Multicomponent Targets Research Articles

MTORC1 controls fasting-induced ketogenesis and its modulation by ageing

The multi-component mechanistic target of rapamycin complex 1 (mTORC1) kinase is the central node of a mammalian pathway that coordinates cell growth with the availability of nutrients, energy and growth factors. Progress has been made in the identification of mTORC1 pathway components and in understanding their functions in cells, but there is relatively little known about the role of the pathway in vivo. Specifically, we have little knowledge regarding the role mTOCR1 has in liver physiology. In fasted animals, the liver performs numerous functions that maintain whole-body homeostasis, including the production of ketone bodies for peripheral tissues to use as energy sources. Here we show that mTORC1 controls ketogenesis in mice in response to fasting. We find that liver-specific loss of TSC1 (tuberous sclerosis 1), an mTORC1 inhibitor, leads to a fasting-resistant increase in liver size, and to a pronounced defect in ketone body production and ketogenic gene expression on fasting. The loss of raptor (regulatory associated protein of mTOR, complex 1) an essential mTORC1 component, has the opposite effects. In addition, we find that the inhibition of mTORC1 is required for the fasting-induced activation of PPARα (peroxisome proliferator activated receptor α), the master transcriptional activator of ketogenic genes, and that suppression of NCoR1 (nuclear receptor co-repressor 1), a co-repressor of PPARα, reactivates ketogenesis in cells and livers with hyperactive mTORC1 signalling. Like livers with activated mTORC1, livers from aged mice have a defect in ketogenesis, which correlates with an increase in mTORC1 signalling. Moreover, we show that the suppressive effects of mTORC1 activation and ageing on PPARα activity and ketone production are not additive, and that mTORC1 inhibition is sufficient to prevent the ageing-induced defect in ketogenesis. Thus, our findings reveal that mTORC1 is a key regulator of PPARα function and hepatic ketogenesis and suggest a role for mTORC1 activity in promoting the ageing of the liver.

Preparation of silicon oxycarbide films by laser ablation of SiO/3C–SiC multicomponent targets

Amorphous silicon oxycarbide (SiOC) films were prepared on Si (1 0 0) substrates by laser ablation at 773 K using mixed targets with different ratios of SiO to 3C–SiC. The structure and composition of the as-deposited films as a function of target content were investigated. With increasing the SiO content in the targets, the contents of Si–C and Si–O–C bonds decreased while that of Si–O bond increased. The mixing ratio of the targets had a dominant effect on the film composition and the stoichiometry of silicon oxycarbide films could be controlled by varying the mixing ratio of the targets.

A dual active‐restrictive approach to incorporating environmental flow targets into existing reservoir operation rules

Environmental flow schemes may be implemented through active or restrictive strategies. The former may be applied via reservoir releases, and the latter can be executed by reducing water demands. We present a dual active‐restrictive approach to devising the optimal reservoir operation rules that aim to secure off‐stream water supplies while maximizing environmental benefits. For the active part, a multicomponent environmental flow target (including the minimum and monthly flows) is incorporated in the operation rules. For the restrictive counterpart, we use a novel demands partitioning and prioritizing (DPP) approach to reallocating the demands of various sectors. The DPP approach partitions the existing off‐stream demand and newly incorporated environmental demand and reassembles the two as the first‐ and second‐priority demands. Water is reallocated to each demand according to the ratios derived from the prioritized demands. The proposed approach is coupled with a multicriteria optimization framework to seek the optimal operation rules for the existing Feitsui Reservoir system (Taiwan) under various scenarios. The best overall performance is achieved by an optimal dual strategy whose operational parameters are all determined by optimization. The optimal environmental flow target may well be a top‐priority constant base flow rather than the variable quantities. The active strategy would outperform the restrictive one. For the former, a top‐priority base flow target is essential; for the latter, the off‐stream demand can become vanishingly small in compensation for the eliminated base flow target, thus promoting the monthly flow target as nearly the top‐priority demand. For either the active or restrictive strategy, a prioritized environmental flow demand would provide a path toward the optimal overall performance. A significantly improved overall performance over the existing operation rules is unlikely if the active and restrictive parameters are both favorable to the off‐stream demand.

Determination of angle dependence of sputtering yield for a multicomponent target by the time characteristics of the sputtering process

A method for determining the variations of sputtering yield of multicomponent target based on studies of time characteristics of the sputtered particles flux has been proposed and tested on an example of the angle dependence of sputtering yield. Time dependences of variation in the fluxes of the sputtered atoms of multicomponent oxides at different incidence angles of Ar ions were studied. Angular dependences of the sputtering yield for these compounds were obtained by direct measurements and computations. It has been shown that the angular dependence of the sputtering yield in a stationary mode can be obtained from the time dependences of the fluxes of the sputtered particles.

Low-velocity ion slowing down in binary ionic mixtures

We focus our attention on the low ion velocity stopping mechanisms in a multicomponent and dense target plasmas built of quasi-classical electron fluids neutralizing binary ionic mixtures such as deuterium–tritium of current fusion interest, proton-helium like iron in the solar interior or proton-helium ions considered in planetology, as well as other mixtures of fiducial concern in the heavy ion beam production of warm dense matter at Bragg peak conditions. The target plasma is taken in a multicomponent dielectric formulation à la Fried-Conte. We stress out the occurrence of projectile ion velocities (so-called critical) for which target electron slowing down equals that of the given target ion components. The corresponding multi-quadrature computations, albeit rather heavy, can be monitored analytically through a very compact code operating a PC cluster. Slowing down results are systematically scanned w.r.t. target temperature, electron density as well as ion composition.

Propagation of the high power laser pulse in multicomponent cluster targets

We present the results of 3D PIC and 2D PIC simulations of the ultra short high irradiance laser pulse interaction with targets where the plasma containing multicomponent cluster targets and multicluster cloud is imbedded in an underdense plasma. In both cases the laser radiation expels the electrons from the clusters and ejects them into the wake plasma wave generated by the ultrashort laser pulse in the underdense plasma. This provides a novel mechanism for the electron injection into the wake field for acceleration.

Extraction of mixed-order multicomponent ship target signals from broadened sea clutter in bistatic shipborne surface wave radar

A dynamic geometry model was built to describe the Doppler-broadening characteristics of the first-order Bragg lines for bistatic shipborne surface wave radar. They are time-varying because the Doppler frequency shifts of sea echoes are simultaneously modulated by the velocity components projected from the unavoidably different motions of both platforms, which is more complex than its counterpart in the monostatic mode. The geometrical relation is used to obtain the received signal model: strong first-order sea clutter interferences and submerged ship targets with constant and non-constant speeds are considered as mixed-order multicomponent polynomial-phase signals (mc-PPSs) and both second-order sea clutter continuum and atmospheric noise as additive noise. Then, a scheme based on the product high-order ambiguity function is proposed to extract the targets; it is a recursive procedure in which the first-order sea clutter is removed by an existing time–space cascaded filtering method. Monte Carlo simulations show the validity and efficiency of the proposed scheme.

Physical aspects of the pulsed laser deposition technique: The stoichiometric transfer of material from target to film

The physical processes of pulsed laser deposition (PLD) change strongly from the initial light absorption in a target to the final deposition and growth of a film. One of the primary advantages of PLD is the stoichiometric transfer of material from target to a film on a substrate. Even for a stoichiometric flow of material from a multicomponent target, the simultaneous arrival of the target atoms is not sufficient to ensure a stoichiometric film growth. The laser fluence has to be sufficiently high to induce ablation rather than pure evaporation from target, but a high fluence may lead to preferential (self)sputtering and possibly implantation of the light atoms in the film. A background gas of a sufficiently high pressure may reduce sputtering of the film, but may lead the preferential diffusion of the light component to the substrate. The importance of these processes during the entire PLD process will be discussed.

Low velocity ion stopping in binary ionic mixtures

Attention is focused on the low ion velocity stopping mechanisms in multicomponent and dense target plasmas built of quasiclassical electron fluids neutralizing binary ionic mixtures, such as, deuterium-tritium of current fusion interest, proton-heliumlike iron in the solar interior or proton-helium ions considered in planetology, as well as other mixtures of fiducial concern in the heavy ion beam production of warm dense matter at Bragg peak conditions. The target plasma is taken in a multicomponent dielectric formulation à la Fried–Conte. The occurrence of projectile ion velocities (so-called critical) for which target electron slowing down equals that of given target ion components is also considered. The corresponding multiquadrature computations, albeit rather heavy, can be monitored analytical through a very compact code operating a PC cluster. Slowing down results are systematically scanned with respect to target temperature and electron density, as well as ion composition.

Computational study of the generation of crystal defects in a bcc metal target irradiated by short laser pulses

The generation of crystal defects in a Cr target irradiated by a short, 200 fs, laser pulse is investigated in computer simulations performed with a computational model that combines the classical molecular dynamics method with a continuum description of the laser excitation of conduction band electrons, electron-phonon coupling, and electron heat conduction. Interatomic interactions are described by the embedded atom method (EAM) potential with a parametrization designed for Cr. The potential is tested by comparing the properties of the EAM Cr material with experimental data and predictions of density functional theory calculations. The simulations are performed at laser fluences close to the threshold for surface melting. Fast temperature variation and strong thermoelastic stresses produced by the laser pulse are causing surface melting and epitaxial resolidification, transient appearance of a high density of stacking faults along the {110} planes, and generation of a large number of point defects (vacancies and self-interstitials). The stacking faults appear as a result of internal shifts in the crystal undergoing a rapid uniaxial expansion in the direction normal to the irradiated surface. The stacking faults are unstable and disappear shortly after the laser-induced tensile stress wave leaves the surface region of the target. Thermally activated generation of vacancy-interstitial pairs during the initial temperature spike and quick escape of highly mobile self-interstitials to the melting front or the free surface of the target, along with the formation of vacancies at the solid-liquid interface during the fast resolidification process, result in a high density of vacancies, on the order of ${10}^{\ensuremath{-}3}$ per lattice site, created in the surface region of the target. The strong supersaturation of vacancies can be related to the incubation effect in multipulse laser ablation/damage and should play an important role in mixing/alloying of multicomponent or composite targets.

Measurements of electron temperature and density of multi-component plasma plume formed by laser-blow-off of LiF-C film

The evolution features of electrons and ions generated by laser-blow-off (LBO) of a multi-component LiF-C target have been studied using optical spectroscopic and Langmuir probe (LP) techniques. In addition to the hydrodynamic plume splitting, multi-peak structures are reported in the temporal profiles of ions measured by the LP. We propose that the observed multi-peaks arise due to the mass dependent expansion velocity of different elements present in the plasma plume. The temporal evolutions of electron density and temperature are reported in vacuum and in a 10−2 mbar argon environment. The electron temperature of the LBO plume was found to be higher than the electron temperature of laser produced plasma from solids. It was observed that the LP was perturbing the evolving plasma plume when it was placed at a short distance from the target. We have experimentally determined the distance between the target and LP beyond which it did not perturb the characteristic features of plume expansion. No previous data related to LBO plasma exist for a direct comparison with the present results.

IMPACT: A facility to study the interaction of low-energy intense particle beams with dynamic heterogeneous surfaces

The Interaction of Materials with Particles and Components Testing (IMPACT) experimental facility is furnished with multiple ion sources and in situ diagnostics to study the modification of surfaces undergoing physical, chemical, and electronic changes during exposure to energetic particle beams. Ion beams with energies in the range between 20 and 5000 eV can bombard samples at flux levels in the range of 10(10)-10(15) cm(-2) s(-1); parameters such as ion angle of incidence and exposed area are also controllable during the experiment. IMPACT has diagnostics that allow full characterization of the beam, including a Faraday cup, a beam imaging system, and a retarding field energy analyzer. IMPACT is equipped with multiple diagnostics, such as electron (Auger, photoelectron) and ion scattering spectroscopies that allow different probing depths of the sample to monitor compositional changes in multicomponent and/or layered targets. A unique real-time erosion diagnostic based on a dual quartz crystal microbalance measures deposition from an eroding surface with rates smaller than 0.01 nm/s, which can be converted to a sputter yield measurement. The monitoring crystal can be rotated and placed in the target position so that the deposited material on the quartz crystal oscillator surface can be characterized without transfer outside of the vacuum chamber.

Human Immunity and the Design of Multi-Component, Single Target Vaccines

BackgroundInclusion of multiple immunogens to target a single organism is a strategy being pursued for many experimental vaccines, especially where it is difficult to generate a strongly protective response from a single immunogen. Although there are many human vaccines that contain multiple defined immunogens, in almost every case each component targets a different pathogen. As a consequence, there is little practical experience for deciding where the increased complexity of vaccines with multiple defined immunogens vaccines targeting single pathogens will be justifiable.Methodology/Principal FindingsA mathematical model, with immunogenicity parameters derived from a database of human responses to established vaccines, was used to predict the increase in the efficacy and the proportion of the population protected resulting from addition of further immunogens. The gains depended on the relative protection and the range of responses in the population to each immunogen and also to the correlation of the responses between immunogens. In most scenarios modeled, the gain in overall efficacy obtained by adding more immunogens was comparable to gains obtained from a single immunogen through the use of better formulations or adjuvants. Multi-component single target vaccines were more effective at decreasing the proportion of poor responders than increasing the overall efficacy of the vaccine in a population.Conclusions/SignificanceInclusion of limited number of antigens in a vaccine aimed at targeting a single organism will increase efficacy, but the gains are relatively modest and for a practical vaccine there are constraints that are likely to limit multi-component single target vaccines to a small number of key antigens. The model predicts that this type of vaccine will be most useful where the critical issue is the reduction in proportion of poor responders.

Multi-component nitride coatings derived from Ti–Al–Cr–Si–V target in RF magnetron sputter

The nitride coatings comprised of various constituents Ti, Al, Cr, Si, V were deposited on mild steel by RF magnetron sputtering process. The Ti–Al–Cr–Si–V multi-component target introduced in this study was fabricated by conventional metallurgical method with atomic ratio of each selected element at 1:1:1:1:1. Different coatings were fabricated under various working pressure by adjusting nitrogen flux from 0 to 30 sccm during sputtering. Compositions of the target and the sputtered films were measured by FE-EPMA, and both of them were near equi-molar. According to XRD patterns, amorphous structures were revealed for the metallic and nitride 1 ( N = 46.2 at.%) films. The face centered cubic phases were exhibited by nitride 2 and nitride 3 with nitrogen contents around 58 at.%. Two different surface morphologies were investigated by the AFM, and they were consistent with the nanostructure observed in the XRD pattern. In addition, microhardness of the nitride coatings was measured by nanoindentation, and hardness higher than 30 GPa was exhibited in both nitride 2 and nitride 3. The microhardness test provided evidence that the multi-component nitride could be a potential candidate coating for tool steel.

Hemocompatibility of diamondlike carbon–metal composite thin films

We have investigated the hemocompatibility of diamondlike carbon–silver composite and diamondlike carbon–titanium composite thin films prepared using a multicomponent target pulsed laser deposition process. These materials were examined using transmission electron microscopy, Raman spectroscopy, nanoindentation, electrochemical charge transfer testing, and platelet adhesion testing. Cross-sectional transmission electron microscopy revealed that silver self-assembles into nanoparticle arrays within the diamondlike carbon matrix in the diamondlike carbon–silver composite film. On the other hand, titanium self-assembles into alternating nanometer-thick titanium carbide layers within the diamondlike carbon matrix in the diamondlike carbon–titanium composite film. The hemocompatibility of these materials was examined using electrochemical charge transfer testing and platelet adhesion testing. A few small, widely scattered crystals were observed on the surface of the unalloyed diamondlike carbon film exposed to platelet rich plasma. On the other hand, dense fibrin networks with densely aggregated platelets were observed on the surfaces of diamondlike carbon–silver and diamondlike carbon–titanium composite thin films exposed to platelet rich plasma. Electrochemical testing revealed that the time constant for the diamondlike carbon thin film ( λ = 1) was significantly higher than those for the diamondlike carbon–silver and diamondlike carbon–titanium composite thin films. These results suggest possible uses for diamondlike carbon thin films and diamondlike carbon–metal composite thin films as coatings in next generation cardiovascular implants.

Electrochemical and antimicrobial properties of diamondlike carbon-metal composite films

Implants containing antimicrobial metals may reduce morbidity, mortality, and healthcare costs associated with medical device-related infections. We have deposited diamondlike carbon–silver (DLC–Ag), diamondlike carbon–platinum (DLC–Pt), and diamondlike carbon–silver–platinum (DLC–AgPt) thin films using a multicomponent target pulsed laser deposition process. Transmission electron microscopy of the DLC–silver and DLC–platinum composite films revealed that the silver and platinum self-assemble into nanoparticle arrays within the diamondlike carbon matrix. The diamondlike carbon–silver film possessed hardness and Young’s modulus values of 37 GPa and 331 GPa, respectively. The diamondlike carbon-metal composite films exhibited passive behavior at open-circuit potentials. Low corrosion rates were observed during testing in a phosphate-buffered saline (PBS) electrolyte. In addition, the diamondlike carbon–metal composite films were found to be immune to localized corrosion below 1000 mV (SCE). DLC–silver–platinum films demonstrated exceptional antimicrobial properties against Staphylococcus bacteria. It is believed that a galvanic couple forms between platinum and silver, which accelerates silver ion release and provides more robust antimicrobial activity. Diamondlike carbon–silver–platinum films may provide unique biological functionalities and improved lifetimes for cardiovascular, orthopaedic, biosensor, and implantable microelectromechanical systems.

Multifunctional multi-component PVD coatings for cutting tools

Highly wear resistant PVD coatings are well established in cutting operations. Further efforts to improve the cutting performance need to be focused on all relevant wear mechanisms. Thus, the objectives are an enhancement of the abrasive wear resistance, toughness, oxidation resistance, and reduction of friction. The aim of this work was to investigate properties and cutting performance of new multifunctional multi-component PVD coatings based on Ti 1− x Al x N applied to cutting tools. An industrial cathodic arc-evaporation unit was used to deposit coatings from powder metallurgically produced multi-component targets. Coating structure and chemical composition were characterized using scanning electron microscopy (SEM), energy-dispersive electron probe microanalysis (EPMA) and X-ray diffraction (XRD). Coating hardness and cutting performance were evaluated by Vickers microindentation and cutting tests. The results show a remarkable influence of additional elements on the properties of Ti 1− x Al x N based coatings. Alloying with elements like V, Ta, and B resulted in a significantly increased lifetime in various cutting applications.

Antimicrobial Properties of Diamond-like Carbon-Silver-Platinum Nanocomposite Thin Films

Silver and platinum were incorporated within diamond-like carbon (DLC) thin films using a multicomponent target pulsed laser deposition process. Transmission electron microscopy of the DLC-silver and DLC-platinum composite films reveals that these films self-assemble into particulate nanocomposite structures that possess a high fraction of sp3-hybridized carbon atoms. Nanoindentation testing of DLC-silver nanocomposite films demonstrates that these films possess hardness and Young’s modulus values of approximately 35 and 350 GPa, respectively. DLC-silver-platinum films demonstrated exceptional antimicrobial properties against Staphylococcus and Pseudomonas aeruginosa bacteria.

Transfer of stoichiometry during pulsed laser ablation of multicomponent magnetic targets

Multicomponent magnetic alloy targets were ablated in vacuum with a XeCl excimer laser at three different fluences. The ablated material was collected onto unheated silicon substrates placed at different angles with respect to the target normal at the incident laser spot. Film composition was inferred by Rutherford backscattering spectrometry analyses. Experimental results reveal that the lighter element concentration is larger in films deposited at higher collecting angle. The observed effect is more evident at lower laser fluences. The dependence of composition variations on the collecting angle in the studied multielemental films are attributed to scattering effects among the ablated species in the plume.

Electrical and structural properties of La 0.8Sr 0.2Mn 0.5Co 0.5O 3± δ films produced by pulsed laser deposition

La 0.8Sr 0.2Mn 0.5Co 0.5O 3 (LSMCO) films for the use as contact layers or protective coatings in solid oxide fuel cells (SOFC) have been deposited on glass substrates by pulsed laser deposition (PLD). PLD is an obvious technique for thin film production of complex oxides, because of the ability to transfer material stoichiometrically from a multicomponent target to a growing film. In the present study, films were deposited at substrate temperatures of 473 and 573 K and in different oxygen background pressures. The influence of the process parameters, in particular of the oxygen background gas pressure, on the electrical conductivity and structure of the films is investigated.