735 research outputs found

    Drosophila modifier screens to identify novel neuropsychiatric drugs including aminergic agents for the possible treatment of Parkinson's disease and depression.

    Get PDF
    Small molecules that increase the presynaptic function of aminergic cells may provide neuroprotection in Parkinson's disease (PD) as well as treatments for attention deficit hyperactivity disorder (ADHD) and depression. Model genetic organisms such as Drosophila melanogaster may enhance the detection of new drugs via modifier or 'enhancer/suppressor' screens, but this technique has not been applied to processes relevant to psychiatry. To identify new aminergic drugs in vivo, we used a mutation in the Drosophila vesicular monoamine transporter (dVMAT) as a sensitized genetic background and performed a suppressor screen. We fed dVMAT mutant larvae ∼ 1000 known drugs and quantitated rescue (suppression) of an amine-dependent locomotor deficit in the larva. To determine which drugs might specifically potentiate neurotransmitter release, we performed an additional secondary screen for drugs that require presynaptic amine storage to rescue larval locomotion. Using additional larval locomotion and adult fertility assays, we validated that at least one compound previously used clinically as an antineoplastic agent potentiates the presynaptic function of aminergic circuits. We suggest that structurally similar agents might be used to development treatments for PD, depression and ADHD, and that modifier screens in Drosophila provide a new strategy to screen for neuropsychiatric drugs. More generally, our findings demonstrate the power of physiologically based screens for identifying bioactive agents for select neurotransmitter systems

    Neutron interferometric measurement of the scattering length difference between the triplet and singlet states of n-3^3He

    Full text link
    We report a determination of the n-3^3He scattering length difference Δb′=b1′−b0′=\Delta b^{\prime} = b_{1}^{\prime}-b_{0}^{\prime} = (−5.411-5.411 ±\pm 0.0310.031 (statistical) ±\pm 0.0390.039 (systematic)) fm between the triplet and singlet states using a neutron interferometer. This revises our previous result Δb′=\Delta b^{\prime} = (-5.610 ±\pm 0.0270.027 (statistical) ±\pm 0.0320.032 (systematic) fm obtained using the same technique in 2008. This revision is due to a re-analysis of the 2008 experiment that includes a more robust treatment of the phase shift caused by magnetic field gradients near the 3^3He cell. Furthermore, we more than doubled our original data set from 2008 by acquiring six months of additional data in 2013. Both the new data set and a re-analysis of the older data are in good agreement. Scattering lengths of low Z isotopes are valued for use in few-body nuclear effective field theories, provide important tests of modern nuclear potential models and in the case of 3^3He aid in the interpretation of neutron scattering from quantum liquids. The difference Δb′\Delta b^{\prime} was determined by measuring the relative phase shift between two incident neutron polarizations caused by the spin-dependent interaction with a polarized 3^3He target. The target 3^3He gas was sealed inside a small, flat windowed glass cell that was placed in one beam path of the interferometer. The relaxation of 3^3He polarization was monitored continuously with neutron transmission measurements. The neutron polarization and spin flipper efficiency were determined separately using 3^3He analyzers and two different polarimetry analysis methods. A summary of the measured scattering lengths for n-3^3He with a comparison to nucleon interaction models is given

    Sensitivity of the Numerical Prediction of Turbulent Combustion Dynamics in the LIMOUSINE Combustor

    Get PDF
    The objective of this study is to investigate the sensitivity and accuracy of the reaction flow-field prediction for the LIMOUSINE combustor with regard to choices in computational mesh and turbulent combustion model. The LIMOUSINE combustor is a partially premixed, bluff body-stabilized natural gas combustor designed to operate at 40–80 kW and atmospheric pressure and used to study combustion instabilities. The transient simulation of a turbulent combusting flow with the purpose to study thermoacoustic instabilities is a very time-consuming process. For that reason, the meshing approach leading to accurate numerical prediction, known sensitivity, and minimized amount of mesh elements is important. Since the numerical dissipation (and dispersion) is highly dependent on, and affected by, the geometrical mesh quality, it is of high importance to control the mesh distribution and element size across the computational domain. Typically, the structural mesh topology allows using much fewer grid elements compared to the unstructured grid; however, an unstructured mesh is favorable for flows in complex geometries. To explore computational stability and accuracy, the numerical dissipation of the cold flow with mixing of fuel and air is studied first in the absence of the combustion process. Thereafter, the studies are extended to combustible flows using standard available ansys-cfx combustion models. To validate the predicted variable fields of the combustor's transient reactive flows, the numerical results for dynamic pressure and temperature variations, resolved under structured and unstructured mesh conditions, are compared with experimental data. The obtained results show minor dependence on the used mesh in the velocity and pressure profiles of the investigated grids under nonreacting conditions. More significant differences are observed in the mixing behavior of air and fuel flows. Here, the numerical dissipation of the (unstructured) tetrahedral mesh topology is higher than in the case of the (structured) hexahedral mesh. For that reason, the combusting flow, resolved with the use of the hexahedral mesh, presents better agreement with experimental data and demands less computational effort. Finally, in the paper, the performance of the combustion model for reacting flow is presented and the main issues of the applied combustion modeling are reviewe

    Ohmic Heating Technology and Its Application in Meaty Food: A Review

    Get PDF
    The purpose of the current review paper is to investigate and analyze about the effects of ohmic heating (OH) different application in the field of fish, meat and its product and compare it with other conventional thermal methods of food processing such as thawing, heating, cooking etc. Food quality, food safety, convenience, freshness, healthy food, natural flavor and taste with extended shelf-life are the main criteria for the demand made by today’s consumers. Ohmic heating is a substitute of conventional heating method of food commodities. It has shorter heating times, avoid hot surfaces and help to minimize temperature gradients. Product parameters such as electrical, thermo-physical and rheological properties of the food and process parameters such as the current frequency, electrode material and the geometry of ohmic chamber affect the process. as a result various application of OH are found such as heating, evaporation, dehydration, extraction, waste water treatment, thawing, cooking of different type fish and meat and its product such as meat ball, hamburger patties surmi, beef, turkey etc

    Decoupling of a Neutron Interferometer from Temperature Gradients

    Get PDF
    Neutron interferometry enables precision measurements that are typically operated within elaborate, multi-layered facilities which provide substantial shielding from environmental noise. These facilities are necessary to maintain the coherence requirements in a perfect crystal neutron interferometer which is extremely sensitive to local environmental conditions such as temperature gradients across the interferometer, external vibrations, and acoustic waves. The ease of operation and breadth of applications of perfect crystal neutron interferometry would greatly benefit from a mode of operation which relaxes these stringent isolation requirements. Here, the INDEX Collaboration and National Institute of Standards and Technology demonstrates the functionality of a neutron interferometer in vacuum and characterize the use of a compact vacuum chamber enclosure as a means to isolate the interferometer from spatial temperature gradients and time-dependent temperature fluctuations. The vacuum chamber is found to have no depreciable effect on the performance of the interferometer (contrast) while improving system stability, thereby showing that it is feasible to replace large temperature isolation and control systems with a compact vacuum enclosure for perfect crystal neutron interferometry

    Novel bioactive tetracycline-containing electrospun polymer fibers as a potential antibacterial dental implant coating

    Get PDF
    The purpose of this investigation was to determine the ability of tetracycline-containing fibers to inhibit biofilm formation of peri-implantitis-associated pathogens [i.e., Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn), Prevotella intermedia (Pi), and Aggregatibacter actinomycetemcomitans (Aa)]. Tetracycline hydrochloride (TCH) was added to a poly(DL-lactide) [PLA], poly(ε-caprolactone) [PCL], and gelatin [GEL] polymer blend solution at distinct concentrations to obtain the following fibers: PLA:PCL/GEL (TCH-free, control), PLA:PCL/GEL + 5 % TCH, PLA:PCL/GEL + 10 % TCH, and PLA:PCL/GEL + 25 % TCH. The inhibitory effect of TCH-containing fibers on biofilm formation was assessed by colony-forming units (CFU/mL). Qualitative analysis of biofilm inhibition was done via scanning electron microscopy (SEM). Statistical significance was reported at p < 0.05. Complete inhibition of biofilm formation on the fibers was observed in groups containing TCH at 10 and 25 wt%. Fibers containing TCH at 5 wt% demonstrated complete inhibition of Aa biofilm. Even though a marked reduction in CFU/mL was observed with an increase in TCH concentration, Pi proved to be the most resilient microorganism. SEM images revealed the absence of or a notable decrease in bacterial biofilm on the TCH-containing nanofibers. Collectively, our data suggest that tetracycline-containing fibers hold great potential as an antibacterial dental implant coating
    • …
    corecore