Purpose: Defining prostate cancer (PCa) lesion clinical target volumes (CTVs) for multiparametric magnetic resonance imaging (mpMRI) could support focal boosting or treatment to improve outcomes or lower morbidity, necessitating appropriate CTV margins for mpMRI-defined gross tumor volumes (GTVs). This study aimed to identify CTV margins yielding 95% coverage of PCa tumors for prospective cases with high likelihood. Methods and Materials: Twenty-five men with biopsy-confirmed clinical stage T1 or T2 PCa underwent pre-prostatectomy mpMRI, yielding T2-weighted, dynamic contrast-enhanced, and apparent diffusion coefficient images. Digitized whole-mount histology was contoured and registered to mpMRI scans (error ≤2 mm). Four observers contoured lesion GTVs onmore » each mpMRI scan. CTVs were defined by isotropic and anisotropic expansion from these GTVs and from multiparametric (unioned) GTVs from 2 to 3 scans. Histologic coverage (proportions of tumor area on co-registered histology inside the CTV, measured for Gleason scores [GSs] ≥6 and ≥7) and prostate sparing (proportions of prostate volume outside the CTV) were measured. Nonparametric histologic-coverage prediction intervals defined minimal margins yielding 95% coverage for prospective cases with 78% to 92% likelihood. Results: On analysis of 72 true-positive tumor detections, 95% coverage margins were 9 to 11 mm (GS ≥ 6) and 8 to 10 mm (GS ≥ 7) for single-sequence GTVs and were 8 mm (GS ≥ 6) and 6 mm (GS ≥ 7) for 3-sequence GTVs, yielding CTVs that spared 47% to 81% of prostate tissue for the majority of tumors. Inclusion of T2-weighted contours increased sparing for multiparametric CTVs with 95% coverage margins for GS ≥6, and inclusion of dynamic contrast-enhanced contours increased sparing for GS ≥7. Anisotropic 95% coverage margins increased the sparing proportions to 71% to 86%. Conclusions: Multiparametric magnetic resonance imaging–defined GTVs expanded by appropriate margins may support focal boosting or treatment of PCa; however, these margins, accounting for interobserver and intertumoral variability, may preclude highly conformal CTVs. Multiparametric GTVs and anisotropic margins may reduce the required margins and improve prostate sparing.« less

Overexpression of MpCYS4, a phytocystatin gene from Malus prunifolia (Willd.) Borkh., delays natural and stress-induced leaf senescence in apple.

PubMed

Tan, Yanxiao; Yang, Yingli; Li, Chao; Liang, Bowen; Li, Mingjun; Ma, Fengwang

2017-06-01

Phytocystatins are a well-characterized class of naturally occurring protease inhibitors that prevent the catalysis of papain-like cysteine proteases. The action of cystatins in stress tolerance has been studied intensively, but relatively little is known about their functions in plants during leaf senescence. Here, we examined the potential roles of the apple cystatin, MpCYS4, in leaf photosynthesis as well as the concentrations and composition of leaf proteins when plants encounter natural or stress-induced senescence. Overexpression of this gene in apple rootstock M26 effectively slowed the senescence-related declines in photosynthetic activity and chlorophyll concentrations and prevented the action of cysteine proteinases during the process of degrading proteins (e.g., Rubisco) in senescing leaves. Moreover, MpCYS4 alleviated the associated oxidative damage and enhanced the capacity of plants to eliminate reactive oxygen species by activating antioxidant enzymes such as ascorbate peroxidase, peroxidase, and catalase. Consequently, plant cells were protected against damage from free radicals during leaf senescence. Based on these results, we conclude that MpCYS4 functions in delaying natural and stress-induced senescence of apple leaves. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Rectified tunneling current response of bio-functionalized metal-bridge-metal junctions.

PubMed

Liu, Yaqing; Offenhäusser, Andreas; Mayer, Dirk

2010-01-15

Biomolecular bridged nanostructures allow direct electrical addressing of electroactive biomolecules, which is of interest for the development of bioelectronic and biosensing hybrid junctions. In the present paper, the electroactive biomolecule microperoxidase-11 (MP-11) was integrated into metal-bridge-metal (MBM) junctions assembled from a scanning tunneling microscope (STM) setup. Before immobilization of MP-11, the Au working electrode was first modified by a self-assembled monolayer of 1-undecanethiol (UDT). A symmetric and potential independent response of current-bias voltage (I(t)/V(b)) was observed for the Au (substrate)/UDT/Au (tip) junction. However, the I(t)/V(b) characteristics became potential dependent and asymmetrical after binding of MP-11 between the electrodes of the junction. The rectification ratio of the asymmetric current response varies with gate electrode modulation. A resonant tunneling process between metal electrode and MP-11 enhances the tunneling current and is responsible for the observed rectification. Our investigations demonstrated that functional building blocks of proteins can be reassembled into new conceptual devices with operation modes deviating from their native function, which could prove highly useful in the design of future biosensors and bioelectronic devices. Copyright 2009 Elsevier B.V. All rights reserved.

Conditioning to ethanol in the fruit fly-a study using an inhibitor of ADH.

PubMed

Cadieu, N; Cadieu, J -C.; El Ghadraoui, L; Grimal, A; Lamboeuf, Y

1999-06-01

To identify processes involved in the choice of ethanol by adult Drosophila, flies homozygous Adh(F), reared in the absence of alcohol were placed in contact with: a) an ethanol-free medium, b) a medium containing ethanol, c) a medium supplemented with 4-methylpyrazole (4-MP, an inhibitor of the ADH pathway), d) a medium containing ethanol and 4-MP. The choice of ethanol over a medium without ethanol was evaluated by measuring the duration of extension of the proboscis of the flies in each of the media. A slight preference for the ethanol-supplemented medium was observed in the naive flies, which was enhanced by previous exposure to ethanol. Exposure to ethanol and 4-MP, however, led to an avoidance of ethanol. There was a reduction in ADH activity on treatment of the flies with 4-MP, and signs of malaise (reduced locomotor activity, loss of balance) were observed in the flies who ingested both ethanol and inhibitor. We concluded that the preference for ethanol stems from an associative learning related to ethanol utilization. Inhibition of enzymes of ADH pathway led to a conditioned aversion due to disturbance of ethanol metabolism giving rise to malaise.

Analysis of mobile fronthaul bandwidth and wireless transmission performance in split-PHY processing architecture.

PubMed

Miyamoto, Kenji; Kuwano, Shigeru; Terada, Jun; Otaka, Akihiro

2016-01-25

We analyze the mobile fronthaul (MFH) bandwidth and the wireless transmission performance in the split-PHY processing (SPP) architecture, which redefines the functional split of centralized/cloud RAN (C-RAN) while preserving high wireless coordinated multi-point (CoMP) transmission/reception performance. The SPP architecture splits the base stations (BS) functions between wireless channel coding/decoding and wireless modulation/demodulation, and employs its own CoMP joint transmission and reception schemes. Simulation results show that the SPP architecture reduces the MFH bandwidth by up to 97% from conventional C-RAN while matching the wireless bit error rate (BER) performance of conventional C-RAN in uplink joint reception with only 2-dB signal to noise ratio (SNR) penalty.

Raman mapping and in situ SERS spectroelectrochemical studies of 6-mercaptopurine SAMs on the gold electrode.

PubMed

Yang, Haifeng; Liu, Yanli; Liu, Zhimin; Yang, Yu; Jiang, Jianhui; Zhang, Zongrang; Shen, Guoli; Yu, Ruqin

2005-02-24

The self-assembled monolayers (SAMs) of 6-mercaptopurine (6MP) were formed at the roughened polycrystalline gold surfaces in acid and alkaline media. The time-dependent Raman mapping spectral analysis in conjunction with the quantum calculations for the vibrational modes using ab initio BLYP/6-31G method suggested that both of the resulted 6MP SAMs adopted the same adsorption mode through the S atom of pyrimidine moiety and the N7 atom of the imidazole moiety anchoring the gold surface in a vertical way. The in situ surface-enhanced Raman scattering spectroelectrochemical experiment was conducted to examine the stability of the SAMs at various bias potentials. It was found that the detaching process of the 6MP SAMs from the surface involved one electron reduction as the voltage was applied at ca. 0.7 V vs a standard calomel electrode.

Template-free fabrication of silicon micropillar/nanowire composite structure by one-step etching

PubMed Central

2012-01-01

A template-free fabrication method for silicon nanostructures, such as silicon micropillar (MP)/nanowire (NW) composite structure is presented. Utilizing an improved metal-assisted electroless etching (MAEE) of silicon in KMnO4/AgNO3/HF solution and silicon composite nanostructure of the long MPs erected in the short NWs arrays were generated on the silicon substrate. The morphology evolution of the MP/NW composite nanostructure and the role of self-growing K2SiF6 particles as the templates during the MAEE process were investigated in detail. Meanwhile, a fabrication mechanism based on the etching of silver nanoparticles (catalyzed) and the masking of K2SiF6 particles is proposed, which gives guidance for fabricating different silicon nanostructures, such as NW and MP arrays. This one-step method provides a simple and cost-effective way to fabricate silicon nanostructures. PMID:23043719

Imaging Neural Activity Using Thy1-GCaMP Transgenic mice

PubMed Central

Chen, Qian; Cichon, Joseph; Wang, Wenting; Qiu, Li; Lee, Seok-Jin R.; Campbell, Nolan R.; DeStefino, Nicholas; Goard, Michael J.; Fu, Zhanyan; Yasuda, Ryohei; Looger, Loren L.; Arenkiel, Benjamin R.; Gan, Wen-Biao; Feng, Guoping

2014-01-01

Summary The ability to chronically monitor neuronal activity in the living brain is essential for understanding the organization and function of the nervous system. The genetically encoded green fluorescent protein based calcium sensor GCaMP provides a powerful tool for detecting calcium transients in neuronal somata, processes, and synapses that are triggered by neuronal activities. Here we report the generation and characterization of transgenic mice that express improved GCaMPs in various neuronal subpopulations under the control of the Thy1 promoter. In vitro and in vivo studies show that calcium transients induced by spontaneous and stimulus-evoked neuronal activities can be readily detected at the level of individual cells and synapses in acute brain slices, as well as chronically in awake behaving animals. These GCaMP transgenic mice allow investigation of activity patterns in defined neuronal populations in the living brain, and will greatly facilitate dissecting complex structural and functional relationships of neural networks. PMID:23083733

Prescription Drug Abuse - Multiple Languages

MedlinePlus

... Spanish) PDF The basics - Opioids, part 1 - English MP3 The basics - Opioids, part 1 - español (Spanish) MP3 The basics - Opioids, part 1 - English MP4 The ... español (Spanish) PDF Pain - Opioids, part 2 - English MP3 Pain - Opioids, part 2 - español (Spanish) MP3 Pain - ...

Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system : appendix online 2 : I\\0x2010 205 NB speed flow plots.

DOT National Transportation Integrated Search

2008-12-01

The appendix includes various speed flow plots, including: I-205 NB, Gladstone MP 11.05; I-205 NB, Gladstone Hway MP 12.94; I-205 NB, Lawnfield MP 13.58; I-205 NB, Sunnybrook MP 14.32; I-205 NB, Sunnyside MP 14.7; I-205 NB, Johnson Creek MP 16.2; I-2...

Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system : appendix online 4 : I\\0x2010205 NB flow\\0x2010occupancy plots.

DOT National Transportation Integrated Search

2008-12-01

The appendix includes various flow-occupancy plots, including: I-205 NB, Gladstone MP 11.05; I-205 NB, Gladstone Hway MP 12.94; I-205 NB, Lawnfield MP 13.58; I-205 NB, Sunnybrook MP 14.32; I-205 NB, Sunnyside MP 14.7; I-205 NB, Johnson Creek MP 16.2;...

Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system : appendix online 3 : I\\0x2010205 NB speed\\0x2010occupancy plots.

DOT National Transportation Integrated Search

2008-12-01

The appendix includes various speed-occupancy plots, including: I-205 NB, Gladstone MP 11.05; I-205 NB, Gladstone Hway MP 12.94; I-205 NB, Lawnfield MP 13.58; I-205 NB, Sunnybrook MP 14.32; I-205 NB, Sunnyside MP 14.7; I-205 NB, Johnson Creek MP 16.2...

Pilot-scale UV/H2O2 advanced oxidation process for municipal reuse water: Assessing micropollutant degradation and estrogenic impacts on goldfish (Carassius auratus L.).

PubMed

Shu, Zengquan; Singh, Arvinder; Klamerth, Nikolaus; McPhedran, Kerry; Bolton, James R; Belosevic, Miodrag; Gamal El-Din, Mohamed

2016-09-15

Low concentrations (ng/L-μg/L) of emerging micropollutant contaminants in municipal wastewater treatment plant effluents affect the possibility to reuse these waters. Many of those micropollutants elicit endocrine disrupting effects in aquatic organisms resulting in an alteration of the endocrine system. A potential candidate for tertiary municipal wastewater treatment of these micropollutants is ultraviolet (UV)/hydrogen peroxide (H2O2) as an advanced oxidation process (AOP) which was currently applied to treat the secondary effluent of the Gold Bar Wastewater Treatment Plant (GBWWTP) in Edmonton, AB, Canada. A new approach is presented to predict the fluence-based degradation rate constants (kf') of environmentally occurring micropollutants including carbamazepine [(0.87-1.39) × 10(-3) cm(2)/mJ] and 2,4-Dichlorophenoxyacetic acid (2,4-D) [(0.60-0.91) × 10(-3) cm(2)/mJ for 2,4-D] in a medium pressure (MP) UV/H2O2 system based on a previous bench-scale investigation. Rather than using removal rates, this approach can be used to estimate the performance of the MP UV/H2O2 process for degrading trace contaminants of concern found in municipal wastewater. In addition to the ability to track contaminant removal/degradation, evaluation of the MP UV/H2O2 process was also accomplished by identifying critical ecotoxicological endpoints (i.e., estrogenicity) of the treated wastewater. Using quantitative PCR, mRNA levels of estrogen-responsive (ER) genes ERα1, ERα2, ERβ1, ERβ2 and NPR as well as two aromatase encoding genes (CYP19a and CYP19b) in goldfish (Carassius auratus L.) were measured during exposure to the GBWWTP effluent before and after MP UV/H2O2 treatment (a fluence of 1000 mJ/cm(2) and 20 mg/L of H2O2) in spring, summer and fall. Elevated expression of estrogen-responsive genes in goldfish exposed to UV/H2O2 treated effluent (a 7-day exposure) suggested that the UV/H2O2 process may induce acute estrogenic disruption to goldfish principally because of the possible formation of various oxidation by-products. However, prolonged exposure of goldfish (60 days) in UV/H2O2 treated effluent showed a restoration trend of ER gene expressions, especially in the summer. Collectively, our findings provide valuable indications regarding the long-term in vivo assessment of the MP UV/H2O2 process for removing/degrading endocrine disrupting compounds detected in the municipal wastewater effluents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploring EUV and SAQP pattering schemes at 5nm technology node

NASA Astrophysics Data System (ADS)

Hamed Fatehy, Ahmed; Kotb, Rehab; Lafferty, Neal; Jiang, Fan; Word, James

2018-03-01

For years, Moore's law keeps driving the semiconductors industry towards smaller dimensions and higher density chips with more devices. Earlier, the correlation between exposure source's wave length and the smallest resolvable dimension, mandated the usage of Deep Ultra-Violent (DUV) optical lithography system which has been used for decades to sustain Moore's law, especially when immersion lithography was introduced with 193nm ArF laser sources. As dimensions of devices get smaller beyond Deep Ultra-Violent (DUV) optical resolution limits, the need for Extremely Ultra-Violent (EUV) optical lithography systems was a must. However, EUV systems were still under development at that time for the mass-production in semiconductors industry. Theretofore, Multi-Patterning (MP) technologies was introduced to swirl about DUV optical lithography limitations in advanced nodes beyond minimum dimension (CD) of 20nm. MP can be classified into two main categories; the first one is to split the target itself across multiple masks that give the original target patterns when they are printed. This category includes Double, Triple and Quadruple patterning (DP, TP, and QP). The second category is the Self-Aligned Patterning (SAP) where the target is divided into Mandrel patterns and non-Mandrel patterns. The Mandrel patterns get printed first, then a self-aligned sidewalls are grown around these printed patterns drawing the other non-Mandrel targets, afterword, a cut mask(s) is used to define target's line-ends. This approach contains Self-Aligned-Double Pattering (SADP) and Self-Aligned- Quadruple-Pattering (SAQP). DUV and MP along together paved the way for the industry down to 7nm. However, with the start of development at the 5nm node and the readiness of EUV, the differentiation question is aroused again, which pattering approach should be selected, direct printing using EUV or DUV with MP, or a hybrid flow that contains both DUV-MP and EUV. In this work we are comparing two potential pattering techniques for Back End Of Line (BEOL) metal layers in the 5nm technology node, the first technique is Single Exposure EUV (SE-EUV) with a Direct Patterning EUV lithography process, and the second one is Self-Aligned Quadruple Patterning (SAQP) with a hybrid lithography processes, where the drawn metal target layer is decomposed into a Mandrel mask and Blocks/Cut mask, Mandrel mask is printed using DUV 193i lithography process, while Block/Cut Mask is printed using SE-EUV lithography process. The pros and cons of each technique are quantified based on Edge-Placement-Error (EPE) and Process Variation Band (PVBand) measured at 1D and 2D edges. The layout used in this comparison is a candidate layout for Foundries 5nm process node.

Magnetic resonance imaging in prostate cancer detection and management: a systematic review.

PubMed

Monni, Fabio; Fontanella, Paolo; Grasso, Angelica; Wiklund, Peter; Ou, Yen-Chuan; Randazzo, Marco; Rocco, Bernardo; Montanari, Emanuele; Bianchi, Giampaolo

2017-12-01

The aim of our work was to evaluate the role of multi-parametric magnetic resonance imaging (mpMRI) in detection and management of prostate cancer (PC); specifically investigating the efficacy of mpMRI-based biopsy techniques in terms of diagnostic yield of significant prostate neoplasm and the improved management of patients who choose conservative treatments or active surveillance. A systematic and critical analysis through Medline, Embase, Scopus and Web of Science databases was carried out in March 2016, following the PRISMA ("Preferred Reporting Items for Systematic Reviews and Meta-Analyses") statement. The search was conducted using the following key words: "MRI/TRUS-fusion biopsy," "PIRADS," "prostate cancer," "magnetic resonance imaging (MRI)," "multiparametric MRI (mpMRI)," "systematic prostate biopsy (SB)," "targeted prostate biopsy (TPB)." English language articles were reviewed for inclusion ability. Sixty-six studies were selected in order to evaluate the characteristics and limitations of traditional sample biopsy, the role of mpMRI in detection of PC, specifically the increased degree of diagnostic accuracy of targeted prostate biopsy compared to systematic biopsy (12 cores), and to transperineal saturation biopsies with trans-rectal ultrasound (TRUS) only. MpMRI can detect index lesions in approximately 90% of cases when compared to prostatectomy specimen. The diagnostic performance of biparametric MRI (T2w + DWI) is not inferior to mpMRI, offering valid options to diminish cost- and time-consumption. Since approximately 10% of significant lesions are still MRI-invisible, systematic cores biopsy seem to still be necessary. The analysis of the different techniques shows that in-bore MRI-guided biopsy and MRI/TRUS-fusion-guided biopsy are superior in detection of significant PC compared to visual estimation alone. MpMRI proved to be very effective in active surveillance, as it prevents underdetection of significant PC and it assesses low-risk disease accurately. In higher-risk disease, presurgical MRI may change the clinically-based surgical plan in up to a third of cases. Targeted prostate biopsy, guided by mpMRI, is able to improve diagnostic accuracy and to reduce the detection of insignificant PC. Since the negative predictive value (NPV) of mpMRI is still imperfect, systematic cores biopsy should not be omitted for optimal staging of disease. A process of a progressive and periodic evolution in the detection and radiological classification of prostate lesions (such as PIRADS), is still needed in patients in active surveillance and in radical prostatectomy planning.

Dynamic population mapping using mobile phone data.

PubMed

Deville, Pierre; Linard, Catherine; Martin, Samuel; Gilbert, Marius; Stevens, Forrest R; Gaughan, Andrea E; Blondel, Vincent D; Tatem, Andrew J

2014-11-11

During the past few decades, technologies such as remote sensing, geographical information systems, and global positioning systems have transformed the way the distribution of human population is studied and modeled in space and time. However, the mapping of populations remains constrained by the logistics of censuses and surveys. Consequently, spatially detailed changes across scales of days, weeks, or months, or even year to year, are difficult to assess and limit the application of human population maps in situations in which timely information is required, such as disasters, conflicts, or epidemics. Mobile phones (MPs) now have an extremely high penetration rate across the globe, and analyzing the spatiotemporal distribution of MP calls geolocated to the tower level may overcome many limitations of census-based approaches, provided that the use of MP data is properly assessed and calibrated. Using datasets of more than 1 billion MP call records from Portugal and France, we show how spatially and temporarily explicit estimations of population densities can be produced at national scales, and how these estimates compare with outputs produced using alternative human population mapping methods. We also demonstrate how maps of human population changes can be produced over multiple timescales while preserving the anonymity of MP users. With similar data being collected every day by MP network providers across the world, the prospect of being able to map contemporary and changing human population distributions over relatively short intervals exists, paving the way for new applications and a near real-time understanding of patterns and processes in human geography.

Dynamic population mapping using mobile phone data

PubMed Central

Deville, Pierre; Martin, Samuel; Gilbert, Marius; Stevens, Forrest R.; Gaughan, Andrea E.; Blondel, Vincent D.; Tatem, Andrew J.

2014-01-01

During the past few decades, technologies such as remote sensing, geographical information systems, and global positioning systems have transformed the way the distribution of human population is studied and modeled in space and time. However, the mapping of populations remains constrained by the logistics of censuses and surveys. Consequently, spatially detailed changes across scales of days, weeks, or months, or even year to year, are difficult to assess and limit the application of human population maps in situations in which timely information is required, such as disasters, conflicts, or epidemics. Mobile phones (MPs) now have an extremely high penetration rate across the globe, and analyzing the spatiotemporal distribution of MP calls geolocated to the tower level may overcome many limitations of census-based approaches, provided that the use of MP data is properly assessed and calibrated. Using datasets of more than 1 billion MP call records from Portugal and France, we show how spatially and temporarily explicit estimations of population densities can be produced at national scales, and how these estimates compare with outputs produced using alternative human population mapping methods. We also demonstrate how maps of human population changes can be produced over multiple timescales while preserving the anonymity of MP users. With similar data being collected every day by MP network providers across the world, the prospect of being able to map contemporary and changing human population distributions over relatively short intervals exists, paving the way for new applications and a near real-time understanding of patterns and processes in human geography. PMID:25349388

Neuronal mechanisms of motor learning and motor memory consolidation in healthy old adults.

PubMed

Berghuis, K M M; Veldman, M P; Solnik, S; Koch, G; Zijdewind, I; Hortobágyi, T

2015-06-01

It is controversial whether or not old adults are capable of learning new motor skills and consolidate the performance gains into motor memory in the offline period. The underlying neuronal mechanisms are equally unclear. We determined the magnitude of motor learning and motor memory consolidation in healthy old adults and examined if specific metrics of neuronal excitability measured by magnetic brain stimulation mediate the practice and retention effects. Eleven healthy old adults practiced a wrist extension-flexion visuomotor skill for 20 min (MP, 71.3 years), while a second group only watched the templates without movements (attentional control, AC, n = 11, 70.5 years). There was 40 % motor learning in MP but none in AC (interaction, p < 0.001) with the skill retained 24 h later in MP and a 16 % improvement in AC. Corticospinal excitability at rest and during task did not change, but when measured during contraction at 20 % of maximal force, it strongly increased in MP and decreased in AC (interaction, p = 0.002). Intracortical inhibition at rest and during the task decreased and facilitation at rest increased in MP, but these metrics changed in the opposite direction in AC. These neuronal changes were especially profound at retention. Healthy old adults can learn a new motor skill and consolidate the learned skill into motor memory, processes that are most likely mediated by disinhibitory mechanisms. These results are relevant for the increasing number of old adults who need to learn and relearn movements during motor rehabilitation.

Denervation affects regenerative responses in MRL/MpJ and repair in C57BL/6 ear wounds

PubMed Central

Buckley, Gemma; Wong, Jason; Metcalfe, Anthony D; Ferguson, Mark W J

2012-01-01

The MRL/MpJ mouse displays the rare ability amongst mammals to heal injured ear tissue without scarring. Numerous studies have shown that the formation of a blastema-like structure leads to subsequent tissue regeneration in this model, indicating many parallels with amphibian limb regeneration and mammalian embryogenesis. We have recently shown that the MRL/MpJ mouse also possesses an enhanced capacity for peripheral nerve regeneration within the ear wound. Indeed, nerves are vital for the initial phase of blastema formation in the amphibian limb. In this study we investigated the capacity for wound regeneration in a denervated ear. The left ears of MRL/MpJ mice and C57BL/6 (a control strain known to have a poorer regenerative capacity) were surgically denervated at the base via an incision and nerve transection, immediately followed by a 2-mm ear punch wound. Immunohistochemical analysis showed a lack of neurofilament expression in the denervated ear wound. Histology revealed that denervation prevented blastema formation and chrondrogenesis, and also severely hindered normal healing, with disrupted re-epithelialisation, increasing wound size and progressive necrosis towards the ear tip. Denervation of the ear obliterated the regenerative capacity of the MRL/MpJ mouse, and also had a severe negative effect on the ear wound repair mechanisms of the C57BL/6 strain. These data suggest that innervation may be important not only for regeneration but also for normal wound repair processes. PMID:22066944

Sex Differences in the Physiological and Behavioral Effects of Chronic Oral Methylphenidate Treatment in Rats

PubMed Central

Robison, Lisa S.; Michaelos, Michalis; Gandhi, Jason; Fricke, Dennis; Miao, Erick; Lam, Chiu-Yim; Mauceri, Anthony; Vitale, Melissa; Lee, Junho; Paeng, Soyeh; Komatsu, David E.; Hadjiargyrou, Michael; Thanos, Panayotis K.

2017-01-01

Methylphenidate (MP) is a psychostimulant prescribed for Attention Deficit Hyperactivity Disorder. Previously, we developed a dual bottle 8-h-limited-access-drinking-paradigm for oral MP treatment of rats that mimics the pharmacokinetic profile of treated patients. This study assessed sex differences in response to this treatment. Male and female Sprague Dawley rats were assigned to one of three treatment groups at 4 weeks of age (n = 12/group): Control (water), low dose (LD) MP, and high dose (HD) MP. Rats drank 4 mg/kg MP (LD) or 30 mg/kg MP (HD) during the first hour, and 10 mg/kg (LD) or 60 mg/kg MP (HD) for the remaining 7 h each day. Throughout 3 months of treatment, rats were monitored for body weight, food intake, and fluid intake; as well as tested for open field behavior, circadian activity, novel object recognition, and social interaction. Chronic MP treated rats exhibited reduced fluid intake during distinct treatment weeks to a greater extent in males, and reduced total fluid intake in males only. HD MP treatment decreased body weight in both sexes, while HD MP increased total food intake in females only, likely to offset energy deficits resulting from MP-induced hyperactivity. LD and HD MP increased locomotor activity in the open field, particularly in females and during later treatment weeks. MP dose-dependently increased activity during the dark cycle of circadian testing in females, while in males hyperactivity was only exhibited by HD rats. HD MP increased center activity to a greater extent in males, while MP increased rearing behavior in females only. MP had no effect on social behavior or novel object recognition in either sex. This study concludes that chronic oral MP treatment at clinically-relevant dosages has significant effects on food intake, body weight, open field behavior, and wake cycle activity. Particularly marked sex differences were apparent for locomotor activity, with females being significantly more sensitive to the hyperactivating effects of the drug. These findings suggest that chronic MP exposure beginning in adolescence can have significant behavioral effects that are both dose- and sex-dependent, and raise concerns regarding the reversibility of these effects post-discontinuation of treatment. PMID:28400722

Distinct Subtypes of Microparticle-containing Immune Complexes Are Associated with Disease Activity, Damage, and Carotid Intima-media Thickness in Systemic Lupus Erythematosus.

PubMed

Fortin, Paul R; Cloutier, Nathalie; Bissonnette, Vincent; Aghdassi, Ellie; Eder, Lihi; Simonyan, David; Laflamme, Nathalie; Boilard, Eric

2016-11-01

Microparticles (MP) are small extracellular vesicles present in body fluids. MP originate from different cellular lineages, principally from platelets in blood, and may expose phosphatidylserine (PS). In systemic lupus erythematosus (SLE), MP harbor immunoglobulin G (IgG), thereby forming MP-containing immune complexes (mpIC). We aimed to verify an association between SLE disease activity, damage, and surrogate markers of atherosclerosis and MP harboring IgG, taking into account the platelet origin and PS exposure of MP. MP expressing surface IgG, platelet antigen (CD41+), and PS were quantified using flow cytometry in plasma of 191 women with SLE. Carotid ultrasounds (US) were available in 113 patients. Spearman correlation analysis was used to analyze whether levels of MP were associated with the following outcomes: SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and carotid US plaques and intima-media thickness (CIMT) as surrogates for vascular damage. We found CD41+ MP harboring IgG present in SLE. A positive correlation was found between SLEDAI-2K and levels of CD41+ MP harboring IgG and exposing (p = 0.027) and non-exposing PS (p = 0.001). Conversely, SDI (p = 0.024) and CIMT (p = 0.016) correlated with concentrations of CD41- MP harboring IgG and exposing PS. Associations were independent of low-density lipoprotein cholesterol level, body mass index, and antimalarial drug use. Different subtypes of mpIC are produced in SLE and are associated with distinct clinical characteristics such as disease activity and vascular damage. The assessment of MP subtypes might serve for the design of predictive markers of disease activity and vascular damage in patients.

Sequence variations in RepMP2/3 and RepMP4 elements reveal intragenomic homologous DNA recombination events in Mycoplasma pneumoniae.

PubMed

Spuesens, Emiel B M; Oduber, Minoushka; Hoogenboezem, Theo; Sluijter, Marcel; Hartwig, Nico G; van Rossum, Annemarie M C; Vink, Cornelis

2009-07-01

The gene encoding major adhesin protein P1 of Mycoplasma pneumoniae, MPN141, contains two DNA sequence stretches, designated RepMP2/3 and RepMP4, which display variation among strains. This variation allows strains to be differentiated into two major P1 genotypes (1 and 2) and several variants. Interestingly, multiple versions of the RepMP2/3 and RepMP4 elements exist at other sites within the bacterial genome. Because these versions are closely related in sequence, but not identical, it has been hypothesized that they have the capacity to recombine with their counterparts within MPN141, and thereby serve as a source of sequence variation of the P1 protein. In order to determine the variation within the RepMP2/3 and RepMP4 elements, both within the bacterial genome and among strains, we analysed the DNA sequences of all RepMP2/3 and RepMP4 elements within the genomes of 23 M. pneumoniae strains. Our data demonstrate that: (i) recombination is likely to have occurred between two RepMP2/3 elements in four of the strains, and (ii) all previously described P1 genotypes can be explained by inter-RepMP recombination events. Moreover, the difference between the two major P1 genotypes was reflected in all RepMP elements, such that subtype 1 and 2 strains can be differentiated on the basis of sequence variation in each RepMP element. This implies that subtype 1 and subtype 2 strains represent evolutionarily diverged strain lineages. Finally, a classification scheme is proposed in which the P1 genotype of M. pneumoniae isolates can be described in a sequence-based, universal fashion.

Modifying mesoporous silica nanoparticles to avoid the metabolic deactivation of 6-mercaptopurine and methotrexate in combinatorial chemotherapy.

PubMed

Wang, Wenjing; Fang, Chenjie; Wang, Xiaozhu; Chen, Yuxi; Wang, Yaonan; Feng, Wei; Yan, Chunhua; Zhao, Ming; Peng, Shiqi

2013-07-21

Mesoporous silica nanoparticles with amino and thiol groups (MSNSN) were prepared and covalently modified with methotrexate and 6-mercaptopurine to form 6-MP-MSNSN-MTX. In the presence of DTT, 6-MP-MSNSN-MTX gradually releases 6-MP. In rat plasma, 6-MP-MSNSN-MTX effectively inhibits the metabolic deactivation of 6-MP and MTX. 6-MP-MSNSN-MTX could be an agent for long-acting chemotherapy.

A ROSE-based OpenMP 3.0 Research Compiler Supporting Multiple Runtime Libraries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, C; Quinlan, D; Panas, T

2010-01-25

OpenMP is a popular and evolving programming model for shared-memory platforms. It relies on compilers for optimal performance and to target modern hardware architectures. A variety of extensible and robust research compilers are key to OpenMP's sustainable success in the future. In this paper, we present our efforts to build an OpenMP 3.0 research compiler for C, C++, and Fortran; using the ROSE source-to-source compiler framework. Our goal is to support OpenMP research for ourselves and others. We have extended ROSE's internal representation to handle all of the OpenMP 3.0 constructs and facilitate their manipulation. Since OpenMP research is oftenmore » complicated by the tight coupling of the compiler translations and the runtime system, we present a set of rules to define a common OpenMP runtime library (XOMP) on top of multiple runtime libraries. These rules additionally define how to build a set of translations targeting XOMP. Our work demonstrates how to reuse OpenMP translations across different runtime libraries. This work simplifies OpenMP research by decoupling the problematic dependence between the compiler translations and the runtime libraries. We present an evaluation of our work by demonstrating an analysis tool for OpenMP correctness. We also show how XOMP can be defined using both GOMP and Omni and present comparative performance results against other OpenMP compilers.« less

Synthesis of nitrosobenzene via photocatalytic oxidation of aniline over MgO/TiO2 under visible light irradiation

NASA Astrophysics Data System (ADS)

Chen, Jinsong; Xiong, Jinhua; Song, Yujie; Yu, Yan; Wu, Ling

2018-05-01

MgO/TiO2 (Degussa P25 TiO2) composites were prepared and were used as visible-light-driven photocatalysts for the oxidation of aniline to nitrosobenzene under oxygen atmosphere. The typical sample with 5 wt% MgO loaded P25 (MP5) shows comparable photocatalytic activity with 2 wt% Pt/P25. The analyzed results of XPS indicate that the lattice oxygen in the MP5 possess higher electron density than those in P25. The electron-rich lattice oxygen, formed as a result of MgO loaded, would facilitate the deprontonation of aniline. A new peak at 3310 cm-1 was observed in in-situ FTIR spectrum for aniline adsorbed on the sample MP5, suggesting that anilino species were formed. These species may be produced via the deprontonation of aniline and result in the formation of the surface complexes. Further XPS studies for aniline adsorbed on the catalysts also indicate the existence of the surface complexes. Under visible light irradiation, the electrons may excite from the surface complexes and initiate the oxidation processes. Finally, speculated photocatalytic processes for the oxidation of aniline to nitrosobenzene were proposed at molecular level.

Computer-Aided Parallelizer and Optimizer

NASA Technical Reports Server (NTRS)

Jin, Haoqiang

2011-01-01

The Computer-Aided Parallelizer and Optimizer (CAPO) automates the insertion of compiler directives (see figure) to facilitate parallel processing on Shared Memory Parallel (SMP) machines. While CAPO currently is integrated seamlessly into CAPTools (developed at the University of Greenwich, now marketed as ParaWise), CAPO was independently developed at Ames Research Center as one of the components for the Legacy Code Modernization (LCM) project. The current version takes serial FORTRAN programs, performs interprocedural data dependence analysis, and generates OpenMP directives. Due to the widely supported OpenMP standard, the generated OpenMP codes have the potential to run on a wide range of SMP machines. CAPO relies on accurate interprocedural data dependence information currently provided by CAPTools. Compiler directives are generated through identification of parallel loops in the outermost level, construction of parallel regions around parallel loops and optimization of parallel regions, and insertion of directives with automatic identification of private, reduction, induction, and shared variables. Attempts also have been made to identify potential pipeline parallelism (implemented with point-to-point synchronization). Although directives are generated automatically, user interaction with the tool is still important for producing good parallel codes. A comprehensive graphical user interface is included for users to interact with the parallelization process.

Misc Tandem Pix

Science.gov Websites

looking east.jpg 183 KB UNIS Ion Source 111 KB MP-7 Low Energy.jpg 138 KB MP-7 Object West.jpg 117 KB MP-7 Object Middle.jpg 120 KB MP-7 Object East.jpg 142 KB MP-7 Image.jpg 151 KB SEU area in TR-4 looking

Mechanical properties and biocompatibility of melt processed, self-reinforced ultrahigh molecular weight polyethylene.

PubMed

Huang, Yan-Fei; Xu, Jia-Zhuang; Li, Jian-Shu; He, Ben-Xiang; Xu, Ling; Li, Zhong-Ming

2014-08-01

The low efficiency of fabrication of ultrahigh molecular weight polyethylene (UHMWPE)-based artificial knee joint implants is a bottleneck problem because of its extremely high melt viscosity. We prepared melt processable UHMWPE (MP-UHMWPE) by addition of 9.8 wt% ultralow molecular weight polyethylene (ULMWPE) as a flow accelerator. More importantly, an intense shear flow was applied during injection molding of MP-UHMWPE, which on one hand, promoted the self-diffusion of UHMWPE chains, thus effectively reducing the structural defects; on the other hand, increased the overall crystallinity and induced the formation of self-reinforcing superstructure, i.e., interlocked shish-kebabs and oriented lamellae. Aside from the good biocompatibility, and the superior fatigue and wear resistance to the compression-molded UHMWPE, the injection-molded MP-UHMWPE exhibits a noteworthy enhancement in tensile properties and impact strength, where the yield strength increases to 46.3 ± 4.4 MPa with an increment of 128.0%, the ultimate tensile strength and Young's modulus rise remarkably up to 65.5 ± 5.0 MPa and 1248.7 ± 45.3 MPa, respectively, and the impact strength reaches 90.6 kJ/m(2). These results suggested such melt processed and self-reinforced UHMWPE parts hold a great application promise for use of knee joint implants, particularly for younger and more active patients. Our work sets up a new method to fabricate high-performance UHMWPE implants by tailoring the superstructure during thermoplastic processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Methylphenidate and the response to growth hormone treatment in short children born small for gestational age.

PubMed

Renes, Judith S; de Ridder, Maria A J; Breukhoven, Petra E; Lem, Annemieke J; Hokken-Koelega, Anita C S

2012-01-01

Growth hormone (GH) treatment has become a frequently applied growth promoting therapy in short children born small for gestational age (SGA). Children born SGA have a higher risk of developing attention deficit hyperactivity disorder (ADHD). Treatment of ADHD with methylphenidate (MP) has greatly increased in recent years, therefore more children are being treated with GH and MP simultaneously. Some studies have found an association between MP treatment and growth deceleration, but data are contradictory. To explore the effects of MP treatment on growth in GH-treated short SGA children Anthropometric measurements were performed in 78 GH-treated short SGA children (mean age 10.6 yr), 39 of whom were also treated with MP (SGA-GH/MP). The SGA-GH/MP group was compared to 39 SGA-GH treated subjects. They were matched for sex, age and height at start of GH, height SDS at start of MP treatment and target height SDS. Serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels were yearly determined. Growth, serum IGF-I and IGFBP-3 levels during the first three years of treatment were analyzed using repeated measures regression analysis. The SGA-GH/MP group had a lower height gain during the first 3 years than the SGA-GH subjects, only significant between 6 and 12 months of MP treatment. After 3 years of MP treatment, the height gain was 0.2 SDS (± 0.1 SD) lower in the SGA-GH/MP group (P = 0.17). Adult height was not significantly different between the SGA-GH/MP and SGA-GH group (-1.9 SDS and -1.9 SDS respectively, P = 0.46). Moreover, during the first 3 years of MP treatment IGF-I and IGFBP-3 measurements were similar in both groups. MP has some negative effect on growth during the first years in short SGA children treated with GH, but adult height is not affected.

High glucose increases the formation and pro-oxidative activity of endothelial microparticles.

PubMed

Burger, Dylan; Turner, Maddison; Xiao, Fengxia; Munkonda, Mercedes N; Akbari, Shareef; Burns, Kevin D

2017-09-01

Individuals with diabetes exhibit increases in circulating endothelial microparticles (eMPs, also referred to as endothelial microvesicles), which are associated with endothelial dysfunction and a heightened risk of cardiovascular complications. We have shown that eMPs are markers and mediators of vascular injury although their role in diabetes is unclear. We hypothesised that the composition and biological activity of eMPs are altered in response to high glucose exposure. We assessed the effects of high glucose on eMP formation, composition and signalling in cultured HUVECs. eMPs were isolated from the media of HUVECs cultured under conditions of normal glucose (eMP NG ), high glucose (eMP HG ) or osmotic control of L-glucose (eMP LG ). eMP size, concentration and surface charge were assessed by nanoparticle tracking analysis and flow cytometry. eMP protein composition was assessed by liquid chromatography-tandem mass spectrometry, and eMP-mediated effects on coagulation, reactive oxygen species (ROS) production and vessel function were assessed. Exposure of HUVECs to high glucose for 24 h caused a threefold increase in eMP formation, increased mean particle size (269 ± 18 nm vs 226 ± 11 nm) and decreased surface charge. Compared with eMP NG or eMP LG , eMP HG possessed approximately threefold greater pro-coagulant activity, stimulated HUVEC ROS production to a greater extent (~250% of eMP NG ) and were more potent inhibitors of endothelial-dependent relaxation. Proteomic analysis of eMPs identified 1212 independent proteins of which 68 were exclusively found in eMP HG . Gene ontology analysis revealed that eMP HG -exclusive proteins were associated with signalling pathways related to blood coagulation, cell signalling and immune cell activation. Our results indicate that elevated glucose is a potent stimulus for eMP formation that also alters their molecular composition leading to increased bioactivity. Such effects may contribute to progressive endothelial injury and subsequent cardiovascular complications in diabetes.

6-Mercaptopurine transport by equilibrative nucleoside transporters in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBTs.

PubMed

Lee, Na-young; Sai, Yoshimichi; Nakashima, Emi; Ohtsuki, Sumio; Kang, Young-sook

2011-09-01

Recently, more women were provided with 6-mercaptopurine (6-MP) during pregnancy. Therefore, we attempted to clarify the transport mechanisms of 6-MP through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of 6-MP was time- and ATP dependent, but sodium independent in TR-TBTs. 6-MP was eliminated over 50% from the cells within 30 min. The uptake of 6-MP was saturable with Michaelis-Menten constant values of 198 μM and 250 μM in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. 6-Thioguanine, azathioprine, and hypoxantine, structural analogues of 6-MP, strongly inhibited [(14) C]6-MP uptake. Equilibrative nucleoside transporter (ENT) inhibitors, adenosine and uridine, significantly inhibited [(14) C]6-MP uptake. However, several organic anions and cations had no effect on [(14) C]6-MP uptake in TR-TBTs. These results suggest that sodium-independent transporters, ENTs, may be involved in 6-MP uptake at the placenta. In addition, multidrug resistance protein (MRP) inhibitors, methotrexate, probenecid, cefmetazole, and sulfinpyrazone, significantly increased the accumulation of [(14) C]6-MP in the cells. It is indicated that 6-MP may be eliminated across the blood-placental barrier via MRPs. TR-TBTs expressed mRNA of ENT1, ENT2, MRP4, and MRP5. These findings are important for the therapy of acute lymphoblastic leukemia and autoimmune diseases of pregnant women, and should be useful data in elucidating teratogenicity of 6-MP during pregnancy. Copyright © 2011 Wiley-Liss, Inc.

Mental practice for upper limb rehabilitation after stroke: a systematic review and meta-analysis.

PubMed

Park, Si-Woon; Kim, Jae-Hyung; Yang, Yun-Jung

2018-06-14

Mental practice (MP) is usually provided in combination with other therapies, and new developments for neurofeedback to support MP have been made recently. The objectives of this study were to evaluate the effectiveness of MP and to investigate the intervention characteristics including neurofeedback that may affect treatment outcome. The Cochrane Central Register of Controlled Trials, PubMed, Embase, KoreaMed, Scopus, Web of Science, PEDro, and CIRRIE were searched from inception to March 2017 for randomized controlled trials to assess the effect of MP for upper limb rehabilitation after stroke. Fugl-Meyer Assessment (FMA) was used as the outcome measure for meta-analysis. Twenty-five trials met the inclusion criteria, and 15 trials were eligible for meta-analysis. Among the trials selected for meta-analysis, MP was added to conventional therapy in eight trials or to modified constraint-induced movement therapy in one trial. The other trials provided neurofeedback to support MP: MP-guided neuromuscular electrical stimulation (NMES) in four trials and MP-guided robot-assisted therapy (RAT) in two trials. MP added to conventional therapy resulted in significantly higher FMA gain than conventional therapy alone. MP-guided NMES showed superior result than conventional NMES as well. However, the FMA gain of MP-guided RAT was not significantly higher than RAT alone. We suggest that MP is an effective complementary therapy either given with neurofeedback or not. Neurofeedback applied to MP showed different results depending on the therapy provided. This study has limitations because of heterogeneity and inadequate quality of trials. Further research is requested.

Mental practice with interactive 3D visual aids enhances surgical performance.

PubMed

Yiasemidou, Marina; Glassman, Daniel; Mushtaq, Faisal; Athanasiou, Christos; Williams, Mark-Mon; Jayne, David; Miskovic, Danilo

2017-10-01

Evidence suggests that Mental Practice (MP) could be used to finesse surgical skills. However, MP is cognitively demanding and may be dependent on the ability of individuals to produce mental images. In this study, we hypothesised that the provision of interactive 3D visual aids during MP could facilitate surgical skill performance. 20 surgical trainees were case-matched to one of three different preparation methods prior to performing a simulated Laparoscopic Cholecystectomy (LC). Two intervention groups underwent a 25-minute MP session; one with interactive 3D visual aids depicting the relevant surgical anatomy (3D-MP group, n = 5) and one without (MP-Only, n = 5). A control group (n = 10) watched a didactic video of a real LC. Scores relating to technical performance and safety were recorded by a surgical simulator. The Control group took longer to complete the procedure relative to the 3D&MP condition (p = .002). The number of movements was also statistically different across groups (p = .001), with the 3D&MP group making fewer movements relative to controls (p = .001). Likewise, the control group moved further in comparison to the 3D&MP condition and the MP-Only condition (p = .004). No reliable differences were observed for safety metrics. These data provide evidence for the potential value of MP in improving performance. Furthermore, they suggest that 3D interactive visual aids during MP could potentially enhance performance, beyond the benefits of MP alone. These findings pave the way for future RCTs on surgical preparation and performance.

The investigation of the binding of 6-mercaptopurine to site I on human serum albumin.

PubMed

Sochacka, Jolanta; Baran, Wojciech

2012-12-01

6-Mercaptopurine (6-MP) is one of a large series of purine analogues which has been found active against human leukemias. The equilibrium dialysis, circular dichroism (CD) and molecular docking were employed to study the binding of 6-MP to human serum albumin (HSA). The binding of 6-MP to HSA in the equilibrium dialysis experiment was detected by measuring the displacement of 6-MP by specific markers for site I on HSA, warfarin (RWF), phenylbutazone (PhB) and n-butyl p-aminobenzoate (ABE). It was shown, according to CD data, that binding of 6-MP to HSA leads to alteration of HSA secondary structure. Based on the findings from displacement experiment and molecular docking simulation it was found that 6-MP was located within binding cavity of subdomain IIA and the space occupied by site markers overlapped with that of 6-MP. Displacement of 6-MP by the RWF or PhB was not up the level expected for a competitive mechanism, therefore displacement of 6-MP was rather by non-cooperative than that the direct competition. Instead, in case of the interaction between ABE and 6-MP, when the little enhancement of the binding of ABE by 6-MP was found, the interaction could be via a positively cooperative mechanism.

Nature and position of functional group on thiopurine substrates influence activity of xanthine oxidase--enzymatic reaction pathways of 6-mercaptopurine and 2-mercaptopurine are different.

PubMed

Tamta, Hemlata; Kalra, Sukirti; Thilagavathi, Ramasamy; Chakraborti, Asit K; Mukhopadhyay, Anup K

2007-02-01

Xanthine oxidase-catalyzed hydroxylation reactions of the anticancer drug 6-mercaptopurine (6-MP) and its analog 2-mercaptopurine (2-MP) as well as 6-thioxanthine (6-TX) and 2-thioxanthine (2-TX) have been studied using UV-spectroscopy, high pressure liquid chromatography, photodiode array, and liquid chromatography-based mass spectral analysis. It is shown that 6-MP and 2-MP are oxidatively hydroxylated through different pathways. Enzymatic hydroxylation of 6-MP forms 6-thiouric acid in two steps involving 6-TX as the intermediate, whereas 2-MP is converted to 8-hydroxy-2-mercaptopurine as the expected end product in one step. Surprisingly, in contrast to the other thiopurines, enzymatic hydroxylation of 2-MP showed a unique hyperchromic effect at 264 nm as the reaction proceeded. However, when 2-TX is used as the substrate, it is hydroxylated to 2-thiouric acid. The enzymatic hydroxylation of 2-MP is considerably faster than that of 6-MP, while 6-TX and 2-TX show similar rates under identical reaction conditions. The reason why 2-MP is a better substrate than 6-MP and how the chemical nature and position of the functional groups present on the thiopurine substrates influence xanthine oxidase activity are discussed.

Improved human islet preparations using Glucocorticoid and Exendin-4

PubMed Central

Miki, Atsushi.; Ricordi, Camillo.; Yamamoto, Toshiyuki.; Sakuma, Yasunaru.; Misawa, Ryosuke.; Mita, Atsuyoshi.; Inverardi, Luca.; Alejandro, Rodolfo; Ichii, Hirohito.

2014-01-01

Objectives The effects of Glucocorticoid during culture on human islet cells have been controversial. Exendin-4 (EX) enhances the insulin secretion and significantly improves clinical outcomes in islet cell transplantation. In this study, we examined the effects of Glucocorticoids and exendin-4 on human islet cells during pre-transplant culture. Methods Methylprednisolone (MP) and/or EX were added to the standard culture medium for clinical islet cell transplantation. Islets were cultured for 24 hours with three different conditions (Control: no additives, MP alone, MP+EX). Beta cell fractional viability, cellular composition, multiple cytokine/chemokine production, multiple phosphorylation proteins and glucose induced insulin secretion were evaluated. Results Viable beta cell survival in MP and MP+EX group was significantly higher than in the control group. EX prevented MP induced reduction of insulin secretion. MP supplementation to the culture medium decreased cytokine and chemokine production. Moreover, Erk1/2 phosphorylation was significantly increased by MP and MP+EX. Conclusions Glucocorticoid supplementation into culture media significantly decreased the cytokine/chemokine production and increased the Erk1/2 phosphorylation, resulting in the improvement of human beta cell survival. In addition, EX maintained the insulin secretion suppressed by MP. The supplementation of MP and EX together could be a useful strategy to create suitable human islets for transplantation. PMID:25036907

Cell-derived microparticles and vascular pregnancy complications: a systematic and comprehensive review.

PubMed

Alijotas-Reig, Jaume; Palacio-Garcia, Carles; Llurba, Elisa; Vilardell-Tarres, Miquel

2013-02-01

To assess current studies on the relationship between cell-derived microparticles (cMP) and recurrent miscarriages (RM) and pre-eclampsia (PE), and review the relationships between cMP and inflammatory and clot pathways, antiphospholipid antibodies (aPL), cytokines, and pregnancy complications. Systematic and comprehensive review of the literature from January 2000 to January 2012. Vall d'Hebron University Hospital. Women with recurrent miscarriages or PE, healthy nonpregnant women, and healthy pregnant women. None. Comparison of cMP numbers and types among groups. Platelet and endothelial cMP are increased in women with normal pregnancies compared with nonpregnant healthy women. Only five case-control studies regarding cMP and RM and 16 on cMP and PE were found to match our objective. Three of five articles referring to RM showed differences in cMP numbering, and 13 of 16 on cMP and PE showed differences in some type of cMP compared with controls. Cell-derived microparticles were raised in normal pregnancy. Recurrent miscarriage seems to be related to endothelial and platelet cell activation and/or consumption. An increase in almost all cMP types was observed in PE. A relationship between cMP and endothelial activation and proinflammatory status seems to exist. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cell-to-cell movement of Alfalfa mosaic virus can be mediated by the movement proteins of Ilar-, bromo-, cucumo-, tobamo- and comoviruses and does not require virion formation.

PubMed

Sánchez-Navarro, Jesús A; Carmen Herranz, María; Pallás, Vicente

2006-03-01

RNA 3 of Alfalfa mosaic virus (AMV) encodes the movement protein (MP) and coat protein (CP). Chimeric RNA 3 with the AMV MP gene replaced by the corresponding MP gene of Prunus necrotic ringspot virus, Brome mosaic virus, Cucumber mosaic virus or Cowpea mosaic virus efficiently moved from cell-to-cell only when the expressed MP was extended at its C-terminus with the C-terminal 44 amino acids of AMV MP. MP of Tobacco mosaic virus supported the movement of the chimeric RNA 3 whether or not the MP was extended with the C-terminal AMV MP sequence. The replacement of the CP gene in RNA 3 by a mutant gene encoding a CP defective in virion formation did not affect cell-to-cell transport of the chimera's with a functional MP. A GST pull-down technique was used to demonstrate for the first time that the C-terminal 44 amino acids of the MP of a virus belonging to the family Bromoviridae interact specifically with AMV virus particles. Together, these results demonstrate that AMV RNA 3 can be transported from cell-to-cell by both tubule-forming and non-tubule-forming MPs if a specific MP-CP interaction occurs.

Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study: correlation with coagulopathy

PubMed Central

Matijevic, Nena; Wang, Yao-Wei W.; Wade, Charles E.; Holcomb, John B.; Cotton, Bryan A.; Schreiber, Martin A.; Muskat, Peter; Fox, Erin E.; del Junco, Deborah J.; Cardenas, Jessica C.; Rahbar, Mohammad H.; Cohen, Mitchell Jay

2014-01-01

Background Trauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding. Methods As part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 trauma patients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) ≥35 sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)]. Results 21.7% of patients were coagulopathic with the median (IQR) APTT of 44 sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p<0.001), and enhanced TG (p<0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathic patients (all p<0.001). Conclusions Cellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathic patients, while lower levels of TF-bearing PMPs were associated with substantial bleeding. PMID:25086657

Geochemical Origin of Biological Molecules

NASA Astrophysics Data System (ADS)

Bassez, Marie-Paule

2013-04-01

A model for the geochemical origin of biological molecules is presented. Rocks such as peridotites and basalts, which contain ferromagnesian minerals, evolve in the presence of water. Their hydrolysis is an exothermic reaction which generates heat and a release of H2 and of minerals with modified structures. The hydrogen reacts with the CO2 embedded inside the rock or with the CO2 of the environment to form CO in an hydrothermal process. With the N2 of the environment, and with an activation source arising from cosmic radiation, ferromagnesian rocks might evolve towards the abiotic formation of biological molecules, such as peptide like macromolecules which produce amino acids after acid hydrolysis. The reactions concerned are described. The production of hydrothermal CO is discussed in geological sites containing ferromagnesian silicate minerals and the low intensity of the Earth's magnetic field during Paleoarchaean Era is also discussed. It is concluded that excitation sources arising from cosmic radiation were much more abundant during Paleoarchaean Era and that macromolecular structures of biological relevance might consequently form during Archaean Eon, as a product of the chemical evolution of the rocks and of their mineral contents. This synthesis of abiotically formed biological molecules is consecutively discussed for meteorites and other planets such as Mars. This model for the geochemical origin of biological molecules has first been proposed in 2008 in the context of reactions involving catalysers such as kaolinite [Bassez 2008a] and then presented in conferences and articles [Bassez 2008b, 2009, 2012; Bassez et al. 2009a to 2012b]. BASSEZ M.P. 2008a Synthèse prébiotique dans les conditions hydrothermales, CNRIUT'08, Lyon 29-30/05/2008, Conf. and open access article:http://liris.cnrs.fr/~cnriut08/actes/ 29 mai 11h-12h40. BASSEZ M.P. 2008b Prebiotic synthesis under hydrothermal conditions, ISSOL'08, P2-6, Firenze-Italy, 24-29/08/2008. Poster at the Conference and abstract in OLEB, 2008, 39 (3-4) 223. BASSEZ M.P. 2009 Prebiotic synthesis under hydothermal conditions, C. R. Chimie, Académie des Sciences, Paris 12 (6-7) : 801-807. BASSEZ M.P. 2012 A model for a geochemical origin of life in preparation BASSEZ M.P., TAKANO Y., OHKOUCHI N. 2009a Organic analysis of peridotite rocks from Ashadze and Logatchev hydrothermal sites, Int. J. Mol. Sci. 10(7): 2986-2998. BASSEZ M.P., TAKANO Y., OHKOUCHI N. 2009b Organic analysis of peridotite rocks from the MAR, AGU fall meeting, P43C-1441, San Francisco, 14-18/12/2009. BASSEZ M.P., TAKANO Y. 2010a Prebiotic organic globules, Nature Precedings: Posted 21 Jul http://hdl:10101/npre.2010.4694.1. BASSEZ M.P., TAKANO Y., OHKOUCHI N. 2010b Organic analysis of peridotite rocks, First chemical steps towards the Origin of Life colloquium, Turin 16-17/09/2010. BASSEZ M.P., TAKANO Y., OHKOUCHI N. 2011a A search for prebiotic molecular signatures inside rocks, Geobiology in Space exploration workshop, P sans n°, Marrakech 07-14/02/2011. BASSEZ M.P., TAKANO Y., OHKOUCHI N. 2011b Detection of molecular biosignatures inside rocks, Origins 2011 ISSOL and Bioastronomy conference, P2-17, Montpellier, 04-08/07/2011. BASSEZ M.P., TAKANO Y., 2011c Organic microstructures, Origins 2011 ISSOL and Bioastronomy conference, P2-34, Montpellier, 04-08/07/2011. BASSEZ M.P., TAKANO Y. KOBAYASHI K. 2011d Prebiotic organic microstructures, Nature Precedings: Posted 14 Nov. http://hdl.handle.net/10101/npre.2011.4694.2 BASSEZ M.P., TAKANO Y., KOBAYASHI K. 2012a Prebiotic organic microstructures, Origin of Life Gordon Research Conference P4, Galveston, 08-13/01/2012. BASSEZ M.P., TAKANO Y., KOBAYASHI K. 2012b Prebiotic organic microstructures, Orig. Life Evol. Biosph. 42 (4) : 307-316.

Experimental Assessment of Different Receiver Structures for Underwater Acoustic Communications over Multipath Channels

PubMed Central

Zhang, Guosong; Hovem, Jens M.; Dong, Hefeng

2012-01-01

Underwater communication channels are often complicated, and in particular multipath propagation may cause intersymbol interference (ISI). This paper addresses how to remove ISI, and evaluates the performance of three different receiver structures and their implementations. Using real data collected in a high-frequency (10–14 kHz) field experiment, the receiver structures are evaluated by off-line data processing. The three structures are multichannel decision feedback equalizer (DFE), passive time reversal receiver (passive-phase conjugation (PPC) with a single channel DFE), and the joint PPC with multichannel DFE. In sparse channels, dominant arrivals represent the channel information, and the matching pursuit (MP) algorithm which exploits the channel sparseness has been investigated for PPC processing. In the assessment, it is found that: (1) it is advantageous to obtain spatial gain using the adaptive multichannel combining scheme; and (2) the MP algorithm improves the performance of communications using PPC processing. PMID:22438755

Protective effect of polysaccharide from maca (Lepidium meyenii) on Hep-G2 cells and alcoholic liver oxidative injury in mice.

PubMed

Zhang, Lijun; Zhao, Qingsheng; Wang, Liwei; Zhao, Mingxia; Zhao, Bing

2017-06-01

To study the characterization and hepatoprotective activity of polysaccharide from maca (Lepidium meyenii), the main polysaccharide from maca (MP-1) was obtained by DEAE-52 cellulose column. The average molecular weight of MP-1 was 1067.3kDa and the polysaccharide purity was 91.63%. In order to assess the antioxidant activities of MP-1, four kinds of methods were used, including scavenging hydroxyl radical, DPPH, superoxide anion radical, and FRAP, and the results indicated high antioxidant activities. Furthermore, hepatoprotective activity of MP-1 was studied both in vitro and vivo. In vitro, the alcohol induced Hep-G2 cells model was established to evaluate the protective effect of MP-1, which demonstrated MP-1 can alleviate alcohol damage in Hep-G2 cells. In vivo, the Institute　of　Cancer　Researcch (ICR) mice were used to evaluate hepatoprotecive effects of MP-1 on alcoholic liver disease (ALD). Supplement with MP-1 supressed the triglyceride level both in serum and in hepatic tissue. In addition, MP-1 ameliorated serous transaminases increase induced by alcohol, including aspartate transaminase, alanine aminotransferase, and γ-glutamyl transpeptidase. Moreover, MP-1 also dramatically increased the superoxide dismutase, glutathione peroxidase, and glutathione s-transferase levels in alcoholic mice. Meantime, histopathologic results MP-1 lighten inflammation induced by alcohol. These results indicate that MP-1 possesses hepatoprotective activity against hepatic injury induced by alcohol. Copyright © 2017 Elsevier B.V. All rights reserved.

User's Guide for TOUGH2-MP - A Massively Parallel Version of the TOUGH2 Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Earth Sciences Division; Zhang, Keni; Zhang, Keni

TOUGH2-MP is a massively parallel (MP) version of the TOUGH2 code, designed for computationally efficient parallel simulation of isothermal and nonisothermal flows of multicomponent, multiphase fluids in one, two, and three-dimensional porous and fractured media. In recent years, computational requirements have become increasingly intensive in large or highly nonlinear problems for applications in areas such as radioactive waste disposal, CO2 geological sequestration, environmental assessment and remediation, reservoir engineering, and groundwater hydrology. The primary objective of developing the parallel-simulation capability is to significantly improve the computational performance of the TOUGH2 family of codes. The particular goal for the parallel simulator ismore » to achieve orders-of-magnitude improvement in computational time for models with ever-increasing complexity. TOUGH2-MP is designed to perform parallel simulation on multi-CPU computational platforms. An earlier version of TOUGH2-MP (V1.0) was based on the TOUGH2 Version 1.4 with EOS3, EOS9, and T2R3D modules, a software previously qualified for applications in the Yucca Mountain project, and was designed for execution on CRAY T3E and IBM SP supercomputers. The current version of TOUGH2-MP (V2.0) includes all fluid property modules of the standard version TOUGH2 V2.0. It provides computationally efficient capabilities using supercomputers, Linux clusters, or multi-core PCs, and also offers many user-friendly features. The parallel simulator inherits all process capabilities from V2.0 together with additional capabilities for handling fractured media from V1.4. This report provides a quick starting guide on how to set up and run the TOUGH2-MP program for users with a basic knowledge of running the (standard) version TOUGH2 code, The report also gives a brief technical description of the code, including a discussion of parallel methodology, code structure, as well as mathematical and numerical methods used. To familiarize users with the parallel code, illustrative sample problems are presented.« less

Bone repair of critical size defects treated with mussel powder associated or not with bovine bone graft: histologic and histomorphometric study in rat calvaria.

PubMed

Trotta, Daniel Rizzo; Gorny, Clayton; Zielak, João César; Gonzaga, Carla Castiglia; Giovanini, Allan Fernando; Deliberador, Tatiana Miranda

2014-09-01

The objective of this study was to evaluate the bone repair of critical size defects treated with mussel powder with or without additional bovine bone. Critical size defects of 5 mm were realized in the calvaria of 70 rats, which were randomly divided in 5 groups - Control (C), Autogenous Bone (AB), Mussel Powder (MP), Mussel Powder and Bovine Bone (MP-BB) and Bovine Bone (BB). Histological and histomorphometric analysis were performed 30 and 90 days after the surgical procedures (ANOVA e Tukey p < 0.05). After 30 days, the measures of remaining particles were: 28.36% (MP-BB), 26.63% (BB) and 8.64% (MP) with a statistically significant difference between BB and MP. The percentage of osseous matrix after 30 days was, AB (55.17%), 23.31% (BB), 11.66% (MP) and 10.71% (MP-BB) with statistically significant differences among all groups. After 90 days the figures were 25.05% (BB), 21.53% (MP-BB) and 1.97% (MP) with statistically significant differences between MP-BB and MP. Percentages of new bone formation after 90 days were 89.47% (AB), 35.70% (BB), 26.48% (MP-BB) and 7.37% (MP) with statistically significant differences between AB and the other groups. Within the limits of this study, we conclude that mussel powder, with or without additional bovine bone, did not induce new bone formation and did not repair critical size defects in rat calvaria. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Cell-derived microparticles promote coagulation after moderate exercise.

PubMed

Sossdorf, Maik; Otto, Gordon P; Claus, Ralf A; Gabriel, Holger H W; Lösche, Wolfgang

2011-07-01

Cell-derived procoagulant microparticles (MP) might be able to contribute to exercise-induced changes in blood hemostasis. This study aimed to examine (i) the concentration and procoagulant activity of cell-derived MP after a moderate endurance exercise and (ii) the differences in the release, clearance, and activity of MP before and after exercise between trained and untrained individuals. All subjects performed a single bout of physical exercise on a bicycle ergometer for 90 min at 80% of their individual anaerobic threshold. MP were identified and quantified by flow cytometry measurements. Procoagulant activity of MP was measured by a prothrombinase activity assay as well as tissue factor-induced fibrin formation in MP-containing plasma. At baseline, no differences were observed for the absolute number and procoagulant activities of MP between trained and untrained subjects. However, trained individuals had a lower number of tissue factor-positive monocyte-derived MP compared with untrained individuals. In trained subjects, exercise induced a significant increase in the number of MP derived from platelets, monocytes, and endothelial cells, with maximum values at 45 min after exercise and returned to basal levels at 2 h after exercise. Untrained subjects revealed a similar increase in platelet-derived MP, but their level was still increased at 2 h after exercise, indicating a reduced clearance compared with trained individuals. Procoagulant activities of MP were increased immediately after exercise and remained elevated up to 2 h after exercise. We conclude that increased levels of MP were found in healthy individuals after an acute bout of exercise, that the amount of circulating MP contributes to an exercise-induced increase of hemostatic potential, and that there were differences in kinetic and dynamic characteristics between trained and untrained individuals.

Post-coma persons emerged from a minimally conscious state and showing multiple disabilities learn to manage a radio-listening activity.

PubMed

Lancioni, Giulio E; Singh, Nirbhay N; O'Reilly, Mark F; Sigafoos, Jeff; Colonna, Fabio; Buonocunto, Francesca; Sacco, Valentina; Megna, Marisa; Oliva, Doretta

2012-01-01

This study assessed microswitch-based technology to enable three post-coma adults, who had emerged from a minimally conscious state but presented motor and communication disabilities, to operate a radio device. The material involved a modified radio device, a microprocessor-based electronic control unit, a personal microswitch, and an amplified MP3 player. The study was carried out according to a non-concurrent multiple baseline design across participants. During the intervention, all three participants learned to operate the radio device, changing stations and tuning on some of them longer amounts of time than on others (i.e., suggesting preferences among the topics covered by those stations). They also ended a number of sessions before the maximum length of time allowed for them had elapsed. The practical (rehabilitation) implications of the findings were discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

VizieR Online Data Catalog: ChaMP X-ray point source catalog (Kim+, 2007)

NASA Astrophysics Data System (ADS)

Kim, M.; Kim, D.-W.; Wilkes, B. J.; Green, P. J.; Kim, E.; Anderson, C. S.; Barkhouse, W. A.; Evans, N. R.; Ivezic, Z.; Karovska, M.; Kashyap, V. L.; Lee, M. G.; Maksym, P.; Mossman, A. E.; Silverman, J. D.; Tananbaum, H. D.

2009-01-01

We present the Chandra Multiwavelength Project (ChaMP) X-ray point source catalog with ~6800 X-ray sources detected in 149 Chandra observations covering ~10deg2. The full ChaMP catalog sample is 7 times larger than the initial published ChaMP catalog. The exposure time of the fields in our sample ranges from 0.9 to 124ks, corresponding to a deepest X-ray flux limit of f0.5-8.0=9x10-16ergs/cm2/s. The ChaMP X-ray data have been uniformly reduced and analyzed with ChaMP-specific pipelines and then carefully validated by visual inspection. The ChaMP catalog includes X-ray photometric data in eight different energy bands as well as X-ray spectral hardness ratios and colors. To best utilize the ChaMP catalog, we also present the source reliability, detection probability, and positional uncertainty. (10 data files).

Arctic sea ice is an important temporal sink and means of transport for microplastic.

PubMed

Peeken, Ilka; Primpke, Sebastian; Beyer, Birte; Gütermann, Julia; Katlein, Christian; Krumpen, Thomas; Bergmann, Melanie; Hehemann, Laura; Gerdts, Gunnar

2018-04-24

Microplastics (MP) are recognized as a growing environmental hazard and have been identified as far as the remote Polar Regions, with particularly high concentrations of microplastics in sea ice. Little is known regarding the horizontal variability of MP within sea ice and how the underlying water body affects MP composition during sea ice growth. Here we show that sea ice MP has no uniform polymer composition and that, depending on the growth region and drift paths of the sea ice, unique MP patterns can be observed in different sea ice horizons. Thus even in remote regions such as the Arctic Ocean, certain MP indicate the presence of localized sources. Increasing exploitation of Arctic resources will likely lead to a higher MP load in the Arctic sea ice and will enhance the release of MP in the areas of strong seasonal sea ice melt and the outflow gateways.

Assessment of Orbital-Optimized MP2.5 for Thermochemistry and Kinetics: Dramatic Failures of Standard Perturbation Theory Approaches for Aromatic Bond Dissociation Energies and Barrier Heights of Radical Reactions.

PubMed

Soydaş, Emine; Bozkaya, Uğur

2015-04-14

An assessment of orbital-optimized MP2.5 (OMP2.5) [ Bozkaya, U.; Sherrill, C. D. J. Chem. Phys. 2014, 141, 204105 ] for thermochemistry and kinetics is presented. The OMP2.5 method is applied to closed- and open-shell reaction energies, barrier heights, and aromatic bond dissociation energies. The performance of OMP2.5 is compared with that of the MP2, OMP2, MP2.5, MP3, OMP3, CCSD, and CCSD(T) methods. For most of the test sets, the OMP2.5 method performs better than MP2.5 and CCSD, and provides accurate results. For barrier heights of radical reactions and aromatic bond dissociation energies OMP2.5-MP2.5, OMP2-MP2, and OMP3-MP3 differences become obvious. Especially, for aromatic bond dissociation energies, standard perturbation theory (MP) approaches dramatically fail, providing mean absolute errors (MAEs) of 22.5 (MP2), 17.7 (MP2.5), and 12.8 (MP3) kcal mol(-1), while the MAE values of the orbital-optimized counterparts are 2.7, 2.4, and 2.4 kcal mol(-1), respectively. Hence, there are 5-8-folds reductions in errors when optimized orbitals are employed. Our results demonstrate that standard MP approaches dramatically fail when the reference wave function suffers from the spin-contamination problem. On the other hand, the OMP2.5 method can reduce spin-contamination in the unrestricted Hartree-Fock (UHF) initial guess orbitals. For overall evaluation, we conclude that the OMP2.5 method is very helpful not only for challenging open-shell systems and transition-states but also for closed-shell molecules. Hence, one may prefer OMP2.5 over MP2.5 and CCSD as an O(N(6)) method, where N is the number of basis functions, for thermochemistry and kinetics. The cost of the OMP2.5 method is comparable with that of CCSD for energy computations. However, for analytic gradient computations, the OMP2.5 method is only half as expensive as CCSD.

Purification and biochemical characterization of a novel ecto-apyrase, MP67, from Mimosa pudica.

PubMed

Okuhata, Riku; Takishima, Takeshi; Nishimura, Naoaki; Ueda, Shogo; Tsuchiya, Takahide; Kanzawa, Nobuyuki

2011-09-01

We have previously reported the presence of an apyrase in Mimosa pudica. However, only limited information is available for this enzyme. Thus, in this study, the apyrase was purified to homogeneity. The purified enzyme had a molecular mass of around 67 kD and was able to hydrolyze both nucleotide triphosphate and nucleotide diphosphate as substrates. The ratio of ATP to ADP hydrolysis velocity of the purified protein was 0.01 in the presence of calcium ion, showing extremely high substrate specificity toward ADP. Thus, we designated this novel apyrase as MP67. A cDNA clone of MP67 was obtained using primers designed from the amino acid sequence of trypsin-digested fragments of the protein. In addition, rapid amplification of cDNA ends-polymerase chain reaction was performed to clone a conventional apyrase (MpAPY2). Comparison of the deduced amino acid sequences showed that MP67 is similar to ecto-apyrases; however, it was distinct from conventional apyrase based on phylogenetic classification. MP67 and MpAPY2 were expressed in Escherichia coli, and the recombinant proteins were purified. The recombinant MP67 showed high substrate specificity toward ADP rather than ATP. A polyclonal antibody raised against the recombinant MP67 was used to examine the tissue distribution and localization of native MP67 in the plant. The results showed that MP67 was ubiquitously distributed in various tissues, most abundantly in leaves, and was localized to plasma membranes. Thus, MP67 is a novel ecto-apyrase with extremely high substrate specificity for ADP.

Purification and Biochemical Characterization of a Novel Ecto-Apyrase, MP67, from Mimosa pudica1[C][W][OA

PubMed Central

Okuhata, Riku; Takishima, Takeshi; Nishimura, Naoaki; Ueda, Shogo; Tsuchiya, Takahide; Kanzawa, Nobuyuki

2011-01-01

We have previously reported the presence of an apyrase in Mimosa pudica. However, only limited information is available for this enzyme. Thus, in this study, the apyrase was purified to homogeneity. The purified enzyme had a molecular mass of around 67 kD and was able to hydrolyze both nucleotide triphosphate and nucleotide diphosphate as substrates. The ratio of ATP to ADP hydrolysis velocity of the purified protein was 0.01 in the presence of calcium ion, showing extremely high substrate specificity toward ADP. Thus, we designated this novel apyrase as MP67. A cDNA clone of MP67 was obtained using primers designed from the amino acid sequence of trypsin-digested fragments of the protein. In addition, rapid amplification of cDNA ends-polymerase chain reaction was performed to clone a conventional apyrase (MpAPY2). Comparison of the deduced amino acid sequences showed that MP67 is similar to ecto-apyrases; however, it was distinct from conventional apyrase based on phylogenetic classification. MP67 and MpAPY2 were expressed in Escherichia coli, and the recombinant proteins were purified. The recombinant MP67 showed high substrate specificity toward ADP rather than ATP. A polyclonal antibody raised against the recombinant MP67 was used to examine the tissue distribution and localization of native MP67 in the plant. The results showed that MP67 was ubiquitously distributed in various tissues, most abundantly in leaves, and was localized to plasma membranes. Thus, MP67 is a novel ecto-apyrase with extremely high substrate specificity for ADP. PMID:21788364

Preclinical medical students’ understandings of academic and medical professionalism: visual analysis of mind maps

PubMed Central

Rees, Charlotte E

2017-01-01

Introduction Several studies have begun to explore medical students’ understandings of professionalism generally and medical professionalism specifically. Despite espoused relationships between academic (AP) and medical professionalism (MP), previous research has not yet investigated students’ conceptualisations of AP and MP and the relationships between the two. Objectives The current study, based on innovative visual analysis of mind maps, therefore aims to contribute to the developing literature on how professionalism is understood. Methods We performed a multilayered analysis of 98 mind maps from 262 first-year medical students, including analysing textual and graphical elements of AP, MP and the relationships between AP and MP. Results The most common textual attributes of AP were learning, lifestyle and personality, while attributes of MP were knowledge, ethics and patient-doctor relations. Images of books, academic caps and teachers were used most often to represent AP, while images of the stethoscope, doctor and red cross were used to symbolise MP. While AP-MP relations were sometimes indicated through co-occurring text, visual connections and higher-order visual metaphors, many students struggled to articulate the relationships between AP and MP. Conclusions While the mind maps’ textual attributes shared similarities with those found in previous research, suggesting the universality of some professionalism attributes, our study provides new insights into students’ conceptualisations of AP, MP and AP-MP relationships. We encourage medical educators to help students develop their understandings of AP, MP and AP-MP relationships, plus consider the feasibility and value of mind maps as a source of visual data for medical education research. PMID:28821520

Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome.

PubMed

Aleman, T S; Duncan, J L; Bieber, M L; de Castro, E; Marks, D A; Gardner, L M; Steinberg, J D; Cideciyan, A V; Maguire, M G; Jacobson, S G

2001-07-01

To determine macular pigment (MP) in patients with inherited retinal degeneration and the response of MP and vision to supplementation of lutein. Patients with retinitis pigmentosa (RP) or Usher syndrome and normal subjects had MP optical density profiles measured with heterochromatic flicker photometry. Serum carotenoids, visual acuity, foveal sensitivity, and retinal thickness (by optical coherence tomography [OCT]) were quantified. The effects on MP and central vision of 6 months of lutein supplementation at 20 mg/d were determined. MP density in the patients as a group did not differ from normal. Among patients with lower MP, there was a higher percentage of females, smokers, and light-colored irides. Disease expression tended to be more severe in patients with lower MP. Inner retinal thickness by OCT correlated positively with MP density in the patients. After supplementation, all participants showed an increase in serum lutein. Only approximately half the patients showed a statistically significant increase in MP. Retinal nonresponders had slightly greater disease severity but were otherwise not distinguishable from responders. Central vision was unchanged after supplementation. Factors previously associated with lower or higher MP density in normal subjects showed similar associations in RP and Usher syndrome. In addition, MP in patients may be affected by stage of retinal disease, especially that leading to abnormal foveal architecture. MP could be augmented by supplemental lutein in many but not all patients. There was no change in central vision after 6 months of lutein supplementation, but long-term influences on the natural history of these retinal degenerations require further study.

Assessment of the overlap metric in the context of RI-MP2 and atomic batched tensor decomposed MP2

NASA Astrophysics Data System (ADS)

Schmitz, Gunnar; Christiansen, Ove

2018-06-01

The resolution-of-the-identity approximation (RI) is a standard tool to accelerate the evaluation of two electron repulsion integrals. However introducing further approximations on top of for example RI-MP2, makes it important to check again the made choices. Usually the so called Coulomb metric is used. An alternative is the less accurate overlap metric, which has the benefit of a faster decay with distance. We encountered both choices in our atomic batched tensor decomposed MP2 (AB-MP2) and went with the Coulomb metric for the safe choice. In this work we re-investigate the choice of Coulomb and overlap metric for RI-MP2 and AB-MP2.

Accurate estimation of camera shot noise in the real-time

NASA Astrophysics Data System (ADS)

Cheremkhin, Pavel A.; Evtikhiev, Nikolay N.; Krasnov, Vitaly V.; Rodin, Vladislav G.; Starikov, Rostislav S.

2017-10-01

Nowadays digital cameras are essential parts of various technological processes and daily tasks. They are widely used in optics and photonics, astronomy, biology and other various fields of science and technology such as control systems and video-surveillance monitoring. One of the main information limitations of photo- and videocameras are noises of photosensor pixels. Camera's photosensor noise can be divided into random and pattern components. Temporal noise includes random noise component while spatial noise includes pattern noise component. Temporal noise can be divided into signal-dependent shot noise and signal-nondependent dark temporal noise. For measurement of camera noise characteristics, the most widely used methods are standards (for example, EMVA Standard 1288). It allows precise shot and dark temporal noise measurement but difficult in implementation and time-consuming. Earlier we proposed method for measurement of temporal noise of photo- and videocameras. It is based on the automatic segmentation of nonuniform targets (ASNT). Only two frames are sufficient for noise measurement with the modified method. In this paper, we registered frames and estimated shot and dark temporal noises of cameras consistently in the real-time. The modified ASNT method is used. Estimation was performed for the cameras: consumer photocamera Canon EOS 400D (CMOS, 10.1 MP, 12 bit ADC), scientific camera MegaPlus II ES11000 (CCD, 10.7 MP, 12 bit ADC), industrial camera PixeLink PL-B781F (CMOS, 6.6 MP, 10 bit ADC) and video-surveillance camera Watec LCL-902C (CCD, 0.47 MP, external 8 bit ADC). Experimental dependencies of temporal noise on signal value are in good agreement with fitted curves based on a Poisson distribution excluding areas near saturation. Time of registering and processing of frames used for temporal noise estimation was measured. Using standard computer, frames were registered and processed during a fraction of second to several seconds only. Also the accuracy of the obtained temporal noise values was estimated.

Thigmomorphogenesis: the role of ethylene in the response of Pinus taeda and Abies fraseri to mechanical perturbation

NASA Technical Reports Server (NTRS)

Telewski, F. W.; Jaffe, M. J.

1986-01-01

Ethylene production was monitored for 48 h in two half-sibs of Pinus taeda L. grown in the greenhouse and given mechanical perturbation (MP) by flexing; and for 22 h in Abies fraseri (Pursh) Poir. grown in the field and exposed to wind-mediated MP. Both species produced a peak of ethylene 18 h after MP. Seedlings of P. taeda exposed to MP for the duration of the growing season (preconditioned) produced less ethylene compared to non-MP controls, with a peak production at 8 h. One half-sib which responded to MP by an increase in radial growth produced 16 times more ethylene than another half-sib which had no significant change in radial growth. Preconditioned A. fraseri produced no significant quantities of ethylene after MP. The production of wound ethylene appears to be different from MP-induced ethylene. When an ethylene-generating solution was applied to P. taeda seedlings, it mimicked many of the morphological and mechanical characteristics of MP seedlings. The putative role of ethylene in the thigmomorphogenetic response is addressed.

Cognitive Psychology and Mathematical Thinking.

ERIC Educational Resources Information Center

Greer, Brian

1981-01-01

This review illustrates aspects of cognitive psychology relevant to the understanding of how people think mathematically. Developments in memory research, artificial intelligence, visually mediated processes, and problem-solving research are discussed. (MP)

Low temperature physical properties of Co-35Ni-20Cr-10Mo alloy MP35N®

NASA Astrophysics Data System (ADS)

Lu, J.; Toplosky, V. J.; Goddard, R. E.; Han, K.

2017-09-01

Multiphase Co-35Ni-20Cr-10Mo alloy MP35N® is a high strength alloy with excellent corrosion resistance. Its applications span chemical, medical, and food processing industries. Thanks to its high modulus and high strength, it found applications in reinforcement of ultra-high field pulsed magnets. Recently, it has also been considered for reinforcement in superconducting wires used in ultra-high field superconducting magnets. For these applications, accurate measurement of its physical properties at cryogenic temperatures is very important. In this paper, physical properties including electrical resistivity, specific heat, thermal conductivity, and magnetization of as-received and aged samples are measured from 2 to 300 K. The electrical resistivity of the aged sample is slightly higher than the as-received sample, both showing a weak linear temperature dependence in the entire range of 2-300 K. The measured specific heat Cp of 430 J/kg-K at 295 K agrees with a theoretical prediction, but is significantly smaller than the values in the literature. The thermal conductivity between 2 and 300 K is in good agreement with the literature which is only available above 77 K. Magnetic property of MP35N® changes significantly with aging. The as-received sample exhibits Curie paramagnetism with a Curie constant C = 0.175 K. While the aged sample contains small amounts of a ferromagnetic phase even at room temperature. The measured MP35N® properties will be useful for the engineering design of pulsed magnets and superconducting magnets using MP35N® as reinforcement.

Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

PubMed

Gold, Samuel A; Hale, Graham R; Bloom, Jonathan B; Smith, Clayton P; Rayn, Kareem N; Valera, Vladimir; Wood, Bradford J; Choyke, Peter L; Turkbey, Baris; Pinto, Peter A

2018-05-21

Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx. A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement. Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy. A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.

Investigating membrane nanoporation induced by bipolar pulsed electric fields via second harmonic generation

NASA Astrophysics Data System (ADS)

Moen, E. K.; Ibey, B. L.; Beier, H. T.; Armani, A. M.

2016-09-01

Electric pulses have become an effective tool for transporting cargo (DNA, drugs, etc.) across cell membranes. This enhanced transport is believed to occur through temporary pores formed in the plasma membrane. Traditionally, millisecond duration, monopolar (MP) pulses are used for electroporation, but bipolar (BP) pulses have proven equally effective as MP pulses with the added advantage of less cytotoxicity. With the goal of further reducing cytotoxic effects and inducing non-thermal, intra-cellular effects, researchers began investigating reduced pulse durations, pushing into the nanosecond regime. Cells exposed to these MP, nanosecond pulsed electric fields (nsPEFs) have shown increased repairable membrane permeability and selective channel activation. However, attempts to improve this further by moving to the BP pulse regime has proven unsuccessful. In the present work, we use second harmonic generation imaging to explore the structural effects of bipolar nsPEFs on the plasma membrane. By varying the temporal spacing between the pulse phases over several orders of magnitude and comparing the response to a single MP case, we systematically examine the disparity in cellular response. Our circuit-based model predicts that, as the temporal spacing increases several orders of magnitude, nanoporation increases and eventually exceeds the MP case. On the whole, our experimental data agree with this assertion; however, a detailed analysis of the data sets demonstrates that biological processes may play a larger role in the observed response than previously thought, dominating the effect for temporal spacing up to 5 μs. These findings could ultimately lead to understanding the biophysical mechanism underlying all electroporation.

Parallelization of interpolation, solar radiation and water flow simulation modules in GRASS GIS using OpenMP

NASA Astrophysics Data System (ADS)

Hofierka, Jaroslav; Lacko, Michal; Zubal, Stanislav

2017-10-01

In this paper, we describe the parallelization of three complex and computationally intensive modules of GRASS GIS using the OpenMP application programming interface for multi-core computers. These include the v.surf.rst module for spatial interpolation, the r.sun module for solar radiation modeling and the r.sim.water module for water flow simulation. We briefly describe the functionality of the modules and parallelization approaches used in the modules. Our approach includes the analysis of the module's functionality, identification of source code segments suitable for parallelization and proper application of OpenMP parallelization code to create efficient threads processing the subtasks. We document the efficiency of the solutions using the airborne laser scanning data representing land surface in the test area and derived high-resolution digital terrain model grids. We discuss the performance speed-up and parallelization efficiency depending on the number of processor threads. The study showed a substantial increase in computation speeds on a standard multi-core computer while maintaining the accuracy of results in comparison to the output from original modules. The presented parallelization approach showed the simplicity and efficiency of the parallelization of open-source GRASS GIS modules using OpenMP, leading to an increased performance of this geospatial software on standard multi-core computers.

Thylakoid-Deposited Micro-Pillar Electrodes for Enhanced Direct Extraction of Photosynthetic Electrons

PubMed Central

Ryu, DongHyun; Kim, Yong Jae; Kim, Seon Il; Hong, Hyeonaug; Ahn, Hyun S.

2018-01-01

Photosynthesis converts solar energy to electricity in a highly efficient manner. Since only water is needed as fuel for energy conversion, this highly efficient energy conversion process has been rigorously investigated. In particular, photosynthetic apparatus, such as photosystem II (PSII), photosystem I (PSI), or thylakoids, have been isolated from various plants to construct bio-hybrid anodes. Although PSII or PSI decorated anodes have shown potentials, there still remain challenges, such as poor stability of PSII-based systems or need for electron donors other than water molecules of PSI-based systems. Thylakoid membranes are relatively stable after isolation and they contain all the necessary photosynthetic apparatus including the PSII and PSI. To increase electrical connections between thylakoids and anodes, nanomaterials such as carbon nanotubes, nanowires, nanoparticles, or graphene have been employed. However, since they rely on the secondary electrical connections between thylakoids and anodes; it is desired to achieve larger direct contacts between them. Here, we aimed to develop micro-pillar (MP) array anodes to maximize direct contact with thylakoids. The thylakoid morphology was analyzed and the MP array was designed to maximize direct contact with thylakoids. The performance of MP anodes and a photosynthetic fuel cell based on MP electrodes was demonstrated and analyzed. PMID:29587387

CYTOKINES AS THE PREDICTORS OF SEVERE MYCOPLASMA PNEUMONIAE PNEUMONIA IN CHILDREN (REVIEW).

PubMed

Chkhaidze, I; Kapanadze, N

2017-06-01

In spite of many attempts to differentiate bacterial from viral disease and predict severity and outcome, the etiologic diagnosis of paediatric community acquired pneumonia and the estimation of potential outcomes remain unsolved problems in most cases. Mycoplasma pneumoniae is one of the major pathogens causing CAP in children. Although MP infection was traditionally thought to be a self-limited process, more and more severe cases even fatal cases of MP infections were reported in recent years. So it is essential for pediatricians to recognize severe or refractory or severe MP early, treat it promptly and prevent the progress of the disease. In recent years, several new biomarkers have been tested in children with CAP. Some of the biomarkers used for etiologic diagnosis in children with CAP and they also have been used the MP infection severity. Among traditional biomarkers, several cytokines appears to be effective both in selection of bacterial cases and in evaluation of severity. However, a precise cut-off level able to separate bacterial from viral cases and mild from severe cases has not been defined. Further studies enrolled with a large number of children with Mycoplasma pneumoniae is needed to be carried out to identify the potential utility of different cytokines as the good predictors.

Nonmydriatic fluorescence-based quantitative imaging of human macular pigment distributions

NASA Astrophysics Data System (ADS)

Sharifzadeh, Mohsen; Bernstein, Paul S.; Gellermann, Werner

2006-10-01

We have developed a CCD-camera-based nonmydriatic instrument that detects fluorescence from retinal lipofuscin chromophores ("autofluorescence") as a means to indirectly quantify and spatially image the distribution of macular pigment (MP). The lipofuscin fluorescence intensity is reduced at all retinal locations containing MP, since MP has a competing absorption in the blue-green wavelength region. Projecting a large diameter, 488 nm excitation spot onto the retina, centered on the fovea, but extending into the macular periphery, and comparing lipofuscin fluorescence intensities outside and inside the foveal area, it is possible to spatially map out the distribution of MP. Spectrally selective detection of the lipofuscin fluorescence reveals an important wavelength dependence of the obtainable image contrast and deduced MP optical density levels, showing that it is important to block out interfering fluorescence contributions in the detection setup originating from ocular media such as the lens. Measuring 70 healthy human volunteer subjects with no ocular pathologies, we find widely varying spatial extent of MP, distinctly differing distribution patterns of MP, and strongly differing absolute MP levels among individuals. Our population study suggests that MP imaging based on lipofuscin fluorescence is useful as a relatively simple, objective, and quantitative noninvasive optical technique suitable to rapidly screen MP levels and distributions in healthy humans with undilated pupils.

Regulation of IL-10 expression by upstream stimulating factor (USF-1) in glioma-associated microglia.

PubMed

Zhang, Leying; Handel, Michelle Van; Schartner, Jill M; Hagar, Aaron; Allen, Grant; Curet, Marjorie; Badie, Behnam

2007-03-01

Understanding the local CNS immune response to neoplasms is essential in the development of immune-based treatments for malignant brain tumors. Using rodent glioma models, we have recently found tumor-associated microglia/macrophages (MG/MP) to be less responsive to known MG/MP activators such as CpG, LPS and IFN-gamma. To understand the mechanism of MG/MP suppression, nuclear extracts from rodent intracranial C6 gliomas, C6 glioma-associated MG/MP, normal brain, and normal MG/MP were obtained and studied using Electrophoretic Mobility Shift Assay (EMSA). Among the nuclear factors studied (AP-1, IRF, USF-1 and Stat-1) only USF-1, which is constitutively expressed in most cells, was down-regulated in tumor-associated MG/MP, but not normal MG/MP. Because tumor-associated MG/MP had higher expression of IL-10 (but not TNF-alpha or TGF-beta), we evaluated the role of USF-1 on IL-10 expression. siRNA mediated inhibition of USF-1 expression in primary MG/MP cultures resulted in up-regulation of IL-10 mRNA but not TNF-alpha or TGF-beta. These findings suggest that USF-1 may play a role in IL-10 regulation in MG/MP in brain tumors.

Pharmacogenetic determinants of mercaptopurine disposition in children with acute lymphoblastic leukemia.

PubMed

Adam de Beaumais, Tiphaine; Jacqz-Aigrain, Evelyne

2012-09-01

The backbone of drug therapy used in acute lymphoblastic leukemia (ALL) in children includes 6-mercaptopurine (6-MP). Intracellular metabolism of this prodrug is a key component of the therapeutic response. Many metabolizing enzymes are involved in 6-MP disposition and active 6-MP metabolites are represented by 6-thioguanine nucleotides (6-TGN) and methylated metabolites primarily methylated by the thiopurine S-methyltransferase enzyme (TPMT). The genetic polymorphism affecting TPMT activity displays an important inter-subject variability in metabolites pharmacokinetics and influences the balance between 6-MP efficacy and toxicity: patients with high 6-TGN levels are at risk of myelosuppression while patients with high levels of methylated derivates are at hepatotoxic risk. However, the genetic TPMT polymorphism does not explain all 6-MP adverse events and some severe toxicities leading to life-threatening conditions remain unexplained. Additional single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in 6-MP metabolism and 6-MP transporters may also be responsible for this inter-individual 6-MP response variability. This review presents the pharmacogenetic aspects of 6-MP metabolism in great detail. We have focused on published data on ALL treatment supporting the great potential of 6-MP pharmacogenetics to improve efficacy, tolerance, and event-free survival rates in children with ALL.

Optimization of a GCaMP calcium indicator for neural activity imaging.

PubMed

Akerboom, Jasper; Chen, Tsai-Wen; Wardill, Trevor J; Tian, Lin; Marvin, Jonathan S; Mutlu, Sevinç; Calderón, Nicole Carreras; Esposti, Federico; Borghuis, Bart G; Sun, Xiaonan Richard; Gordus, Andrew; Orger, Michael B; Portugues, Ruben; Engert, Florian; Macklin, John J; Filosa, Alessandro; Aggarwal, Aman; Kerr, Rex A; Takagi, Ryousuke; Kracun, Sebastian; Shigetomi, Eiji; Khakh, Baljit S; Baier, Herwig; Lagnado, Leon; Wang, Samuel S-H; Bargmann, Cornelia I; Kimmel, Bruce E; Jayaraman, Vivek; Svoboda, Karel; Kim, Douglas S; Schreiter, Eric R; Looger, Loren L

2012-10-03

Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Recent efforts in protein engineering have significantly increased the performance of GECIs. The state-of-the art single-wavelength GECI, GCaMP3, has been deployed in a number of model organisms and can reliably detect three or more action potentials in short bursts in several systems in vivo. Through protein structure determination, targeted mutagenesis, high-throughput screening, and a battery of in vitro assays, we have increased the dynamic range of GCaMP3 by severalfold, creating a family of "GCaMP5" sensors. We tested GCaMP5s in several systems: cultured neurons and astrocytes, mouse retina, and in vivo in Caenorhabditis chemosensory neurons, Drosophila larval neuromuscular junction and adult antennal lobe, zebrafish retina and tectum, and mouse visual cortex. Signal-to-noise ratio was improved by at least 2- to 3-fold. In the visual cortex, two GCaMP5 variants detected twice as many visual stimulus-responsive cells as GCaMP3. By combining in vivo imaging with electrophysiology we show that GCaMP5 fluorescence provides a more reliable measure of neuronal activity than its predecessor GCaMP3. GCaMP5 allows more sensitive detection of neural activity in vivo and may find widespread applications for cellular imaging in general.

Intraindividual Comparison of 18F-PSMA-1007 PET/CT, Multiparametric MRI, and Radical Prostatectomy Specimens in Patients with Primary Prostate Cancer: A Retrospective, Proof-of-Concept Study.

PubMed

Kesch, Claudia; Vinsensia, Maria; Radtke, Jan P; Schlemmer, Heinz P; Heller, Martina; Ellert, Elena; Holland-Letz, Tim; Duensing, Stefan; Grabe, Nils; Afshar-Oromieh, Ali; Wieczorek, Kathrin; Schäfer, Martin; Neels, Oliver C; Cardinale, Jens; Kratochwil, Clemens; Hohenfellner, Markus; Kopka, Klaus; Haberkorn, Uwe; Hadaschik, Boris A; Giesel, Frederik L

2017-11-01

68 Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT represents an advanced method for the staging of primary prostate cancer (PCa) and diagnosis of recurrent or metastatic PCa. However, because of the narrow availability of 68 Ga the development of alternative tracers is of high interest. The objective of this study was to examine the value of the new PET tracer 18 F-PSMA-1007 for the staging of local disease by comparing it with multiparametric MRI (mpMRI) and radical prostatectomy (RP) histopathology. Methods: In 2016, 18 F-PSMA-1007 PET/CT was performed in 10 men with biopsy-confirmed high-risk PCa. Nine patients underwent mpMRI in the process of primary diagnosis. Consecutively, RP was performed in all 10 men. Agreement analysis was performed retrospectively. PSMA staining was added for representative sections in RP specimen slices. Localization and agreement analysis of 18 F-PSMA-1007 PET/CT, mpMRI, and RP specimens was performed by dividing the prostate into 38 sections as described in the prostate imaging reporting and data system (PI-RADS) (version 2). Sensitivity, specificity, positive predictive values, negative predictive values (NPVs), and accuracy were calculated for total and near-total agreement. Results: 18 F-PSMA-1007 PET/CT had an NPV of 68% and an accuracy of 75%, and mpMRI had an NPV of 88% and an accuracy of 73% for total agreement. Near-total agreement analysis resulted in an NPV of 91% and an accuracy of 93% for 18 F-PSMA-1007 PET/CT and 91% and 87% for mpMRI, respectively. Retrospective combination of mpMRI and PET/CT had an accuracy of 81% for total and 93% for near-total agreement. Conclusion: Comparison with RP histopathology demonstrates that 18 F-PSMA-1007 PET/CT is promising for accurate local staging of PCa. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Differential role of thiopurine methyltransferase in the cytotoxic effects of 6-mercaptopurine and 6-thioguanine on human leukemia cells.

PubMed

Karim, Hazhar; Ghalali, Aram; Lafolie, Pierre; Vitols, Sigurd; Fotoohi, Alan K

2013-07-26

The thiopurine antimetabolites, 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are inactive pro-drugs that require intracellular metabolism for activation to cytotoxic metabolites. Thiopurine methyltransferase (TPMT) is one of the most important enzymes in this process metabolizing both 6-MP and 6-TG to different methylated metabolites including methylthioinosine monophosphate (meTIMP) and methylthioguanosine monophosphate (meTGMP), respectively, with different suggested pharmacological and cytotoxic properties. While meTIMP is a potent inhibitor of de novo purine synthesis (DNPS) and significantly contributes to the cytotoxic effects of 6-MP, meTGMP, does not add much to the effects of 6-TG, and the cytotoxicity of 6-TG seems to be more dependent on incorporation of thioguanine nucleotides (TGNs) into DNA rather than inhibition of DNPS. In order to investigate the role of TPMT in metabolism and thus, cytotoxic effects of 6-MP and 6-TG, we knocked down the expression of the gene encoding the TPMT enzyme using specifically designed small interference RNA (siRNA) in human MOLT4 leukemia cells. The knock-down was confirmed at RNA, protein, and enzyme function levels. Apoptosis was determined using annexin V and propidium iodide staining and FACS analysis. The results showed a 34% increase in sensitivity of MOLT4 cells to 1μM 6-TG after treatment with TPMT-targeting siRNA, as compared to cells transfected with non-targeting siRNA, while the sensitivity of the cells toward 6-MP was not affected significantly by down-regulation of the TPMT gene. This differential contribution of the enzyme TPMT to the cytotoxicity of the two thiopurines is probably due to its role in formation of the meTIMP, the cytotoxic methylated metabolite of 6-MP, while in case of 6-TG methylation by TPMT substantially deactivates the drug. Copyright © 2013 Elsevier Inc. All rights reserved.

Purification, antitumor and immunomodulatory activity of polysaccharides from soybean residue fermented with Morchella esculenta.

PubMed

Li, Shuhong; Gao, Ang; Dong, Shuang; Chen, Ye; Sun, Shuang; Lei, Zhongfang; Zhang, Zhenya

2017-03-01

Crude polysaccharides (MPS) from soybean residue fermented with Morchella esculenta were extracted and purified by DEAE Sephadex A-50 chromatography and Sephadex G-100 size-exclusion chromatography in sequence. Three main fractions MP-1, MP-3 and MP-4 were obtained during the purification steps. The recovery rates based on MPS used were 26.2%, 29.1% and 18.7% for MP-1, MP-3 and MP-4 respectively. The monosaccharide composition, ultraviolet spectrum, infrared spectrum and NMR of the three fractions were analyzed. Furthermore, the influence of polysaccharides fractions upon activation of macrophage cells (RAW 264.7), antitumor activities of the human hepatocellular cell line (HepG-2) and human cervical carcinoma cells (Hela) in vitro were evaluated. The results indicated that the proliferation of MP-3 on RAW 264.7 was 313.57% at 25μg/mL, which is high while MP-1 had a higher growth inhibition effect on HepG-2 cells of 68.01% at concentration of 50μg/mL. The fractions of MP-1, MP-3 and MP-4 induced apoptosis in HepG-2 cells and Hela cells by arresting cell cycle progression at the G 0 /G 1 phase. These findings suggest that the purified polysaccharides fractions may be a potent candidate for human hepatocellular and cervical carcinoma treatment and prevention in functional foods and pharmacological fields. Copyright © 2016 Elsevier B.V. All rights reserved.

PD Trafficking of Potato Leaf Roll Virus Movement Protein in Arabidopsis Depends on Site-specific Protein Phosphorylation

PubMed Central

Sonnewald, Uwe

2011-01-01

Many plant viruses encode for specialized movement proteins (MP) to facilitate passage of viral material to and through plasmodesmata (PD). To analyze intracellular trafficking of potato leaf roll virus (PLRV) movement protein (MP17) we performed GFP fusion experiments with distinct deletion variants of MP17. These studies revealed that the C-terminus of MP17 is essential but not sufficient for PD targeting. Interestingly, fusion of GFP to three C-terminal MP17 deletion variants resulted in the accumulation of GFP in chloroplasts. This indicates that MP17 harbors hidden plastid targeting sequences. Previous studies showed that posttranslational protein phosphorylation influences PD targeting of MP and virus spread. Analysis of MP17-derived phospho-peptides by mass spectrometry revealed four phosphorylated serine residues (S71, S79, S137, and S140). Site-directed mutagenesis of S71/S79 and S137/S140 showed that the C-terminal serine residues S137/S140 are dispensable for PD targeting. However, exchange of S71/S79 to A71/A79 abolished PD targeting of the mutated MP17 protein. To mimic phosphorylation of S71/S79 both amino acids were substituted by aspartic acid. The resulting D71/D79 variant of MP17 was efficiently targeted to PD. Further deletion analysis showed that PD targeting of MP17 is dependent on the C-terminus, phosphorylation of S71 and/or S79 and a N-terminal domain. PMID:22645527

Sun light mediated synthesis of gold nanoparticles as carrier for 6-mercaptopurine: Preparation, characterization and toxicity studies in zebrafish embryo model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganeshkumar, Moorthy; Sastry, Thotapalli Parvathaleswara; Sathish Kumar, Muniram

2012-09-15

Highlights: ► Gold nanoparticles prepared using eco-friendly method with good in vitro stability. ► Can be used as drug delivery system. ► Did not show any toxicity in zebrafish embryo. ► More toxic to cancer cells when compared to N-Au-Mp and Mp. -- Abstract: The objective of this study is to synthesize green chemistry based gold nanoparticles by sun light irradiation method. The prepared gold nanoparticles (AuNPs) were modified using folic acid and then coupled with 6-mercaptopurine. These modified nanoparticles were used as a tool for targeted drug delivery to treat laryngeal cancer. In the present study, novel bionanocomposites containingmore » nutrient agar coated gold nano particles (N-AuNPs) coupled with 6-mercaptopurine (drug) (N-AuNPs-Mp), folic acid (ligand) (N-AuNPs-Mp-Fa) and rhodamine (dye) (N-AuNPs-Rd), a fluorescent agent, were prepared and characterized by IR, UV, TEM, Particle size analysis and in vitro stability. The toxicity and fluorescence of N-Au was studied using zebrafish embryo model. The in vitro cytotoxicity of free Mp, N-Au-Mp and N-Au-Mp-Fa against HEp-2 cells was compared and found that the amount of Mp required to achieve 50% of growth of inhibition (IC{sub 50}) was much lower in N-Au-Mp-Fa than in free Mp and N-Au-Mp.« less

The Effects of Group Diffusion of Cognitive Effort on Attitudes: An Information-Processing View.

ERIC Educational Resources Information Center

Petty, Richard E.; And Others

1980-01-01

Two experiments were conducted to test the hypothesis that persons process a stimulus less extensively when they are part of a group that is responsible for the task than when they are individually responsible. Subjects were college students. (Author/MP)

Compression of surface myoelectric signals using MP3 encoding.

PubMed

Chan, Adrian D C

2011-01-01

The potential of MP3 compression of surface myoelectric signals is explored in this paper. MP3 compression is a perceptual-based encoder scheme, used traditionally to compress audio signals. The ubiquity of MP3 compression (e.g., portable consumer electronics and internet applications) makes it an attractive option for remote monitoring and telemedicine applications. The effects of muscle site and contraction type are examined at different MP3 encoding bitrates. Results demonstrate that MP3 compression is sensitive to the myoelectric signal bandwidth, with larger signal distortion associated with myoelectric signals that have higher bandwidths. Compared to other myoelectric signal compression techniques reported previously (embedded zero-tree wavelet compression and adaptive differential pulse code modulation), MP3 compression demonstrates superior performance (i.e., lower percent residual differences for the same compression ratios).

Preclinical medical students' understandings of academic and medical professionalism: visual analysis of mind maps.

PubMed

Janczukowicz, Janusz; Rees, Charlotte E

2017-08-18

Several studies have begun to explore medical students' understandings of professionalism generally and medical professionalism specifically. Despite espoused relationships between academic (AP) and medical professionalism (MP), previous research has not yet investigated students' conceptualisations of AP and MP and the relationships between the two. The current study, based on innovative visual analysis of mind maps, therefore aims to contribute to the developing literature on how professionalism is understood. We performed a multilayered analysis of 98 mind maps from 262 first-year medical students, including analysing textual and graphical elements of AP, MP and the relationships between AP and MP. The most common textual attributes of AP were learning, lifestyle and personality, while attributes of MP were knowledge, ethics and patient-doctor relations. Images of books, academic caps and teachers were used most often to represent AP, while images of the stethoscope, doctor and red cross were used to symbolise MP. While AP-MP relations were sometimes indicated through co-occurring text, visual connections and higher-order visual metaphors, many students struggled to articulate the relationships between AP and MP. While the mind maps' textual attributes shared similarities with those found in previous research, suggesting the universality of some professionalism attributes, our study provides new insights into students' conceptualisations of AP, MP and AP-MP relationships. We encourage medical educators to help students develop their understandings of AP, MP and AP-MP relationships, plus consider the feasibility and value of mind maps as a source of visual data for medical education research. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Calciuric effects of protein and potassium bicarbonate but not of sodium chloride or phosphate can be detected acutely in adult women and men.

PubMed

Whiting, S J; Anderson, D J; Weeks, S J

1997-05-01

An acute load test was used to test the influence of dietary factors on urinary calcium excretion. In study 1, 10 fasting premenopausal women consumed test meals providing a moderate amount of protein (MP; 23 g), MP plus 23 mmol KHCO3 (MP+K), MP plus 23 mmol NaCl (MP+Na), and a high amount of protein (HP; 53 g), HP plus 70 mmol KHCO3 (HP+K), and HP plus 70 mmol NaCl (HP+Na). Protein was casein:lactalbumin (80:20), except for the treatments with added sodium chloride, to which only casein was added. In study 2, the effects of HP and HP plus 50 mmol KHCO3 (HP+K) were compared with those of MP or MP plus 7.5 mmol phosphate (MP+Pi), equaling the additional phosphate of HP, in 10 adult men. Subjects completed all treatments in random order. In study 1, the peak of calcium excretion was at 3 h for all treatments, except for HP+K, which indicated an acute hypocalciuric effect of potassium. Unexpectedly, there was no hypercalciuric effect of adding sodium chloride, nor was urine sodium increased. In study 2, calcium excretion was significantly higher with HP than with MP+Pi but not with MP at 3 h, indicating an acute hypercalciuric effect of protein alone. A hypocalciuric effect of potassium (HP+K compared with HP) but not of phosphate (MP compared with MP+Pi) was seen. An acute load test measuring changes 3 h postload was appropriate for examining the calciuric effects of protein and potassium bicarbonate, but not those of sodium chloride or phosphate in adults.

Mechanism of Sulfide Binding by Ferric Hemeproteins.

PubMed

Boubeta, Fernando M; Bieza, Silvina A; Bringas, Mauro; Estrin, Darío A; Boechi, Leonardo; Bari, Sara E

2018-06-19

The reaction of hydrogen sulfide (H 2 S) with hemeproteins is a key physiological reaction; still, its mechanism and implications are not completely understood. In this work, we propose a combination of experimental and theoretical tools to shed light on the reaction in model system microperoxidase 11 (MP11-Fe III ) and myoglobin (Mb-Fe III ), from the estimation of the intrinsic binding constants of the species H 2 S and hydrosulfide (HS - ), and the computational description of the overall binding process. Our results show that H 2 S and HS - are the main reactive species in Mb-Fe III and MP11-Fe III , respectively, and that the magnitude of their intrinsic binding constants are similar to most of the binding constants reported so far for hemeproteins systems and model compounds. However, while the binding of HS - to Mb-Fe III was negligible, the binding of H 2 S to MP11-Fe III was significant, providing a frame for a discriminated analysis of both species and revealing differential mechanistic aspects. A joint inspection of the kinetic data and the free energy profiles of the binding processes suggests that a dissociative mechanism with the release of a coordinated water molecule as rate limiting step is operative in the binding of H 2 S to Mb-Fe III and that the binding of HS - is prevented in the access to the protein matrix. For the MP11-Fe III case, where no access restrictions for the ligands are present, an associative component in the mechanism seems to be operative. Overall, the results suggest that if accessing the active site then both H 2 S and HS - are capable of binding a ferric heme moiety.

Coronal multichannel polarimeter for Lomnický štít Observatory. (Slovak Title: Koronálny multikanálový polarimeter pre observatórium Lomnický štít)

NASA Astrophysics Data System (ADS)

Rybák, J.; Ambróz, J.; Gömöry, P.; Kozák, M.; Kučera, A.; Tomczyk, S.; Sewell, S.; Summers, R.; Sutherland, L.; Watt, A.

2010-12-01

The contribution presents the process of development and preparation of the Coronal Multi-channel Polarimeter (COMP-S) for the Lomnický štít Observatory of the SAS Astronomy Institute. The design of the device is based on the experience gained in recent years with the CoMP (High Altitude Observatory / NCAR; Boulder, USA) instrument. The device will be a combination of two main optical components: the Lyot tunable filter and polarimeter, and is prepared specifically for one of the 20 cm Zeiss coronagraph at the Lomnický štít Observatory where it will be installed in 2011. CoMP-S will differ from its predecessor in several respects. The most important difference is that CoMP-S will be able to observe the corona and chromospheric emission lines in the wavelength range from 530 to 1083 nm. This feature will be achieved using superachromatic wave plates and dichroic polarizers with wide bandwidth. Furthermore, in the CoMP-S instrument new SWIFT liquid crystals of Meadowlark Optics company will be used as variable retarders instead of nematic liquid crystal retarders (LCVR) which will considerably shorten the measuring process. Ferroelectric liquid crystals will provide measurements of the full Stokes vector with nearly optimal polarization throughout the whole instrument bandwidth. Recently developed sCMOS cameras are to provide diffraction limit resolution of observations, with the 860x680 arc second field and 30-frames-per-second cadence. The device will be used in the Astronomical Observatory of SAS at Lomnický štít primarily for spectrum polarimetry of prominences and coronal loops of the active solar regions.

Using archived ITS data to measure the operational benefits of a system-wide adaptive ramp metering system : appendix online 5 : I-205 NB ramp flow & ML speed-flow plots.

DOT National Transportation Integrated Search

2008-12-01

The appendix includes various ramp flow and ML speed-flow plots, including: I-205 NB, Gladstone MP 11.05; I-205 NB, Gladstone Hway MP 12.94; I-205 NB, Lawnfield MP 13.58; I-205 NB, Sunnybrook MP 14.32; I-205 NB, Sunnyside MP 14.7; I-205 NB, Johnson C...

The Effects of Varying Ratios of Physical and Mental Practice, and Task Difficulty on Performance of a Tonal Pattern

ERIC Educational Resources Information Center

Cahn, Dan

2008-01-01

Sixty undergraduate students who had completed at least one semester of jazz improvisation were assigned to either: (a) physical practice (PP); (b) mental practice (MP); (c) combined 66 percent PP and 33 percent MP (66%PP:33%MP); and (d) combined 33 percent PP and 66 percent MP (33%PP:66%MP) groups. Subjects were to perform a 3-1-7-5 tonal pattern…

Apheresis platelet concentrates contain platelet-derived and endothelial cell-derived microparticles.

PubMed

Rank, A; Nieuwland, R; Liebhardt, S; Iberer, M; Grützner, S; Toth, B; Pihusch, R

2011-02-01

Microparticles (MP) are membrane vesicles with thrombogenic and immunomodulatory properties. We determined MP subgroups from resting platelets, activated platelets and endothelial cells in donors and apheresis platelet concentrates (PC). MP were double stained with annexin V and CD61 (platelet-derived MP; PMP), P-selectin or CD63 (MP from activated platelets) and CD144 plus E-selectin (endothelial cell-derived MP; EMP) and detected by flow cytometry in platelet donors (n=36) and apheresis PC (n=11; Trima™). PC contained MP, mainly from resting platelets [93% (90-95)], and minor fractions of PMP from activated platelets [P-selectin(+) or CD63(+); 4·8% (3·2-7·7) and 2·6% (2·0-4·0)]. Compared to donors, levels of annexin V+ MP, PMP, P-selectin(+) and CD63(+) MP were 1·7-, 2·3-, 8·6- and 3·1-fold higher in PC (all P<0·05). During storage (1-5 days), levels of annexin V+ MP and PMP did not increase, although small increases in the fraction of P-selectin(+) or CD63(+) MP occurred (both P<0·05). PC also contained EMP, which were 2·6- to 3·7-fold enriched in PC compared to donors (P<0·05). Transfusion of apheresis PC also results in transfusion of HLA-carrying PMP and EMP. This might counteract the aim of reducing transfused HLA load by leucodepletion. The increases in PMP exposing P-selectin or CD63 reflect mild platelet activation during storage. We conclude that in leucodepleted platelet apheresis using fluidized particle bed technology, MP are harvested mainly from the donor by apheresis. Improvement in apheresis technology might reduce MP load. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Multipoint to multipoint routing and wavelength assignment in multi-domain optical networks

NASA Astrophysics Data System (ADS)

Qin, Panke; Wu, Jingru; Li, Xudong; Tang, Yongli

2018-01-01

In multi-point to multi-point (MP2MP) routing and wavelength assignment (RWA) problems, researchers usually assume the optical networks to be a single domain. However, the optical networks develop toward to multi-domain and larger scale in practice. In this context, multi-core shared tree (MST)-based MP2MP RWA are introduced problems including optimal multicast domain sequence selection, core nodes belonging in which domains and so on. In this letter, we focus on MST-based MP2MP RWA problems in multi-domain optical networks, mixed integer linear programming (MILP) formulations to optimally construct MP2MP multicast trees is presented. A heuristic algorithm base on network virtualization and weighted clustering algorithm (NV-WCA) is proposed. Simulation results show that, under different traffic patterns, the proposed algorithm achieves significant improvement on network resources occupation and multicast trees setup latency in contrast with the conventional algorithms which were proposed base on a single domain network environment.

Analysis of histological findings obtained combining US/mp-MRI fusion-guided biopsies with systematic US biopsies: mp-MRI role in prostate cancer detection and false negative.

PubMed

Faiella, Eliodoro; Santucci, Domiziana; Greco, Federico; Frauenfelder, Giulia; Giacobbe, Viola; Muto, Giovanni; Zobel, Bruno Beomonte; Grasso, Rosario Francesco

2018-02-01

To evaluate the diagnostic accuracy of mp-MRI correlating US/mp-MRI fusion-guided biopsy with systematic random US-guided biopsy in prostate cancer diagnosis. 137 suspected prostatic abnormalities were identified on mp-MRI (1.5T) in 96 patients and classified according to PI-RADS score v2. All target lesions underwent US/mp-MRI fusion biopsy and prostatic sampling was completed by US-guided systematic random 12-core biopsies. Histological analysis and Gleason score were established for all the samples, both target lesions defined by mp-MRI, and random biopsies. PI-RADS score was correlated with the histological results, divided in three groups (benign tissue, atypia and carcinoma) and with Gleason groups, divided in four categories considering the new Grading system of the ISUP 2014, using t test. Multivariate analysis was used to correlate PI-RADS and Gleason categories to PSA level and abnormalities axial diameter. When the random core biopsies showed carcinoma (mp-MRI false-negatives), PSA value and lesions Gleason median value were compared with those of carcinomas identified by mp-MRI (true-positives), using t test. There was statistically significant difference between PI-RADS score in carcinoma, atypia and benign lesions groups (4.41, 3.61 and 3.24, respectively) and between PI-RADS score in Gleason < 7 group and Gleason > 7 group (4.14 and 4.79, respectively). mp-MRI performance was more accurate for lesions > 15 mm and in patients with PSA > 6 ng/ml. In systematic sampling, 130 (11.25%) mp-MRI false-negative were identified. There was no statistic difference in Gleason median value (7.0 vs 7.06) between this group and the mp-MRI true-positives, but a significant lower PSA median value was demonstrated (7.08 vs 7.53 ng/ml). mp-MRI remains the imaging modality of choice to identify PCa lesions. Integrating US-guided random sampling with US/mp-MRI fusion target lesions sampling, 3.49% of false-negative were identified.

Distributed Finite Element Analysis Using a Transputer Network

NASA Technical Reports Server (NTRS)

Watson, James; Favenesi, James; Danial, Albert; Tombrello, Joseph; Yang, Dabby; Reynolds, Brian; Turrentine, Ronald; Shephard, Mark; Baehmann, Peggy

1989-01-01

The principal objective of this research effort was to demonstrate the extraordinarily cost effective acceleration of finite element structural analysis problems using a transputer-based parallel processing network. This objective was accomplished in the form of a commercially viable parallel processing workstation. The workstation is a desktop size, low-maintenance computing unit capable of supercomputer performance yet costs two orders of magnitude less. To achieve the principal research objective, a transputer based structural analysis workstation termed XPFEM was implemented with linear static structural analysis capabilities resembling commercially available NASTRAN. Finite element model files, generated using the on-line preprocessing module or external preprocessing packages, are downloaded to a network of 32 transputers for accelerated solution. The system currently executes at about one third Cray X-MP24 speed but additional acceleration appears likely. For the NASA selected demonstration problem of a Space Shuttle main engine turbine blade model with about 1500 nodes and 4500 independent degrees of freedom, the Cray X-MP24 required 23.9 seconds to obtain a solution while the transputer network, operated from an IBM PC-AT compatible host computer, required 71.7 seconds. Consequently, the $80,000 transputer network demonstrated a cost-performance ratio about 60 times better than the $15,000,000 Cray X-MP24 system.

Association of Hospital Costs With Complications Following Total Gastrectomy for Gastric Adenocarcinoma.

PubMed

Selby, Luke V; Gennarelli, Renee L; Schnorr, Geoffrey C; Solomon, Stephen B; Schattner, Mark A; Elkin, Elena B; Bach, Peter B; Strong, Vivian E

2017-10-01

Postoperative complications are associated with increased hospital costs following major surgery, but the mechanism by which they increase cost and the categories of care that drive this increase are poorly described. To describe the association of postoperative complications with hospital costs following total gastrectomy for gastric adenocarcinoma. This retrospective analysis of a prospectively collected gastric cancer surgery database at a single National Cancer Institute-designated comprehensive cancer center included all patients undergoing curative-intent total gastrectomy for gastric adenocarcinoma between January 2009 and December 2012 and was conducted in 2015 and 2016. Ninety-day normalized postoperative costs. Hospital accounting system costs were normalized to reflect Medicare reimbursement levels using the ratio of hospital costs to Medicare reimbursement and categorized into major cost categories. Differences between costs in Medicare proportional dollars (MP $) can be interpreted as the amount that would be reimbursed to an average hospital by Medicare if it paid differentially based on types and extent of postoperative complications. In total, 120 patients underwent curative-intent total gastrectomy for stage I through III gastric adenocarcinoma between 2009 and 2012. Of these, 79 patients (65.8%) were men, and the median (interquartile range) age was 64 (52-70) years. The 51 patients (42.5%) who underwent an uncomplicated total gastrectomy had a mean (SD) normalized cost of MP $12 330 (MP $2500), predominantly owing to the cost of surgical care (mean [SD] cost, MP $6830 [MP $1600]). The 34 patients (28.3%) who had a major complication had a mean (SD) normalized cost of MP $37 700 (MP $28 090). Surgical care was more expensive in these patients (mean [SD] cost, MP $8970 [MP $2750]) but was a smaller contributor to total cost (24%) owing to increased costs from room and board (mean [SD] cost, MP $11 940 [MP $8820]), consultations (mean [SD] cost, MP $3530 [MP $2410]), and intensive care unit care (mean [SD] cost, MP $7770 [MP $14 310]). Major complications were associated with tripled normalized costs following curative-intent total gastrectomy. Most of the excess costs were related to the treatment of complications. Interventions that decrease the number or severity of postoperative complications could result in substantial cost savings.

Emission Inventory of Halogenated greenhouse gases in China during 1980-2050

NASA Astrophysics Data System (ADS)

Fang, X.; Velders, G. J. M.; Ravishankara, A. R.; Molina, M.; Su, S.; Zhang, J.; Zhou, X.; Hu, J.; Prinn, R. G.

2015-12-01

China is currently the largest producer and consumer of ozone-depleting substances (ODSs) which are regulated by the Montreal Protocol (MP). Many ODSs are also powerful greenhouse gases (GHGs). The Multilateral Fund has subsidized ~1 billion US dollars for the ODS phase out in China, and thus the return on this investment is of great interest. This study gives a comprehensive emission inventory in China from 1980 to 2013 of halocarbons including ODSs and their alternatives, the hydrofluorocarbons (HFCs) that are also greenhouse gases. We then project these emissions up to 2050 according to the MP and several policy options. Total emissions of ODS and HFCs were estimated to be ~500 CO2-eq Tg/yr in 2013 which are equivalent to ~5% of total GHG emissions in China including fossil fuel CO2 emissions. Our estimate shows that China has succeeded in substantially reducing CFC-11-equivalent emissions (to protect the ozone layer), and CO2-equivalent emissions (to protect climate) of ODSs since the mid-1990s when their phase out started in China in compliance with the MP. Furthermore, the avoided CO2-eq emissions due to compliance with the MP are even greater compared to the reduced emissions, for example net cumulative avoided emissions during 19 year period between 1995-2013 are comparable to the current one year CO2 emissions from fossil fuels in China. We find that HFC CO2-eq emissions increased rapidly in last decade, which make up ~2% in 2005 to ~20% of total halocarbon CO2-eq emissions in 2013. Under a baseline scenario in which HFCs are used as alternatives in the ongoing phase out of HCFCs in China, emissions of HFCs are predicted to be important components of both China's and global future GHG emissions. However, potential exists for minimizing China's HFC emissions under mitigation scenarios. Our conclusions about China's past and future ODS and HFC emission trajectories are likely to apply to other developing countries, with important implications for mitigating global GHG emissions.

NDL-v2.0: A new version of the numerical differentiation library for parallel architectures

NASA Astrophysics Data System (ADS)

Hadjidoukas, P. E.; Angelikopoulos, P.; Voglis, C.; Papageorgiou, D. G.; Lagaris, I. E.

2014-07-01

We present a new version of the numerical differentiation library (NDL) used for the numerical estimation of first and second order partial derivatives of a function by finite differencing. In this version we have restructured the serial implementation of the code so as to achieve optimal task-based parallelization. The pure shared-memory parallelization of the library has been based on the lightweight OpenMP tasking model allowing for the full extraction of the available parallelism and efficient scheduling of multiple concurrent library calls. On multicore clusters, parallelism is exploited by means of TORC, an MPI-based multi-threaded tasking library. The new MPI implementation of NDL provides optimal performance in terms of function calls and, furthermore, supports asynchronous execution of multiple library calls within legacy MPI programs. In addition, a Python interface has been implemented for all cases, exporting the functionality of our library to sequential Python codes. Catalog identifier: AEDG_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEDG_v2_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 63036 No. of bytes in distributed program, including test data, etc.: 801872 Distribution format: tar.gz Programming language: ANSI Fortran-77, ANSI C, Python. Computer: Distributed systems (clusters), shared memory systems. Operating system: Linux, Unix. Has the code been vectorized or parallelized?: Yes. RAM: The library uses O(N) internal storage, N being the dimension of the problem. It can use up to O(N2) internal storage for Hessian calculations, if a task throttling factor has not been set by the user. Classification: 4.9, 4.14, 6.5. Catalog identifier of previous version: AEDG_v1_0 Journal reference of previous version: Comput. Phys. Comm. 180(2009)1404 Does the new version supersede the previous version?: Yes Nature of problem: The numerical estimation of derivatives at several accuracy levels is a common requirement in many computational tasks, such as optimization, solution of nonlinear systems, and sensitivity analysis. For a large number of scientific and engineering applications, the underlying functions correspond to simulation codes for which analytical estimation of derivatives is difficult or almost impossible. A parallel implementation that exploits systems with multiple CPUs is very important for large scale and computationally expensive problems. Solution method: Finite differencing is used with a carefully chosen step that minimizes the sum of the truncation and round-off errors. The parallel versions employ both OpenMP and MPI libraries. Reasons for new version: The updated version was motivated by our endeavors to extend a parallel Bayesian uncertainty quantification framework [1], by incorporating higher order derivative information as in most state-of-the-art stochastic simulation methods such as Stochastic Newton MCMC [2] and Riemannian Manifold Hamiltonian MC [3]. The function evaluations are simulations with significant time-to-solution, which also varies with the input parameters such as in [1, 4]. The runtime of the N-body-type of problem changes considerably with the introduction of a longer cut-off between the bodies. In the first version of the library, the OpenMP-parallel subroutines spawn a new team of threads and distribute the function evaluations with a PARALLEL DO directive. This limits the functionality of the library as multiple concurrent calls require nested parallelism support from the OpenMP environment. Therefore, either their function evaluations will be serialized or processor oversubscription is likely to occur due to the increased number of OpenMP threads. In addition, the Hessian calculations include two explicit parallel regions that compute first the diagonal and then the off-diagonal elements of the array. Due to the barrier between the two regions, the parallelism of the calculations is not fully exploited. These issues have been addressed in the new version by first restructuring the serial code and then running the function evaluations in parallel using OpenMP tasks. Although the MPI-parallel implementation of the first version is capable of fully exploiting the task parallelism of the PNDL routines, it does not utilize the caching mechanism of the serial code and, therefore, performs some redundant function evaluations in the Hessian and Jacobian calculations. This can lead to: (a) higher execution times if the number of available processors is lower than the total number of tasks, and (b) significant energy consumption due to wasted processor cycles. Overcoming these drawbacks, which become critical as the time of a single function evaluation increases, was the primary goal of this new version. Due to the code restructure, the MPI-parallel implementation (and the OpenMP-parallel in accordance) avoids redundant calls, providing optimal performance in terms of the number of function evaluations. Another limitation of the library was that the library subroutines were collective and synchronous calls. In the new version, each MPI process can issue any number of subroutines for asynchronous execution. We introduce two library calls that provide global and local task synchronizations, similarly to the BARRIER and TASKWAIT directives of OpenMP. The new MPI-implementation is based on TORC, a new tasking library for multicore clusters [5-7]. TORC improves the portability of the software, as it relies exclusively on the POSIX-Threads and MPI programming interfaces. It allows MPI processes to utilize multiple worker threads, offering a hybrid programming and execution environment similar to MPI+OpenMP, in a completely transparent way. Finally, to further improve the usability of our software, a Python interface has been implemented on top of both the OpenMP and MPI versions of the library. This allows sequential Python codes to exploit shared and distributed memory systems. Summary of revisions: The revised code improves the performance of both parallel (OpenMP and MPI) implementations. The functionality and the user-interface of the MPI-parallel version have been extended to support the asynchronous execution of multiple PNDL calls, issued by one or multiple MPI processes. A new underlying tasking library increases portability and allows MPI processes to have multiple worker threads. For both implementations, an interface to the Python programming language has been added. Restrictions: The library uses only double precision arithmetic. The MPI implementation assumes the homogeneity of the execution environment provided by the operating system. Specifically, the processes of a single MPI application must have identical address space and a user function resides at the same virtual address. In addition, address space layout randomization should not be used for the application. Unusual features: The software takes into account bound constraints, in the sense that only feasible points are used to evaluate the derivatives, and given the level of the desired accuracy, the proper formula is automatically employed. Running time: Running time depends on the function's complexity. The test run took 23 ms for the serial distribution, 25 ms for the OpenMP with 2 threads, 53 ms and 1.01 s for the MPI parallel distribution using 2 threads and 2 processes respectively and yield-time for idle workers equal to 10 ms. References: [1] P. Angelikopoulos, C. Paradimitriou, P. Koumoutsakos, Bayesian uncertainty quantification and propagation in molecular dynamics simulations: a high performance computing framework, J. Chem. Phys 137 (14). [2] H.P. Flath, L.C. Wilcox, V. Akcelik, J. Hill, B. van Bloemen Waanders, O. Ghattas, Fast algorithms for Bayesian uncertainty quantification in large-scale linear inverse problems based on low-rank partial Hessian approximations, SIAM J. Sci. Comput. 33 (1) (2011) 407-432. [3] M. Girolami, B. Calderhead, Riemann manifold Langevin and Hamiltonian Monte Carlo methods, J. R. Stat. Soc. Ser. B (Stat. Methodol.) 73 (2) (2011) 123-214. [4] P. Angelikopoulos, C. Paradimitriou, P. Koumoutsakos, Data driven, predictive molecular dynamics for nanoscale flow simulations under uncertainty, J. Phys. Chem. B 117 (47) (2013) 14808-14816. [5] P.E. Hadjidoukas, E. Lappas, V.V. Dimakopoulos, A runtime library for platform-independent task parallelism, in: PDP, IEEE, 2012, pp. 229-236. [6] C. Voglis, P.E. Hadjidoukas, D.G. Papageorgiou, I. Lagaris, A parallel hybrid optimization algorithm for fitting interatomic potentials, Appl. Soft Comput. 13 (12) (2013) 4481-4492. [7] P.E. Hadjidoukas, C. Voglis, V.V. Dimakopoulos, I. Lagaris, D.G. Papageorgiou, Supporting adaptive and irregular parallelism for non-linear numerical optimization, Appl. Math. Comput. 231 (2014) 544-559.

Actions of 2-methylpiperidine (MP) and its interactions with (-)-nicotine (N) in the dog and rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sloan, J.W.; Martin, W.R.; Bostwick, M.

1986-03-01

(+/-)-MP is a highly specific drug for enhancing the binding of (+/-)-(/sup 3/H)N in the rat brain P/sub 2/ preparation. Competition studies employing (+/-)-(/sup 3/H)N as the labelled ligand show that this activity resides in the (+) isomer. Saturation studies employing (+/-)-(/sup 3/H)MP indicate that it binds to a very high affinity site which is presumed to be an up-regulatory site. Studies were conducted where (+/-)-MP was injected through an implanted cannula into the 4th ventricle of intact beagle-type dogs. (+/-)-MP, like low doses of (+)-N, another drug which has specificity in enhancing the binding of (+/-)-, and (-)- andmore » (+)-(/sup 3/H)N, produced EEG synchronization and miosis. (-)-N produced analgesia where as (+/-)-MP produced hyperalgesia. In the urethane-pentobarbital anethetized rats, the i.v. infusion of (+)-MP (600 ..mu..g/kg/min for 10 min), had no effect on heart rate, blood pressure or respiration. Pretreatment with (+)-MP delayed and decreased the bradycardia, vasodepression, and enhanced tidal volume produced by (-)-N infusion (60 ..mu..g/kg/min). These data show that the pharmacologic actions of MP are different from (-)-N and hexamethonium and that MP, which enhances the binding of (+/-)- and (-)-(/sup 3/H)N at the high affinity site, appears to exert opposite effects to and antagonistic effects against (-)-N.« less

Optimization of a GCaMP calcium indicator for neural activity imaging

PubMed Central

Akerboom, Jasper; Chen, Tsai-Wen; Wardill, Trevor J.; Tian, Lin; Marvin, Jonathan S.; Mutlu, Sevinç; Calderón, Nicole Carreras; Esposti, Federico; Borghuis, Bart G.; Sun, Xiaonan Richard; Gordus, Andrew; Orger, Michael B.; Portugues, Ruben; Engert, Florian; Macklin, John J.; Filosa, Alessandro; Aggarwal, Aman; Kerr, Rex; Takagi, Ryousuke; Kracun, Sebastian; Shigetomi, Eiji; Khakh, Baljit S.; Baier, Herwig; Lagnado, Leon; Wang, Samuel S.-H.; Bargmann, Cornelia I.; Kimmel, Bruce E.; Jayaraman, Vivek; Svoboda, Karel; Kim, Douglas S.; Schreiter, Eric R.; Looger, Loren L.

2012-01-01

Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Recent efforts in protein engineering have significantly increased the performance of GECIs. The state-of-the art single-wavelength GECI, GCaMP3, has been deployed in a number of model organisms and can reliably detect three or more action potentials (APs) in short bursts in several systems in vivo. Through protein structure determination, targeted mutagenesis, high-throughput screening, and a battery of in vitro assays, we have increased the dynamic range of GCaMP3 by several-fold, creating a family of “GCaMP5” sensors. We tested GCaMP5s in several systems: cultured neurons and astrocytes, mouse retina, and in vivo in Caenorhabditis chemosensory neurons, Drosophila larval neuromuscular junction and adult antennal lobe, zebrafish retina and tectum, and mouse visual cortex. Signal-to-noise ratio was improved by at least 2–3-fold. In the visual cortex, two GCaMP5 variants detected twice as many visual stimulus-responsive cells as GCaMP3. By combining in vivo imaging with electrophysiology we show that GCaMP5 fluorescence provides a more reliable measure of neuronal activity than its predecessor GCaMP3. GCaMP5 allows more sensitive detection of neural activity in vivo and may find widespread applications for cellular imaging in general. PMID:23035093

Rift Valley fever virus MP-12 vaccine encoding Toscana virus NSs retains neuroinvasiveness in mice.

PubMed

Indran, Sabarish V; Lihoradova, Olga A; Phoenix, Inaia; Lokugamage, Nandadeva; Kalveram, Birte; Head, Jennifer A; Tigabu, Bersabeh; Smith, Jennifer K; Zhang, Lihong; Juelich, Terry L; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro

2013-07-01

Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-β gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV.

Loading cisplatin onto 6-mercaptopurine covalently modified MSNS: a nanomedicine strategy to improve the outcome of cisplatin therapy

PubMed Central

Lv, Xiaojie; Zhao, Ming; Wang, Yuiji; Hu, Xi; Wu, Jianhui; Jiang, Xueyun; Li, Shan; Cui, Chunying; Peng, Shiqi

2016-01-01

In the treatment of cancer patients, cisplatin (CDDP) exhibits serious cardiac and renal toxicities, while classical combinations related to CDDP are unable to solve these problems and may result in worse prognosis. Alternately, this study covalently conjugated 6-mercaptopurine (6MP) onto the surface of mercapto-modified mesoporous silica nanoparticles (MSNS) to form MSNS-6MP and loaded CDDP into the holes on the surface of MSNS-6MP to form MSNS-6MP/CDDP, a tumor-targeting nano-releasing regime for CDDP and 6MP specifically. In the S180 mouse model, the anti-tumor activity and overall survival of MSNS-6MP/CDDP (50 mg·kg−1·day−1, corresponding to 1 mg·kg−1·day−1 of 6MP and 5 mg·kg−1·day−1 of CDDP) were significantly higher than those of CDDP alone (5 mg·kg−1·day−1) or CDDP (5 mg·kg−1·day−1) plus 6MP (1 mg·kg−1·day−1). The assays of serum alanine aminotransferase, aspartate aminotransferase and creatinine, as well as the images of myocardium and kidney histology, support that MSNS-6MP/CDDP is able to completely eliminate liver, kidney and heart toxicities induced by CDDP alone or CDDP plus 6MP. PMID:27942204

Loading cisplatin onto 6-mercaptopurine covalently modified MSNS: a nanomedicine strategy to improve the outcome of cisplatin therapy.

PubMed

Lv, Xiaojie; Zhao, Ming; Wang, Yuiji; Hu, Xi; Wu, Jianhui; Jiang, Xueyun; Li, Shan; Cui, Chunying; Peng, Shiqi

2016-01-01

In the treatment of cancer patients, cisplatin (CDDP) exhibits serious cardiac and renal toxicities, while classical combinations related to CDDP are unable to solve these problems and may result in worse prognosis. Alternately, this study covalently conjugated 6-mercaptopurine (6MP) onto the surface of mercapto-modified mesoporous silica nanoparticles (MSNS) to form MSNS-6MP and loaded CDDP into the holes on the surface of MSNS-6MP to form MSNS-6MP/CDDP, a tumor-targeting nano-releasing regime for CDDP and 6MP specifically. In the S180 mouse model, the anti-tumor activity and overall survival of MSNS-6MP/CDDP (50 mg·kg -1 ·day -1 , corresponding to 1 mg·kg -1 ·day -1 of 6MP and 5 mg·kg -1 ·day -1 of CDDP) were significantly higher than those of CDDP alone (5 mg·kg -1 ·day -1 ) or CDDP (5 mg·kg -1 ·day -1 ) plus 6MP (1 mg·kg -1 ·day -1 ). The assays of serum alanine aminotransferase, aspartate aminotransferase and creatinine, as well as the images of myocardium and kidney histology, support that MSNS-6MP/CDDP is able to completely eliminate liver, kidney and heart toxicities induced by CDDP alone or CDDP plus 6MP.

Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia.

PubMed

Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas; Rosthøj, Susanne; Nersting, Jacob

2015-05-01

High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue to prevent toxicities, but myelosuppression can also be prevented by pre-HD-MTX 6MP dose reductions. Accordingly, we monitored pre-HD-MTX erythrocyte levels of methylated 6MP metabolites (Ery-MeMP) and of thioguanine nucleotides (Ery-6TGN) as well as DNA-incorporated thioguanine nucleotides (DNA-TGN) in circulating leucocytes to identify patients at highest risk of post-HD-MTX myelosuppression. In multiple linear regression analyses of neutrophil and thrombocyte nadir values (adjusted for gender, age, risk group and 6MP dose) after 48 HD-MTX courses in 17 childhood ALL patients on MTX/6MP maintenance therapy, the pre-HD-MTX DNA-TGN levels in neutrophils (P < 0.0001), Ery-MeMP (P < 0.0001) and Ery-6TGN (P = 0.01) levels were significant predictors of post-HD-MTX neutrophil nadirs, whereas Ery-MeMP (P < 0.0001) was the only predictor of post-HD-MTX thrombocyte nadir. In conclusion, pre-HD-MTX 6MP metabolite levels may be applicable for 6MP dose adjustments to prevent HD-MTX-induced myelosuppression.

Rift Valley fever virus MP-12 vaccine encoding Toscana virus NSs retains neuroinvasiveness in mice

PubMed Central

Indran, Sabarish V.; Lihoradova, Olga A.; Phoenix, Inaia; Lokugamage, Nandadeva; Kalveram, Birte; Head, Jennifer A.; Tigabu, Bersabeh; Smith, Jennifer K.; Zhang, Lihong; Juelich, Terry L.; Gong, Bin; Freiberg, Alexander N.

2013-01-01

Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-β gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV. PMID:23515022

Low energy isomers of (H{sub 2}O){sub 25} from a hierarchical method based on Monte Carlo temperature basin paving and molecular tailoring approaches benchmarked by MP2 calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahu, Nityananda; Gadre, Shridhar R., E-mail: gadre@iitk.ac.in, E-mail: sotiris.xantheas@pnnl.gov; Rakshit, Avijit

2014-10-28

We report new global minimum candidate structures for the (H{sub 2}O){sub 25} cluster that are lower in energy than the ones reported previously and correspond to hydrogen bonded networks with 42 hydrogen bonds and an interior, fully coordinated water molecule. These were obtained as a result of a hierarchical approach based on initial Monte Carlo Temperature Basin Paving sampling of the cluster's Potential Energy Surface with the Effective Fragment Potential, subsequent geometry optimization using the Molecular Tailoring Approach with the fragments treated at the second order Møller-Plesset (MP2) perturbation (MTA-MP2) and final refinement of the entire cluster at the MP2more » level of theory. The MTA-MP2 optimized cluster geometries, constructed from the fragments, were found to be within <0.5 kcal/mol from the minimum geometries obtained from the MP2 optimization of the entire (H{sub 2}O){sub 25} cluster. In addition, the grafting of the MTA-MP2 energies yields electronic energies that are within <0.3 kcal/mol from the MP2 energies of the entire cluster while preserving their energy rank order. Finally, the MTA-MP2 approach was found to reproduce the MP2 harmonic vibrational frequencies, constructed from the fragments, quite accurately when compared to the MP2 ones of the entire cluster in both the HOH bending and the OH stretching regions of the spectra.« less

Noah-MP-Crop: Introducing dynamic crop growth in the Noah-MP land surface model

NASA Astrophysics Data System (ADS)

Liu, Xing; Chen, Fei; Barlage, Michael; Zhou, Guangsheng; Niyogi, Dev

2016-12-01

Croplands are important in land-atmosphere interactions and in the modification of local and regional weather and climate; however, they are poorly represented in the current version of the coupled Weather Research and Forecasting/Noah with multiparameterization (Noah-MP) land surface modeling system. This study introduced dynamic corn (Zea mays) and soybean (Glycine max) growth simulations and field management (e.g., planting date) into Noah-MP and evaluated the enhanced model (Noah-MP-Crop) at field scales using crop biomass data sets, surface heat fluxes, and soil moisture observations. Compared to the generic dynamic vegetation and prescribed-leaf area index (LAI)-driven methods in Noah-MP, the Noah-MP-Crop showed improved performance in simulating leaf area index (LAI) and crop biomass. This model is able to capture the seasonal and annual variability of LAI and to differentiate corn and soybean in peak values of LAI as well as the length of growing seasons. Improved simulations of crop phenology in Noah-MP-Crop led to better surface heat flux simulations, especially in the early period of growing season where current Noah-MP significantly overestimated LAI. The addition of crop yields as model outputs expand the application of Noah-MP-Crop to regional agriculture studies. There are limitations in the use of current growing degree days (GDD) criteria to predict growth stages, and it is necessary to develop a new method that combines GDD with other environmental factors, to more accurately define crop growth stages. The capability introduced in Noah-MP allows further crop-related studies and development.

Lobster on the Sidewalk: Understanding and Helping Children with Fears.

ERIC Educational Resources Information Center

Rubin, Roberta I.; And Others

1979-01-01

Discusses the cognitive processes and emotional needs that influence developmental changes related to fears and suggests some techniques which adults may use to help children cope with their fears. (Author/MP)

Space Environmental Effects on Materials and Processes

NASA Technical Reports Server (NTRS)

Sabbann, Leslie M.

2009-01-01

The Materials and Processes (M&P) Branch of the Structural Engineering Division at Johnson Space Center (JSC) seeks to uphold the production of dependable space hardware through materials research, which fits into NASA's purpose of advancing human exploration, use, and development of space. The Space Environmental Effects projects fully support these Agency goals. Two tasks were assigned to support M&P. Both assignments were to further the research of material behavior outside of Earth's atmosphere in order to determine which materials are most durable and safe to use in space for mitigating risks. One project, the Materials on International Space Station Experiments (MISSE) task, was to compile data from International Space Station (ISS) experiments to pinpoint beneficial space hardware. The other project was researching the effects on composite materials of exposure to high doses of radiation for a Lunar habitat project.

77 FR 43657 - Progressive Rail, Incorporated-Discontinuance of Service Exemption-in Barron County, WI

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

....05 at or near Rice Lake. The Lines are owned by WCL and have been operated by PGR since 2004 under...), Poskin (MP 85.4), Barron (MP 91.10), Cameron (MP 96.1), and Rice Lake (MP 56.05). \\1\\ See Progressive...

Focal dose escalation for prostate cancer using 68Ga-HBED-CC PSMA PET/CT and MRI: a planning study based on histology reference.

PubMed

Zamboglou, Constantinos; Thomann, Benedikt; Koubar, Khodor; Bronsert, Peter; Krauss, Tobias; Rischke, Hans C; Sachpazidis, Ilias; Drendel, Vanessa; Salman, Nasr; Reichel, Kathrin; Jilg, Cordula A; Werner, Martin; Meyer, Philipp T; Bock, Michael; Baltas, Dimos; Grosu, Anca L

2018-05-02

Focal radiation therapy has gained of interest in treatment of patients with primary prostate cancer (PCa). The question of how to define the intraprostatic boost volume is still open. Previous studies showed that multiparametric MRI (mpMRI) or PSMA PET alone could be used for boost volume definition. However, other studies proposed that the combined usage of both has the highest sensitivity in detection of intraprostatic lesions. The aim of this study was to demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of radiation therapy dose painting using 68 Ga-HBED-CC PSMA PET/CT, mpMRI or the combination of both in primary PCa. Ten patients underwent PSMA PET/CT and mpMRI followed by prostatectomy. Three gross tumour volumes (GTVs) were created based on PET (GTV-PET), mpMRI (GTV-MRI) and the union of both (GTV-union). Two plans were generated for each GTV. Plan95 consisted of whole-prostate IMRT to 77 Gy in 35 fractions and a simultaneous boost to 95 Gy (Plan95 PET /Plan95 MRI /Plan95 union ). Plan80 consisted of whole-prostate IMRT to 76 Gy in 38 fractions and a simultaneous boost to 80 Gy (Plan80 PET /Plan80 MRI /Plan80 union ). TCPs were calculated for GTV-histo (TCP-histo), which was delineated based on PCa distribution in co-registered histology slices. NTCPs were assessed for bladder and rectum. Dose constraints of published protocols were reached in every treatment plan. Mean TCP-histo were 99.7% (range: 97%-100%) and 75.5% (range: 33%-95%) for Plan95 union and Plan80 union , respectively. Plan95 union had significantly higher TCP-histo values than Plan95 MRI (p = 0.008) and Plan95 PET (p = 0.008). Plan80 union had significantly higher TCP-histo values than Plan80 MRI (p = 0.012), but not than Plan80 PET (p = 0.472). Plan95 MRI had significantly lower NTCP-rectum than Plan95 union (p = 0.012). No significant differences in NTCP-rectum and NTCP-bladder were observed for all other plans (p > 0.05). IMRT dose escalation on GTVs based on mpMRI, PSMA PET/CT and the combination of both was feasible. Boosting GTV-union resulted in significantly higher TCP-histo with no or minimal increase of NTCPs compared to the other plans.

Comparative Toxicity of Preservatives on Immortalized Corneal and Conjunctival Epithelial Cells

PubMed Central

Ahdoot, Michael; Marcus, Edward; Asbell, Penny A.

2009-01-01

Abstract Purpose Nearly all eye drops contain preservatives to decrease contamination. Nonpreservatives such as disodium-ethylene diamine tetra-acetate (EDTA) and phosphate-buffered saline are also regularly added as buffering agents. These components can add to the toxicity of eye drops and cause ocular surface disease. To evaluate the potential toxicity of these common components and their comparative effects on the ocular surface, a tissue culture model utilizing immortalized corneal and conjunctival epithelial cells was utilized. Methods Immortalized human conjunctival and corneal epithelial cells were grown. At confluency, medium was replaced with 100 μL of varying concentrations of preservatives: benzalkonium chloride (BAK), methyl paraben (MP), sodium perborate (SP), chlorobutanol (Cbl), and stabilized thimerosal (Thi); varying concentrations of buffer: EDTA; media (viable control); and formalin (dead control). After 1 h, solutions were replaced with 150 μL of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazonium bromide). After 4 h, solutions decanted, 100 μL of acid isopropanol added, and the optical density determined at 572 nm to evaluate cell viability. Results Conjunctival and corneal cell toxicity was seen with all preservatives. Depending upon concentration, BAK exhibited from 56% to 89% toxicity. In comparison, Cbl exhibited from 50% to 86%, MP from 30% to 76%, SP from 23% to 59%, and Thi from 70% to 95%. EDTA with minimal toxicity (from 6% to 59%) was indistinguishable from SP. Conclusions Generally, the order of decreasing toxicity at the most commonly used concentrations: Thi (0.0025%) > BAK (0.025%) > Cbl (0.25%) > MP (0.01%) > SP (0.0025%) ≈ EDTA (0.01%). Even at low concentration, these agents will cause some degree of ocular tissue damage. PMID:19284328

Controlled circumferential renal sympathetic denervation with preservation of the renal arterial wall using intraluminal ultrasound: a next-generation approach for treating sympathetic overactivity.

PubMed

Sakakura, Kenichi; Roth, Austin; Ladich, Elena; Shen, Kai; Coleman, Leslie; Joner, Michael; Virmani, Renu

2015-02-01

The Paradise Ultrasound Renal Denervation System is a next-generation catheter-based device which was used to investigate whether the target ablation area can be controlled by changing ultrasound energy and duration to optimise nerve injury while preventing damage to the arterial wall. Five ultrasound doses were tested in a thermal gel model. Catheter-based ultrasound denervation was performed in 15 swine (29 renal arteries) to evaluate five different doses in vivo, and animals were euthanised at seven days for histopathologic assessment. In the gel model, the peak temperature was highest in the low power-long duration (LP-LD) dose, followed by the mid-low power-mid duration (MLP-MD) dose and the mid-high power-short duration (MHP-SD) dose, and lowest in the mid power-short duration (MP-SD) dose and the high power-ultra short duration (HP-USD) dose. In the animal study, total ablation area was significantly greater in the LP-LD group, followed by the MLP-MD group, and it was least in the HP-USD, MP-SD and MHP-SD groups (p=0.02). Maximum distance was significantly greater in the LP-LD group, followed by the MLP-MD group, the MHP-SD group, and the HP-USD group, and shortest in the MP-SD group (p=0.007). The short spare distance was not different among the five groups (p=0.38). Renal artery damage was minimal, while preserving significant nerve damage in all groups. The Paradise Ultrasound Renal Denervation System is a controllable system where total ablation area and depth of ablation can be optimised by changing ultrasound power and duration while sparing renal arterial tissue damage but allowing sufficient peri-arterial nerve damage.

Genetic Instability of Breast Cancer Cells Induced by Aberrant Expression of hMpS1

DTIC Science & Technology

2004-09-01

and function of the mitotic spindle is dependent on the MpS1 protein kinase. The components of mitotic spindle checkpoints were first identified in...yeast and their homologs of higher organisms were then identified and characterized. These include Bubl, Bub2, Bub3, Madl, Mad2, Mad3 and MpS1 . MpS 1...spindle checkpoint and centrosome duplication (1-6). Although several recent reports demonstrated that vertebrate MpS1 proteins regulate the spindle

Data processing system for the Sneg-2MP experiment

NASA Technical Reports Server (NTRS)

Gavrilova, Y. A.

1980-01-01

The data processing system for scientific experiments on stations of the "Prognoz" type provides for the processing sequence to be broken down into a number of consecutive stages: preliminary processing, primary processing, secondary processing. The tasks of each data processing stage are examined for an experiment designed to study gamma flashes of galactic origin and solar flares lasting from several minutes to seconds in the 20 kev to 1000 kev energy range.

On the Performance of an Algebraic MultigridSolver on Multicore Clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, A H; Schulz, M; Yang, U M

2010-04-29

Algebraic multigrid (AMG) solvers have proven to be extremely efficient on distributed-memory architectures. However, when executed on modern multicore cluster architectures, we face new challenges that can significantly harm AMG's performance. We discuss our experiences on such an architecture and present a set of techniques that help users to overcome the associated problems, including thread and process pinning and correct memory associations. We have implemented most of the techniques in a MultiCore SUPport library (MCSup), which helps to map OpenMP applications to multicore machines. We present results using both an MPI-only and a hybrid MPI/OpenMP model.

Azathioprine suppresses the mixed lymphocyte reaction of patients with Lesch-Nyhan syndrome.

PubMed Central

Szawlowski, P W; Al-Safi, S A; Dooley, T; Maddocks, J L

1985-01-01

The mixed lymphocyte reaction of Lesch-Nyhan patients (HGPRT deficient) was used to study the immunosuppressive effects of azathioprine and 6-mercaptopurine (6-MP). Mitogen stimulated lymphocytes of these patients are highly resistant to azathioprine and 6-MP. When both stimulator and responder lymphocytes in the MLR were HGPRT deficient, azathioprine (36 microM) was much more inhibitory than 6-MP (100 microM). Azathioprine produced inhibition of 98.2% and 78.5% compared with the values of 63.9% and 30.6% for 6-MP. The difference in inhibitory activity between azathioprine and 6-MP was reduced when normal stimulator lymphocytes were cultured with HGPRT deficient responder lymphocytes in the MLR. These results provide very strong evidence that the nucleotide metabolites of azathioprine and 6-MP are unnecessary for immunosuppression. They also suggest that azathioprine and 6-MP interfere with antigenic triggering of the MLR. PMID:2934083

Health Information in Modern Standard Arabic (al-ʻArabīyat ul-fuṣḥá)

MedlinePlus

... fuṣḥá (Modern Standard Arabic) MP4 Healthy Roads Media Tornadoes - English MP3 Tornadoes - al-ʻArabīyat ul-fuṣḥá (Modern Standard Arabic) MP3 Tornadoes - English MP4 Tornadoes - al-ʻArabīyat ul-fuṣḥá (Modern ...

Registration of Mp718 and Mp719 germplasm lines of maize

USDA-ARS?s Scientific Manuscript database

Maize (Zea mays L.) germplasm lines Mp718 (Reg. No. GP-xxxx, PI 662045) and Mp719 (Reg. No. GP-xxxx, PI 662046) were developed and released by USDA-ARS in cooperation with the Mississippi Agricultural and Forestry Experiment Station, Mississippi State, Mississippi, as sources of resistance to aflat...

Changes in the structural and gel properties of pork myofibrillar protein induced by catechin modification.

PubMed

Jia, Na; Wang, Letian; Shao, Junhua; Liu, Dengyong; Kong, Baohua

2017-05-01

Different concentrations of catechin (0, 10, 50, 100 and 200μmol/g protein) were added to pork myofibrillar protein (MP) suspensions, and the related changes in protein conformational and gel properties were investigated. The results showed that catechin at 200μmol/g protein led to the greatest increase in the surface hydrophobicity of MP. A significant loss of thiols (SH) content was observed in MP in the presence of catechin. The low concentration of catechin of 10μmol/g led to slight changes in the MP gel strength and water-holding capacity. However, catechin at higher concentrations (50, 100 and 200μmol/g protein) caused severe deterioration of MP gelation. The microstructure and dynamic rheological properties confirmed the unfavorable effect of catechin on the MP gel properties. The results indicate that catechin caused changes in MP conformational and gel properties, which may be due to the catechin-MP covalent interactions and the exposure of hydrophobic domains caused by catechin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of polystyrene microbeads in marine planktonic crustaceans.

PubMed

Gambardella, Chiara; Morgana, Silvia; Ferrando, Sara; Bramini, Mattia; Piazza, Veronica; Costa, Elisa; Garaventa, Francesca; Faimali, Marco

2017-11-01

Plastic debris accumulates in the marine environment, fragmenting into microplastics (MP), causing concern about their potential toxic effects when ingested by marine organisms. The aim of this study was to verify whether 0.1µm polystyrene beads are likely to trigger lethal and sub-lethal responses in marine planktonic crustaceans. MP build-up, mortality, swimming speed alteration and enzyme activity (cholinesterases, catalase) were investigated in the larval stages of Amphibalanus amphitrite barnacle and of Artemia franciscana brine shrimp exposed to a wide range of MP concentrations (from 0.001 to 10mgL -1 ) for 24 and 48h. The results show that MP were accumulated in crustaceans, without affecting mortality. Swimming activity was significantly altered in crustaceans exposed to high MP concentrations (> 1mgL -1 ) after 48h. Enzyme activities were significantly affected in all organisms exposed to all the above MP concentrations, indicating that neurotoxic effects and oxidative stress were induced after MP treatment. These findings provide new insight into sub-lethal MP effects on marine crustaceans. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantification of microplastic mass and removal rates at wastewater treatment plants applying Focal Plane Array (FPA)-based Fourier Transform Infrared (FT-IR) imaging.

PubMed

Simon, Márta; van Alst, Nikki; Vollertsen, Jes

2018-05-17

This paper presents a method for microplastic (MP) mass quantification using a Focal Plane Array-based Fourier Transform Infrared imaging technique. It discusses the issue that particle number is not a conserved base quantity and hence less suited than mass to compare independent studies on MP in the environment. It concludes that MP mass should be included when quantifying MP pollution in the environment, supplementing the conventional approach of reporting particle numbers. Applying mass as the unit of MP measurement, the paper presents data showing that Danish wastewater treatment plants discharge around 3 t/year of MP in the size range 10-500 μm. This value corresponds to an annual per capita emission from these plants of 0.56 g MP/(capita year). The distribution of polymer types by mass and particle number differed because the size of MP particles of the different material types varied. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The effect of tailor-made additives on crystal growth of methyl paraben: Experiments and modelling

NASA Astrophysics Data System (ADS)

Cai, Zhihui; Liu, Yong; Song, Yang; Guan, Guoqiang; Jiang, Yanbin

2017-03-01

In this study, methyl paraben (MP) was selected as the model component, and acetaminophen (APAP), p-methyl acetanilide (PMAA) and acetanilide (ACET), which share the similar molecular structure as MP, were selected as the three tailor-made additives to study the effect of tailor-made additives on the crystal growth of MP. HPLC results indicated that the MP crystals induced by the three additives contained MP only. Photographs of the single crystals prepared indicated that the morphology of the MP crystals was greatly changed by the additives, but PXRD and single crystal diffraction results illustrated that the MP crystals were the same polymorph only with different crystal habits, and no new crystal form was found compared with other references. To investigate the effect of the additives on the crystal growth, the interaction between additives and facets was discussed in detail using the DFT methods and MD simulations. The results showed that APAP, PMAA and ACET would be selectively adsorbed on the growth surfaces of the crystal facets, which induced the change in MP crystal habits.

Immuno-analysis of microparticles: probing at the limits of detection

PubMed Central

Latham, Sharissa L.; Tiberti, Natalia; Gokoolparsadh, Naveena; Holdaway, Karen; Olivier Couraud, Pierre; Grau, Georges E. R.; Combes, Valery

2015-01-01

Microparticle (MP) research is clouded by debate regarding the accuracy and validity of flow cytometry (FCM) as an analytical methodology, as it is influenced by many variables including the pre-analytical conditions, instruments physical capabilities and detection parameters. This study utilises a simplistic in vitro system for generating MP, and through comparative analysis with immuno-electron microscopy (Immuno-EM) assesses the strengths and limitations of probe selection and high-sensitivity FCM. Of the markers examined, MP were most specifically labelled with phosphatidylserine ligands, annexin V and lactadherin, although only ~60% MP are PS positive. Whilst these two ligands detect comparable absolute MP numbers, they interact with the same population in distinct manners; annexin V binding is enhanced on TNF induced MP. CD105 and CD54 expression were, as expected, consistent and enhanced following TNF activation respectively. Their labelling however accounted for as few as 30–40% of MP. The greatest discrepancies between FCM and I-EM were observed in the population solely labelled for the surface antigen. These findings demonstrate that despite significant improvements in resolution, high-sensitivity FCM remains limited in detecting small-size MP expressing low antigen levels. This study highlights factors to consider when selecting endothelial MP probes, as well as interpreting and representing data. PMID:26553743

Impact of acellular hemoglobin-based oxygen carriers on brain apoptosis in rats.

PubMed

Vandegriff, Kim D; Malavalli, Ashok; Lohman, Jeff; Young, Mark A; Terraneo, Laura; Virgili, Eleonora; Bianciardi, Paola; Caretti, Anna; Samaja, Michele

2014-08-01

Extracellular hemoglobin (Hb)-based oxygen carriers (HBOCs) are under extensive consideration as oxygen therapeutics. Their effects on cellular mechanisms related to apoptosis are of particular interest, because the onset of proapoptotic pathways may give rise to tissue damage. The objective was to assess whether the properties of the Hb that replaces blood during an isovolemic hemodilution would modulate apoptotic-response mechanisms in rat brain and whether such signaling favors cytoprotection or damage. We exposed rats to exchange transfusion (ET; 50% blood volume and isovolemic replacement with Hextend [negative colloid control], MP4OX [PEGylated HBOC with high oxygen affinity], and ααHb [αα-cross-linked HBOC with low oxygen affinity; n=4-6/group]). Sham rats acted as control. Animals were euthanized at 2, 6, and 12 hours after ET; brain tissue was harvested and processed for analysis. In MP4OX animals, the number of neurons that overexpressed the hypoxia-inducible factor (HIF)-1α was higher than in ααHb, particularly at the early time points. In addition, MP4OX was associated with greater phosphorylation of protein kinase B (Akt), a well-known cytoprotective factor. Indeed, the degree of apoptosis, measured as terminal deoxynucleotidyl transferase-positive neurons and caspase-3 cleavage, ranked in order of MP4OX < Hextend < ααHb. Even though both HBOCs showed increased levels of HIF-1α compared to shams or Hextend-treated animals, differences in signaling events resulted in very different outcomes for the two HBOCs. ααHb-treated brain tissue showed significant neuronal damage, measured as apoptosis. This was in stark contrast to the protection seen with MP4OX, apparently due to recruitment of Akt and neuronal specific HIF-1α pathways. © 2014 Sangart, Inc. Transfusion © 2014 AABB.

Landscape-level estimation of nitrogen removal in coastal Louisiana wetlands: potential sinks under different restoration scenarios

USGS Publications Warehouse

Rivera-Monroy, Victor H.; Branoff, Benjamin; Meselhe, Ehab; McCorquodale, Alex; Dortch, Mark; Steyer, Gregory D.; Visser, Jenneke; Wang, Hongqing

2013-01-01

Coastal eutrophication in the northern Gulf of Mexico (GOM) is the primary anthropogenic contributor to the largest zone of hypoxic bottom waters in North America. Although biologically mediated processes such as denitrification (Dn) are known to act as sinks for inorganic nitrogen, it is unknown what contribution denitrification makes to landscape-scale nitrogen budgets along the coast. As the State of Louisiana plans the implementation of a 2012 Coastal Master Plan (MP) to help restore its wetlands and protect its coast, it is critical to understand what effect potential restoration projects may have in altering nutrient budgets. As part of the MP, a spatial statistical approach was developed to estimate nitrogen removal under varying scenarios of future conditions and coastal restoration project implementation. In every scenario of future conditions under which MP implementation was modeled, more nitrogen () was removed from coastal waters when compared with conditions under which no action is taken. Overall, the MP increased coast-wide average nitrogen removal capacity (NRC) rates by up to 0.55 g N m−2 y−1 compared with the “future without action” (FWOA) scenario, resulting in a conservative estimate of up to 25% removal of the annual + load of the Mississippi-Atchafalaya rivers (956,480 t y−1). These results are spatially correlated, with the lower Mississippi River and Chenier Plain exhibiting the greatest change in NRC. Since the implementation of the MP can maintain, and in some regions increase the NRC, our results show the need to preserve the functionality of wetland habitats and use this ecosystem service (i.e. Dn) to decrease eutrophication of the GOM.

Safety, Tolerability and Immunogenicity of Pentavalent Rotavirus Vaccine Manufactured by a Modified Process.

PubMed

Martinón-Torres, Federico; Greenberg, David; Varman, Meera; Killar, John A; Hille, Darcy; Strable, Erica L; Stek, Jon E; Kaplan, Susan S

2017-04-01

Rotavirus is the leading cause of severe diarrhea in infants and young children. The current formulation of pentavalent rotavirus vaccine (RV5) must be stored refrigerated at 2-8°C. A modified formulation of RV5 (RV5mp) has been developed with stability at 37°C for 7 days and an expiry extended to 36 months when stored at 2-8°C. This study (ClinicalTrials.gov identifier: NCT01600092; EudraCT number: 2012-001611-23) evaluated the safety, tolerability and immunogenicity of RV5mp versus the currently marketed RV5 in infants. To maintain blinding, both vaccine formulations were stored refrigerated at 2-8°C for the duration of the study. Immunogenicity endpoints were (1) serum neutralizing antibody titers to human rotavirus serotypes G1, G2, G3, G4 and P1A[8] and (2) proportion of subjects with a ≥3-fold rise from baseline for serum neutralizing antibody to human rotavirus serotypes G1, G2, G3, G4 and P1A[8] and serum antirotavirus immunoglobulin A. The RV5mp group (n = 505) and RV5 group (n = 509) had comparable safety profiles. There were no deaths and no vaccine-related serious adverse events in this study. With respect to immunogenicity, RV5mp was noninferior compared with RV5. Serum neutralizing antibody responses by country and breast-feeding status were generally consistent with the overall results. RV5mp enhances storage requirements while maintaining the immunogenicity and safety profile of the currently licensed RV5. A vaccine that is stable at room temperature may be more convenient for vaccinators, particularly in places where the cold chain is unreliable, and ultimately will permit more widespread use.

Direct Position Determination of Unknown Signals in the Presence of Multipath Propagation

PubMed Central

Yu, Hongyi

2018-01-01

A novel geolocation architecture, termed “Multiple Transponders and Multiple Receivers for Multiple Emitters Positioning System (MTRE)” is proposed in this paper. Existing Direct Position Determination (DPD) methods take advantage of a rather simple channel assumption (line of sight channels with complex path attenuations) and a simplified MUltiple SIgnal Classification (MUSIC) algorithm cost function to avoid the high dimension searching. We point out that the simplified assumption and cost function reduce the positioning accuracy because of the singularity of the array manifold in a multi-path environment. We present a DPD model for unknown signals in the presence of Multi-path Propagation (MP-DPD) in this paper. MP-DPD adds non-negative real path attenuation constraints to avoid the mistake caused by the singularity of the array manifold. The Multi-path Propagation MUSIC (MP-MUSIC) method and the Active Set Algorithm (ASA) are designed to reduce the dimension of searching. A Multi-path Propagation Maximum Likelihood (MP-ML) method is proposed in addition to overcome the limitation of MP-MUSIC in the sense of a time-sensitive application. An iterative algorithm and an approach of initial value setting are given to make the MP-ML time consumption acceptable. Numerical results validate the performances improvement of MP-MUSIC and MP-ML. A closed form of the Cramér–Rao Lower Bound (CRLB) is derived as a benchmark to evaluate the performances of MP-MUSIC and MP-ML. PMID:29562601

Changing patterns of localization of the tobacco mosaic virus movement protein and replicase to the endoplasmic reticulum and microtubules during infection

NASA Technical Reports Server (NTRS)

Heinlein, M.; Padgett, H. S.; Gens, J. S.; Pickard, B. G.; Casper, S. J.; Epel, B. L.; Beachy, R. N.; Evans, M. L. (Principal Investigator)

1998-01-01

Tobacco mosaic virus (TMV) derivatives that encode movement protein (MP) as a fusion to the green fluorescent protein (MP:GFP) were used in combination with antibody staining to identify host cell components to which MP and replicase accumulate in cells of infected Nicotiana benthamiana leaves and in infected BY-2 protoplasts. MP:GFP and replicase colocalized to the endoplasmic reticulum (ER; especially the cortical ER) and were present in large, irregularly shaped, ER-derived structures that may represent "viral factories." The ER-derived structures required an intact cytoskeleton, and microtubules appeared to redistribute MP:GFP from these sites during late stages of infection. In leaves, MP:GFP accumulated in plasmodesmata, whereas in protoplasts, the MP:GFP was targeted to distinct, punctate sites near the plasma membrane. Treating protoplasts with cytochalasin D and brefeldin A at the time of inoculation prevented the accumulation of MP:GFP at these sites. It is proposed that the punctate sites anchor the cortical ER to plasma membrane and are related to sites at which plasmodesmata form in walled cells. Hairlike structures containing MP:GFP appeared on the surface of some of the infected protoplasts and are reminiscent of similar structures induced by other plant viruses. We present a model that postulates the role of the ER and cytoskeleton in targeting the MP and viral ribonucleoprotein from sites of virus synthesis to the plasmodesmata through which infection is spread.

Direct Position Determination of Unknown Signals in the Presence of Multipath Propagation.

PubMed

Du, Jianping; Wang, Ding; Yu, Wanting; Yu, Hongyi

2018-03-17

A novel geolocation architecture, termed "Multiple Transponders and Multiple Receivers for Multiple Emitters Positioning System (MTRE)" is proposed in this paper. Existing Direct Position Determination (DPD) methods take advantage of a rather simple channel assumption (line of sight channels with complex path attenuations) and a simplified MUltiple SIgnal Classification (MUSIC) algorithm cost function to avoid the high dimension searching. We point out that the simplified assumption and cost function reduce the positioning accuracy because of the singularity of the array manifold in a multi-path environment. We present a DPD model for unknown signals in the presence of Multi-path Propagation (MP-DPD) in this paper. MP-DPD adds non-negative real path attenuation constraints to avoid the mistake caused by the singularity of the array manifold. The Multi-path Propagation MUSIC (MP-MUSIC) method and the Active Set Algorithm (ASA) are designed to reduce the dimension of searching. A Multi-path Propagation Maximum Likelihood (MP-ML) method is proposed in addition to overcome the limitation of MP-MUSIC in the sense of a time-sensitive application. An iterative algorithm and an approach of initial value setting are given to make the MP-ML time consumption acceptable. Numerical results validate the performances improvement of MP-MUSIC and MP-ML. A closed form of the Cramér-Rao Lower Bound (CRLB) is derived as a benchmark to evaluate the performances of MP-MUSIC and MP-ML.

6-Mercaptopurine, an activator of Nur77, enhances transcriptional activity of HIF-1alpha resulting in new vessel formation.

PubMed

Yoo, Y-G; Na, T-Y; Yang, W-K; Kim, H-J; Lee, I-K; Kong, G; Chung, J-H; Lee, M-O

2007-05-31

Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a central role in oxygen homeostasis. Previously, we reported that the orphan nuclear receptor Nur77 functions in stabilizing HIF-1alpha. Here, we demonstrate that 6-mercaptopurine (6-MP), an activator of the NR4A family members, enhances transcriptional activity of HIF-1. 6-MP enhanced the protein-level of HIF-1alpha as well as vascular endothelial growth factor (VEGF) in a dose- and time-dependent manner. The induction of HIF-1alpha was abolished by the transfection of either a dominant-negative Nur77 mutant or si-Nur77, indicating a critical role of Nur77 in the 6-MP action. The HIF-1alpha protein level remained up to 60 min in the presence of 6-MP when de novo protein synthesis was blocked by cycloheximide, suggesting that 6-MP induces stabilization of the HIF-1alpha protein. The fact that 6-MP decreased the association of HIF-1alpha with von Hippel-Lindau protein and the acetylation of HIF-1alpha, may explain how 6-MP induced stability of HIF-1alpha. Further, 6-MP induced the transactivation function of HIF-1alpha by recruiting co-activator cyclic-AMP-response-element-binding protein. Finally, 6-MP enhanced the expression of HIF-1alpha and VEGF, and the formation of capillary tubes in human umbilical vascular endothelial cells. Together, our results provide a new insight for 6-MP action in the stabilization of HIF-1alpha and imply a potential application of 6-MP in hypoxia-associated human vascular diseases.

Phosphatidylserine lipids and membrane order precisely regulate the activity of Polybia-MP1 peptide.

PubMed

Alvares, Dayane S; Ruggiero Neto, João; Ambroggio, Ernesto E

2017-06-01

Polybia-MP1 (IDWKKLLDAAKQIL-NH 2 ) is a lytic peptide from the Brazilian wasp venom with known anti-cancer properties. Previous evidence indicates that phosphatidylserine (PS) lipids are relevant for the lytic activity of MP1. In agreement with this requirement, phosphatidylserine lipids are translocated to the outer leaflet of cells, and are available for MP1 binding, depending on the presence of liquid-ordered domains. Here, we investigated the effect of PS on MP1 activity when this lipid is reconstituted in membranes of giant or large liposomes with different lipid-phase states. By monitoring the membrane and soluble luminal content of giant unilamellar vesicles (GUVs), using fluorescence confocal microscopy, we were able to determine that MP1 has a pore-forming activity at the membrane level. Liquid-ordered domains, which were phase-separated within the membrane of GUVs, influenced the pore-forming activity of MP1. Experiments evaluating the membrane-binding and lytic activity of MP1 on large unilamellar vesicles (LUVs), with the same lipid composition as GUVs, demonstrated that there was synergy between liquid-ordered domains and PS, which enhanced both activities. Based on our findings, we propose that the physicochemical properties of cancer cell membranes, which possess a much higher concentration of PS than normal cells, renders them susceptible to MP1 binding and lytic pore formation. These results can be correlated with MP1's potent and selective anti-cancer activity and pave the way for future research to develop cancer therapies that harness and exploit the properties of MP1. Copyright © 2017 Elsevier B.V. All rights reserved.

The accuracy of quantum chemical methods for large noncovalent complexes

PubMed Central

Pitoňák, Michal; Řezáč, Jan; Pulay, Peter

2013-01-01

We evaluate the performance of the most widely used wavefunction, density functional theory, and semiempirical methods for the description of noncovalent interactions in a set of larger, mostly dispersion-stabilized noncovalent complexes (the L7 data set). The methods tested include MP2, MP3, SCS-MP2, SCS(MI)-MP2, MP2.5, MP2.X, MP2C, DFT-D, DFT-D3 (B3-LYP-D3, B-LYP-D3, TPSS-D3, PW6B95-D3, M06-2X-D3) and M06-2X, and semiempirical methods augmented with dispersion and hydrogen bonding corrections: SCC-DFTB-D, PM6-D, PM6-DH2 and PM6-D3H4. The test complexes are the octadecane dimer, the guanine trimer, the circumcoronene…adenine dimer, the coronene dimer, the guanine-cytosine dimer, the circumcoronene…guanine-cytosine dimer, and an amyloid fragment trimer containing phenylalanine residues. The best performing method is MP2.5 with relative root mean square deviation (rRMSD) of 4 %. It can thus be recommended as an alternative to the CCSD(T)/CBS (alternatively QCISD(T)/CBS) benchmark for molecular systems which exceed current computational capacity. The second best non-DFT method is MP2C with rRMSD of 8 %. A method with the most favorable “accuracy/cost” ratio belongs to the DFT family: BLYP-D3, with an rRMSD of 8 %. Semiempirical methods deliver less accurate results (the rRMSD exceeds 25 %). Nevertheless, their absolute errors are close to some much more expensive methods such as M06-2X, MP2 or SCS(MI)-MP2, and thus their price/performance ratio is excellent. PMID:24098094

A method to assess the migration properties of cell-derived microparticles within a living tissue.

PubMed

Hoang, Thang Q; Rampon, Christine; Freyssinet, Jean-Marie; Vriz, Sophie; Kerbiriou-Nabias, Danièle

2011-09-01

Cells undergoing activation or apoptosis exhibit plasma membrane changes, leading to the formation of shed vesicles (microparticles, MP). Although their effects on recipient cells in vitro, and their ability to support inflammatory or thrombotic events in the circulation have been studied, the spreading of such vesicles in tissues is still elusive. Our aim was to set up a method to examine the behavior of these vesicles in vivo. We examined the persistence of green-fluorescent microparticles (fMP), prepared after Ca2+ ionophore activation (iono-fMP) or apoptogenic treatment (eto-fMP) of human Jurkat T lymphoblastic or non-hematopoietic embryonic kidney (HEK) cell lines, following injection in zebrafish embryos 2h after egg fertilization. One hour post-injection, iono-fMP issued from both cell types formed a fluorescent dispersal in the intercellular space of embryos. In contrast, eto-fMP or MP deprived of sialic acid at their membrane, gathered together at the site of injection. We propose a method characterizing the abilities of MP to spread in the intercellular space. We showed that MP produced by apoptosis of T cells and those deprived of sialic acid at their membrane do not diffuse within the living cells. On the contrary, MP shed upon calcium induced activation of T and HEK cells, diffuse at a distance and spread in the intercellular space. The fate of injected MP relies on the type of induction rather than the cell species and results provide a model to test the ability of vesicles to interact locally or to spread outside of the site of production. Copyright © 2011 Elsevier B.V. All rights reserved.

Genetic stability of Rift Valley fever virus MP-12 vaccine during serial passages in culture cells.

PubMed

Lokugamage, Nandadeva; Ikegami, Tetsuro

2017-01-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa which affects both ruminants and humans. RVF causes serious damage to the livestock industry and is also a threat to public health. The Rift Valley fever virus has a segmented negative-stranded RNA genome consisting of Large (L)-, Medium (M)-, and Small (S)-segments. The live-attenuated MP-12 vaccine is immunogenic in livestock and humans, and is conditionally licensed for veterinary use in the U.S. The MP-12 strain encodes 23 mutations (nine amino acid substitutions) and is attenuated through a combination of mutations in the L-, M-, and S-segments. Among them, the M-U795C, M-A3564G, and L-G3104A mutations contribute to viral attenuation through the L- and M-segments. The M-U795C, M-A3564G, L-U533C, and L-G3750A mutations are also independently responsible for temperature-sensitive (ts) phenotype. We hypothesized that a serial passage of the MP-12 vaccine in culture cells causes reversions of the MP-12 genome. The MP-12 vaccine and recombinant rMP12-ΔNSs16/198 were serially passaged 25 times. Droplet digital PCR analysis revealed that the reversion occurred at L-G3750A during passages of MP-12 in Vero or MRC-5 cells. The reversion also occurred at M-A3564G and L-U533C of rMP12-ΔNSs16/198 in Vero cells. Reversion mutations were not found in MP-12 or the variant, rMP12-TOSNSs, in the brains of mice with encephalitis. This study characterized genetic stability of the MP-12 vaccine and the potential risk of reversion mutation at the L-G3750A ts mutation after excessive viral passages in culture cells.

Concordance of macular pigment measurements obtained using customized heterochromatic flicker photometry, dual-wavelength autofluorescence, and single-wavelength reflectance.

PubMed

Dennison, Jessica L; Stack, Jim; Beatty, Stephen; Nolan, John M

2013-11-01

This study compares in vivo measurements of macular pigment (MP) obtained using customized heterochromatic flicker photometry (cHFP; Macular Metrics Densitometer(™)), dual-wavelength fundus autofluorescence (Heidelberg Spectralis(®) HRA + OCT MultiColor) and single-wavelength fundus reflectance (Zeiss Visucam(®) 200). MP was measured in one eye of 62 subjects on each device. Data from 49 subjects (79%) was suitable for analysis. Agreement between the Densitometer and Spectralis was investigated at various eccentricities using a variety of quantitative and graphical methods, including: Pearson correlation coefficient to measure degree of scatter (precision), accuracy coefficient, concordance correlation coefficient (ccc), paired t-test, scatter and Bland-Altman plots. The relationship between max MP from the Visucam and central MP from the Spectralis and Densitometer was investigated using regression methods. Agreement was strong between the Densitometer and Spectralis at all central eccentricities (e.g. at 0.25° eccentricity: accuracy = 0.97, precision = 0.90, ccc = 0.87). Regression analysis showed a very weak relationship between the Visucam and Densitometer (e.g. Visucam max on Densitometer central MP: R(2) = 0.008, p = 0.843). Regression analysis also demonstrated a weak relationship between MP measured by the Spectralis and Visucam (e.g. Visucam max on Spectralis central MP: R(2) = 0.047, p = 0.348). MP values obtained using the Heidelberg Spectralis are comparable to MP values obtained using the Densitometer. In contrast, MP values obtained using the Zeiss Visucam are not comparable with either the Densitometer or the Spectralis MP measuring devices. Taking cHFP as the current standard to which other MP measuring devices should be compared, the Spectralis is suitable for use in a clinical and research setting, whereas the Visucam is not. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analysis of Levodopa Content in Commercial Mucuna pruriens Products Using High-Performance Liquid Chromatography with Fluorescence Detection.

PubMed

Soumyanath, Amala; Denne, Tanya; Hiller, Amie; Ramachandran, Shaila; Shinto, Lynne

2018-02-01

Mucuna pruriens (MP) seeds contain levodopa (up to 2% by weight) and have been used in traditional Indian medicine to treat an illness named "Kampavata," now understood to be Parkinson's disease (PD). Studies have shown MP to be beneficial, and even superior, to levodopa alone in treating PD symptoms. Commercial products containing MP are readily available from online and retail sources to patients and physicians. Products often contain extracts of MP seeds, with significantly higher levodopa content than the seeds. However, MP products have limited regulatory controls with respect to quality and content of active ingredient. The aim of this study was to apply a quantitative method to determine levodopa content in readily available MP products that might be used by patients or in research studies. Levodopa present in six commercial MP products was quantified by solvent extraction followed by reversed-phase high-performance liquid chromatography (HPLC) coupled to fluorescence detection (FD). Certificates of analysis (COA) were obtained, from manufacturers of MP products, to assess the existence and implementation of specifications for levodopa content. HPLC-FD analysis revealed that the levodopa content of the six commercial MP products varied from 6% to 141% of individual label claims. No product contained levodopa within normal pharmacopeial limits of 90%-110% label claim. The maximum daily dose of levodopa delivered by the products varied from 14.4 to 720 mg/day. COAs were inconsistent in specifications for and verification of levodopa content. The commercial products tested varied widely in levodopa content, sometimes deviating widely from the label claim. These deficiencies could impact efficacy and safety of MP products used by PD patients and compromise the results of scientific studies on MP products. The HPLC-FD method described in this study could be utilized by both manufacturers and scientific researchers to verify levodopa content of MP products.

Tautomerization, molecular structure, transition state structure, and vibrational spectra of 2-aminopyridines: a combined computational and experimental study.

PubMed

Al-Otaibi, Jamelah S

2015-01-01

2-amino pyridine derivatives have attracted considerable interest because they are useful precursors for the synthesis of a variety of heterocyclic compounds possessing a medicinal value. In this work we aim to study both structural and electronic as well as high quality vibrational spectra for 2-amino-3-methylpyridine (2A3MP) and 2-amino-4-methylpyridine (2A4MP). Møller-Plesset perturbation theory (MP2/6-31G(d) and MP2/6-31++G(d,p) methods were used to investigate the structure and vibrational analysis of (2A3MP) and (2A4MP). Tautomerization of 2A4MP was investigated by Density Functional Theory (DFT/B3LYP) method in the gas phase. For the first time, all tautomers including NH → NH conversions as well as those usually omitted, NH → CH and CH → CH, were considered. The canonical structure (2A4MP1) is the most stable tautomer. It is 13.60 kcal/mole more stable than the next (2A4MP2). Transition state structures of pyramidal N inversion and proton transfer were computed at B3LYP/6-311++G(d,p). Barrier to transition state of hydrogen proton transfer is calculated as 44.81 kcal/mol. Transition state activation energy of pyramidal inversion at amino N is found to be 0.41 kcal/mol using the above method. Bond order and natural atomic charges were also calculated at the same level. The raman and FT-IR spectra of (2A3MP) and (2A4MP) were measured (4000-400 cm(-1)). The optimized molecular geometries, frequencies and vibrational bands intensity were calculated at ab initio (MP2) and DFT(B3LYP) levels of theory with 6-31G(d), 6-31++G(d,p) and 6-311++G(d,p) basis sets. The vibrational frequencies were compared with experimentally measured FT-IR and FT-Raman spectra. Reconsidering the vibrational analysis of (2A3MP) and (2A4MP) with more accurate FT-IR machine and highly accurate animation programs result in new improved vibrational assignments. Sophisticated quantum mechanics methods enable studying the transition state structure for different chemical systems.

Mucuna pruriens (L.) DC chemo sensitize human breast cancer cells via downregulation of prolactin-mediated JAK2/STAT5A signaling.

PubMed

Sinha, Sonam; Sharma, Sonal; Vora, Jaykant; Shah, Heta; Srivastava, Anshu; Shrivastava, Neeta

2018-05-10

Mucuna pruriens (L.) DC (MP) is an ancient Indian medicinal plant traditionally used to treat Parkinson's disease. L-Dopa (LD), precursor of dopamine is abundantly found in the seeds of MP. L-dopa is a natural inhibitor of prolactin (PRL) hormone which is required to maintain lactation in women but it's over production (hyperprolactinemia) plays critical role in advancement of breast cancer. We aim to examine the pharmacological effect of LD and MP on this hyperprolactinemia associated breast cancer and related signaling for effective management of the disease. We also investigated chemo-sensitizing effect of MP on hyperprolactinemia-mediated cisplatin resistance. Methanolic seed extract of MP were prepared and analysed using HPLC. Effect of LD and MP on the cellular viability of breast cancer cells (T47D, MCF-7, MDA-MB-468 and MDA-MB-231) were evaluated using MTT assay. Further, effect of LD and MP on colony forming potential, DNA damage, cell cycle distribution and apoptosis was determined using agar/agarose method, comet assay and annexin and PI method followed by FACS analysis. To reveal the molecular mechanism involved in the anti-cancer activity of MP, transcriptional and translational level analysis of the key proteins involved in the PRL-mediated signaling, was performed using RT-PCR and western blot analysis. The effect of MP extract on PRL-mediated signaling was validated using dopaminergic agonist bromocriptine. MP extract and cisplatin was given in different combination with appropriate controls to check their effect on chemo-resistivity of breast cancer cells. Our results demonstrated that MP seed extract has the potential to inhibit cellular proliferation of PRL expressing T47D and MCF-7 breast cancer cells via induction of DNA damage, G1 phase of cell cycle arrest and apoptosis more effectively as compare to LD. Further, MP-mediated anti-cancerous effect was associated with the downregulation of PRL expression, further suppressing the JAK2/STAT5A/Cyclin D1 signaling pathway which has been validated using dopaminergic agonist bromocriptine. Cancer-related hyperprolactinemia confers cisplatin resistance, we observed that MP via PRL inhibition, enhances cisplatin efficacy after their combinatorial treatment in breast cancer cells. Collectively, our study suggests that MP could be recommended as dietary supplement along with the chemotherapeutic agents against breast cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

Mercaptopurine Ingestion Habits, Red Cell Thioguanine Nucleotide Levels, and Relapse Risk in Children With Acute Lymphoblastic Leukemia: A Report From the Children’s Oncology Group Study AALL03N1

PubMed Central

Landier, Wendy; Hageman, Lindsey; Chen, Yanjun; Kornegay, Nancy; Evans, William E.; Bostrom, Bruce C.; Casillas, Jacqueline; Dickens, David S.; Angiolillo, Anne L.; Lew, Glen; Maloney, Kelly W.; Mascarenhas, Leo; Ritchey, A. Kim; Termuhlen, Amanda M.; Carroll, William L.; Relling, Mary V.; Wong, F. Lennie

2017-01-01

Purpose Children with acute lymphoblastic leukemia (ALL) are generally instructed to take mercaptopurine (6-MP) in the evening and without food or dairy products. This study examines the association between 6-MP ingestion habits and 6-MP adherence, red cell thioguanine nucleotide (TGN) levels, and risk of relapse in children with TMPT wild-type genotype. Methods Participants included 441 children with ALL receiving oral 6-MP for maintenance. Adherence was monitored over 48,086 patient-days using the Medication Event Monitoring System; nonadherence was defined as adherence rate < 95%. 6-MP ingestion habits examined included: takes 6-MP with versus never with food, takes 6-MP with versus never with dairy, and takes 6-MP in the evening versus morning versus varying times. Results Median age at study was 6 years (range, 2 to 20 years); 43.8% were nonadherent. Certain 6-MP ingestion habits were associated with nonadherence (taking 6-MP with dairy [odds ratio (OR), 1.9; 95% CI, 1.3 to 2.9; P = .003] and at varying times [OR, 3.4; 95% CI, 1.8 to 6.3; P = .0001]). After adjusting for adherence and other prognosticators, there was no association between 6-MP ingestion habits and relapse risk (6-MP with food: hazard ratio [HR], 0.7; 95% CI, 0.3 to 1.9; P = .5; with dairy: HR, 0.3; 95% CI, 0.07 to 1.5; P = .2; taken in evening/night: HR, 1.1; 95% CI, 0.2 to 7.8; P = .9; at varying times: HR, 0.3; 95% CI, 0.04 to 2.7; P = .3). Among adherent patients, there was no association between red cell TGN levels and taking 6-MP with food versus without (206.1 ± 107.1 v 220.6 ± 121.6; P = .5), with dairy versus without (220.1 ± 87.8 v 216.3 ± 121.3; P =.7), or in the evening/night versus morning/midday versus varying times (218.8 ± 119.7 v 195.5 ± 82.3 v 174.8 ± 93.4; P = .6). Conclusion Commonly practiced restrictions surrounding 6-MP ingestion might not influence outcome but may hinder adherence. Future recommendations regarding 6-MP intake during maintenance therapy for childhood ALL should aim to simplify administration. PMID:28339328

Mercaptopurine Ingestion Habits, Red Cell Thioguanine Nucleotide Levels, and Relapse Risk in Children With Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group Study AALL03N1.

PubMed

Landier, Wendy; Hageman, Lindsey; Chen, Yanjun; Kornegay, Nancy; Evans, William E; Bostrom, Bruce C; Casillas, Jacqueline; Dickens, David S; Angiolillo, Anne L; Lew, Glen; Maloney, Kelly W; Mascarenhas, Leo; Ritchey, A Kim; Termuhlen, Amanda M; Carroll, William L; Relling, Mary V; Wong, F Lennie; Bhatia, Smita

2017-05-20

Purpose Children with acute lymphoblastic leukemia (ALL) are generally instructed to take mercaptopurine (6-MP) in the evening and without food or dairy products. This study examines the association between 6-MP ingestion habits and 6-MP adherence, red cell thioguanine nucleotide (TGN) levels, and risk of relapse in children with TMPT wild-type genotype. Methods Participants included 441 children with ALL receiving oral 6-MP for maintenance. Adherence was monitored over 48,086 patient-days using the Medication Event Monitoring System; nonadherence was defined as adherence rate < 95%. 6-MP ingestion habits examined included: takes 6-MP with versus never with food, takes 6-MP with versus never with dairy, and takes 6-MP in the evening versus morning versus varying times. Results Median age at study was 6 years (range, 2 to 20 years); 43.8% were nonadherent. Certain 6-MP ingestion habits were associated with nonadherence (taking 6-MP with dairy [odds ratio (OR), 1.9; 95% CI, 1.3 to 2.9; P = .003] and at varying times [OR, 3.4; 95% CI, 1.8 to 6.3; P = .0001]). After adjusting for adherence and other prognosticators, there was no association between 6-MP ingestion habits and relapse risk (6-MP with food: hazard ratio [HR], 0.7; 95% CI, 0.3 to 1.9; P = .5; with dairy: HR, 0.3; 95% CI, 0.07 to 1.5; P = .2; taken in evening/night: HR, 1.1; 95% CI, 0.2 to 7.8; P = .9; at varying times: HR, 0.3; 95% CI, 0.04 to 2.7; P = .3). Among adherent patients, there was no association between red cell TGN levels and taking 6-MP with food versus without (206.1 ± 107.1 v 220.6 ± 121.6; P = .5), with dairy versus without (220.1 ± 87.8 v 216.3 ± 121.3; P =.7), or in the evening/night versus morning/midday versus varying times (218.8 ± 119.7 v 195.5 ± 82.3 v 174.8 ± 93.4; P = .6). Conclusion Commonly practiced restrictions surrounding 6-MP ingestion might not influence outcome but may hinder adherence. Future recommendations regarding 6-MP intake during maintenance therapy for childhood ALL should aim to simplify administration.

Impact of microbial efficiency to predict MP supply when estimating protein requirements of growing beef cattle from performance.

PubMed

Watson, A K; Klopfenstein, T J; Erickson, G E; MacDonald, J C; Wilkerson, V A

2017-07-01

Data from 16 trials were compiled to calculate microbial CP (MCP) production and MP requirements of growing cattle on high-forage diets. All cattle were individually fed diets with 28% to 72% corn cobs in addition to either alfalfa, corn silage, or sorghum silage at 18% to 60% of the diet (DM basis). The remainder of the diet consisted of protein supplement. Source of protein within the supplement varied and included urea, blood meal, corn gluten meal, dry distillers grains, feather meal, meat and bone meal, poultry by-product meal, soybean meal, and wet distillers grains. All trials included a urea-only treatment. Intake of all cattle within an experiment was held constant, as a percentage of BW, established by the urea-supplemented group. In each trial the base diet (forage and urea supplement) was MP deficient. Treatments consisted of increasing amounts of test protein replacing the urea supplement. As protein in the diet increased, ADG plateaued. Among experiments, ADG ranged from 0.11 to 0.73 kg. Three methods of calculating microbial efficiency were used to determine MP supply. Gain was then regressed against calculated MP supply to determine MP requirement for maintenance and gain. Method 1 (based on a constant 13% microbial efficiency as used by the beef NRC model) predicted an MP maintenance requirement of 3.8 g/kg BW and 385 g MP/kg gain. Method 2 calculated microbial efficiency using low-quality forage diets and predicted MP requirements of 3.2 g/kg BW for maintenance and 448 g/kg for gain. Method 3 (based on an equation predicting MCP yield from TDN intake, proposed by the Beef Cattle Nutrient Requirements Model [BCNRM]) predicted MP requirements of 3.1 g/kg BW for maintenance and 342 g/kg for gain. The factorial method of calculating MP maintenance requirements accounts for scurf, endogenous urinary, and metabolic fecal protein losses and averaged 4.2 g/kg BW. Cattle performance data demonstrate formulating diets to meet the beef NRC model recommended MP maintenance requirement (3.8 g/kg S) works well when using 13% microbial efficiency. Therefore, a change in how microbial efficiency is calculated necessitates a change in the proposed MP maintenance requirement to not oversupply or undersupply RUP. Using the 2016 BCNRM to predict MCP production and formulate diets to meet MP requirements also requires changing the MP maintenance requirement to 3.1 g/kg BW.

Performance evaluation of canny edge detection on a tiled multicore architecture

NASA Astrophysics Data System (ADS)

Brethorst, Andrew Z.; Desai, Nehal; Enright, Douglas P.; Scrofano, Ronald

2011-01-01

In the last few years, a variety of multicore architectures have been used to parallelize image processing applications. In this paper, we focus on assessing the parallel speed-ups of different Canny edge detection parallelization strategies on the Tile64, a tiled multicore architecture developed by the Tilera Corporation. Included in these strategies are different ways Canny edge detection can be parallelized, as well as differences in data management. The two parallelization strategies examined were loop-level parallelism and domain decomposition. Loop-level parallelism is achieved through the use of OpenMP,1 and it is capable of parallelization across the range of values over which a loop iterates. Domain decomposition is the process of breaking down an image into subimages, where each subimage is processed independently, in parallel. The results of the two strategies show that for the same number of threads, programmer implemented, domain decomposition exhibits higher speed-ups than the compiler managed, loop-level parallelism implemented with OpenMP.

The excited-state decay of 1-methyl-2(1H)-pyrimidinone is an activated process.

PubMed

Ryseck, Gerald; Schmierer, Thomas; Haiser, Karin; Schreier, Wolfgang; Zinth, Wolfgang; Gilch, Peter

2011-07-11

The photophysics of 1-methyl-2(1H)-pyrimidinone (1MP) dissolved in water is investigated by steady-state and time-resolved fluorescence, UV/Vis absorption, and IR spectroscopy. In the experiments, excitation light is tuned to the lowest-energy absorption band of 1MP peaking at 302 nm. At room temperature (291 K) its fluorescence lifetime amounts to 450 ps. With increasing temperature this lifetime decreases and equals 160 ps at 338 K. Internal conversion (IC) repopulating the ground state and intersystem crossing (ISC) to a triplet state are the dominant decay channels of the excited singlet state. At room temperature both channels contribute equally to the decay, that is, the quantum yields of IC and ISC are both approximately 0.5. The temperature dependence of UV/Vis transient absorption signals shows that the activation energy of the IC process (2140 cm(-1)) is higher than that of the ISC process (640 cm(-1)). Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Melicope ptelefolia leaf extracts exhibit antioxidant activity and exert anti-proliferative effect with apoptosis induction on four different cancer cell lines.

PubMed

Kabir, Mohammad Faujul; Mohd Ali, Johari; Abolmaesoomi, Mitra; Hashim, Onn Haji

2017-05-05

Melicope ptelefolia is a well-known herb in a number of Asian countries. It is often used as vegetable salad and traditional medicine to address various ailments. However, not many studies have been currently done to evaluate the medicinal benefits of M. ptelefolia (MP). The present study reports antioxidant, anti-proliferative, and apoptosis induction activities of MP leaf extracts. Young MP leaves were dried, powdered and extracted sequentially using hexane (HX), ethyl acetate (EA), methanol (MeOH) and water (W). Antioxidant activity was evaluated using ferric reducing antioxidant power (FRAP), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radicals scavenging and cellular antioxidant activity (CAA) assays. Anti-proliferative activity was evaluated through cell viability assay, using the following four human cancer cell lines: breast (HCC1937, MDA-MB-231), colorectal (HCT116) and liver (HepG2). The anti-proliferative activity was further confirmed through cell cycle and apoptosis assays, including annexin-V/7-aminoactinomycin D staining and measurements of caspase enzymes activation and inhibition. Overall, MP-HX extract exhibited the highest antioxidant potential, with IC 50 values of 267.73 ± 5.58 and 327.40 ± 3.80 μg/mL for ABTS and DPPH radical-scavenging assays, respectively. MP-HX demonstrated the highest CAA activity in Hs27 cells, with EC 50 of 11.30 ± 0.68 μg/mL, while MP-EA showed EC 50 value of 37.32 ± 0.68 μg/mL. MP-HX and MP-EA showed promising anti-proliferative activity towards the four cancer cell lines, with IC 50 values that were mostly below 100 μg/mL. MP-HX showed the most notable anti-proliferative activity against MDA-MB-231 (IC 50  = 57.81 ± 3.49 μg/mL) and HCT116 (IC 50  = 58.04 ± 0.96 μg/mL) while MP-EA showed strongest anti-proliferative activity in HCT116 (IC 50  = 64.69 ± 0.72 μg/mL). The anticancer potential of MP-HX and MP-EA were also demonstrated by their ability to induce caspase-dependent apoptotic cell death in all of the cancer cell lines tested. Cell cycle analysis suggested that both the MP-HX and MP-EA extracts were able to disrupt the cell cycle in most of the cancer cell lines. MP-HX and MP-EA extracts demonstrated notable antioxidant, anti-proliferative, apoptosis induction and cancer cell cycle inhibition activities. These findings reflect the promising potentials of MP to be a source of novel phytochemical(s) with health promoting benefits that are also valuable for nutraceutical industry and cancer therapy.

Gold recovery from low concentrations using nanoporous silica adsorbent

NASA Astrophysics Data System (ADS)

Aledresse, Adil

The development of high capacity adsorbents with uniform porosity denoted 5%MP-HMS (5% Mercaptopropyl-Hexagonal Mesoporous Structure) to extract gold from noncyanide solutions is presented. The preliminary studies from laboratory simulated noncyanide gold solutions show that the adsorption capacities of these materials are among the highest reported. The high adsorption saturation level of these materials, up to 1.9 mmol/g (37% of the adsorbent weight) from gold chloride solutions (potassium tetrachloroaurate) and 2.9 mmol/g (57% of the adsorbent weight) from gold bromide solutions (potassium tetrabromoaurate) at pH = 2, is a noteworthy feature of these materials. This gold loading from [AuC4]- and [AuBr4 ]- solutions corresponds to a relative Au:S molar ratio of 2.5:1 and 3.8:1, respectively. These rates are significantly higher than the usual 1:1 (Au:S) ratio expected for metal ion binding with the material. The additional gold ions loaded have been spontaneously reduced to metallic gold in the mesoporous material. Experimental studies indicated high maximum adsorptions of gold as high as 99.9% recovery. Another promising attribute of these materials is their favourable adsorption kinetics. The MP-HMS reaches equilibrium (saturation) in less than 1 minute of exposure in gold bromide and less than 10 minutes in gold chloride. The MP-HMS materials adsorption is significantly improved by agitation and the adsorption capacity of Au (III) ions increases with the decrease in pH. The recovery of adsorbed gold and the regeneration of spent adsorbent were investigated for MP-HMS adsorbent. The regenerated adsorbent (MP-HMS) maintained its adsorption capacity even after repeated use and all the gold was successfully recovered from the spent adsorbent. For the fist time, a promising adsorbent system has been found that is capable of effectively concentrating gold thiosulphate complexes, whereas conventional carbon-inpulp (CIP) and carbon-in-leach (CIL) systems fail. The gold adsorption shows the high affinity of the mesoporous material to the gold-thiosulphate ([Au (S2O3)2]3- ) ions. A high adsorption saturation level for these materials was found, up to 0.25 mmol (5 mg) Au/g of HMS from gold-thiosulphate solutions. When ammonia was added to the thiosulphate solutions, with or without added copper, the mesoporous material (HMS) achieved the maximum adsorption, 0.24 mmol (47 mg) Au/g of HMS at pH = 7, where as 0.14 mmol (28 mg) Au/g was adsorbed from ammonia-thiosulphate solution at pH > 6. For the fist time, a promising adsorbent system has been found that is capable of effectively concentrating gold thiosulphate complexes, whereas conventional carbon-in-pulp (CIP) and carbon-in-leach (CIL) systems fail. For process design of gold adsorption by HMS particles, certain engineering conditions and practical limitations have to be considered, including particle size of the MP-HMS. Therefore, several experiments have been conducted to enlarge the size of the very fine MP-HMS particles to a size (1--2mm) satisfying the engineering requirements for process design in a real practical and industrial process. The agglomerated mesoporous materials, using sodium metasilicate (Na 2SiO3) binder, adsorbed gold ions in the range of 51%--63% of what the parent HMS powder adsorb. That means the agglomerates can adsorb 19--23% of their own weight (or 190--230 mg Au per one gram of the agglomerated HMS) from [AuCL4]- which is still very satisfactory and acceptable comparing to the current used adsorbents.

Progress towards more uniform assessment and reporting of soil disturbance for operations, research, and sustainability protocols.

Treesearch

Michael P. Curran; Richard E. Miller; Steven W. Howes; Douglas G. Maynard; Thomas A. Terry; Ronald L. Heninger; Thomas Niemann; Ken van Rees; Robert F. Powers; Stephen H. Schoenholtz

2005-01-01

International protocols, such as those of the Montreal Process (MP), specify desired outcomes without specifying the process and components required to attain those outcomes. We suggest that the process and its components are critical to achieve desired outcomes. We discuss recent progress in northwestern North America, on three topics that will facilitate development...

Hydrolysis mechanism of methyl parathion evidenced by Q-Exactive mass spectrometry.

PubMed

Liu, Yuan; Zhang, Caixiang; Liao, Xiaoping; Luo, Yinwen; Wu, Sisi; Wang, Jianwei

2015-12-01

Organophosphorus pesticides (OPPs), a kind of widely used pesticides, are currently attracting great attention due to their adverse effects on human central nervous systems, particularly in children. Although the hydrolysis behavior of OPPs has been studied well, its hydrolysis mechanism remained controversial, especially at various pH conditions, partly due to their relatively complex structures and abundant moieties that were prone to be attacked by nucleophiles. The Q-Exactive mass spectrometer, part of those hybrid high-resolution mass spectrometers (HRMS), was used to determine hydrolysis products of methyl parathion (MP), a kind of OPPs in situ buffer aqueous solution with pH ranging from 1 to 13 in this study. Most of the complex hydrolysis products of MP were identified due to the high sensitivity and accuracy of HRMS. The results demonstrated that the hydrolysis rate and pathway of MP were strong pH dependent. With the increase of pH, the hydrolysis rate of MP increased, and two different reaction mechanisms were identified: SN (2)@P pathway dominated the hydrolysis process at high pH (e.g., pH ≥ 11) while SN (2)@C was the main behavior at low pH (e.g., pH ≤ 9). This study helps understand the hydrolysis mechanism of OPPs at various pH and extends the use of Q-Exactive mass spectrometry in identifying organic pollutants and their degradation products in environmental matrices.

Reaction of a chemotherapeutic agent, 6-mercaptopurine, with a direct-acting, electrophilic carcinogen, benzo[a]pyrene-7,8-diol 9,10-epoxide.

PubMed

MacLeod, M C; Stewart, E; Daylong, A; Lew, L K; Evans, F E

1991-01-01

The chemotherapeutic agent 6-mercaptopurine (6-MP) has been shown to react covalently with the ultimate carcinogenic metabolite of benzo[a]pyrene, 7-r,8-t-dihydroxy-9-t,10-t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), in aqueous solution, forming a single adduct. NMR studies of the HPLC-purified product were consistent with its identification as 10(S)-(6'-mercaptopurinyl)-7,8,9-trihydroxy-7,8,9,10- tetrahydrobenzo[a]pyrene. Reaction kinetics were analyzed by using both HPLC separation of the products formed and a spectrophotometric assay for adduct formation. A simple model in which direct reaction between 6-MP and BPDE takes place without formation of a physical complex was found to adequately predict the dependence of product ratios on 6-MP concentration. Variations in the observed rate constant for this reaction with changes in temperature, pH, and buffer concentration were determined and compared to the effects of these variables on the observed rate constant for BPDE hydrolysis. In each case, the processes were affected quite differently, suggesting that different rate-determining steps are involved. The data suggest that the reaction mechanism involves SN2 attack of the anion of 6-MP, formed by ionization of the sulfhydryl group, on carbon 10 of BPDE, resulting in a trans-9,10 reaction product.

Screening, isolation and optimization of anti–white spot syndrome virus drug derived from marine plants

PubMed Central

Chakraborty, Somnath; Ghosh, Upasana; Balasubramanian, Thangavel; Das, Punyabrata

2014-01-01

Objective To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various marine floral ecosystems and to evaluate the efficacy of the same in host–pathogen interaction model. Methods Thirty species of marine plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. By means of chemical processes, the purified anti-WSSV plant isolate, MP07X was derived. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug. Results Nine plant isolates exhibited significant survivability in host. The drug MP07X thus formulated showing 85% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of MP07X required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 1 000 mg/kg body weight/day survived at the rate of 85%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection. Conclusions The drug MP07X derived from Rhizophora mucronata is a potent anti-WSSV drug. PMID:25183065

Tracing nitrogenous disinfection byproducts after medium pressure UV water treatment by stable isotope labeling and high resolution mass spectrometry.

PubMed

Kolkman, Annemieke; Martijn, Bram J; Vughs, Dennis; Baken, Kirsten A; van Wezel, Annemarie P

2015-04-07

Advanced oxidation processes are important barriers for organic micropollutants (e.g., pharmaceuticals, pesticides) in (drinking) water treatment. Studies indicate that medium pressure (MP) UV/H2O2 treatment leads to a positive response in Ames mutagenicity tests, which is then removed after granulated activated carbon (GAC) filtration. The formed potentially mutagenic substances were hitherto not identified and may result from the reaction of photolysis products of nitrate with (photolysis products of) natural organic material (NOM). In this study we present an innovative approach to trace the formation of disinfection byproducts (DBPs) of MP UV water treatment, based on stable isotope labeled nitrate combined with high resolution mass spectrometry. It was shown that after MP UV treatment of artificial water containing NOM and nitrate, multiple nitrogen containing substances were formed. In total 84 N-DBPs were detected at individual concentrations between 1 to 135 ng/L bentazon-d6 equivalents, with a summed concentration of 1.2 μg/L bentazon-d6 equivalents. The chemical structures of three byproducts were confirmed. Screening for the 84 N-DBPs in water samples from a full-scale drinking water treatment plant based on MP UV/H2O2 treatment showed that 22 of the N-DBPs found in artificial water were also detected in real water samples.

49 CFR 212.213 - Motive power and equipment (MP&E) inspector.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Motive power and equipment (MP&E) inspector. 212... Inspection Personnel § 212.213 Motive power and equipment (MP&E) inspector. (a) The MP&E inspector is... Appliance Standards (49 CFR part 231), and Power Brake Standards (49 CFR part 232), to make reports of those...

Thermal Decomposition of Nd3(+), Sr2(+) and Pb2(+) Exchanged Beta’’ Aluminas,

DTIC Science & Technology

1987-07-01

reconstructive recrystallization process is responsible for the formation of the MP phase; this perhaps is a surprising result. The decomposition processes of Nd3... eutectics may be present. A general trend for all decompositions of metastable substituted " aluminas would therefore seem to be that when occurring

On-field study of anaerobic digestion full-scale plants (part I): an on-field methodology to determine mass, carbon and nutrients balance.

PubMed

Schievano, Andrea; D'Imporzano, Giuliana; Salati, Silvia; Adani, Fabrizio

2011-09-01

The mass balance (input/output mass flows) of full-scale anaerobic digestion (AD) processes should be known for a series of purposes, e.g. to understand carbon and nutrients balances, to evaluate the contribution of AD processes to elemental cycles, especially when digestates are applied to agricultural land and to measure the biodegradation yields and the process efficiency. In this paper, three alternative methods were studied, to determine the mass balance in full-scale processes, discussing their reliability and applicability. Through a 1-year survey on three full-scale AD plants and through 38 laboratory-scale batch digesters, the congruency of the considered methods was demonstrated and a linear equation was provided that allows calculating the wet weight losses (WL) from the methane produced (MP) by the plant (WL=41.949*MP+20.853, R(2)=0.950, p<0.01). Additionally, this new tool was used to calculate carbon, nitrogen, phosphorous and potassium balances of the three observed AD plants. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Role for 2-Methyl Pyrrole in the Browning of 4-Oxopentanal and Limonene Secondary Organic Aerosol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aiona, Paige K.; Lee, Hyun Ji; Lin, Peng

“Brown Carbon” (BrC) is a type of organic particulate matter that absorbs visible and near ultraviolet radiation. Reactions of carbonyls in secondary organic aerosol (SOA) produced from limonene with ammonia (NH3) or ammonium sulfate (AS) are known to produce BrC with a distinctive absorption band at 500 nm. Although the general mechanism for this process has been proposed in previous studies, the specific molecular structures of the light-absorbing species remain unclear. This study examined the browning processes occurring in aqueous solutions of AS and 4-oxopentanal (4-OPA), which has a 1,4-dicarbonyl structural motif present in many limonene SOA compounds. The reactionmore » of 4-OPA with AS in a bulk aqueous solution produces a 2-methyl pyrrole (2-MP) intermediate, which is not a strong light absorber by itself, but can react further with carbonyl compounds leading to the eventual formation of BrC chromophores. The direct involvement of 2-MP in the browning process was demonstrated by reacting 2-MP with 4-OPA and with limonene SOA, both of which produced BrC chromophores with distinctive absorption bands at visible wavelengths. The formation of BrC in reaction of 4-OPA with AS and ammonium nitrate (AN) was found to be accelerated by evaporation of the solution suggesting an important role of the dehydration processes in BrC formation from 1,4- dicarbonyls. 4-OPA was also found to produce BrC in aqueous reactions with a broad spectrum of amino acids and amines. The results suggest that 4-OPA may be the smallest atmospherically relevant compound capable of browning by the same mechanism as limonene SOA.« less

The ten-year single-center experience with 6-mercaptopurine in the treatment of inflammatory bowel disease.

PubMed

Glazier, Kenneth D; Palance, Adam L; Griffel, Louis H; Das, Kiron M

2005-01-01

To report the 10-year experience of a single center in treating patients with refractory inflammatory bowel disease (IBD) with relatively lower dose of 6-mercaptopurine (6-MP). The charts of 285 patients with IBD (Crohn's disease 160 and ulcerative colitis 125) receiving 6-MP were reviewed. Clinical response, subsequent breakthrough while taking 6-MP, and relapse rates when 6-MP was discontinued and side effects were assessed. Ninety-three percent of the patients were taking 50 to 75 mg/day of 6-MP. Complete remission was achieved in 62%, partial remission in 14.5%, and failure to achieve remission in 23.5% of the patients. Of complete responders, 27.5% had breakthrough while continuing 6-MP. Nine percent of those that achieved a complete remission experienced a relapse after 6-MP was discontinued. Side effects included leukopenia (11.2%), abnormal liver function tests (3.8%), various infections, including pneumonia (3.1%), pancreatitis (2.5%), nausea (2.1%), headache (2.8%), fever (1.4%), hair loss (1%), and rash (0.7%). Two cancers occurred while taking 6-MP: melanoma on the finger and a fatal colonic lymphoma. Four patients continued 6-MP throughout pregnancies and had normal outcomes. In our experience 6-MP is relatively safe and appears to be as effective at a lower dosage (0.84 mg/kg per day) compared with the recommended higher dosage (1-1.5 mg/kg per day), when leukopenia was more frequent. Serious side effects, although rare, need to be monitored.

Effect Of Electromagnetic Waves Emitted From Mobile Phone On Brain Stem Auditory Evoked Potential In Adult Males.

PubMed

Singh, K

2015-01-01

Mobile phone (MP) is commonly used communication tool. Electromagnetic waves (EMWs) emitted from MP may have potential health hazards. So, it was planned to study the effect of electromagnetic waves (EMWs) emitted from the mobile phone on brainstem auditory evoked potential (BAEP) in male subjects in the age group of 20-40 years. BAEPs were recorded using standard method of 10-20 system of electrode placement and sound click stimuli of specified intensity, duration and frequency.Right ear was exposed to EMW emitted from MP for about 10 min. On comparison of before and after exposure to MP in right ear (found to be dominating ear), there was significant increase in latency of II, III (p < 0.05) and V (p < 0.001) wave, amplitude of I-Ia wave (p < 0.05) and decrease in IPL of III-V wave (P < 0.05) after exposure to MP. But no significant change was found in waves of BAEP in left ear before vs after MP. On comparison of right (having exposure routinely as found to be dominating ear) and left ears (not exposed to MP), before exposure to MP, IPL of IIl-V wave and amplitude of V-Va is more (< 0.001) in right ear compared to more latency of III and IV wave (< 0.001) in left ear. After exposure to MP, the amplitude of V-Va was (p < 0.05) more in right ear compared to left ear. In conclusion, EMWs emitted from MP affects the auditory potential.

Clinical Value of Mercaptopurine After Failing Azathioprine Therapy in Patients With Inflammatory Bowel Disease.

PubMed

Meijer, Berrie; Seinen, Margien L; Leijte, Niek N W; Mulder, Chris J J; van Bodegraven, Adriaan A; de Boer, Nanne K H

2016-08-01

Thiopurines have been widely accepted as immunosuppressive therapy in inflammatory bowel disease. However, many patients have to discontinue thiopurines due to intolerance or ineffectiveness. A therapeutically beneficial effect of switching from azathioprine (AZA) to mercaptopurine (MP) after developing adverse events (AEs) has been reported. The authors assessed the clinical value of MP therapy after AZA discontinuation due to intolerance and, secondary, due to ineffectiveness. In this retrospective single-center study, the authors analyzed data from patients in whom AZA therapy had failed and who were subsequently treated with MP. Thirty-eight patients initiated MP therapy after intolerance to AZA. Intolerance reoccurred in 22 (58%) patients and the remaining 16 (42%) tolerated MP. In 18 out of 48 patients (38%), the AEs that led to discontinuation of MP were similar to those of AZA. A longer duration of prior AZA use was more common in patients who were subsequently tolerant for MP (5.3 versus 1.2 months; P = 0.04). Twenty-two patients discontinued AZA due to ineffectiveness. Eight (36%) patients had clinical benefit from a switch to MP. Six out of these 8 (75%) patients used allopurinol alongside MP, due to ineffectiveness based on a skewed thiopurine metabolism. Patients were more likely to have clinical benefit if the interval between both thiopurines was longer (4.4 versus 0.01 months; P < 0.05). The authors showed that a noteworthy number of patients benefitted therapeutically from a switch from AZA to MP when failing due to intolerance or ineffectiveness; however, the percentage was lower than previously reported in literature.

The relation between the macular carotenoids, lutein and zeaxanthin, and temporal vision.

PubMed

Renzi, Lisa M; Hammond, Billy R

2010-07-01

Lutein (L) and zeaxanthin (Z) are the dominant carotenoids within the central retina (there, termed macular pigment, MP) and brain (approximately 70% of total carotenoid concentration). Past studies have shown that MP is related to many static indicators of visual performance, such as visibility and disability glare. It has also been shown that MP is related to a dynamic measure of visual performance, the critical flicker fusion threshold (CFF). In this study, we examine whether MP is related to CFF in a larger sample. We also test the relation between MP and the more complete temporal contrast sensitivity function (TCSF). A total of 70 participants were assessed for a comparison of MP and the full temporal function. A separate pool of 354 participants was assessed for a MP and CFF comparison. Peak MP density was measured psychophysically (via heterochromatic flicker photometry) using a 1-degree diameter test. CFF was measured using a 1-degree 570 nm test varied at 100% modulation. The full TCSF was measured centrally using a 1-degree, 660 nm test (the modulation depth of which could be adjusted directly by the subject) centered within a 5.5-degree, 660 nm surround. A small fixation point was used to test a 7-degree parafoveal site. MP density was positively related to temporal function as assessed by the full TCSF in the center (n = 70, r = -0.29, p < 0.01) but not at the parafoveal location (p < 0.07). MP was also positively related to critical flicker fusion thresholds (n = 354, r = 0.21, p < 0.0001).

Negative impact of prolonged cold storage time before machine perfusion preservation in donation after circulatory death kidney transplantation.

PubMed

Paloyo, Siegfredo; Sageshima, Junichiro; Gaynor, Jeffrey J; Chen, Linda; Ciancio, Gaetano; Burke, George W

2016-10-01

Kidney grafts are often preserved initially in static cold storage (CS) and subsequently on hypothermic machine perfusion (MP). However, the impact of CS/MP time on transplant outcome remains unclear. We evaluated the effect of prolonged CS/MP time in a single-center retrospective cohort of 59 donation after circulatory death (DCD) and 177 matched donation after brain death (DBD) kidney-alone transplant recipients. With mean overall CS/MP times of 6.0 h/30.0 h, overall incidence of delayed graft function (DGF) was higher in DCD transplants (30.5%) than DBD transplants (7.3%, P < 0.0001). In logistic regression, DCD recipient (P < 0.0001), longer CS time (P = 0.0002), male recipient (P = 0.02), and longer MP time (P = 0.08) were associated with higher DGF incidence. In evaluating the joint effects of donor type (DBD vs. DCD), CS time (<6 vs. ≥6 h), and MP time (<36 vs. ≥36 h) on DGF incidence, one clearly sees an unfavorable effect of MP time ≥36 h (P = 0.003) across each donor type and CS time stratum, whereas the unfavorable effect of CS time ≥6 h (P = 0.01) is primarily seen among DCD recipients. Prolonged cold ischemia time had no unfavorable effect on renal function or graft survival at 12mo post-transplant. Long CS/MP time detrimentally affects early DCD/DBD kidney transplant outcome when grafts were mainly preserved by MP; prolonged CS time before MP has a particularly negative impact in DCD kidney transplantation. © 2016 Steunstichting ESOT.

Screening of snoring with an MP3 recorder.

PubMed

Kreivi, Hanna-Riikka; Salmi, Tapani; Maasilta, Paula; Bachour, Adel

2013-03-01

Snoring patients seeking medical assistance represent a wide range of clinical and sleep study findings from nonsleepy nonapneic snoring to severe obstructive sleep apnea syndrome. The prevalence of snoring is high and it significantly impacts quality of life. Its objective diagnosis usually requires a sleep study. We developed a system to analyze snoring sounds with a Moving Picture Experts Group Layer-3 Audio (MP3) recorder device and present its value in the screening of snoring. We recorded snoring sounds during in-lab polysomnography (PSG) in 200 consecutive patients referred for a suspicion of obstructive sleep apnea. Snoring was recorded during the PSG with two microphones: one attached to the throat and the other to the ceiling; an MP3 device was attached to the patient's collar. Snoring was confirmed when the MP3 acoustic signal exceeded twice the median value of the acoustic signal for the entire recording. Results of the MP3 snoring recording were compared to the snoring recordings from the PSG. MP3 recording proved technically successful for 87% of the patients. The Pearson correlation between PSG snoring and MP3 snoring was highly significant at 0.77 (p < 0.001). The MP3 recording device underestimated the snoring time by a mean ± SD of 32 ± 55 min. The recording of snoring with an MP3 device provides reliable information about the patient's snoring.

Correlation between capillary oxygen saturation and small intestinal wall thickness in the equine colic patient

PubMed Central

Mirle, Elisabeth; Wogatzki, Anna; Kunzmann, Robert; Schoenfelder, Axel M; Litzke, Lutz F

2017-01-01

The surgical evaluation of haemorrhagic infarcted intestine and the decision for or against bowel resection require a lot of experience and are subjective. The aim of this prospective, clinical study was to examine the correlation between oxygen saturation and small intestinal wall (IW) thickness, using two objective methods. In 22 colicky horses, the blood flow, oxygen saturation and relative amount of haemoglobin were measured intraoperatively via laser Doppler and white light spectroscopy (O2C, oxygen to see, LEA Medizintechnik) at six measuring points (MPs) in small and large intestines. Furthermore, the IW thickness was measured ultrasonographically. Nine of 22 horses had an increased small IW thickness greater than 4 mm (Freeman 2002, Scharner and others 2002, le Jeune and Whitcomb 2014) at measuring point 1 (MP1) (strangulated segment), four horses had a thickened bowel wall at measuring point 3 (MP3) (poststenotic) and one at measuring point 2 (MP2). The oxygen saturation was 0 at MP1 in six horses, at MP3 in two horses and at MP2 (prestenotic) in one. Oxygen saturation and small IW thickness were independent of each other at MP1 and MP2. At MP3, the two parameters were negatively correlated. In summary, it is not possible to draw conclusions about oxygen saturation based on IW thickness. PMID:28761667

Correlation between capillary oxygen saturation and small intestinal wall thickness in the equine colic patient.

PubMed

Mirle, Elisabeth; Wogatzki, Anna; Kunzmann, Robert; Schoenfelder, Axel M; Litzke, Lutz F

2017-01-01

The surgical evaluation of haemorrhagic infarcted intestine and the decision for or against bowel resection require a lot of experience and are subjective. The aim of this prospective, clinical study was to examine the correlation between oxygen saturation and small intestinal wall (IW) thickness, using two objective methods. In 22 colicky horses, the blood flow, oxygen saturation and relative amount of haemoglobin were measured intraoperatively via laser Doppler and white light spectroscopy (O2C, oxygen to see, LEA Medizintechnik) at six measuring points (MPs) in small and large intestines. Furthermore, the IW thickness was measured ultrasonographically. Nine of 22 horses had an increased small IW thickness greater than 4 mm (Freeman 2002, Scharner and others 2002, le Jeune and Whitcomb 2014) at measuring point 1 (MP1) (strangulated segment), four horses had a thickened bowel wall at measuring point 3 (MP3) (poststenotic) and one at measuring point 2 (MP2). The oxygen saturation was 0 at MP1 in six horses, at MP3 in two horses and at MP2 (prestenotic) in one. Oxygen saturation and small IW thickness were independent of each other at MP1 and MP2. At MP3, the two parameters were negatively correlated. In summary, it is not possible to draw conclusions about oxygen saturation based on IW thickness.

The Problem of Defining Intelligence.

ERIC Educational Resources Information Center

Lubar, David

1981-01-01

The major philosophical issues surrounding the concept of intelligence are reviewed with respect to the problems surrounding the process of defining and developing artificial intelligence (AI) in computers. Various current definitions and problems with these definitions are presented. (MP)

Mobile Phone Appropriation of Students and Staff at an Institution of Higher Learning

ERIC Educational Resources Information Center

Karim, Nor Shahriza Abdul; Oyebisi, Ishaq Oyefolahan; Mahmud, Murni

2010-01-01

Purpose: The purpose of this paper is to investigate the adoption and appropriation of mobile phone (MP) technologies by building on the technology appropriation theories. The paper also looks into the choice of MP use through various attractors, the purposes of MP use and the extent of use of various MP applications and features by the targeted…

Characterization of a novel plantain Asr gene, MpAsr, that is regulated in response to infection of Fusarium oxysporum f. sp. cubense and abiotic stresses.

PubMed

Liu, Hai-Yan; Dai, Jin-Ran; Feng, Dong-Ru; Liu, Bing; Wang, Hong-Bin; Wang, Jin-Fa

2010-03-01

Asr (abscisic acid, stress, ripening induced) genes are typically upregulated by a wide range of factors, including drought, cold, salt, abscisic acid (ABA) and injury; in addition to plant responses to developmental and environmental signals. We isolated an Asr gene, MpAsr, from a suppression subtractive hybridization (SSH) cDNA library of cold induced plantain (Musa paradisiaca) leaves. MpAsr expression was upregulated in Fusarium oxysporum f. sp. cubense infected plantain leaves, peels and roots, suggesting that MpAsr plays a role in plantain pathogen response. In addition, a 581-bp putative promoter region of MpAsr was isolated via genome walking and cis-elements involved in abiotic stress and pathogen-related responses were detected in this same region. Furthermore, the MpAsr promoter demonstrated positive activity and inducibility in tobacco under F. oxysporum f. sp. cubense infection and ABA, cold, dehydration and high salt concentration treatments. Interestingly, transgenic Arabidopsis plants overexpressing MpAsr exhibited higher drought tolerance, but showed no significant decreased sensitivity to F. oxysporum f. sp. cubense. These results suggest that MpAsr might be involved in plant responses to both abiotic stress and pathogen attack.

Fungal lectin MpL enables entry of protein drugs into cancer cells and their subcellular targeting.

PubMed

Å Urga, Simon; Nanut, Milica Perišić; Kos, Janko; Sabotič, Jerica

2017-04-18

Lectins have been recognized as promising carrier molecules for targeted drug delivery. They specifically bind carbohydrate moieties on cell membranes and trigger cell internalization. Fungal lectin MpL (Macrolepiota procera lectin) does not provoke cancer cell cytotoxicity but is able to bind aminopeptidase N (CD13) and integrin α3β1, two glycoproteins that are overexpressed on the membrane of tumor cells. Upon binding, MpL is endocytosed in a clathrin-dependent manner and accumulates initially in the Golgi apparatus and, finally, in the lysosomes. For effective binding and internalization a functional binding site on the α-repeat is needed. To test the potential of MpL as a carrier for delivering protein drugs to cancer cells we constructed fusion proteins consisting of MpL and the cysteine peptidase inhibitors cystatin C and clitocypin. The fused proteins followed the same endocytic route as the unlinked MpL. Peptidase inhibitor-MpL fusions impaired both the intracellular degradation of extracellular matrix and the invasiveness of cancer cells. MpL is thus shown in vitro to be a lectin that can enable protein drugs to enter cancer cells, enhance their internalization and sort them to lysosomes and the Golgi apparatus.

Can Motor Proficiency in Preschool Age Affect Physical Activity in Adolescence?

PubMed

Venetsanou, Fotini; Kambas, Antonis

2017-05-01

This study investigated if motor proficiency (MP) in preschool age associate with physical activity (PA) in adolescence. In 2004, the Bruininks-Oseretsky Test of Motor Proficiency-Short Form (BOTMP-SF) (7) was administered to 413 children, aged 4-6 years, who were classified to MP groups according to their BOTMP-SF total score (TS). In 2014, the PA of 106 former participants (47 boys, 59 girls) was measured with Omron pedometers. MP [three (high; above average; average)] × gender (two) ANOVA and Bonferroni tests were computed on average of steps/week. A significant interaction between the two factors was revealed (F = 15.27, p < .001, η 2 =.153), indicating that MP influenced male and female PA differently. Only in average MP group, males presented higher PA than females, whereas there were no differences between the two genders in the higher MP groups. Moreover, the only significant difference in PA among male groups was that between high and above average MP groups, while in females there were significant differences among all groups. High MP at preschool age positively associated with the PA in adolescence, especially in females. Emphasis on the development of proficient young movers might be beneficial for lifelong PA.

NASA-STD-6016 Standard Materials and Processes Requirements for Spacecraft

NASA Technical Reports Server (NTRS)

Hirsch, David B.

2009-01-01

The standards for materials and processes surrounding spacecraft are discussed. Presentation focused on minimum requirements for Materials and Processes (M&P) used in design, fabrication, and testing of flight components for NASA manned, unmanned, robotic, launch vehicle, lander, in-space and surface systems, and spacecraft program/project hardware elements.Included is information on flammability, offgassing, compatibility requirements, and processes; both metallic and non-metallic materials are mentioned.

Immediate effect of mental practice with and without mirror therapy on muscle activation in hemiparetic stroke patients.

PubMed

Caires, Tamise Aguiar; Rodrigues Martinho Fernandes, Luciane Fernanda; Patrizzi, Lislei Jorge; de Almeida Oliveira, Rafael; Pascucci Sande de Souza, Luciane Aparecida

2017-10-01

Mental practice (MP) consists of the repeated mental rehearsal of a physical skill without movement, called motor imagery (MI). Studies show that MP and MI associated mirror therapy (MPMT) may improve muscle control of the upper limbs in hemiparesis. This study aimed to evaluate muscle activation during active flexion of the wrist (MA), MP, and MPMT in patients with history of stroke and hemiparesis. Individuals diagnosed with stroke showing sequelae of upper limb hemiparesis were enrolled. The flexor carpi ulnaris was analyzed using electromyography during tasks (MA, MP, MPMT) involving wrist flexion. Greater electromyographic activity was detected during MP and MPMT techniques compared to active movement (p = 0.02). There was no significant difference between MP and MPMT (p = 0.56). These results were found in both the affected limb and unaffected limb. Immediate effects on muscle activation are experienced during MP and MPMT, and muscle activity was similar with both therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Non-Invasive in vivo Mapping and Long-Term Monitoring of Magnetic Nanoparticles in Different Organs of Animals

NASA Astrophysics Data System (ADS)

Nikitin, Maxim; Yuriev, Mikhail; Brusentsov, Nikolai; Vetoshko, Petr; Nikitin, Petr

2010-12-01

Quantitative detection of magnetic nanoparticles (MP) in vivo is very important for various biomedical applications. Our original detection method based on non-linear MP magnetization has been modified for non-invasive in vivo mapping of the MP distribution among different organs of rats. A novel highly sensitive room-temperature device equipped with an external probe has been designed and tested for quantification of MP within 20-mm depth from the animal skin. Results obtained by external in vivo scanning of rats by the probe and ex vivo MP quantification in different organs of rats well correlated. The method allows long-term in vivo study of MP evolution, clearance and redistribution among different organs of the animal. Experiments showed that dynamics in vivo strongly depend on MP characteristics (size, material, coatings, etc.), site of injection and dose. The developed detection method combined with the magnetic nanolabels can substitute the radioactive labeling in many applications.

Effects of microplastics on juveniles of the common goby (Pomatoschistus microps): confusion with prey, reduction of the predatory performance and efficiency, and possible influence of developmental conditions.

PubMed

Carlos de Sá, Luís; Luís, Luís G; Guilhermino, Lúcia

2015-01-01

Microplastics (MP) are ubiquitous contaminants able to cause adverse effects on organisms. Three hypotheses were tested here: early Pomatoschistus microps juveniles can ingest MP; the presence of MP may reduce fish predatory performance and efficiency; developmental conditions may influence the preyselection capability of fish. Predatory bioassays were carried out with juveniles from two estuaries with differences in environmental conditions: Minho (M-est) and Lima (L-est) Rivers (NW Iberian coast). Polyethylene MP spheres (3 types) alone and in combination with Artemia nauplii were offered as prey.All the MP types were ingested, suggesting confusion with food. Under simultaneous exposure to MP and Artemia, L-est fish showed a significant reduction of the predatory performance (65%) and efficiency (upto 50%), while M-est fish did not, suggesting that developmental conditions may influence the preyselection capability of fish. The MP-induced reduction of food intake may decrease individual and population fitness.

Magnetic biocatalysts of pectinase and cellulase: Synthesis and characterization of two preparations for application in grape juice clarification.

PubMed

Dal Magro, Lucas; Silveira, Vitória C C; de Menezes, Eliana Weber; Benvenutti, Edilson Valmir; Nicolodi, Sabrina; Hertz, Plinho F; Klein, Manuela P; Rodrigues, Rafael C

2018-04-07

In the present study, we prepared two different magnetic biocatalysts of pectinase and cellulase: carrier-free magnetic CLEAs (CLEA-MP*) and immobilization on glutaraldehyde-activated magnetite (Enz-Glu-MP*). The biocatalysts were compared to their magnetic properties, immobilization parameters, stability and grape juice clarification. Enz-Glu-MP* presented higher magnetic properties than CLEA-MP*, whereas this presented higher surface area and pore volume. The K M of the enzyme immobilized on Enz-Glu-MP* was 25.65mM, lower in comparison to the CLEA-MP* (33.83mM). On the other hand, CLEA-MP* was the most active and stable biocatalyst, presenting higher recovered activity (33.4% of cellulase), higher thermal stability (2.39 stabilization factor) and improved reusability (8cycles). The integration of magnetic technology with enzymatic immobilization emerges as a possibility to increase the recover and reuse of biocatalysts for application in juice technology. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis of Potential Prophylactic Agents Against Cyanide Intoxication

DTIC Science & Technology

1993-05-06

34/21) S 2,6-C 2 Ad 72 mp 139" CsH3C12NO 163 (lie mp 139.5-140.5") 6 4-OMe A 45 Mp 73-79e CH 7N0% (lit t mp 73-741) 7 2-OMe A 50 Mp 66" C*HNO 126 (litf...Form. Found cation. Compd. No. Reactants Yield, % Mp, *C (cation.anion) %C %H %N anion Part A. 1 -Alkoxypyridinium salts. 14 2,3-Mes, 87 120-122 CH ...111 + 4(C6H6CVs O, 28.62 3.22 4.40 ..... (MeO)2SO2 _OSO 2 CH s ) is 4-OMe,6 + 78 46-48 CSH 121NO 2 34.18 4.30 4.91 154, 126 Ed (CsH12NO2-) 34.02

Infants Encode Phonetic Detail during Cross-Situational Word Learning

PubMed Central

Escudero, Paola; Mulak, Karen E.; Vlach, Haley A.

2016-01-01

Infants often hear new words in the context of more than one candidate referent. In cross-situational word learning (XSWL), word-object mappings are determined by tracking co-occurrences of words and candidate referents across multiple learning events. Research demonstrates that infants can learn words in XSWL paradigms, suggesting that it is a viable model of real-world word learning. However, these studies have all presented infants with words that have no or minimal phonological overlap (e.g., BLICKET and GAX). Words often contain some degree of phonological overlap, and it is unknown whether infants can simultaneously encode fine phonological detail while learning words via XSWL. We tested 12-, 15-, 17-, and 20-month-olds’ XSWL of eight words that, when paired, formed non-minimal pairs (MPs; e.g., BON–DEET) or MPs (e.g., BON–TON, DEET–DIT). The results demonstrated that infants are able to learn word-object mappings and encode them with sufficient phonetic detail as to identify words in both non-minimal and MP contexts. Thus, this work suggests that infants are able to simultaneously discriminate phonetic differences between words and map words to referents in an implicit learning paradigm such as XSWL. PMID:27708605

In vivo monitor oxidative burst induced by Cd2+ stress for the oilseed rape (Brassica napus L.) based on electrochemical microbiosensor.

PubMed

Xu, Qiao; Wei, Fang; Wang, Zhan; Yang, Qin; Zhao, Yuan-Di; Chen, Hong

2010-01-01

Since the mechanism of Cd(2+) stress for plants is not clear, an in vivo method to monitor Cd(2+) stress for plants is necessary. However, oxidative burst (OB) is a signal messenger in the process of Cd(2+) stress for plants. To establish an electrochemical method with poly-o-phenylenediamine and Pt microparticle modified Pt electrode (POPD-Pt-MP-Pt) as a microbiosensor for the in vivo detection of oxidative burst induced by Cd(2+) stress in oilseed rape (Brassica napus L.). The optimal fabrication of POPD-Pt-MP-Pt biosensor was achieved. Electrochemical signal was collected by amperometry. After oilseed rape was exposed to 84.9 mM CdCl(2) stress, three oxidative bursts were observed in oilseed rape by amperometry at 3.3 h, 8.4 h and 13.2 h, respectively. However, there was no obvious signal observed in the controlled assay. This contribution presents the in vivo monitoring of the OB process induced by Cd(2+) stress in oilseed rape by POPD-Pt-MP-Pt microbiosensor in real-time. The novel electrochemical microbiosensor not only facilitates the real-time study in plant self-defence response to the adverse environment such as Cd(2+) stress, but also provides an effective tool for probing the self-defence mechanism in plants.

Increasing feasibility of the field-programmable gate array implementation of an iterative image registration using a kernel-warping algorithm

NASA Astrophysics Data System (ADS)

Nguyen, An Hung; Guillemette, Thomas; Lambert, Andrew J.; Pickering, Mark R.; Garratt, Matthew A.

2017-09-01

Image registration is a fundamental image processing technique. It is used to spatially align two or more images that have been captured at different times, from different sensors, or from different viewpoints. There have been many algorithms proposed for this task. The most common of these being the well-known Lucas-Kanade (LK) and Horn-Schunck approaches. However, the main limitation of these approaches is the computational complexity required to implement the large number of iterations necessary for successful alignment of the images. Previously, a multi-pass image interpolation algorithm (MP-I2A) was developed to considerably reduce the number of iterations required for successful registration compared with the LK algorithm. This paper develops a kernel-warping algorithm (KWA), a modified version of the MP-I2A, which requires fewer iterations to successfully register two images and less memory space for the field-programmable gate array (FPGA) implementation than the MP-I2A. These reductions increase feasibility of the implementation of the proposed algorithm on FPGAs with very limited memory space and other hardware resources. A two-FPGA system rather than single FPGA system is successfully developed to implement the KWA in order to compensate insufficiency of hardware resources supported by one FPGA, and increase parallel processing ability and scalability of the system.

Logical reasoning versus information processing in the dual-strategy model of reasoning.

PubMed

Markovits, Henry; Brisson, Janie; de Chantal, Pier-Luc

2017-01-01

One of the major debates concerning the nature of inferential reasoning is between counterexample-based strategies such as mental model theory and statistical strategies underlying probabilistic models. The dual-strategy model, proposed by Verschueren, Schaeken, & d'Ydewalle (2005a, 2005b), which suggests that people might have access to both kinds of strategy has been supported by several recent studies. These have shown that statistical reasoners make inferences based on using information about premises in order to generate a likelihood estimate of conclusion probability. However, while results concerning counterexample reasoners are consistent with a counterexample detection model, these results could equally be interpreted as indicating a greater sensitivity to logical form. In order to distinguish these 2 interpretations, in Studies 1 and 2, we presented reasoners with Modus ponens (MP) inferences with statistical information about premise strength and in Studies 3 and 4, naturalistic MP inferences with premises having many disabling conditions. Statistical reasoners accepted the MP inference more often than counterexample reasoners in Studies 1 and 2, while the opposite pattern was observed in Studies 3 and 4. Results show that these strategies must be defined in terms of information processing, with no clear relations to "logical" reasoning. These results have additional implications for the underlying debate about the nature of human reasoning. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Dissolution of Olivine, Siderite, and Basalt at 80 Deg C in 0.1 M H2SO4 in a Flow Through Process: Insights into Acidic Weathering on Mars

NASA Technical Reports Server (NTRS)

Golden, D. C.; Ming, D. W.; Hausrath, E. M.; Morris, R. V.; Niles, P. B.; Achilles, C. N.; Ross, D. K.; Cooper, B. L.; Gonzalex, C. P.; Mertzman, S. A.

2012-01-01

The occurrence of jarosite, other sulfates (e.g., Mg-and Ca-sulfates), and hematite along with silicic-lastic materials in outcrops of sedimentary materials at Meridiani Planum (MP) and detection of silica rich deposits in Gusev crater, Mars, are strong indicators of local acidic aqueous processes [1,2,3,4,5]. The formation of sediments at Meridiani Planum may have involved the evaporation of fluids derived from acid weathering of Martian basalts and subsequent diagenesis [6,7]. Also, our previous work on acid weathering of basaltic materials in a closed hydro-thermal system was focused on the mineralogy of the acid weathering products including the formation of jarosite and gray hematite spherules [8,9,10]. The object of this re-search is to extend our earlier qualitative work on acidic weathering of rocks to determine acidic dissolution rates of Mars analog basaltic materials at 80 C using a flow-thru reactor. We also characterized residual phases, including poorly crystalline or amorphous phases and precipitates, that remained after the treatments of olivine, siderite, and basalt which represent likely MP source rocks. This study is a stepping stone for a future simulation of the formation of MP rocks under a range of T and P.

Assessment of symptomatic and neuroprotective efficacy of Mucuna pruriens seed extract in rodent model of Parkinson's disease.

PubMed

Kasture, Sanjay; Pontis, Silvia; Pinna, Annalisa; Schintu, Nicoletta; Spina, Liliana; Longoni, Rosanna; Simola, Nicola; Ballero, Mauro; Morelli, Micaela

2009-02-01

Mucuna pruriens (MP) has long been used in Indian traditional medicine as support in the treatment of Parkinson's disease. However, no systematic preclinical studies that aimed at evaluating the efficacy of this substance are available to date. This study undertook an extensive evaluation of the antiparkinsonian effects of an extract of MP seeds known to contain, among other components, 12.5% L: -dihydroxyphenylalanine (L: -DOPA), as compared to equivalent doses of L: -DOPA. Moreover, the neuroprotective efficacy of MP and its potential rewarding effects were evaluated. The results obtained reveal how an acute administration of MP extract at a dose of 16 mg/kg (containing 2 mg/kg of L: -DOPA) consistently antagonized the deficit in latency of step initiation and adjusting step induced by a unilateral 6-hydroxydopamine lesion, whereas L: -DOPA was equally effective only at the doses of 6 mg/kg. At the same dosage, MP significantly improved the placement of the forelimb in vibrissae-evoked forelimb placing, suggesting a significant antagonistic activity on both motor and sensory-motor deficits. The effects of MP extract were moreover investigated by means of the turning behavior test and in the induction of abnormal involuntary movements (AIMs) after either acute or subchronic administration. MP extract acutely induced a significantly higher contralateral turning behavior than L: -DOPA (6 mg/kg) when administered at a dose of 48 mg/kg containing 6 mg/kg of L: -DOPA. On subchronic administration, both MP extract (48 mg/kg) and L: -DOPA (6 mg/kg) induced sensitization of contralateral turning behavior; however, L: -DOPA alone induced a concomitant sensitization in AIMs suggesting that the dyskinetic potential of MP is lower than that of L: -DOPA. MP (48 mg/kg) was also effective in antagonizing tremulous jaw movements induced by tacrine, a validated test reproducing parkinsonian tremor. Furthermore, MP induced no compartment preference in the place preference test, indicating the lack of components characterized by rewarding effects in the extract. Finally, in a subchronic mice model of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine hydrochloride (MPTP)-induced dopamine neuron degeneration, MP extract did not prove capable of preventing either tyrosine hydroxylase decrease induced by MPTP or astroglial or microglial activation as assessed by means of GFAP and CD11b immunohistochemistry, supporting the absence of neuroprotective effects by MP. Characterization MP extract strongly supports its antiparkinsonian activity.

Technical Note: Evaluation of a 160-mm/256-row CT scanner for whole-heart quantitative myocardial perfusion imaging.

PubMed

So, Aaron; Imai, Yasuhiro; Nett, Brian; Jackson, John; Nett, Liz; Hsieh, Jiang; Wisenberg, Gerald; Teefy, Patrick; Yadegari, Andrew; Islam, Ali; Lee, Ting-Yim

2016-08-01

The authors investigated the performance of a recently introduced 160-mm/256-row CT system for low dose quantitative myocardial perfusion (MP) imaging of the whole heart. This platform is equipped with a gantry capable of rotating at 280 ms per full cycle, a second generation of adaptive statistical iterative reconstruction (ASiR-V) to correct for image noise arising from low tube voltage potential/tube current dynamic scanning, and image reconstruction algorithms to tackle beam-hardening, cone-beam, and partial-scan effects. Phantom studies were performed to investigate the effectiveness of image noise and artifact reduction with a GE Healthcare Revolution CT system for three acquisition protocols used in quantitative CT MP imaging: 100, 120, and 140 kVp/25 mAs. The heart chambers of an anthropomorphic chest phantom were filled with iodinated contrast solution at different concentrations (contrast levels) to simulate the circulation of contrast through the heart in quantitative CT MP imaging. To evaluate beam-hardening correction, the phantom was scanned at each contrast level to measure the changes in CT number (in Hounsfield unit or HU) in the water-filled region surrounding the heart chambers with respect to baseline. To evaluate cone-beam artifact correction, differences in mean water HU between the central and peripheral slices were compared. Partial-scan artifact correction was evaluated from the fluctuation of mean water HU in successive partial scans. To evaluate image noise reduction, a small hollow region adjacent to the heart chambers was filled with diluted contrast, and contrast-to-noise ratio in the region before and after noise correction with ASiR-V was compared. The quality of MP maps acquired with the CT system was also evaluated in porcine CT MP studies. Myocardial infarct was induced in a farm pig from a transient occlusion of the distal left anterior descending (LAD) artery with a catheter-based interventional procedure. MP maps were generated from the dynamic contrast-enhanced (DCE) heart images taken at baseline and three weeks after the ischemic insult. Their results showed that the phantom and animal images acquired with the CT platform were minimally affected by image noise and artifacts. For the beam-hardening phantom study, changes in water HU in the wall surrounding the heart chambers greatly reduced from >±30 to ≤ ± 5 HU at all kVp settings except one region at 100 kVp (7 HU). For the cone-beam phantom study, differences in mean water HU from the central slice were less than 5 HU at two peripheral slices with each 4 cm away from the central slice. These findings were reproducible in the pig DCE images at two peripheral slices that were 6 cm away from the central slice. For the partial-scan phantom study, standard deviations of the mean water HU in 10 successive partial scans were less than 5 HU at the central slice. Similar observations were made in the pig DCE images at two peripheral slices with each 6 cm away from the central slice. For the image noise phantom study, CNRs in the ASiR-V images were statistically higher (p < 0.05) than the non-ASiR-V images at all kVp settings. MP maps generated from the porcine DCE images were in excellent quality, with the ischemia in the LAD territory clearly seen in the three orthogonal views. The study demonstrates that this CT system can provide accurate and reproducible CT numbers during cardiac gated acquisitions across a wide axial field of view. This CT number fidelity will enable this imaging tool to assess contrast enhancement, potentially providing valuable added information beyond anatomic evaluation of coronary stenoses. Furthermore, their results collectively suggested that the 100 kVp/25 mAs protocol run on this CT system provides sufficient image accuracy at a low radiation dose (<3 mSv) for whole-heart quantitative CT MP imaging.

A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior

PubMed Central

Thanos, Panayotis K.; Robison, Lisa S.; Steier, Jessica; Hwang, Yu Fen; Cooper, Thomas; Swanson, James M.; Komatsu, David E.; Hadjiargyrou, Michael; Volkow, Nora D.

2015-01-01

Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (i.e. quicker and higher peak concentrations). Here, we evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic the clinical drug delivery profile. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20, 30, or 60 mg/kg/day; as well as dual-dosages of 4 and 10 mg/kg/day, 20 and 30 mg/kg/day, or 30 and 60 mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 h of drinking the high dose). Blood was sampled and plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60 mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~30 ng/mL), while the 4/10 mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~8 ng/mL). Treatment with the higher dual-dosage (HD: 30/60 mg/kg) resulted in hyperactivity, while the lower (LD: 4/10 mg/kg) had no effect. Next, chronic effects of these dual-dosages were assessed on behavior throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle; decreased exploratory behavior; and increased anxiolytic behavior. These findings suggest that this dual-dosage-drinking-paradigm can be used to examine the effects of clinically relevant pharmacokinetic doses of MP, and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes. PMID:25641666

A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior.

PubMed

Thanos, Panayotis K; Robison, Lisa S; Steier, Jessica; Hwang, Yu Fen; Cooper, Thomas; Swanson, James M; Komatsu, David E; Hadjiargyrou, Michael; Volkow, Nora D

2015-04-01

Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (quicker and higher peak concentrations). We evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic clinical drug delivery. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20, 30, or 60mg/kg/day; as well as dual-dosages of 4 and 10mg/kg/day, 20 and 30mg/kg/day, or 30 and 60mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 h of drinking the high dose). Plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~30ng/mL), while the 4/10mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~8ng/mL). Treatment with the higher dual-dosage (HD: 30/60mg/kg) resulted in hyperactivity, while the lower (LD: 4/10mg/kg) had no effect. Chronic effects of these dual-dosages were assessed throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle, decreased exploratory behavior, and increased anxiolytic behavior. Findings suggest that these dual-dosage-drinking-paradigms can be used to examine the effects of clinically relevant pharmacokinetic doses of MP and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes. Copyright © 2015 Elsevier Inc. All rights reserved.

Thread-Level Parallelization and Optimization of NWChem for the Intel MIC Architecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shan, Hongzhang; Williams, Samuel; Jong, Wibe de

In the multicore era it was possible to exploit the increase in on-chip parallelism by simply running multiple MPI processes per chip. Unfortunately, manycore processors' greatly increased thread- and data-level parallelism coupled with a reduced memory capacity demand an altogether different approach. In this paper we explore augmenting two NWChem modules, triples correction of the CCSD(T) and Fock matrix construction, with OpenMP in order that they might run efficiently on future manycore architectures. As the next NERSC machine will be a self-hosted Intel MIC (Xeon Phi) based supercomputer, we leverage an existing MIC testbed at NERSC to evaluate our experiments.more » In order to proxy the fact that future MIC machines will not have a host processor, we run all of our experiments in tt native mode. We found that while straightforward application of OpenMP to the deep loop nests associated with the tensor contractions of CCSD(T) was sufficient in attaining high performance, significant effort was required to safely and efficiently thread the TEXAS integral package when constructing the Fock matrix. Ultimately, our new MPI OpenMP hybrid implementations attain up to 65x better performance for the triples part of the CCSD(T) due in large part to the fact that the limited on-card memory limits the existing MPI implementation to a single process per card. Additionally, we obtain up to 1.6x better performance on Fock matrix constructions when compared with the best MPI implementations running multiple processes per card.« less

Thread-level parallelization and optimization of NWChem for the Intel MIC architecture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shan, Hongzhang; Williams, Samuel; de Jong, Wibe

In the multicore era it was possible to exploit the increase in on-chip parallelism by simply running multiple MPI processes per chip. Unfortunately, manycore processors' greatly increased thread- and data-level parallelism coupled with a reduced memory capacity demand an altogether different approach. In this paper we explore augmenting two NWChem modules, triples correction of the CCSD(T) and Fock matrix construction, with OpenMP in order that they might run efficiently on future manycore architectures. As the next NERSC machine will be a self-hosted Intel MIC (Xeon Phi) based supercomputer, we leverage an existing MIC testbed at NERSC to evaluate our experiments.more » In order to proxy the fact that future MIC machines will not have a host processor, we run all of our experiments in native mode. We found that while straightforward application of OpenMP to the deep loop nests associated with the tensor contractions of CCSD(T) was sufficient in attaining high performance, significant e ort was required to safely and efeciently thread the TEXAS integral package when constructing the Fock matrix. Ultimately, our new MPI+OpenMP hybrid implementations attain up to 65× better performance for the triples part of the CCSD(T) due in large part to the fact that the limited on-card memory limits the existing MPI implementation to a single process per card. Additionally, we obtain up to 1.6× better performance on Fock matrix constructions when compared with the best MPI implementations running multiple processes per card.« less

Complete data preparation flow for Massively Parallel E-Beam lithography on 28nm node full-field design

NASA Astrophysics Data System (ADS)

Fay, Aurélien; Browning, Clyde; Brandt, Pieter; Chartoire, Jacky; Bérard-Bergery, Sébastien; Hazart, Jérôme; Chagoya, Alexandre; Postnikov, Sergei; Saib, Mohamed; Lattard, Ludovic; Schavione, Patrick

2016-03-01

Massively parallel mask-less electron beam lithography (MP-EBL) offers a large intrinsic flexibility at a low cost of ownership in comparison to conventional optical lithography tools. This attractive direct-write technique needs a dedicated data preparation flow to correct both electronic and resist processes. Moreover, Data Prep has to be completed in a short enough time to preserve the flexibility advantage of MP-EBL. While the MP-EBL tools have currently entered an advanced stage of development, this paper will focus on the data preparation side of the work for specifically the MAPPER Lithography FLX-1200 tool [1]-[4], using the ASELTA Nanographics Inscale software. The complete flow as well as the methodology used to achieve a full-field layout data preparation, within an acceptable cycle time, will be presented. Layout used for Data Prep evaluation was one of a 28 nm technology node Metal1 chip with a field size of 26x33mm2, compatible with typical stepper/scanner field sizes and wafer stepping plans. Proximity Effect Correction (PEC) was applied to the entire field, which was then exported as a single file to MAPPER Lithography's machine format, containing fractured shapes and dose assignments. The Soft Edge beam to beam stitching method was employed in the specific overlap regions defined by the machine format as well. In addition to PEC, verification of the correction was included as part of the overall data preparation cycle time. This verification step was executed on the machine file format to ensure pattern fidelity and accuracy as late in the flow as possible. Verification over the full chip, involving billions of evaluation points, is performed both at nominal conditions and at Process Window corners in order to ensure proper exposure and process latitude. The complete MP-EBL data preparation flow was demonstrated for a 28 nm node Metal1 layout in 37 hours. The final verification step shows that the Edge Placement Error (EPE) is kept below 2.25 nm over an exposure dose variation of 8%.

Delusion of inanimate doubles: description of a case of focal retrograde amnesia.

PubMed

Abbate, Carlo; Trimarchi, Pietro Davide; Salvi, Gian Pietro; Quarenghi, Anna Maria; Vergani, Carlo; Luzzatti, Claudio

2012-01-01

This paper reports the case of a patient, M.P., who developed delusion of inanimate doubles, without Capgras syndrome, after traumatic brain injury. His delusional symptoms were studied longitudinally and the cognitive impairments associated with delusion were investigated. Data suggest that M.P. did 'perceive' the actual differences between doubles and originals rather than 'confabulate' them. The cognitive profile, characterized by retrograde episodic amnesia, but neither object processing impairment nor confabulations, supports this hypothesis. The study examines the nature of object misidentification based on Ellis' and Staton's account and proposes a new account based on concurrent unbiased retrieval of semantic memory traces and biased recollection of episodic memory traces.

Refined separation of combined Fe–Hf from rock matrices for isotope analyses using AG-MP-1M and Ln-Spec chromatographic extraction resins

PubMed Central

Cheng, Ting; Nebel, Oliver; Sossi, Paolo A.; Chen, Fukun

2014-01-01

A combined procedure for separating Fe and Hf from a single rock digestion is presented. In a two-stage chromatographic extraction process, a purified Fe fraction is first quantitatively separated from the rock matrix using AG-MP-1M resin in HCl. Hafnium is subsequently isolated using a modified version of a commonly applied method using Eichrom LN-Spec resin. Our combined method includes:•Purification of Fe from the rock matrix using HCl, ready for mass spectrometric analysis.•Direct loading of the matrix onto the resin that is used for Hf purification.•Collection of a Fe-free Hf fraction. PMID:26150946

Association of Mycoplasma pneumoniae infection with increased risk of asthma in children.

PubMed

Yin, Sha-Sha; Ma, Feng-Lian; Gao, Xing

2017-05-01

The present study was conducted to investigate the relationship between Mycoplasma pneumoniae (MP) infection and the risk of asthma among children by detecting the rate of MP immunoglobulin M (MP-IgM) and the eosinophil (EOS) count. A total of 139 asthmatic children were enrolled as the case group and assigned into three groups: Group A (aged <3 years, n=42), group B (aged 3-8 years, n=45) and group C (aged >8 years, n=52). Additionally, 115 healthy children were enrolled in the control group. Enzyme-linked immunosorbent assay was used to measure the MP-IgM-positive rate. EOS count was detected in the experimental and control groups by using a hemocytometer analyzer. A meta-analysis was performed by using the Comprehensive Meta-Analysis version 2.0 software. The positive rates of the MP-IgM and EOS count in the experimental group were significantly higher than those in control group (both P<0.001). Furthermore, the asthmatic children in group C had a higher MP-IgM-positive rate and EOS count as compared to those in groups A and B, respectively (all P<0.05). Results from groups A and B were not statistically significant (all P>0.05). The meta-analysis further confirmed that asthmatic children had a higher MP-IgM-positive rate as compared to the healthy controls (P<0.001). Age-stratified analysis revealed that the MP-IgM-positive rate in asthmatic children aged ≥8 and <8 years was significantly higher than that in the healthy controls (P=0.003 and P<0.001). Asthmatic children had a higher MP-IgM-positive rate and EOS count as compared with controls, suggesting that the MP infection may be closely associated with the risk of asthma. Additionally, the positive rate of MP-IgM may indicate an important biological marker in predicting the development of asthma.

6-Mercaptopurine reduces cytokine and Muc5ac expression involving inhibition of NFκB activation in airway epithelial cells.

PubMed

Kurakula, Kondababu; Hamers, Anouk A; van Loenen, Pieter; de Vries, Carlie J M

2015-06-19

Mucus hypersecretion and excessive cytokine synthesis is associated with many of the pathologic features of chronic airway diseases such as asthma. 6-Mercaptopurine (6-MP) is an immunosuppressive drug that is widely used in several inflammatory disorders. Although 6-MP has been used to treat asthma, its function and mechanism of action in airway epithelial cells is unknown. Confluent NCI-H292 and MLE-12 epithelial cells were pretreated with 6-MP followed by stimulation with TNFα or PMA. mRNA levels of cytokines and mucins were measured by RT-PCR. Western blot analysis was performed to assess the phosphorylation of IκBα and luciferase assays were performed using an NFκB reporter plasmid to determine NFκB activity. Periodic Acid Schiff staining was used to assess the production of mucus. 6-MP displayed no effect on cell viability up to a concentration of 15 μM. RT-PCR analysis showed that 6-MP significantly reduces TNFα- and PMA-induced expression of several proinflammatory cytokines in NCI-H292 and MLE-12 cells. Consistent with this, we demonstrated that 6-MP strongly inhibits TNFα-induced phosphorylation of IκBα and thus attenuates NFκB luciferase reporter activity. In addition, 6-MP decreases Rac1 activity in MLE-12 cells. 6-MP down-regulates gene expression of the mucin Muc5ac, but not Muc2, through inhibition of activation of the NFκB pathway. Furthermore, PMA- and TNFα-induced mucus production, as visualized by Periodic Acid Schiff (PAS) staining, is decreased by 6-MP. Our data demonstrate that 6-MP inhibits Muc5ac gene expression and mucus production in airway epithelial cells through inhibition of the NFκB pathway, and 6-MP may represent a novel therapeutic target for mucus hypersecretion in airway diseases.

High Temperature Induced Anthocyanin Inhibition and Active Degradation in Malus profusion

PubMed Central

Rehman, Rana Naveed Ur; You, Yaohua; Zhang, Lei; Goudia, Bachir Daoura; Khan, Abdul Rehman; Li, Pengmin; Ma, Fangwang

2017-01-01

The red fleshed fruits of Malus profusion represent gradual color loss during high temperature in summer, potentially due to active degradation of anthocyanin. The objective of this study was to examine both physiological and molecular evidence of anthocyanin degradation. Malus crabapple fruits were exposed to either room temperature (RT = 18 ± 2°C: 25 ± 2°C) or high temperature (HT = 33 ± 2°C: 25 ± 2°C) regimens (12 h: 12 h) under hypoxic (2%) or normoxic (21%) oxygen levels. The results showed that the concentration of cyanidin 3-galactoside (cy-3-gal) was dramatically reduced following HT treatments due to a significant down-regulation of anthocyanin biosynthetic genes (MpCHS, MpDFR, MpLDOX, MpUFGT, and MpMYB10). Among other repressor MYBs, MpMYB15 expression was high following HT treatment of the fruit. HT led to the generation of a substantial concentration of H2O2 due to enhanced activities of superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA) content and cell sap pH value. Similarly, transcript levels of MpVHA-B1 and MpVHA-B2 were reduced which are involved in the vacuolar transportation of anthocyanin. The enzymatic degradation of anthocyanin was eventually enhanced coupled with the oxidative activities of peroxidase (POD) and H2O2. Conversely, the RT treatments potentially enhanced anthocyanin content by stabilizing physiological attributes (such as MDA, H2O2, and pH, among others) and sustaining sufficient biosynthetic gene expression levels. Quantitative real-time PCR analysis indicated that the transcription of MpPOD1, MpPOD8 and MpPOD9 genes in fruit tissues was up-regulated due to HT treatment and that hypoxic conditions seems more compatible with the responsible POD isoenzymes involved in active anthocyanin degradation. The results of the current study could be useful for understanding as well as elucidating the physiological phenomenon and molecular signaling cascade underlying active anthocyanin degradation in Malus crops. PMID:28848597

Characterization of mutant tobacco mosaic virus coat protein that interferes with virus cell-to-cell movement.

PubMed

Bendahmane, Mohammed; Szecsi, Judit; Chen, Iju; Berg, R Howard; Beachy, Roger N

2002-03-19

Expression of tobacco mosaic virus (TMV) coat protein (CP) in plants confers resistance to infection by TMV and related tobamoviruses. Certain mutants of the CP (CP(T42W)) provide much greater levels of resistance than wild-type (wt) CP. In the present work, infection induced by RNA transcripts of TMV clones that contain wt CP or mutant CP(T42W) fused to the green fluorescent protein (GFP) (TMV-CP:GFP, TMV-CP(T42W):GFP) and clones harboring TMV movement protein (MP):GFP were followed in nontransgenic and transgenic tobacco BY-2 protoplasts and Nicotiana tabaccum Xanthi-nn plants that express wt CP or CP(T42W). On nontransgenic and wt CP transgenic plants, TMV-CP:GFP produced expanding, highly fluorescent disk-shaped areas. On plants expressing CP(T42W), infection by TMV-CP:GFP or TMV-MP:GFP-CP produced infection sites of smaller size that were characterized by low fluorescence, reflecting reduced levels of virus spread and reduced accumulation of both CP:GFP and MP:GFP. TMV-CP(T42W):GFP failed to produce visible infection sites on nontransgenic plants, yet produced normal infection sites on MP-transgenic plants that produce MP. TMV infection of transgenic BY-CP(T42W) protoplasts resulted in very low levels of MP accumulation, whereas on BY-CP protoplasts (containing wt CP), infection produced higher levels of MP than in nontransgenic BY-2 cells. The results suggest that wt CP has a positive effect on the production of MP, whereas the CP(T42W) has a negative effect on MP accumulation and/or function. This effect results in very high levels of resistance to TMV infection in plants containing CP(T42W). This report shows that the CP of a plant virus regulates production of the MP, and that a mutant CP interferes with MP accumulation and cell-to-cell movement of infection.

Green fluorescent genetically encoded calcium indicator based on calmodulin/M13-peptide from fungi.

PubMed

Barykina, Natalia V; Subach, Oksana M; Piatkevich, Kiryl D; Jung, Erica E; Malyshev, Aleksey Y; Smirnov, Ivan V; Bogorodskiy, Andrey O; Borshchevskiy, Valentin I; Varizhuk, Anna M; Pozmogova, Galina E; Boyden, Edward S; Anokhin, Konstantin V; Enikolopov, Grigori N; Subach, Fedor V

2017-01-01

Currently available genetically encoded calcium indicators (GECIs) utilize calmodulins (CaMs) or troponin C from metazoa such as mammals, birds, and teleosts, as calcium-binding domains. The amino acid sequences of the metazoan calcium-binding domains are highly conserved, which may limit the range of the GECI key parameters and cause undesired interactions with the intracellular environment in mammalian cells. Here we have used fungi, evolutionary distinct organisms, to derive CaM and its binding partner domains and design new GECI with improved properties. We applied iterative rounds of molecular evolution to develop FGCaMP, a novel green calcium indicator. It includes the circularly permuted version of the enhanced green fluorescent protein (EGFP) sandwiched between the fungal CaM and a fragment of CaM-dependent kinase. FGCaMP is an excitation-ratiometric indicator that has a positive and an inverted fluorescence response to calcium ions when excited at 488 and 405 nm, respectively. Compared with the GCaMP6s indicator in vitro, FGCaMP has a similar brightness at 488 nm excitation, 7-fold higher brightness at 405 nm excitation, and 1.3-fold faster calcium ion dissociation kinetics. Using site-directed mutagenesis, we generated variants of FGCaMP with improved binding affinity to calcium ions and increased the magnitude of FGCaMP fluorescence response to low calcium ion concentrations. Using FGCaMP, we have successfully visualized calcium transients in cultured mammalian cells. In contrast to the limited mobility of GCaMP6s and G-GECO1.2 indicators, FGCaMP exhibits practically 100% molecular mobility at physiological concentrations of calcium ion in mammalian cells, as determined by photobleaching experiments with fluorescence recovery. We have successfully monitored the calcium dynamics during spontaneous activity of neuronal cultures using FGCaMP and utilized whole-cell patch clamp recordings to further characterize its behavior in neurons. Finally, we used FGCaMP in vivo to perform structural and functional imaging of zebrafish using wide-field, confocal, and light-sheet microscopy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

El-Demerdash, Ebtehal, E-mail: ebtehal_dm@yahoo.com

Methyl palmitate (MP) has been shown earlier to inhibit Kupffer cells and rat peritoneal macrophages. To evaluate the potential of MP to inhibit the activation of other macrophages, RAW cells (macrophages of alveolar origin) were treated with varying concentrations of MP (0.25, 0.5, 1 mM). Assessment of cytotoxicity using MTT assay revealed that 0.25 and 0.5 mM are not toxic to RAW cells. MP was able to inhibit the phagocytic function of RAW cells. Treatment of cells with MP 24 hours prior to LPS stimulation significantly decreased nitric oxide release and altered the pattern of cytokines release; there was amore » significant decrease in TNF-{alpha} and a significant increase in IL-10 compared to the controls. However, there is a non-significant change in IL-6 level. Furthermore, phosphorylation of inhibitory kappa B (I{kappa}B{alpha}) protein was significantly decreased in RAW cells treated with 0.5 mM MP after LPS stimulation. Based upon the in-vitro results, it was examined whether MP treatment will be effective in preventing bleomycin-induced lung inflammation and fibrosis in-vivo. Bleomycin given by itself caused destruction of the lung architecture characterized by pulmonary fibrosis with collapse of air alveoli and emphysematous. Bleomycin induced a significant increase in hydroxyproline level and activated NF-{kappa}B, p65 expression in the lung. MP co-treatment significantly ameliorated bleomycin effects. These results suggest that MP has a potential of inhibiting macrophages in general. The present study demonstrated for the first time that MP has anti-inflammatory and antifibrotic effect that could be through NF-kB inhibition. Thus MP like molecule could be a promising anti-inflammatory and antifibrotic drug. - Research Highlights: >Methyl palmitate is a universal macrophage inhibitor. >It could be a promising nucleus of anti-inflammatory and antifibrotic drugs. >The underlying mechanism of these effects could be through NF-kB inhibition.« less

The cognate coat protein is required for cell-to-cell movement of a chimeric brome mosaic virus mediated by the cucumber mosaic virus movement protein.

PubMed

Nagano, H; Mise, K; Okuno, T; Furusawa, I

1999-12-20

Cucumber mosaic cucumovirus (CMV) and brome mosaic bromovirus (BMV) have many similarities, including the three-dimensional structure of virions, genome organizations, and requirement of the coat protein (CP) for cell-to-cell movement. We have shown that a chimeric BMV with the CMV 3a movement protein (MP) gene instead of its own cannot move from cell to cell in Chenopodium quinoa, a common permissive host for both BMV and CMV. Another chimeric BMV was constructed by replacing both MP and CP genes of BMV with those of CMV (MP/CP-chimera) and tested for its infectivity in C. quinoa, to determine whether the CMV CP has some functions required for the CMV MP-mediated cell-to-cell movement and to exhibit functional difference between CPs of BMV and CMV. Cell-to-cell movement of the MP/CP-chimera occurred, and small local lesions were induced on the inoculated leaves. A frameshift mutation introduced in the CMV CP gene of the MP/CP-chimera resulted in a lack of cell-to-cell movement of the chimeric virus. These results indicate that the viral movement mediated by the CMV MP requires its cognate CP. Deletion of the amino-terminal region in CMV CP, which is not obligatory for CMV movement, also abolished cell-to-cell movement of the MP/CP-chimera. This may suggest some differences in cell-to-cell movement of the MP/CP-chimera and CMV. On the other hand, the sole replacement of BMV CP gene with that of CMV abolished viral cell-to-cell movement, suggesting a possibility that the viral movement mediated by the BMV MP may also require its cognate CP. Functional compatibility between MP and CP in viral cell-to-cell movement is discussed. Copyright 1999 Academic Press.

The evaluation of different treatment protocols for trauma-induced lung injury in rats

PubMed Central

Güzel, Aygül; Katı, Celal; Duran, Latif; Alaçam, Hasan; Gacar, Ayhan; Güvenç, Tolga; Murat, Naci; Şişman, Bülent

2014-01-01

Background Lung contusion is an important factor that affects mortality and morbidity of lung injury after blunt chest trauma (BCT). The present study aims to evaluate the effectiveness of different treatment regimens on BCT-induced lung injury. Methods A total of 35 Sprague Dawley rats were divided into five experimental groups (n=7): sham, control; BCT; BCT + MP, BCT group treated with methylprednisolone (MP; 30 mg/kg on first day and 3 mg/kg/d on the following days); BCT + Q, BCT group treated with quercetin (Q; 50 mg/kg/d for seven days); and BCT + MP + Q, BCT group treated with the same doses of MP and Q. Serum Clara Cell Protein-16 (CC-16), thiobarbituric acid reactive substances (TBARS), and superoxide dismutase (SOD) levels were analyzed to determine histopathological changes in the lung tissues. Results Elevated serum CC-16 and TBARS levels and reduced serum SOD levels were found in the BCT group compared to the Sham group. There was a significant change in the serum CC-16 levels in the BCT + MP group compared to the Sham group. Serum TBARS levels were significantly lower in the BCT + MP and BCT + Q group compared to the BCT group. The combined therapy regimen yielded significantly decreased CC-16 levels and increased serum SOD levels compared to the individual treatment groups. Serum TBARS levels did not significantly differ between the BCT + MP + Q group and the other treatment groups. Compared to the BCT + MP + Q group, the BCT + MP group showed significantly lower alveolar edema (AED) and alveolar exudate (AEX) scores, while the BCT + Q group showed significantly lower peribronchial inflammatory cell infiltration (PICI) and AED scores. Conclusions The combined usage of quercetin and low dose MP treatment after initial high dose MP at the early stage of lung injury after BCT is more effective. PMID:24605218

Identification of microplastic in effluents of waste water treatment plants using focal plane array-based micro-Fourier-transform infrared imaging.

PubMed

Mintenig, S M; Int-Veen, I; Löder, M G J; Primpke, S; Gerdts, G

2017-01-01

The global presence of microplastic (MP) in aquatic ecosystems has been shown by various studies. However, neither MP concentrations nor their sources or sinks are completely known. Waste water treatment plants (WWTPs) are considered as significant point sources discharging MP to the environment. This study investigated MP in the effluents of 12 WWTPs in Lower Saxony, Germany. Samples were purified by a plastic-preserving enzymatic-oxidative procedure and subsequent density separation using a zinc chloride solution. For analysis, attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FT-IR) and focal plane array (FPA)-based transmission micro-FT-IR imaging were applied. This allowed the identification of polymers of all MP down to a size of 20 μm. In all effluents MP was found with quantities ranging from 0 to 5 × 10 1  m -3  MP > 500 μm and 1 × 10 1 to 9 × 10 3  m -3  MP < 500 μm. By far, polyethylene was the most frequent polymer type in both size classes. Quantities of synthetic fibres ranged from 9 × 10 1 to 1 × 10 3  m -3 and were predominantly made of polyester. Considering the annual effluxes of tested WWTPs, total discharges of 9 × 10 7 to 4 × 10 9  MP particles and fibres per WWTP could be expected. Interestingly, one tertiary WWTP had an additionally installed post-filtration that reduced the total MP discharge by 97%. Furthermore, the sewage sludge of six WWTPs was examined and the existence of MP, predominantly polyethylene, revealed. Our findings suggest that WWTPs could be a sink but also a source of MP and thus can be considered to play an important role for environmental MP pollution. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection - recommendations from a UK consensus meeting.

PubMed

Brizmohun Appayya, Mrishta; Adshead, Jim; Ahmed, Hashim U; Allen, Clare; Bainbridge, Alan; Barrett, Tristan; Giganti, Francesco; Graham, John; Haslam, Phil; Johnston, Edward W; Kastner, Christof; Kirkham, Alexander P S; Lipton, Alexandra; McNeill, Alan; Moniz, Larissa; Moore, Caroline M; Nabi, Ghulam; Padhani, Anwar R; Parker, Chris; Patel, Amit; Pursey, Jacqueline; Richenberg, Jonathan; Staffurth, John; van der Meulen, Jan; Walls, Darren; Punwani, Shonit

2018-07-01

To identify areas of agreement and disagreement in the implementation of multi-parametric magnetic resonance imaging (mpMRI) of the prostate in the diagnostic pathway. Fifteen UK experts in prostate mpMRI and/or prostate cancer management across the UK (involving nine NHS centres to provide for geographical spread) participated in a consensus meeting following the Research and Development Corporation and University of California-Los Angeles (UCLA-RAND) Appropriateness Method, and were moderated by an independent chair. The experts considered 354 items pertaining to who can request an mpMRI, prostate mpMRI protocol, reporting guidelines, training, quality assurance (QA) and patient management based on mpMRI levels of suspicion for cancer. Each item was rated for agreement on a 9-point scale. A panel median score of ≥7 constituted 'agreement' for an item; for an item to reach 'consensus', a panel majority scoring was required. Consensus was reached on 59% of items (208/354); these were used to provide recommendations for the implementation of prostate mpMRI in the UK. Key findings include prostate mpMRI requests should be made in consultation with the urological team; mpMRI scanners should undergo QA checks to guarantee consistently high diagnostic quality scans; scans should only be reported by trained and experienced radiologists to ensure that men with unsuspicious prostate mpMRI might consider avoiding an immediate biopsy. Our consensus statements demonstrate a set of criteria that are required for the practical dissemination of consistently high-quality prostate mpMRI as a diagnostic test before biopsy in men at risk. © 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

Assessment of mercaptopurine (6MP) metabolites and 6MP metabolic key-enzymes in childhood acute lymphoblastic leukemia.

PubMed

Wojtuszkiewicz, Anna; Barcelos, Ana; Dubbelman, Boas; De Abreu, Ronney; Brouwer, Connie; Bökkerink, Jos P; de Haas, Valerie; de Groot-Kruseman, Hester; Jansen, Gerrit; Kaspers, Gertjan L; Cloos, Jacqueline; Peters, G J

2014-01-01

Pediatric acute lymphoblastic leukemia (ALL) is treated with combination chemotherapy including mercaptopurine (6MP) as an important component. Upon its uptake, 6MP undergoes a complex metabolism involving many enzymes and active products. The prognostic value of all the factors engaged in this pathway still remains unclear. This study attempted to determine which components of 6MP metabolism in leukemic blasts and red blood cells are important for 6MP's sensitivity and toxicity. In addition, changes in the enzymatic activities and metabolite levels during the treatment were analyzed. In a cohort (N=236) of pediatric ALL patients enrolled in the Dutch ALL-9 protocol, we studied the enzymes inosine-5'-monophosphate dehydrogenase (IMPDH), thiopurine S-methyltransferase (TPMT), hypoxanthine guanine phosphoribosyl transferase (HGPRT), and purine nucleoside phosphorylase (PNP) as well as thioguanine nucleotides (TGN) and methylthioinosine nucleotides (meTINs). Activities of selected enzymes and levels of 6MP derivatives were measured at various time points during the course of therapy. The data obtained and the toxicity related parameters available for these patients were correlated with each other. We found several interesting relations, including high concentrations of two active forms of 6MP--TGN and meTIN--showing a trend toward association with better in vitro antileukemic effect of 6MP. High concentrations of TGN and elevated activity of HGPRT were found to be significantly associated with grade III/IV leucopenia. However, a lot of data of enzymatic activities and metabolite concentrations as well as clinical toxicity were missing, thereby limiting the number of assessed relations. Therefore, although a complex study of 6MP metabolism in ALL patients is feasible, it warrants more robust and strict data collection in order to be able to draw more reliable conclusions.

A search for the optimal duration of treatment with 6-mercaptopurine for ulcerative colitis.

PubMed

Lobel, Efrat Z; Korelitz, Burton I; Xuereb, Mark A; Panagopoulos, Georgia

2004-03-01

6-mercaptopurine has proven to be effective in the treatment and maintenance of remission of ulcerative colitis (UC). The optimal duration of treatment with 6-MP is unknown. The intention of this study was to determine the best duration of treatment with 6-MP in terms of maintenance efficacy once remission has been achieved. We reviewed the records from the inflammatory bowel disease (IBD) center at Lenox Hill Hospital and one large IBD practice in New York City of 334 patients treated with 6-MP for UC. These patients were followed from 4 months to 28.7 yr. Sixty-one patients were treated with 6-MP for at least 6 months and had at least a 3-month disease-free interval off steroids while on the medication. These patients were divided into two groups: Group 1 continued 6-MP and group 2 discontinued the drug at various times for reasons other than relapse. Time to relapse was calculated for both groups. A Kaplan-Meier survival analysis was employed and differences between the two groups were analyzed using the log-rank test. The median time to relapse in group 2 was 24 wk and in group 1 was 58 wk (p < 0.05). There were no significant differences between the two groups in age, gender, extent of disease, use of concomitant 5-ASA products, dose of 6-MP during remission, duration of UC, and duration of treatment with 6-MP before remission was achieved. Discontinuation of treatment with 6-MP while UC is in remission leads to a higher relapse rate than maintenance on 6-MP. Therefore, we favor the indefinite treatment with 6-MP in most patients.

Classification and discrimination of pediatric patients undergoing open heart surgery with and without methylprednisolone treatment by cytomics

NASA Astrophysics Data System (ADS)

Bocsi, Jozsef; Mittag, Anja; Pierzchalski, Arkadiusz; Osmancik, Pavel; Dähnert, Ingo; Tárnok, Attila

2011-02-01

Introduction: Methylprednisolone (MP) is frequently preoperatively administered in children undergoing open heart surgery. The aim of this medication is to inhibit overshooting immune responses. Earlier studies demonstrated cellular and humoral immunological changes in pediatric patients undergoing heart surgeries with and without MP administration. Here in a retrospective study we investigated the modulation of the cellular immune response by MP. The aim was to identify suitable parameters characterizing MP effects by cluster analysis. Methods: Blood samples were analysed from two aged matched groups with surgical correction of septum defects. Group without MP treatment consisted of 10 patients; MP was administered on 21 patients (median dose: 11mg/kg) before cardiopulmonary bypass (CPB). EDTA anticoagulated blood was obtained 24 h preoperatively, after anesthesia, at CPB begin and end (CPB2), 4h, 24h, 48h after surgery, at discharge and at out-patient followup (8.2; 3.3-12.2 month after surgery; median and IQR). Flow cytometry showed the biggest MP relevant changes at CPB2 and 4h postoperatively. They were used for clustering analysis. Classification was made by discriminant analysis and cluster analysis by means of Genes@work software. Results & conclusion: 146 parameters were obtained from analysis. Cross-validation revealed several parameters being able to discriminate between MP groups and to identify immune modulation. MP administration resulted in a delayed activation of monocytes, increased ratio of neutrophils, reduced T-lymphocytes counts. Cluster analysis demonstrated that classification of patients is possible based on the identified cytomics parameters. Further investigation of these parameters might help to understand the MP effects in pediatric open heart surgery.

Apoptosis-inducing activity of HPLC fraction from Voacanga globosa (Blanco) Merr. on the human colon carcinoma cell.

PubMed

Acebedo, Alvin Resultay; Amor, Evangeline Cancio; Jacinto, Sonia Donaldo

2014-01-01

Voacanga globosa (Blanco), a plant endemic to the Philippines, is traditionally used especially by indigenous people of Bataan in the treatment of ulcers, wounds and tumorous growths. This study aimed to provide scientific evidence to therapeutic properties by determining cytotoxic and pro-apoptotic activity of HPLC fractions from leaves on HCT116 human colon carcinoma and A549 human lung carcinoma cell lines. Ethanolic extraction was performed on V globosa leaves followed by hexane and ethyl acetate partitioning. Silica gel column chromatography and high performance liquid chromatography (HPLC) produced MP1, MP2 and MP3 fractions. Cytotoxic activity of the fractions was determined through MTT assay against the cancer cell lines HCT116 and A549 and the non-cancer AA8 Chinese hamster ovarian cell line. Pro-apoptotic activities of the most active fractions were further assessed through DAPI staining, TUNEL assay and JC-1 mitochondrial membrane potential assay with HCT116 cells. While the MP1 fraction exerted no significant activity against all cell lines tested, MP2 and MP3 fractions demonstrated high toxicity against HCT116 and A549 cells. The MP3 fraction induced formation of apoptotic bodies, condensed DNA and other morphological changes consistent with apoptosis of HCT116 cells and TUNEL assay showed significant increase in DNA fragmentation over time. In these cells, the MP3 fraction also induced mitochondrial membrane destabilization, which is generally associated with the beginning of apoptosis. Phytochemical analysis demonstrated the presence only of saponins and terpenoids in the MP3 fraction. The results indicate that the MP3 fraction exerts cytotoxic activity on HCT116 cells via induction of apoptosis triggered by loss of mitochondrial membrane potential crucial for cell survival.

Explicitly correlated benchmark calculations on C8H8 isomer energy separations: how accurate are DFT, double-hybrid, and composite ab initio procedures?

NASA Astrophysics Data System (ADS)

Karton, Amir; Martin, Jan M. L.

2012-10-01

Accurate isomerization energies are obtained for a set of 45 C8H8 isomers by means of the high-level, ab initio W1-F12 thermochemical protocol. The 45 isomers involve a range of hydrocarbon functional groups, including (linear and cyclic) polyacetylene, polyyne, and cumulene moieties, as well as aromatic, anti-aromatic, and highly-strained rings. Performance of a variety of DFT functionals for the isomerization energies is evaluated. This proves to be a challenging test: only six of the 56 tested functionals attain root mean square deviations (RMSDs) below 3 kcal mol-1 (the performance of MP2), namely: 2.9 (B972-D), 2.8 (PW6B95), 2.7 (B3PW91-D), 2.2 (PWPB95-D3), 2.1 (ωB97X-D), and 1.2 (DSD-PBEP86) kcal mol-1. Isomers involving highly-strained fused rings or long cumulenic chains provide a 'torture test' for most functionals. Finally, we evaluate the performance of composite procedures (e.g. G4, G4(MP2), CBS-QB3, and CBS-APNO), as well as that of standard ab initio procedures (e.g. MP2, SCS-MP2, MP4, CCSD, and SCS-CCSD). Both connected triples and post-MP4 singles and doubles are important for accurate results. SCS-MP2 actually outperforms MP4(SDQ) for this problem, while SCS-MP3 yields similar performance as CCSD and slightly bests MP4. All the tested empirical composite procedures show excellent performance with RMSDs below 1 kcal mol-1.

68Ga-PSMA PET/CT vs. mpMRI for locoregional prostate cancer staging: correlation with final histopathology.

PubMed

Berger, I; Annabattula, C; Lewis, J; Shetty, D V; Kam, J; Maclean, F; Arianayagam, M; Canagasingham, B; Ferguson, R; Khadra, M; Ko, R; Winter, M; Loh, H; Varol, C

2018-06-01

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can be used to locate lesions based on PSMA avidity, however guidelines on its use are limited by its infancy. We aimed to compare multiparametric magnetic resonance imaging (mpMRI) and PSMA PET/CT to prostatectomy histopathology. We conducted a chart review from February 2015 to January 2017 of 50 male patients staged for prostate cancer using PSMA PET/CT and mpMRI who then underwent radical prostatectomy. Pre-operative PSMA PET/CT and mpMRI were paired with corresponding histopathology. Correlations, sensitivity, and specificity were used for comparisons. A total of 81 lesions were confirmed by histopathology. Fifty index lesions were detected by histopathology, all of which were detected by PSMA PET/CT (100% detection), and 47 by mpMRI (94% detection). Thirty-one histologically confirmed secondary lesions were detected, 29 of which were detected by PSMA PET/CT (93.5% detection), and 16 by mpMRI (51.6% detection). PSMA had better sensitivity for index lesion localization than mpMRI (81.1 vs. 64.8%). Specificity was similar for PSMA PET/CT and mpMRI (84.6 vs. 82.7%). SUV max of index lesions ranged from 2.9 to 39.6 (M = 9.27 ± 6.41). Index lesion SUV max was positively correlated with PSA (rho = 0.48, p < 0.001) and ISUP grade (rho = 0.51, p < 0.001). PSMA-PET/CT provided superior detection of prostate cancer lesions with better sensitivity than mpMRI. PSMA-PET/CT can be used to enhance locoregional mpMRI to provide improved detection and characterization of lesions.

Identification of hand motion using background subtraction method and extraction of image binary with backpropagation neural network on skeleton model

NASA Astrophysics Data System (ADS)

Fauziah; Wibowo, E. P.; Madenda, S.; Hustinawati

2018-03-01

Capturing and recording motion in human is mostly done with the aim for sports, health, animation films, criminality, and robotic applications. In this study combined background subtraction and back propagation neural network. This purpose to produce, find similarity movement. The acquisition process using 8 MP resolution camera MP4 format, duration 48 seconds, 30frame/rate. video extracted produced 1444 pieces and results hand motion identification process. Phase of image processing performed is segmentation process, feature extraction, identification. Segmentation using bakground subtraction, extracted feature basically used to distinguish between one object to another object. Feature extraction performed by using motion based morfology analysis based on 7 invariant moment producing four different classes motion: no object, hand down, hand-to-side and hands-up. Identification process used to recognize of hand movement using seven inputs. Testing and training with a variety of parameters tested, it appears that architecture provides the highest accuracy in one hundred hidden neural network. The architecture is used propagate the input value of the system implementation process into the user interface. The result of the identification of the type of the human movement has been clone to produce the highest acuracy of 98.5447%. The training process is done to get the best results.

Low energy isomers of (H2O)25 from a hierarchical method based on Monte Carlo Temperature Basin Paving and Molecular Tailoring Approaches benchmarked by full MP2 calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sahu, Nityananda; Gadre, Shridhar R.; Bandyopadhyay, Pradipta

We report new global minimum candidate structures for the (H2O)25 cluster that are lower in energy than the ones reported previously and correspond to hydrogen bonded networks with 42 hydrogen bonds and an interior, fully coordinated water molecule. These were obtained as a result of a hierarchical approach based on initial Monte Carlo Temperature Basin Paving (MCTBP) sampling of the cluster’s Potential Energy Surface (PES) with the Effective Fragment Potential (EFP), subsequent geometry optimization using the Molecular Tailoring fragmentation Approach (MTA) and final refinement at the second order Møller Plesset perturbation (MP2) level of theory. The MTA geometry optimizations usedmore » between 14 and 18 main fragments with maximum sizes between 11 and 14 water molecules and average size of 10 water molecules, whose energies and gradients were computed at the MP2 level. The MTA-MP2 optimized geometries were found to be quite close (within < 0.5 kcal/mol) to the ones obtained from the MP2 optimization of the whole cluster. The grafting of the MTA-MP2 energies yields electronic energies that are within < 5×10-4 a.u. from the MP2 results for the whole cluster while preserving their energy order. The MTA-MP2 method was also found to reproduce the MP2 harmonic vibrational frequencies in both the HOH bending and the OH stretching regions.« less

Circulating cell-derived microparticles in severe preeclampsia and in fetal growth restriction.

PubMed

Alijotas-Reig, Jaume; Palacio-Garcia, Carles; Farran-Codina, Immaculada; Ruiz-Romance, Mar; Llurba, Elisa; Vilardell-Tarres, Miquel

2012-02-01

The behavior of the circulating microparticles (cMP) in severe preeclampsia (PE) and fetal growth restriction (FGR) is disputed. METHOD OF STUDY  Non-matched case-control study. Seventy cases of severe PE/HELLP/FGR were compared to 38 healthy pregnant women. Twenty healthy non-pregnant women acted as a control. cMP were analyzed using flow cytometry. Results are given as total (annexin-A5-ANXA5+), platelet (CD41+), leukocyte (CD45+), endothelial (CD144+CD31+//CD41-), and CD41-negative cMP/μL of plasma. Antiphospholipid antibodies (aPL) were analyzed through usual methods. Platelet and endothelial cMP increased in healthy pregnant women. PE whole group (PE±FGR) showed an increase in endothelial and CD41-negative, but not in platelet-derived, cMP. Comparing PE whole group versus healthy pregnant, we found cMP levels of endothelial and CD41- had increased. The cMP results obtained in PE group were similar to those of the PE whole group. Comparing PE group to isolated FGR, significant CD41-negative cMP increase was found in PE. According to its aPL positivity, a trend to decrease in leukocyte and endothelial-derived cMP was found in PE group. Normal pregnancy is accompanied by endothelial and platelet cell activation. Endothelial cell activation has been shown in PE but not in isolated FGR. In PE, aPL may contribute to endothelial and possibly to leukocyte cell activation. © 2011 John Wiley & Sons A/S.

Lifespan metabolic potential of the unicellular organisms expressed by Boltzmann constant, absolute temperature and proton mass

NASA Astrophysics Data System (ADS)

Atanasov, Atanas Todorov

2016-12-01

The unicellular organisms and phages are the first appeared fundamental living organisms on the Earth. The total metabolic energy (Els, J) of these organisms can be expressed by their lifespan metabolic potential (Als, J/kg) and body mass (M, kg): Els =Als M. In this study we found a different expression - by Boltzmann's constant (k, J/K), nucleon mass (mp+, kg) of protons (and neutrons), body mass (M, kg) of organism or mass (Ms) of biomolecules (proteins, nucleotides, polysaccharides and lipids) building organism, and the absolute temperature (T, K). The found equations are: Els= (M/mp+)kT for phages and Els=(Ms/mp+)kT for the unicellular organisms. From these equations the lifespan metabolic potential can be expressed as: Als=Els/M= (k/mp+)T for phages and Als=Els/M= (k/3.3mp+)T for unicellular organisms. The temperature-normated lifespan metabolic potential (Als/T, J/K.kg) is equals to the ratio between Boltzmann's constant and nucleon mass: Als/T=k/mp+ for phages and Als/T=k/3.3mp+ for unicellular organisms. The numerical value of the k/mp+ ratio is equals to 8.254×103 J/K.kg, and the numerical value of k/3.3mp+ ratio is equal to 2.497×103 J/K.kg. These values of temperature-normated lifespan metabolic potential could be considered fundamental for the unicellular organisms.

Metal exposure in cows grazing pasture contaminated by iron industry: Insights from magnetic particles used as tracers.

PubMed

Ayrault, Sophie; Catinon, Mickaël; Boudouma, Omar; Bordier, Louise; Agnello, Gregory; Reynaud, Stéphane; Tissut, Michel

2016-05-01

Magnetic particles (MP) emitted by an iron smelter were used to investigate the exposure of cows grazing on a grassland polluted by these MP and by large amounts of potentially toxic elements (PTE). The morphology as well as the chemical composition of the MP separated from cow dung were studied. Large amounts of typical MP were found (1.1 g kg(-1) dry weight) in the cow dung sampled from the exposed site, whereas these particles were absent from the reference unpolluted site. The ingested MP were mainly technogenic magnetic particles (TMP) emitted by the smelter. Considering the MP concentration in the grazed grass on the exposed site, it was concluded that cows absorb the MP not only from the grass but also from the soil surface. The results of a mild acidic leaching of the MP suggested that the particles were possibly submitted to a superficial dissolution in the abomasum, pointing at a potential route of transfer of the PTE originating from the TMP and leading into food chains. TMP were only a small part of the anthropogenic contamination having affected the soil and the dung. However, due to their unequivocal signature, TMP are a powerful tracer of the distribution of PTE in the different compartments constituting the food chains and the ecosystems. Furthermore, the measurement of the particle sizes gave evidence that a noticeable proportion of the MP could enter the respiratory tract. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of the Department of Defense Pre-Award Contracting Process

DTIC Science & Technology

2014-12-01

Justification and Approval JBSA Joint Base San Antonio KPIs Key Performance Indicators MAJCOMs Major Command MP Mandatory Commands NAVIAR...meets desired results. Results-based performance measurement establishes key performance indicators ( KPIs ) that determine whether procurement...or goals, and underlying business processes (Cullen, 2009, p. 38). Within each quadrant, Cullen provided examples of KPIs that serve to measure

Automatic Multilevel Parallelization Using OpenMP

NASA Technical Reports Server (NTRS)

Jin, Hao-Qiang; Jost, Gabriele; Yan, Jerry; Ayguade, Eduard; Gonzalez, Marc; Martorell, Xavier; Biegel, Bryan (Technical Monitor)

2002-01-01

In this paper we describe the extension of the CAPO (CAPtools (Computer Aided Parallelization Toolkit) OpenMP) parallelization support tool to support multilevel parallelism based on OpenMP directives. CAPO generates OpenMP directives with extensions supported by the NanosCompiler to allow for directive nesting and definition of thread groups. We report some results for several benchmark codes and one full application that have been parallelized using our system.

Suppression of ovalbumin-induced airway inflammatory responses in a mouse model of asthma by Mimosa pudica extract.

PubMed

Yang, Eun Ju; Lee, Ji-Sook; Yun, Chi-Young; Ryang, Yong Suk; Kim, Jong-Bae; Kim, In Sik

2011-01-01

Asthma is an inflammatory airway disease. The pathogenic mechanisms of asthma include the infiltration of leukocytes and release of cytokines. Mimosa pudica (Mp) has been used traditionally for the treatment of insomnia, diarrhea and inflammatory diseases. Although Mp extract has various therapeutic properties, the effect of this extract on asthma has not yet been reported. This study investigated the suppressive effects of Mp extract on asthmatic responses both in vitro and in vivo. Mp extract was acquired from dried and powdered whole plants of M. pudica using 80% ethanol. BALB/c mice were used for the mouse model of asthma induced by ovalbumin. Mp extract significantly inhibited the HMC-1 cell migration induced by stem cell factor and blocked the release of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in EoL-1 cells. Leukocytosis, eosinophilia and mucus hypersecretion in asthmatic lung were significantly suppressed by Mp extract. The release of ovalbumin-specific IgE in bronchoalveolar lavage fluid and serum was also decreased. Mp extract treatment resulted in no liver cytotoxicity. The Mp extract has inhibitory properties on asthma and may be used as a potent therapeutic agent for allergic lung inflammation. Copyright © 2010 John Wiley & Sons, Ltd.

Effects of local application of methylprednisolone delivered by the C/GP-hydrogel on the recovery of facial nerves.

PubMed

Chao, Xiuhua; Fan, Zhaomin; Han, Yuechen; Wang, Yan; Li, Jianfeng; Chai, Renjie; Xu, Lei; Wang, Haibo

2015-01-01

Local administration of MP delivered by the C/GP-MP-hydrogel can improve the recovery of facial nerve following crush injury. The findings suggested that locally injected MP delivered by C/GP-hydrogel might be a promising treatment for facial nerve damage. In this study, the aim is to assess the effectiveness of locally administrating methylprednisolone(MP) loaded by chitosan-β-glycerophosphate hydrogel (C/GP-hydrogel) on the regeneration of facial nerve crush injury. After the crush of left facial nerves, Wistar rats were randomly divided into four different groups. Then, four different therapies were used to treat the damaged facial nerves. At the 1(st), 2(nd), 3(rd), and 4(th) week after injury, the functional recovery of facial nerves and the morphological changes of facial nerves were assessed. The expression of growth associated protein-43 (GAP-43) protein in the facial nucleus were also evaluated. Locally injected MP delivered by C/GP-hydrogel effectively accelerated the facial functional recovery. In addition, the regenerated facial nerves in the C/GP-MP group were more mature than those in the other groups. The expression of GAP-43 protein was also improved by the MP, especially in the C/GP-MP group.

Strategies for the prevention of MP3-induced hearing loss among adolescents: expert opinions from a Delphi study.

PubMed

Vogel, Ineke; Brug, Johannes; van der Ploeg, Catharina P B; Raat, Hein

2009-05-01

To identify parties involved in the prevention of MP3-induced hearing loss among adolescents and potentially effective prevention strategies and interventions. Thirty experts in fields such as scientific research, medical practice, community health professions, education, youth work, music entertainment, and enforcement authorities participated in a qualitative, electronic, 3-round, Web-based Delphi study. Multiple parties involved in the prevention of MP3-induced hearing loss among adolescents were identified; the most relevant are the adolescents themselves, their parents, manufacturers of MP3 players and earphones, and the authorities. The experts did not expect that adolescents in general would perform the necessary protective behaviors to prevent MP3-induced hearing loss. Two environmental health protection measures were identified as both relevant and feasible to be implemented (ie, authorities encourage manufacturers to produce safer products, and public health campaigns will be held to improve knowledge of the risks of high-volume music, possible protective measures, and consequences of hearing loss). Authorities, the music industry in general, and especially manufacturers of MP3 players and earphones should recognize their responsibility and create a safer MP3-listening environment by taking measures to protect today's youth from the dangers of listening to high-volume music on MP3 players.

Fungal lectin MpL enables entry of protein drugs into cancer cells and their subcellular targeting

PubMed Central

Kos, Janko; Sabotič, Jerica

2017-01-01

Lectins have been recognized as promising carrier molecules for targeted drug delivery. They specifically bind carbohydrate moieties on cell membranes and trigger cell internalization. Fungal lectin MpL (Macrolepiota procera lectin) does not provoke cancer cell cytotoxicity but is able to bind aminopeptidase N (CD13) and integrin α3β1, two glycoproteins that are overexpressed on the membrane of tumor cells. Upon binding, MpL is endocytosed in a clathrin-dependent manner and accumulates initially in the Golgi apparatus and, finally, in the lysosomes. For effective binding and internalization a functional binding site on the α-repeat is needed. To test the potential of MpL as a carrier for delivering protein drugs to cancer cells we constructed fusion proteins consisting of MpL and the cysteine peptidase inhibitors cystatin C and clitocypin. The fused proteins followed the same endocytic route as the unlinked MpL. Peptidase inhibitor-MpL fusions impaired both the intracellular degradation of extracellular matrix and the invasiveness of cancer cells. MpL is thus shown in vitro to be a lectin that can enable protein drugs to enter cancer cells, enhance their internalization and sort them to lysosomes and the Golgi apparatus. PMID:28460472

Determination of 6-mercaptopurine in the presence of uric acid using modified multiwall carbon nanotubes-TiO2 as a voltammetric sensor.

PubMed

Ensafi, Ali A; Karimi-Maleh, H

2012-12-01

In this work, a multiwall carbon nanotubes modified electrode (prepared by incorporating TiO(2) nanoparticles with p-aminophenol as a mediator) was used as voltammetric sensor for the determination of 6-mercaptopurine (6-MP) in the presence of uric acid (UA). The voltammograms of 6-MP and UA in a mixture can be separated from each other by differential pulse voltammetry with a potential difference of 380 mV at a scan rate of 10 mV s(-1). These conditions are sufficient to allow for the determination of 6-MP and UA both individually and simultaneously. The electrocatalytic currents increase linearly with 6-MP concentration in the ranges of 0.09-350 µmol L(-1) (two linear segments with different slopes). The detection limit for 6-MP was 0.065 µmol L(-1) . The RSD% for 1.0 and 15.0 µmol L(-1) 6-MP were 0.7%, and 1.2%, respectively. The kinetic parameters of the system were determined using electrochemical approaches. The method was successfully applied for the determination of 6-MP in drug sample, and 6-MP plus UA in urine samples. Copyright © 2011 John Wiley & Sons, Ltd.

6-mercaptopurine promotes energetic failure in proliferating T cells

PubMed Central

Fernández-Ramos, Ana A.; Marchetti-Laurent, Catherine; Poindessous, Virginie; Antonio, Samantha; Laurent-Puig, Pierre; Bortoli, Sylvie; Loriot, Marie-Anne; Pallet, Nicolas

2017-01-01

The anticancer drug 6-mercaptopurine (6-MP) inhibits de novo purine synthesis and acts as an antiproliferative agent by interfering with protein, DNA and RNA synthesis and promoting apoptosis. Metabolic reprogramming is crucial for tumor progression to foster cancer cells growth and proliferation, and is regulated by mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) as well as the oncogenes Myc and hypoxia inducible factor 1α (HIF-1α). We hypothesized that 6-MP impacts metabolic remodeling through its action on nucleotide synthesis. The aim of our study is to provide a comprehensive characterization of the metabolic changes induced by 6-MP in leukemic T cells. Our results indicate that exposition to 6-MP rapidly reduces intracellular ATP concentration, leading to the activation of AMPK. In turn, mTOR, an AMPK target, was inhibited, and the expression of HIF-1α and Myc was reduced upon 6-MP incubation. As a consequence of these inhibitions, glucose and glutamine fluxes were strongly decreased. Notably, no difference was observed on glucose uptake upon exposition to 6-MP. In conclusion, our findings provide new insights into how 6-MP profoundly impacts cellular energetic metabolism by reducing ATP production and decreasing glycolytic and glutaminolytic fluxes, and how 6-MP modifies human leukemic T cells metabolism with potential antiproliferative effects. PMID:28574837

6-mercaptopurine promotes energetic failure in proliferating T cells.

PubMed

Fernández-Ramos, Ana A; Marchetti-Laurent, Catherine; Poindessous, Virginie; Antonio, Samantha; Laurent-Puig, Pierre; Bortoli, Sylvie; Loriot, Marie-Anne; Pallet, Nicolas

2017-06-27

The anticancer drug 6-mercaptopurine (6-MP) inhibits de novo purine synthesis and acts as an antiproliferative agent by interfering with protein, DNA and RNA synthesis and promoting apoptosis. Metabolic reprogramming is crucial for tumor progression to foster cancer cells growth and proliferation, and is regulated by mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) as well as the oncogenes Myc and hypoxia inducible factor 1α (HIF-1α). We hypothesized that 6-MP impacts metabolic remodeling through its action on nucleotide synthesis. The aim of our study is to provide a comprehensive characterization of the metabolic changes induced by 6-MP in leukemic T cells. Our results indicate that exposition to 6-MP rapidly reduces intracellular ATP concentration, leading to the activation of AMPK. In turn, mTOR, an AMPK target, was inhibited, and the expression of HIF-1α and Myc was reduced upon 6-MP incubation. As a consequence of these inhibitions, glucose and glutamine fluxes were strongly decreased. Notably, no difference was observed on glucose uptake upon exposition to 6-MP. In conclusion, our findings provide new insights into how 6-MP profoundly impacts cellular energetic metabolism by reducing ATP production and decreasing glycolytic and glutaminolytic fluxes, and how 6-MP modifies human leukemic T cells metabolism with potential antiproliferative effects.

Investigation of the binding of AuNPs-6-mercaptopurine and the sensitive detection of 6-mercaptopurine using resonance Rayleigh light scattering.

PubMed

Li, Zhihong; Bi, Shuyun; Wang, Tianjiao; Wang, Yu; Zhou, Huifeng; Wu, Jun

2017-06-01

A highly sensitive method for the detection of 6-mercaptopurine (MP) by resonance Rayleigh light scattering (RLS) method was developed. Gold nanoparticles (AuNPs) were synthesized by a modified seed method and characterized using transmission electron microscopy (TEM). AuNPs were bound to MP via covalent bonding to form the MP-AuNPs complex, which increased the RLS intensity of MP at 347 nm (increased by 65.7%). Under optimum conditions, the magnitude of the enhanced RLS intensity for MP-AuNPs was proportional to MP concentration in the range 0.0681-1.702 μg mL -1 . The linear regression equation was represented as follows: ΔI RLS  = 9.31 + 82.42c (r = 0.9948). The limit of detection (LOD, 3σ) was 3.32 ng mL -1 . The system was applied successfully to detect MP in pharmaceuticals. MP recoveries were 99.9-101.7% with a relative standard deviation (RSD) (n = 5) of 0.59-0.77% for three synthetic samples, and 97.5-110.0% with an RSD of 0.98-2.10% (n = 5) for tablet samples. Copyright © 2016 John Wiley & Sons, Ltd.

Adolescents risky MP3-player listening and its psychosocial correlates.

PubMed

Vogel, Ineke; Brug, Johannes; Van der Ploeg, Catharina P B; Raat, Hein

2011-04-01

Analogue to occupational noise-induced hearing loss, MP3-induced hearing loss may be evolving into a significant social and public health problem. To inform prevention strategies and interventions, this study investigated correlates of adolescents' risky MP3-player listening behavior primarily informed by protection motivation theory. We invited 1687 adolescents (12- to 19-year old) of Dutch secondary schools to complete questionnaires about their MP3-player listening, sociodemographic characteristics and presumed psychosocial determinants of MP3-player listening. Of all participants, 90% reported listening to music through earphones on MP3 players; 28.6% were categorized as listeners at risk for hearing loss due to estimated exposure of 89 dBA for ≥1 hour per day. Compared with listeners not at risk for hearing loss, listeners at risk were more likely not to live with both parents, to experience rewards of listening to high-volume levels, to report a high habit strength related to risky MP3 listening, and were less likely to be motivated to protect their hearing. Habit strength was the strongest correlate of risky listening behavior, suggesting that voluntary behavior change among adolescents might be difficult to achieve and that a multiple strategy approach may be needed to prevent MP3-induced hearing loss.

Quantitative real-time in vivo detection of magnetic nanoparticles by their nonlinear magnetization

NASA Astrophysics Data System (ADS)

Nikitin, M. P.; Torno, M.; Chen, H.; Rosengart, A.; Nikitin, P. I.

2008-04-01

A novel method of highly sensitive quantitative detection of magnetic nanoparticles (MP) in biological tissues and blood system has been realized and tested in real time in vivo experiments. The detection method is based on nonlinear magnetic properties of MP and the related device can record a very small relative variation of nonlinear magnetic susceptibility up to 10-8 at room temperature, providing sensitivity of several nanograms of MP in 0.1ml volume. Real-time quantitative in vivo measurements of dynamics of MP concentration in blood flow have been performed. A catheter that carried the blood flow of a rat passed through the measuring device. After an MP injection, the quantity of MP in the circulating blood was continuously recorded. The method has also been used to evaluate the MP distribution between rat's organs. Its sensitivity was compared with detection of the radioactive MP based on isotope of Fe59. The comparison of magnetic and radioactive signals in the rat's blood and organ samples demonstrated similar sensitivity for both methods. However, the proposed magnetic method is much more convenient as it is safe, less expensive, and provides real-time measurements in vivo. Moreover, the sensitivity of the method can be further improved by optimization of the device geometry.

Salivary Lipid Peroxidation and Total Sialic Acid Levels in Smokers and Smokeless Tobacco Users as Maraş Powder

PubMed Central

Kurtul, Naciye; Gökpınar, Engin

2012-01-01

Maraş powder (MP), a different type of smokeless tobacco (ST) and prepared from a tobacco of species Nicotiana rustica Linn, is widely used in Turkey. We aimed to investigate the effects of MP on salivary total sialic acid (TSA) and malondialdehyde (MDA) levels and to compare these parameters in smokers and MP users (MPUs). The salivary TSA and MDA concentrations were significantly higher in the smokers and MPU than those of control subjects and also in MPU than that of smokers. We have also observed that as the number of cigarettes consumed and MP amount increases, TSA and MDA levels increase too. In smokers, MDA values were significantly correlated with the number of cigarettes smoked and the duration of smoking. In MPU, both MDA and TSA levels were significantly correlated with the duration of MP use and the amount of daily consumed MP. We have concluded increased salivary TSA and MDA levels associated in MPU and smokers. Results can help to evaluate harmful effects of these habits. It is important to point out that bigger change in the measured parameters has been observed for MP use. This observation may be an important indication of harmful effects of ST use as MP. PMID:22577253

40 CFR 60.224 - Test methods and procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the following equation: P=Mp Rp where: Mp=total mass flow rate of phosphorus-bearing feed, Mg/hr (ton... determine the mass flow rate (Mp) of the phosphorus-bearing feed. (ii) The Association of Official...

40 CFR 60.214 - Test methods and procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the following equation: P=Mp Rp where: Mp=total mass flow rate of phosphorus-bearing feed, Mg/hr (ton... determine the mass flow rate (Mp) of the phosphorus-bearing feed. (ii) The Association of Official...

40 CFR 60.214 - Test methods and procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the following equation: P=Mp Rp where: Mp=total mass flow rate of phosphorus-bearing feed, Mg/hr (ton... determine the mass flow rate (Mp) of the phosphorus-bearing feed. (ii) The Association of Official...

40 CFR 60.224 - Test methods and procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the following equation: P=Mp Rp where: Mp=total mass flow rate of phosphorus-bearing feed, Mg/hr (ton... determine the mass flow rate (Mp) of the phosphorus-bearing feed. (ii) The Association of Official...