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The purpose of this study was to design an injectable hydrogel with temperature-sensitive property for safe and high efficient in vivo colon cancer hyperthermia and chemotherapy. Chitosan (CS) solution was injected into the tumor at room temperature and automatically gelled after warming to body temperature in the present of β-glycerophosphate (β-GP). Combined localized tumor photothermal and chemotherapy were achieved by dissolving photothermal material MoS2/Bi2S3-PEG (MBP) nanosheets and drug molecule doxorubicin (DOX) into the hydrogel, and the gel system could encapsulate DOX and MBP nanosheets and prevent them from entering the blood circulation and damaging normal tissues and cells. More importantly, the CS/MBP/DOX (CMD) hydrogel exhibited a photothermal efficiency of 22.18% and 31.42% in the first and second near infrared light (NIR I and NIR II) biowindows respectively at a low MBP concentration (0.5 mg/mL). Besides, the release of the DOX from CMD hydrogel was controllable since the gel temperature could be governed by NIR laser irradiation. Moreover, the chitosan-based hydrogel had antibacterial effects. The designed composite hydrogel is anticipated to act as a platform for the high efficient treatment of tumors owing to the different penetration depths of NIR I and NIR II.

With an excellent near-infrared (NIR) light-responsive property, polypyrrole (PPy) nanoparticle has emerged as a promising NIR photothermal transducing agent for tumor photothermal therapy (PTT). Herein, we reported the PVP mediated one-pot synthesis of colloidal stable and biocompatible PPy nanoparticles (PPy-PVP NPs) for combined tumor photothermal-chemotherapy. The influence of molecular weight and PVP concentration on the spectroscopic characteristic, photothermal feature, drug loading performance, and antitumor efficiency of the resultant PPy-PVP NPs was systematically studied. By choosing PVP with a molecular weight of 360 kDa (concentration of 5 mg/mL) as the template and surface modifier during the synthesis, PPy-PVP NPs with optimal spectroscopic characteristic, photothermal feature, drug loading performance, and antitumor efficiency were synthesized. Findings in this study are anticipated to provide an in-depth understanding of the important character of surface engineering in the rational design and biomedical applications of PPy NPs.

OpenVX is a recently ratified standard that was expressly proposed to facilitate the design of computer-vision (CV) applications used in real-time embedded systems. Despite its real-time focus, OpenVX presents several challenges when validating real-time constraints. Many of these challenges are rooted in the fact that OpenVX only implicitly defines any notion of a schedulable entity. Under OpenVX, CV applications are specified in the form of processing graphs that are inherently considered to execute monolithically end-to-end. This monolithic execution hinders parallelism and can lead to significant processing-capacity loss. Prior work partially addressed this problem by treating graph nodes as schedulable entities, but under OpenVX, these nodes represent rather coarse-grained CV functions, so the available parallelism that can be obtained in this way is quite limited. In this paper, a much more fine-grained approach for scheduling OpenVX graphs is proposed. This approach was designed to enable additional parallelism and to eliminate schedulability-related processing-capacity loss that arises when programs execute on both CPUs and graphics processing units (GPUs). Response-time analysis for this new approach is presented and its efficacy is evaluated via a case study involving an actual CV application.

Transition metal chalcogenides have been investigated as underlying anodes for sodium ion batteries (SIBs). Nevertheless, the unsatisfactory property, which is determined by huge volume variation and low conductivity, restricts their practical applications. The design of micro-nano hierarchitectures is a resultful approach to strengthen structural stability and reaction kinetics during the discharge-charge process. Herein, urchin-like FeS2 hierarchitectures wrapped with reduced graphene oxide and N-doped multi-wall carbon nanotubes (FeS2@N-CNTs@rGO) are designed and synthesized by hydrothermal route. FeS2@N-CNTs@rGO shows high capacity with 578 mAh g−1 at 0.1 A g−1, splendid rate property with 419 mAh g−1 at 5 A g−1 and preeminent capacity retention (≈100%) over 750 cycles at 2 A g−1. The reversible phase transformation, capacitive Na+ storage behaviour and micro-nano hierarchitectures are responsible for the outstanding rate performance.

In recent years, nanomaterials have aroused people's interest in the field of biomedicine. Polypyrrole (PPy) has become a research hotspot because of its simple synthesis, excellent photothermal conversion performance, and high biocompatibility. Here, we report the synthesis of PPy nanoparticles (PPy-PVP NPs) using a vapor deposition method, for tumor photothermal therapy. In this method, the slowly produced volatile pyrrole vapor was absorbed by the PVP (polyvinylpyrrolidone)/FeCl3 aqueous solution. This slow vapor production and absorption allows the formation of uniform PPy-PVP NPs at room temperature. Then, the effects of the molecular weight of PVP on the photothermal property and anti-tumor efficiency of PPy-PVP NPs were compared. It was found that the selection of PVP40kDa as the template and surface linker can ensure a better application performance of the synthesized nanomaterials. This work provides a theoretical basis for the rational design of nano-therapy carriers and biomedical applications.

Xiang Li,1 Yun Gong,2,3 Xiaoqian Zhou,1 Hui Jin,1 Huanhuan Yan,1 Shige Wang,2 Jun Liu11Department of Breast-Thyroid Surgery, Shanghai General Hospital of Nanjing Medical University, Shanghai, People’s Republic of China; 2College of Science, University of Shanghai for Science and Technology, 3Shanghai Publishing and Printing College, Shanghai, People’s Republic of ChinaAbstract: Two-dimensional MoS2 nanosheet has been extensively explored as a photothermal agent for tumor regression; however, its surface modification remains a great challenge. Herein, as an alternative to surface polyethylene glycol modification (PEGylation), a facile approach based on “thin-film” strategy has been proposed for the first time to produce soybean phospholipid-encapsulated MoS2 (SP-MoS2) nanosheets. By simply vacuum-treating MoS2 nanosheets/soybean phospholipid/chloroform dispersion in a rotary evaporator, SP-MoS2 nanosheet was successfully constructed. Owing to the steric hindrance of polymer chains, the surface-coated soybean phospholipid endowed MoS2 nanosheets with excellent colloidal stability. Without showing detectable in vitro and in vivo hemolysis, coagulation, and cyto-/histotoxicity, the constructed SP-MoS2 nanosheets showed good photothermal conversion performance and photothermal stability. SP-MoS2 nanosheet was shown to be a promising platform for in vitro and in vivo breast tumor photothermal therapy. The produced SP-MoS2 nanosheets featured low cost, simple fabrication, and good in vivo hemo-/histocompatibility and hold promising potential for future clinical tumor therapy.Keywords: soybean phospholipid, MoS2 nanosheets, in vivo, photothermal regression, breast tumor

Starvation therapy (ST) and chemodynamic therapy (CDT) are emerging tumor therapy methods in recent years. In this study, a simple approach was reported to prepare MoS2 and glucose oxidase (GOx)-containing sodium alginate (ALG)-Fe3+ (MAF) hydrogel. In the hydrogel, there exists an enzymatic reaction to consume glucose to form hydrogen peroxide (H2O2), and a redox reaction between Fe3+ and MoS2 to form Fe2+ and MoO42-. The formed Fe2+ could be oxidized to Fe3+, which reacts with MAF hydrogel again to continuously produce Fe2+. The consumption of glucose resulted in an obvious tumor ST. Moreover, the produced Fe2+ induced a Fenton reaction to enable the persistent conversion of H2O2 to cytotoxic hydroxyl radicals (·OH) for the CDT of tumors. Together with the high photothermal transforming capability of MoS2, the hydrogel was used for the combined tumor photothermal therapy (PTT), ST, and CDT. This work provides a window for the safe use of enzymes for achieving high tumor therapeutic efficacy.

In this research, a novel nanoenzyme-based theranostic nanoplatform, named PPy@MnO2-BSA (bovine serum albumin (BSA)-modified manganese dioxide (MnO2)/polypyrrole (PPy)) was invented for T1-MRI-guided combined photothermal therapy (PTT) and photodynamic therapy (PDT) of tumors. The materials design was based on the in-situ oxidation and polymerization of pyrrole, using potassium permanganate (KMnO4) as the oxidant. The formed PPy@MnO2-BSA was further used to load with Ce6, via physical absorption. The PPy, with a high absorbance within the near-infrared (NIR) region, endowes the nanoenzyme with outstanding photothermal performance with the photo-to-heat conversion efficiency of 21.05%, while the MnO2, which could reduce the relaxation time of nearby protons, serves to enhance the tumor T1-MRI ability. Moreover, upon exposure to red light, the PPy@MnO2-BSA(Ce6) nanoparticle could produce the cellular toxic reactive oxygen species (ROS, i.e., 1O2) to trigger the tumor PDT. Meanwhile, the nanoparticle could continuously catalyze H2O2 into endogenous oxygen, to not only relieve the hypoxia inside the tumor but also enhance the tumor PDT effect. The in vitro and in vivo experiments both affirmed the great potential of PPy@MnO2-BSA(Ce6) nanoparticle in MRI-guided combined PDT and PTT for tumor. This research lays a solid foundation for the theoretical design and clinical application of theranostic nanoprobe in the future.

Correction for ‘Preparation of electrospray ALG/PDA–PVP nanocomposites and their application in cancer therapy’ by Yangjie Xu et al., Soft Matter, 2020, 16, 132–141.

International audience; We present here the development of multifunctional doxorubicin (DOX)-conjugated poly(amidoamine) (PAMAM) dendrimers as a unique platform for pH-responsive drug release and targeted chemotherapy of cancer cells. In this work, we covalently conjugated DOX onto the periphery of partially acetylated and folic acid (FA)-modified generation 5 (G5) PAMAM dendrimers through a pH-sensitive cis-aconityl linkage to form the G5.NHAc-FA-DOX conjugates. The formed dendrimer conjugates were well characterized using different methods. We show that DOX release from the G5.NHAc-FA-DOX conjugates follows an acid-triggered manner with a higher release rate under an acidic pH condition (pH = 5 or 6, close to the acidic pH of tumor microenvironment) than under a physiological pH condition. Both in vitro cytotoxicity evaluation and cell morphological observation demonstrate that the therapeutic activity of dendrimer-DOX conjugates against cancer cells is absolutely related to the DOX drug released. More importantly, the FA conjugation onto the dendrimers allowed a specific targeting to cancer cells overexpressing FA receptors (FAR), and allowed targeted inhibition of cancer cells. The developed G5.NHAc-FA-DOX conjugates may be used as a promising nanodevice for targeted cancer chemotherapy.

The integration of efficient imaging for diagnosis and synergistic tumor therapy into a single-component nanoplatform is much promising for high efficacy tumor treatment but still in a great challenge. Herein, a smart and versatile nanotheranostic platform based on hollow mesoporous Prussian blue nanoparticles (HMPBs) with perfluoropentane (PFP) and doxorubicin (DOX) inside, has been designed, for the first time, to achieve the distinct in vivo synergistic chemo-thermal tumor therapy and synchronous diagnosis and monitoring by ultrasound (US)/photoacoustic (PA) dual mode imaging. The prepared HMPBs show excellent photothermal conversion properties with large molar extinction coefficient (≈1.2 × 1011m−1 cm−1) and extremely high photothermal conversion efficiency (41.4%). Such a novel theranostic nanoplatform is expected to overcome the inevitable tumor recurrence and metastasis resulting from the inhomogeneous ablation of single thermal therapy, which will find a promising prospect in the application of noninvasive cancer therapy.

Two-dimensional transition metal dichalcogenides, particularly MoS2 nanosheets, have been deemed as a novel category of NIR photothermal transducing agent. Herein, an efficient and versatile one-pot solvothermal synthesis based on "bottom-up" strategy has been, for the first time, proposed for the controlled synthesis of PEGylated MoS2 nanosheets by using a novel "integrated" precursor containing both Mo and S elements. This facile but unique PEG-mediated solvothermal procedure endowed MoS2 nanosheets with controlled size, increased crystallinity and excellent colloidal stability. The photothermal performance of nanosheets was optimized via modulating the particulate size and surface PEGylation. PEGylated MoS2 nanosheets with desired photothermal conversion performance and excellent colloidal and photothermal stability were further utilized for highly efficient photothermal therapy of cancer in a tumor-bearing mouse xenograft. Without showing observable in vitro and in vivo hemolysis, coagulation and toxicity, the optimized MoS2-PEG nanosheets showed promising in vitro and in vivo anti-cancer efficacy.

A templating strategy using crosslinked and functionalized polymeric beads to synthesize silica microspheres with a broad pore size distribution has been developed. The polymer/silica hybrid microspheres were prepared by utilizing the combination of a templating weak cation exchange resin, a structure-directing agent N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride, and a silica precursor tetraethyl orthosilicate. The silica microspheres were then obtained after calcinating the hybrid microspheres. The as-prepared materials were characterized by scanning electron microscopy, mercury intrusion porosimeter, and thermal gravimetric analysis. The results showed that the starting templating beads were about 5 μm in diameter and the formed silica microspheres were less than 3 μm with a pore size range of 10-150 nm, some pores were even extended to beyond 250 nm. It was demonstrated that cellulose tris(3,5-dimethylphenylcarbamate) was readily coated onto the surface of the as-synthesized silica microspheres without any additional surface pretreatment. The coated silica microspheres were uniformly dispersed even with high loading of the chiral stationary phase, which exhibited high resolution chiral separations in high-performance liquid chromatography.

We designed an injectable hydrogel by dissolving MoS2/Bi2S3-PEG (MBP), doxorubicin (DOX) and agar into water for the concurrent tumor photothermal and chemotherapy. The formed solution was able to be intra-tumorally (I.T.) administered into tumor at a relatively high temperature and automatically formed a hydrogel after cooling to body temperature. The resultant Agar/MBP/DOX (AMD) hydrogel can act as a macro-vessel to retain the MBP nanosheet and DOX and restrict their access to body fluid circulation. Moreover, AMD hydrogel did not compromise the photoacoustic and computed tomography imaging capacity, as well as the photothermal and chemotherapy efficiency of MBP nanosheets and DOX. The heat from the photothermal transformation of MBP nanosheet can promote the drug-release from the hydrogel and thus enable an on-demand drug release. Furthermore, antibiotics were also able to be encapsulated in the hydrogel to avoid the potential wound infection during tumor surgery.

We propose a server-based approach to manage a general-purpose graphics processing unit (GPU) in a predictable and efficient manner. Our proposed approach introduces a GPU server task that is dedicated to handling GPU requests from other tasks on their behalf. The GPU server ensures bounded time to access the GPU, and allows other tasks to suspend during their GPU computation to save CPU cycles. By doing so, we address the two major limitations of the existing real-time synchronization-based GPU management approach: busy waiting and long priority inversion. We implemented a prototype of the server-based approach on a real embedded platform. This case study demonstrates the practicality and effectiveness of the server-based approach. Experimental results indicate that the server-based approach yields significant improvements in task schedulability over the existing synchronization-based approach in most practical settings. Although we focus on a GPU in this paper, the server-based approach can also be used for other types of computational accelerators.

We report the fabrication of electrospun nanofibers of polyethylene glycol (PEG)-modified poly (lactic-co-glycolic acid) (PLGA) with a fast release profile for biomedical applications. In this work, PLGA was first covalently modified with methoxy poly (ethylene glycol) amine (mPEG-NH2). The formed PEGylated PLGA (PLGA-PEG) was then mixed with a model drug amoxicillin (AMX) for subsequent fabrication of drug-loaded electrospun nanofibers. The synthesized PLGA-PEG conjugate and the formed drug-loaded PLGA-PEG nanofibers were characterized using different techniques. We show that the modification of PEG does not lead to an appreciable change in the uniform and smooth morphology of PLGA nanofibers. Importantly, the PEGylation modification affords a faster release profile of the encapsulated drug than pure PLGA nanofibers without PEGylation, which may be ascribed to the improved hydrophilicity of the PLGA-PEG polymer. Furthermore, antibacterial activity assay data reveal that the drug-loaded PLGA-PEG nanofibers are able to inhibit the growth of a model bacterium S. aureus. Finally, the hemocompatibility of the drug-loaded PLGA-PEG nanofibers was evaluated by hemolysis and anticoagulant assays, and the cytocompatibility of the fibers was confirmed by cell viability assay and cell morphology observation. We show that the formed drug-loaded PLGA-PEG nanofibers have an excellent hemocompatibility and cytocompatibility. The developed electrospun PLGA-PEG nanofibers may find various applications in the fields of tissue engineering and pharmaceutical sciences.

Autonomous vehicles are an exemplar for forward-looking safety-critical real-time systems where significant computing capacity must be provided within strict size, weight, and power (SWaP) limits. A promising way forward in meeting these needs is to leverage multicore platforms augmented with graphics processing units (GPUs) as accelerators. Such an approach is being strongly advocated by NVIDIA, whose Jetson TX1 board is currently a leading multicore+GPU solution marketed for autonomous systems. Unfortunately, no study has ever been published that expressly evaluates the effectiveness of the TX1, or any other comparable platform, in hosting safety-critical real-time workloads. In this paper, such a study is presented. Specifically, the TX1 is evaluated via benchmarking efforts, blackbox evaluations of GPU behavior, and case-study evaluations involving computer-vision workloads inspired by autonomousdriving use cases. Autonomous vehicles are an exemplar for forward-looking safety-critical real-time systems where significant computing capacity must be provided within strict size, weight, and power (SWaP) limits. A promising way forward in meeting these needs is to leverage multicore platforms augmented with graphics processing units (GPUs) as accelerators. Such an approach is being strongly advocated by NVIDIA, whose Jetson TX1 board is currently a leading multicore+GPU solution marketed for autonomous systems. Unfortunately, no study has ever been published that expressly evaluates the effectiveness of the TX1, or any other comparable platform, in hosting safety-critical real-time workloads. In this paper, such a study is presented. Specifically, the TX1 is evaluated via benchmarking efforts, blackbox evaluations of GPU behavior, and case-study evaluations involving computer-vision workloads inspired by autonomousdriving use cases.

Heterogeneous MPSoCs consisting of cores with different performance/power behaviors are widely used in many power-constrained real-time systems. Both soft-error reliability and lifetime reliability are key concerns in such systems. Although existing work have investigated related problems, they either focus on one of the two reliability concerns or propose complicated scheduling algorithms that cannot adequately address run-time workload and environment variations. This paper introduces an on-line heuristic to maximize soft-error reliability while satisfying a lifetime reliability constraint for soft real-time systems executed on MPSoCs composed of high-performance cores and low-power cores. Based on the run-time cores' frequencies and utilizations, the heuristic performs workload migration between the high-performance cores and low-power cores to achieve improved soft-error reliability. Experimental results from both a hardware platform and a simulator show that the proposed algorithm reduces the probability of faults by at least 30% compared to a number of representative existing approaches while satisfying the same lifetime reliability constraints.

The design and development of multifunctional nanoplatforms for biomedical applications still remains to be challenging. This review reports the recent advances in aqueous-phase synthesis of iron oxide nanoparticles (Fe3O4 NPs) and their composites for magnetic resonance (MR) imaging and photothermal therapy of cancer. Water dispersible and colloidally stable Fe3O4 NPs synthesized via controlled coprecipitation route, hydrothermal route and mild reduction route are introduced. Some of key strategies to improve the r2 relaxivity of Fe3O4 NPs and to enhance their uptake by cancer cells are discussed in detail. These aqueous-phase synthetic methods can also be applied to prepare Fe3O4 NP-based composites for dual-mode molecular imaging applications. More interestingly, aqueous-phase synthesized Fe3O4 NPs are able to be fabricated as multifunctional theranostic agents for multi-mode imaging and photothermal therapy of cancer. This review will provide some meaningful information for the design and development of various Fe3O4 NP-based multifunctional nanoplatforms for cancer diagnosis and therapy.

Development of various nanoscale drug carriers for enhanced antitumor therapy still remains a great challenge. In this study, laponite (LAP) nanodisks encapsulated with anticancer drug doxorubicin (DOX) at an exceptionally high loading efficiency (98.3 ± 0.77%) were used for tumor therapy applications. The long-term in vivo antitumor efficacy and toxicology of the prepared LAP/DOX complexes were analyzed using a tumor-bearing mouse model. Long-term tumor appearance, normalized tumor volume, CD31 staining, and hematoxylin and eosin (HE)-stained tumor sections were used to evaluate the tumor therapy efficacy, while long-term animal body weight changes and HE-stained tissue sections of different major organs were used to evaluate the toxicology of LAP/DOX complexes. Finally, the in vivo biodistribution of magnesium ions and DOX in different organs was analyzed. We showed that under the same DOX concentration, LAP/DOX complexes displayed enhanced tumor inhibition efficacy and afforded the treated mice with dramatically prolonged survival time. In vivo biodistribution data revealed that the reticuloendothelial systems (especially liver) had significantly higher magnesium uptake than other major organs, and the LAP carrier was able to be cleared out of the body at 45 days post treatment. Furthermore, LAP/DOX afforded a higher DOX uptake in the tumor region than free DOX, presumably due to the known enhanced permeability and retention effect. The developed LAP-based drug delivery system with an exceptionally high DOX payload, enhanced in vivo antitumor efficacy, and low systemic toxicity may be used as a promising platform for enhanced tumor therapy.

Highly monodisperse, dendritic, and functionalized mesoporous silica nanospheres (MSNs) with sub-200 nm size were synthesized in a one-pot sol-gel reaction, by a dual-templating micelle system consisting of a partially fluorinated short-chain anionic fluorocarbon surfactant and cetyltrimethylammonium bromide. This kind of anionic fluorocarbon surfactant works simultaneously as a swelling agent to enlarge the pore of the MSNs, an ion-pair agent to the structure-directing silane in the preparation of amine-functionalized MSNs, and a surface tension reducing agent to make the system thermodynamically more stable for producing more uniform MSNs. The particle size and the morphology of the resultant MSNs can be fine-tuned by changing the amount of the fluorocarbon surfactant added and the ratio of the functional group containing organosilane to tetraethoxysilane. Subsequently, the as-prepared MSNs were used as base materials for the preparation of drug delivery nanomaterials through the surface grafting of a pH-sensitive drug-conjugated polymer and fluorescent nanomaterials through the embedding of europium(III) complex or the immobilization of large molecule fluorescein isothiocyanate-bovine serum albumin.

Magnetic Fe3O4 nanospheres with high dispersion, high saturation magnetization and narrow particle size distribution were synthesized by a CaF2 mediated solvothermal method. Next, a nonporous silica layer and a mesoporous silica (mSiO2) layer were uniformly coated on the surface of the magnetic nanospheres sequentially to form Fe3O4@mSiO2 nanoparticles. It was shown that the pore size and thickness of the mSiO2 shell could be fine-tuned by adjusting the composition of the double-template micelle system consisting of a partially fluorinated short-chain anionic fluorocarbon surfactant and cetyltrimethylammonium bromide. Finally, Eu3+ in the BiVO4 host was embedded on the surface of Fe3O4@mSiO2 nanoparticles with the Pechini sol-gel process, thus to form magnetic fluorescent nanoparticles. It was found that the fluorescence of the inorganic nanoparticles can be further enhanced by the complexation of 2-thenoyltrifluoroaceate (TTA) to the Eu3+ on the surface of the nanoparticles. The as-prepared nanoparticles were well characterized and the preparation process was optimized in order to establish a robust preparation method for the multiple functionalized luminescent nanoparticles.

Featured with three-dimensional network structure, polymer hydrogels have found tremendous applications in biomedical fields. In this study, therapeutic-laden Konjac glucomannan (KGM) hydrogel was prepared by injecting polydopamine (PDA)/5-fluorouracil (5-FU)/calcium folinate (CF)/KGM alkaline solution to the target area, for the synergistic tumor photothermal and chemotherapy. In alkaline solution, dopamine can be synchronously polymerized to form PDA, while KGM can be hydrolyzed and transformed into a thermally irreversible KGM hydrogel. Besides, the alkaline condition can increase the solubility of 5-FU. The hydrogel matrix can control the release of 5-FU and CF. PDA renders the composite hydrogel excellent tumor photothermal therapy ability. Moreover, CF can be used as a synergist to enhance the tumor chemotherapy efficiency of 5-FU. With convenient handling, excellent photothermal conversion ability and high biocompatibility, the multifunctional hydrogel system is anticipated to find a promising translational potential in clinical therapeutic applications.

Many companies in the automotive industry have adopted model-driven development in their vehicle software development. As a major automotive company, General Motors (GM) has been using a custom-built, domain-specific modeling language, implemented as an internal proprietary metamodel, to meet the modeling needs in its control software development. Since AUTomotive Open System ARchitecture (AUTOSAR) has been developed as a standard to ease the process of integrating components provided by different suppliers and manufacturers, there has been a growing demand to migrate these GM-specific, legacy models to AUTOSAR models. Given that AUTOSAR defines its own metamodel for various system artifacts in automotive software development, we explore applying model transformations to address the challenges in migrating GM-specific, legacy models to their AUTOSAR equivalents. As a case study, we have built and validated a model transformation using the MDWorkbench tool, the Atlas Transformation Language, and the Metamodel Coverage Checker tool. This paper reports on the case study, makes observations based on our experience to assist in the development of similar types of transformations, and provides recommendations for further research.

Electrospun composite nanofibrous scaffolds have attracted much interest for use as drug delivery vehicles in recent years. Herein, we attempted to first encapsulate the anticancer drug doxorubicin (DOX) using inorganic rod-like nano-hydroxyapatite (n-HA) as a carrier. Then, the DOX-loaded n-HA particles were mixed with poly(lactic-co-glycolic acid) (PLGA) solution to fabricate electrospun hybrid nanofibers. The formation of drug–n-HA complexes and the drug-loaded composite nanofibers were characterized using different techniques. In vitro DOX release behavior was examined using UV-vis spectroscopy under both neutral and acidic conditions. The anticancer activity of the drug-loaded composite nanofibers was evaluated via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) viability assay and phase contrast microscopic morphology observation of a model KB cancer cell line (a human epithelial carcinoma cell line). We show that DOX can be successfully loaded onto the surface of the n-HA and the formed composite fibers have a uniform and continuous fibrous morphology. Importantly, the loaded DOX shows a sustained release profile, and the released DOX from the nanofibers displays non-compromised antitumor activity towards the growth inhibition of KB cells. With the significantly reduced burst release profile and the improved mechanical durability of the composite nanofiber system compared with n-HA-free PLGA nanofibers, the designed organic–inorganic hybrid nanofibers could be used as a versatile drug delivery system for encapsulation and sustained release of different drugs with prolonged therapeutic efficacy for different biomedical applications.

We report the fabrication of a novel carbon nanotube-containing nanofibrous polysaccharide scaffolding material via the combination of electrospinning and layer-by-layer (LbL) self-assembly techniques for tissue engineering applications. In this approach, electrospun cellulose acetate (CA) nanofibers were assembled with positively charged chitosan (CS) and negatively charged multiwalled carbon nanotubes (MWCNTs) or sodium alginate (ALG) via a LbL technique. We show that the 3-dimensional fibrous structures of the CA nanofibers do not appreciably change after the multilayered assembly process except that the surface of the fibers became much rougher than that before assembly. The incorporation of MWCNTs in the multilayered CA fibrous scaffolds tends to endow the fibers with improved mechanical property and promote fibroblast attachment, spreading, and proliferation when compared with CS/ALG multilayer-assembled fibrous scaffolds. The approach to engineering the nanofiber surfaces via LbL assembly likely provides many opportunities for new scaffolding materials design in various tissue engineering applications.

We report a facile approach to fabricating electrospun drug-loaded organic/inorganic hybrid nanofibrous system for antibacterial applications. In this study, nano-hydroxyapatite (n-HA) particles loaded with a model drug, amoxicillin (AMX) were dispersed into poly(lactic-co-glycolic acid) (PLGA) solution to form electrospun hybrid nanofibers. The loading of AMX onto n-HA surfaces (AMX/n-HA) and the formation of AMX/n-HA/PLGA composite nanofibers were characterized using different techniques. We show that AMX can be successfully adsorbed onto the n-HA surface and the formed AMX/n-HA/PLGA composite nanofibers have a uniform and smooth morphology with improved mechanical durability. Cell viability assay and cell morphology observation reveal that the formed AMX/n-HA/PLGA composite nanofibers are cytocompatible. Importantly, the loaded AMX within the n-HA/PLGA hybrid nanofibers shows a sustained release profile and a non-compromised activity to inhibit the growth of a model bacterium, Staphylococcus aureus. With the significantly reduced burst-release profile, good cytocompatibility, improved mechanical durability, as well as the remained antibacterial activity, the developed AMX/n-HA/PLGA composite nanofibers should find various potential applications in the fields of tissue engineering and pharmaceutical science.

The clinical translation potential of mesenchymal stem cells (MSCs) in regenerative medicine has been greatly exploited. With the merits of high surface area to volume ratio, facile control of components, well retained topography, and the capacity to mimic the native extracellular matrix (ECM), nanofibers have received a great deal of attention as bone tissue engineering scaffolds. Electrospinning has been considered as an efficient approach for scale-up fabrication of nanofibrous materials. Electrospun nanofibers are capable of stimulating cell-matrix interaction to form a cell niche, directing cellular behavior, and promoting the MSCs adhesion and proliferation. In this review, we give a comprehensive literature survey on the mechanisms of electrospun nanofibers in supporting the MSCs differentiation. Specifically, the influences of biological and physical osteogenic inductive cues on the MSCs osteogenic differentiation are reviewed. Along with the significant advances in the field, current research challenges and future perspectives are also discussed.

In this paper, we study system performance in passivity based control designs. In particular, we consider the passivation method of [1], we extend it so to use non-positive passivation parameters and transfer functions, and present results to passivate systems that are not finite-gain stable. The passivation parameters are selected according to non-derivative based optimization methods when the system dynamics are unknown. We show that by tuning the passivation parameters, desired system performance can be achieved in addition to guaranteeing passivity for the system. To validate our results, we present simulations in CarSim/Simulink.

We herein report the development of multifunctional folic acid (FA)-targeted Fe3O4 @ Au nanostars (NSs) for targeted multi-mode magnetic resonance (MR)/computed tomography (CT)/photoacoustic (PA) imaging and photothermal therapy (PTT) of tumors. In this present work, citric acid-stabilized Fe3O4/Ag composite nanoparticles prepared by a mild reduction route were utilized as seeds and exposed to the Au growth solution to induce the formation of Fe3O4 @ Au core/shell NSs. Followed by successive decoration of thiolated polyethyleneimine (PEI-SH), FA via a polyethylene glycol spacer and acetylation of the residual PEI amines, multifunctional Fe3O4 @ Au NSs were formed. The designed multifunctional NSs possess excellent colloidal stability, good cytocompatibility in a given concentration range and specific recognition to cancer cells overexpressing FA receptors. Due to co-existence of Fe3O4 core and star-shaped Au shell, the NSs can be used for MR and CT imaging of tumors, respectively. Likewise, the near infrared plasmonic absorption feature also enables the NSs to be used for PA imaging and PTT of tumors. Our study clearly demonstrates a unique theranostic nanoplatform that can be used for high performance multi-mode imaging-guided PTT of tumors, which may be extendable for theranostics of different diseases in translational medicine.

One of the major problems of nanofiber scaffold or other devices like cardiovascular or blood-contacting medical devices is their weak mechanical properties and the lack of hemocompatibility of their surfaces. In this study, halloysite nanotubes (HNTs) and carbon nanotubes (CNTs) were incorporated within poly(lactic-co-glycolic acid) (PLGA) nanofibers and the mechanical property and hemocompatibility of both types of composite nanofibers with different doping levels were thoroughly investigated. The morphology and internal distribution of the doped nanotubes within the nanofibers were characterized using scanning electron microscopy and transmission electron microscopy. Mechanical properties of the electrospun nanofibers were tested using a material testing machine. The hemocompatibility of the composite nanofibers was examined through hemolytic and anticoagulant assay, respectively. We show that the doped HNTs or CNTs are distributed in the nanofibers with a coaxial manner and the incorporation of HNTs or CNTs does not significantly change the morphology of the PLGA nanofibers. Importantly, the incorporation of HNTs or CNTs within PLGA nanofibers significantly improves the mechanical property of PLGA nanofibers, and PLGA nanofibers with or without doping of the HNTs and CNTs display good anticoagulant property and negligible hemolytic effect to human red blood cells. With the enhanced mechanical property, great hemocompatibility, and previously demonstrated biocompatibility of both HNTs- and CNTs-doped composite PLGA nanofibers, these composite nanofibers may be used as therapeutic artificial tissue/organ substitutes for tissue engineering applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

System integration is the elephant in the china store of large-scale cyber-physical system (CPS) design. It would be hard to find any other technology that is more undervalued scientifically and at the same time has bigger impact on the presence and future of engineered systems. The unique challenges in CPS integration emerge from the heterogeneity of components and interactions. This heterogeneity drives the need for modeling and analyzing cross-domain interactions among physical and computational/networking domains and demands deep understanding of the effects of heterogeneous abstraction layers in the design flow. To address the challenges of CPS integration, significant progress needs to be made toward a new science and technology foundation that is model based, precise, and predictable. This paper presents a theory of composition for heterogeneous systems focusing on stability. Specifically, the paper presents a passivity-based design approach that decouples stability from timing uncertainties caused by networking and computation. In addition, the paper describes cross-domain abstractions that provide effective solution for model-based fully automated software synthesis and high-fidelity performance analysis. The design objectives demonstrated using the techniques presented in the paper are group coordination for networked unmanned air vehicles (UAVs) and high-confidence embedded control software design for a quadrotor UAV. Open problems in the area are also discussed, including the extension of the theory of compositional design to guarantee properties beyond stability, such as safety and performance.

Pencil-point spinal needles are popular for combined spinal-epidural analgesia because they cause less dural puncture headache than cutting-edge spinal needles. However, many parturients move, grimace, vocalise or experience paraesthesia or dysaesthesia during dural puncture when performing ‘needle through needle’ combined spinal-epidural analgesia. We compared dural puncture responses induced by pencil-point and cutting-edge needles (both 27 gauge). With institutional approval, 115 parturients presenting for elective caesarean section or labour analgesia were audited. After lignocaine infiltration, a Tuohy-type needle was inserted to loss of resistance to saline at a mid-lumbar interspace, and either a 27 gauge cutting-edge or 27 gauge pencil-point needle was inserted ‘needle through needle’ through the dura. During dural penetration, the occurrence of patient movement, grimacing or vocalisation was noted by a blinded observer, as was the patient's response to the question “Did you feel that?” asked by the anaesthetist. The audit comprised two similar groups of patients (caesarean section, n=30; labour analgesia, n=85). In both groups, grimacing and movement during thecal penetration occurred more frequently with pencil-point needles (P Dural puncture by a 27 gauge pencil-point needle inserted ‘needle through needle’ when instituting combined spinal-epidural analgesia induces more iatrogenic responses than a 27 gauge cutting-edge needle.

Normal saline or air is used to identify loss of resistance during identification of the epidural space for combined spinal-epidural analgesia. Following epidural needle placement using air for loss of resistance, up to 80% of parturients move, grimace, vocalise or experience paraesthesia or dysaesthesia during subsequent dural puncture by a spinal needle. We compared the effects of saline versus air for loss of resistance on the occurrence of these subjective and objective responses during thecal penetration. With institutional approval, 55 parturients presenting for labour analgesia were studied. After infiltration of lignocaine at an L2-L5 vertebral interspace, a 17 gauge Tuohy epidural needle attached to a 5 ml loss of resistance syringe containing either saline or air was inserted and advanced until loss of resistance was identified by injection of 3 to 5 ml of content. During subsequent ‘needle-through-needle’ insertion of a 27 gauge pencil-point spinal needle through the meninges, all subjective and objective patient responses were recorded, as well as each patient's reply to the question “Did you feel that?”. The two groups (n=28, n=27) were comparable. In those given saline and air respectively, 5 (18%) and 12 (44%) parturients responded to and/or acknowledged having perceived dural puncture (P

Model-based methodologies have been widely used to handle the increasing demand for rapid development of high-quality, real-time embedded control software. A key challenge in such model-based design is integration of various ?collaborative? analysis methods to support the automation of the design process. Traditional analysis methods developed for analyzing specific system properties, however, are not designed for such integration, and thus cannot ensure that the information for the analysis will be provided at the design stage where the information is needed. Moreover, many traditional analysis methods depend heavily on complete and accurate design models which can only be applied to post-design verification and are unavailable for automation of the design process involving an early design stage, where implementation details are unknown. This challenge can be met by integrating analysis methods with the design process. We have developed such a framework combined with software modeling, execution platform configuration, and run-time monitoring mechanisms to enable accurate assessment of embedded software quality at early design stages. We have implemented and demonstrated the framework with a toolkit, called AIRES, that integrates software models, a virtual execution platform, and timing and schedulability analysis methods.

Gene therapy has been concerned to be one of the most promising strategies to treat many diseases such as genetic disorders and cancer. However, design of safe and highly efficient gene delivery vectors still remains a great challenge. In this work, we report the use of partially acetylated dendrimer-entrapped gold nanoparticles (Au DENPs) for gene delivery applications. First, partially acetylated generation 5 poly(amidoamine) dendrimers with different acetylation degrees were used as templates to synthesize Au DENPs. The formed Au DENPs were characterized via different techniques and were used to complex two different pDNAs encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The Au DENPs/pDNA polyplexes with different N/P ratios were characterized by gel retardation assay, dynamic light scattering, and zeta potential measurements, and the gene transfection efficiency was evaluated by Luc assay and fluorescence microscopic imaging of the EGFP expression, respectively. We show that despite the partial acetylation (5, 10, 20, and 30 acetyl groups per G5 dendrimer according to the molar feeding ratio), all acetylated Au DENPs are able to effectively compact the pDNA and transfect genes to the model cell line with high efficiency comparable to the Au DENPs without acetylation. With the proven less cytotoxicity of the partially acetylated Au DENPs than that of non-acetylated Au DENPs by cell viability assay, the developed partially acetylated Au DENPs may serve as promising vectors for safe gene delivery applications with non-compromised gene transfection efficiency.

MoS2 nanosheets and a doxorubicin (DOX)-containing poly (lactic-co-glycolic acid) (PLGA)/MoS2 /DOX composite implant are successfully constructed based on the unique phase-changing behavior of PLGA/MoS2 /DOX oleosol within tumors. The fast phase transformation can firmly restrict MoS2 and DOX within tumors, and the integrated MoS2 and DOX can endow the implant with high synergistic photothermal and chemotherapeutic efficiency against tumors.

The increasing performance of modern processors makes virtualization a viable solution for consolidating real-time systems into a single hardware platform. Although real-time task scheduling in a virtual machine can benefit from hierarchical scheduling, unbounded interrupt handling time and vulnerability to interrupt storms make practitioners hesitant to virtualize interrupt-driven real-time applications. In this paper, we propose vINT, an interrupt handling scheme designed for real-time system virtualization. vINT provides a pseudo-VCPU abstraction dedicated for interrupt handling, which overcomes the limits imposed by the timing parameters of virtual CPUs in an analyzable way. vINT also accounts for and enforces interrupt handling and resulting execution flows within a guest virtual machine. vINT does not require any change to the guest OS code, so it can be used for virtualizing proprietary, closed-source OSs. We analyze interrupt handling time as well as VCPU and task schedulability, with and without vINT. Our experimental results indicate that vINT achieves timely interrupt handling while providing as good task schedulability as when it is not used. Our case study based on a prototype implementation on the KVM hyper visor shows that vINT yields significant benefits in reducing interrupt handling time and in protecting real-time tasks against interrupt storms permeating into the virtual machine.

2D PEG-ylated MoS2/Bi2 S3 composite nanosheets are successfully constructed by introducing bismuth ions to react with the two extra S atoms in a (NH4)2 MoS4 molecule precursor for solvothermal synthesis of MoS2. The MBP nanosheets can serve as a promising platform for computed tomography and photoacoustic-imaging-guided tumor diagnosis, as well as combined tumor photothermal therapy and sensitized radiotherapy.

Hollow mesoporous nanomaterials have gained tremendous attention in the fields of nanomedicine and nanobiotechnology. Herein, n-perfluoropentane (PFP)-encapsulated hollow mesoporous Prussian blue (HPB) nanocubes (HPB-PFP) with excellent colloidal stability have been synthesized for concurrent in vivo tumor diagnosis and regression. The HPB shell shows excellent photothermal conversion efficiency that can absorb near-infrared (NIR) laser light and convert it into heat. The generated heat can not only cause tumor ablation by raising the temperature of tumor tissue but also promote the continuous gasification and bubbling of encapsulated liquid PFP with low boiling point. These formed PFP bubbles can cause tissue impedance mismatch, thus apparently enhancing the signal of B-mode ultrasound imaging in vitro and generating an apparent echogenicity signal for tumor tissues of nude mice in vivo. Without showing observable in vitro and in vivo cytotoxicity, the designed biocompatible HPB-PFP nanotheranostics with high colloidal stability and photothermal efficiency are anticipated to find various biomedical applications in activated ultrasound imaging-guided tumor detection and therapy.

The extracellular matrix mimicking property of electrospun polymer nanofibers affords their uses as an ideal scaffold material for differentiation of human mesenchymal stem cells (hMSCs), which is important for various tissue engineering applications. Here, we report the fabrication of electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers incorporated with attapulgite (ATT) nanorods, a clay material for osteogenic differentiation of hMSCs. We show that the incorporation of ATT nanorods does not significantly change the uniform morphology and the hemocompatibility of the PLGA nanofibers; instead the surface hydrophilicity and cytocompatibility of the hybrid nanofibers are slightly improved after doping with ATT. Alkaline phosphatase activity, osteocalcin secretion, calcium content, and von Kossa staining assays reveal that hMSCs are able to be differentiated to form osteoblast-like cells onto both PLGA and PLGA–ATT composite nanofibers in osteogenic medium. Most strikingly, the doped ATT within the PLGA nanofibers is able to induce the osteoblastic differentiation of hMSCs in growth medium without the inducing factor of dexamethasone. The fabricated organic/inorganic hybrid ATT-doped PLGA nanofibers may find many applications in the field of tissue engineering and regenerative medicine.

The virtualization of real-time systems has received much attention for its many benefits, such as the consolidation of individually developed real-time applications while maintaining their implementations. However, the current state of the art still lacks properties required for resource sharing among real-time application tasks in a multi-core virtualization environment. In this paper, we propose vMPCP, a synchronization framework for the virtualization of multi-core real-time systems. Vmpcp exposes the executions of critical sections of tasks in a guest virtual machine to the hyper visor. Using this approach, vMPCP reduces and bounds blocking time on accessing resources shared within and across virtual CPUs (VCPUs) assigned on different physical CPU cores. Vmpcp supports periodic server and deferrable server policies for the VCPU budget replenish policy, with an optional budget overrun to reduce blocking times. We provide the VCPU and task schedulability analyses under vMPCP, with different VCPU budget supply policies, with and without overrun. Experimental results indicate that, under vMPCP, deferrable server outperforms periodic server when overrun is used, with as much as 80% more task sets being schedulable. The case study using our hyper visor implementation shows that vMPCP yields significant benefits compared to a virtualization-unaware multi-core synchronization protocol, with 29% shorter response time on average.

We propose a software architecture based on a combination of object-oriented models and executable formal specifications. In this architecture, the machine control software is viewed as an integration of a set of reusable software components, each modeled with a set of event-based external interfaces for functional definitions, a control logic driver for execution of behavioral specifications, and a set of service protocols for platform adaptation. The behaviors of the entire software can be viewed as an integration of behaviors of components and their integration. Separation of structural specification from behavioral specification enables the controller software structure to be reconfigured independently of application, and software behavior to be reconfigured independently of controller software structure. When the system needs reconfiguration due to changes in either application requirements or the execution platform, the software with our architecture can then be reconfigured by changing reusable components and their interactions in structure for functional capability, and by changing the Control Plan program for behavior. Both types of reconfiguration can be done at the executable code level after the software is implemented. The proposed architecture also supports reconfigurability to facilitate heterogeneous implementations and vendor-neutral products.

Large-pore silica microspheres were synthesized by utilizing weak cation exchange polymer beads as templates, N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride (TMSPTMA) as a structure-directing agent, tetraethoxysilane (TEOS) as a silica precursor, and triethanolamine as a weak base catalyst. The hydrolysis and condensation of the silica precursors occurred inside the templating polymer beads yielded polymer/silica composite microspheres. After the organic polymer templates were removed in the calcination step, large-pore silica microspheres were produced. The effects of different reaction conditions on the morphology, structure and dispersibility of the formed silica microspheres were investigated. It has been shown that when the volume ratio of TMSPTMA, TEOS and triethanolamine was 1:2:2, silica microspheres with pore size range of 50-150 nm and particle size around 2 μm were obtained. The as-prepared silica microspheres were then bonded with chlorodimethyloctadecylsilane (C18), packed into a 50 mm×4.6 mm column, and evaluated for the separations of some common standard proteins and soybean isolation proteins. The results showed that the large-pore silica spheres from this work have potentials for protein separation in HPLC.

Chemical construction of molecularly organic-inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) with silsesquioxane framework is expected to substantially improve their therapeutic performance and enhance the biological effects beneficial for biomedicine. In this work, we report on a simple, controllable, and versatile chemical homology principle to synthesize multiple-hybridized HMONs with varied functional organic groups homogeneously incorporated into the framework (up to quintuple hybridizations). As a paradigm, the hybridization of physiologically active thioether groups with triple distinctive disulfide bonds can endow HMONs with unique intrinsic reducing/acidic- and external high intensity focused ultrasound (HIFU)-responsive drug-releasing performances, improved biological effects (e.g., lowered hemolytic effect and improved histocompatibility), and enhanced ultrasonography behavior. The doxorubicin-loaded HMONs with concurrent thioether and phenylene hybridization exhibit drastically enhanced therapeutic efficiency against cancer growth and metastasis, as demonstrated both in vitro and in vivo.