Vehicle Routing Problems for Drone Delivery
Dorling, Kevin; Heinrichs, Jordan; Messier, Geoffrey G.; Magierowski, Sebastian
2016-01-01
Unmanned aerial vehicles, or drones, have the potential to significantly reduce the cost and time of making last-mile deliveries and responding to emergencies. Despite this potential, little work has gone into developing vehicle routing problems (VRPs) specifically for drone delivery scenarios. Existing VRPs are insufficient for planning drone deliveries: either multiple trips to the depot are not permitted, leading to solutions with excess drones, or the effect of battery and payload weight ...
Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression
2015-10-01
AWARD NUMBER: W81XWH-14-1-0548 TITLE: Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression PRINCIPAL...Sep 2015 4. TITLE AND SUBTITLE Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression 5a. CONTRACT NUMBER 5b. GRANT...In this exploratory award, we are investigating the functional significance of exosomal miRNAs in prostate cancer . We are characterizing the miRNA
Carbon nanotubes part I: preparation of a novel and versatile drug-delivery vehicle
Karimi, Mahdi; Solati, Navid; Amiri, Mohammad; Mirshekari, Hamed; Mohamed, Elmira; Taheri, Mahdiar; Hashemkhani, Mahshid; Saeidi, Ahad; Estiar, Mehrdad Asghari; Kiani, Parnian; Ghasemi, Amir; Basri, Seyed Masoud Moosavi; Aref, Amir R
2015-01-01
Introduction It is 23 years since carbon allotrope known as carbon nanotubes (CNT) was discovered by Iijima, who described them as “rolled graphite sheets inserted into each other”. Since then, CNTs have been studied in nanoelectronic devices. However, CNTs also possess the versatility to act as drug- and gene-delivery vehicles. Areas covered This review covers the synthesis, purification and functionalization of CNTs. Arc discharge, laser ablation and chemical vapor deposition are the principle synthesis methods. Non-covalent functionalization relies on attachment of biomolecules by coating the CNT with surfactants, synthetic polymers and biopolymers. Covalent functionalization often involves the initial introduction of carboxylic acids or amine groups, diazonium addition, 1,3-dipolar cycloaddition or reductive alkylation. The aim is to produce functional groups to attach the active cargo. Expert opinion In this review, the feasibility of CNT being used as a drug-delivery vehicle is explored. The molecular composition of CNT is extremely hydrophobic and highly aggregation-prone. Therefore, most of the efforts towards drug delivery has centered on chemical functionalization, which is usually divided in two categories; non-covalent and covalent. The biomedical applications of CNT are growing apace, and new drug-delivery technologies play a major role in these efforts. PMID:25601356
METHOD OF CHOOSING THE TECHNOLOGY OF VEHICLE OPERATION ON DELIVERY ROUTES
Directory of Open Access Journals (Sweden)
Ye. Nagornyi
2014-10-01
Full Text Available A method for determining the technology of vehicles operation on delivery (team routes, which allows to determine the optimal sequence of cargo delivery to customers by vehicles of certain capacity in order to meet the requirements of cargo owners regarding the conditions of service is offered. Recommendations for creation of an automated system of forming the technology of vehicles operation on delivery routes are developed.
Single-Commodity Vehicle Routing Problem with Pickup and Delivery Service
Directory of Open Access Journals (Sweden)
Goran Martinovic
2008-01-01
Full Text Available We present a novel variation of the vehicle routing problem (VRP. Single commodity cargo with pickup and delivery service is considered. Customers are labeled as either cargo sink or cargo source, depending on their pickup or delivery demand. This problem is called a single commodity vehicle routing problem with pickup and delivery service (1-VRPPD. 1-VRPPD deals with multiple vehicles and is the same as the single-commodity traveling salesman problem (1-PDTSP when the number of vehicles is equal to 1. Since 1-VRPPD specializes VRP, it is hard in the strong sense. Iterative modified simulated annealing (IMSA is presented along with greedy random-based initial solution algorithm. IMSA provides a good approximation to the global optimum in a large search space. Experiment is done for the instances with different number of customers and their demands. With respect to average values of IMSA execution times, proposed method is appropriate for practical applications.
An Update on in Vivo Imaging of Extracellular Vesicles as Drug Delivery Vehicles
Directory of Open Access Journals (Sweden)
Prakash Gangadaran
2018-02-01
Full Text Available Extracellular vesicles (EVs are currently being considered as promising drug delivery vehicles. EVs are naturally occurring vesicles that exhibit many characteristics favorable to serve as drug delivery vehicles. In addition, EVs have inherent properties for treatment of cancers and other diseases. For research and clinical translation of use of EVs as drug delivery vehicles, in vivo tracking of EVs is essential. The latest molecular imaging techniques enable the tracking of EVs in living animals. However, each molecular imaging technique has its certain advantages and limitations for the in vivo imaging of EVs; therefore, understanding the molecular imaging techniques is essential to select the most appropriate imaging technology to achieve the desired imaging goal. In this review, we summarize the characteristics of EVs as drug delivery vehicles and the molecular imaging techniques used in visualizing and monitoring EVs in in vivo environments. Furthermore, we provide a perceptual vision of EVs as drug delivery vehicles and in vivo monitoring of EVs using molecular imaging technologies.
Design of a multi-vehicles delivery tours satisfying duration constraints
Energy Technology Data Exchange (ETDEWEB)
Langevin, A; Soumis, F
1987-01-01
The following organization was studied for the letter and parcel pick-up and delivery problem in an urban environment. The day is divided in periods of time in which each vehicle starts from a sorting centre, travels to a very precise area of the region, picks up and delivers letters and parcels, and returns to the depot to have the collected material sorted out for delivery during the following period. The intent of this approach is to have each zone serviced by one vehicle only, in order to facilitate the work of the dispatcher and routing of each vehicle. A method has been developed of partitioning an urban region into zones to be assigned, each one to a specific vehicle, so as to minimize the total number of vehicles used or the total distance travelled by all vehicles. The first part of the method determines the zones and the average number of points to visit. Then, a first refinement of the method takes into account the daily variability of the demand in each zone, whereas a second refinement examines the advantage of allowing some overlapping of zones for the purpose of having an overloaded vehicle relieved by one from an adjacent zone. 17 refs., 11 figs., 2 tabs.
AAV vectors as gene delivery vehicles in the central nervous system
Broekman, M.L.D.
2006-01-01
Recombinant gene delivery vehicles based on the replication-defective AAV have gained a preeminent position in the field of gene delivery to the brain. Efficient global gene delivery to the CNS is beneficial for the study of gene products is the entire CNS as well as for introducing and expressing
Siregar, B.; Gunawan, D.; Andayani, U.; Sari Lubis, Elita; Fahmi, F.
2017-01-01
Food delivery system is one kind of geographical information systems (GIS) that can be applied through digitation process. The main case in food delivery system is the way to determine the shortest path and food delivery vehicle movement tracking. Therefore, to make sure that the digitation process of food delivery system can be applied efficiently, it is needed to add shortest path determination facility and food delivery vehicle tracking. This research uses A Star (A*) algorithm for determining shortest path and location-based system (LBS) programming for moving food delivery vehicle object tracking. According to this research, it is generated the integrated system that can be used by food delivery driver, customer, and administrator in terms of simplifying the food delivery system. Through the application of shortest path and the tracking of moving vehicle, thus the application of food delivery system in the scope of geographical information system (GIS) can be executed.
Energy Technology Data Exchange (ETDEWEB)
Lammert, M. P.; Burton, J.; Sindler, P.; Duran, A.
2014-10-01
This research project compares laboratory-measured fuel economy of a medium-duty diesel powered hydraulic hybrid vehicle drivetrain to both a conventional diesel drivetrain and a conventional gasoline drivetrain in a typical commercial parcel delivery application. Vehicles in this study included a model year 2012 Freightliner P100H hybrid compared to a 2012 conventional gasoline P100 and a 2012 conventional diesel parcel delivery van of similar specifications. Drive cycle analysis of 484 days of hybrid parcel delivery van commercial operation from multiple vehicles was used to select three standard laboratory drive cycles as well as to create a custom representative cycle. These four cycles encompass and bracket the range of real world in-use data observed in Baltimore United Parcel Service operations. The NY Composite cycle, the City Suburban Heavy Vehicle Cycle cycle, and the California Air Resources Board Heavy Heavy-Duty Diesel Truck (HHDDT) cycle as well as a custom Baltimore parcel delivery cycle were tested at the National Renewable Energy Laboratory's Renewable Fuels and Lubricants Laboratory. Fuel consumption was measured and analyzed for all three vehicles. Vehicle laboratory results are compared on the basis of fuel economy. The hydraulic hybrid parcel delivery van demonstrated 19%-52% better fuel economy than the conventional diesel parcel delivery van and 30%-56% better fuel economy than the conventional gasoline parcel delivery van on cycles other than the highway-oriented HHDDT cycle.
Novel adjuvants & delivery vehicles for vaccines development: a road ahead.
Mohan, Teena; Verma, Priyanka; Rao, D Nageswara
2013-11-01
The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.
Injury severity in delivery-motorcycle to vehicle crashes in the Seoul metropolitan area.
Chung, Younshik; Song, Tai-Jin; Yoon, Byoung-Jo
2014-01-01
More than 56% of motorcycles in Korea are used for the purpose of delivering parcels and food. Since such delivery requires quick service, most motorcyclists commit traffic violations while delivering, such as crossing the centerline, speeding, running a red light, and driving in the opposite direction down one-way streets. In addition, the fatality rate for motorcycle crashes is about 12% of the fatality rate for road traffic crashes, which is considered to be high, although motorcycle crashes account for only 5% of road traffic crashes in South Korea. Therefore, the objective of this study is to analyze the injury severity of vehicle-to-motorcycle crashes that have occurred during delivery. To examine the risk of different injury levels sustained under all crash types of vehicle-to-motorcycle, this study applied an ordered probit model. Based on the results, this study proposes policy implications to reduce the injury severity of vehicle-to-motorcycle crashes during delivery. Copyright © 2013 Elsevier Ltd. All rights reserved.
Intracellular cargo delivery by virus capsid protein-based vehicles: From nano to micro.
Gao, Ding; Lin, Xiu-Ping; Zhang, Zhi-Ping; Li, Wei; Men, Dong; Zhang, Xian-En; Cui, Zong-Qiang
2016-02-01
Cellular delivery is an important concern for the efficiency of medicines and sensors for disease diagnoses and therapy. However, this task is quite challenging. Self-assembly virus capsid proteins might be developed as building blocks for multifunctional cellular delivery vehicles. In this work, we found that SV40 VP1 (Simian virus 40 major capsid protein) could function as a new cell-penetrating protein. The VP1 protein could carry foreign proteins into cells in a pentameric structure. A double color structure, with red QDs (Quantum dots) encapsulated by viral capsids fused with EGFP, was created for imaging cargo delivery and release from viral capsids. The viral capsids encapsulating QDs were further used for cellular delivery of micron-sized iron oxide particles (MPIOs). MPIOs were efficiently delivered into live cells and controlled by a magnetic field. Therefore, our study built virus-based cellular delivery systems for different sizes of cargos: protein molecules, nanoparticles, and micron-sized particles. Much research is being done to investigate methods for efficient and specific cellular delivery of drugs, proteins or genetic material. In this article, the authors describe their approach in using self-assembly virus capsid proteins SV40 VP1 (Simian virus 40 major capsid protein). The cell-penetrating behavior provided excellent cellular delivery and should give a new method for biomedical applications. Copyright © 2015 Elsevier Inc. All rights reserved.
Lignin nanotubes as vehicles for gene delivery into human cells.
Ten, Elena; Ling, Chen; Wang, Yuan; Srivastava, Arun; Dempere, Luisa Amelia; Vermerris, Wilfred
2014-01-13
Lignin nanotubes (LNTs) synthesized from the aromatic plant cell wall polymer lignin in a sacrificial alumina membrane template have as useful features their flexibility, ease of functionalization due to the availability of many functional groups, label-free detection by autofluorescence, and customizable optical properties. In this report we show that the physicochemical properties of LNTs can be varied over a wide range to match requirements for specific applications by using lignin with different subunit composition, a function of plant species and genotype, and by choosing the lignin isolation method (thioglycolic acid, phosphoric acid, sulfuric acid (Klason), sodium hydroxide lignin), which influences the size and reactivity of the lignin fragments. Cytotoxicity studies with human HeLa cells showed that concentrations of up to 90 mg/mL are tolerated, which is a 10-fold higher concentration than observed for single- or multiwalled carbon nanotubes (CNTs). Confocal microscopy imaging revealed that all LNT formulations enter HeLa cells without auxiliary agents and that LNTs made from NaOH-lignin penetrate the cell nucleus. We further show that DNA can adsorb to LNTs. Consequently, exposure of HeLa cells to LNTs coated with DNA encoding the green fluorescent protein (GFP) leads to transfection and expression of GFP. The highest transfection efficiency was obtained with LNTs made from NaOH-lignin due to a combination of high DNA binding capacity and DNA delivery directly into the nucleus. These combined features of LNTs make LNTs attractive as smart delivery vehicles of DNA without the cytotoxicity associated with CNTs or the immunogenicity of viral vectors.
Time Dependent Heterogeneous Vehicle Routing Problem for Catering Service Delivery Problem
Azis, Zainal; Mawengkang, Herman
2017-09-01
The heterogeneous vehicle routing problem (HVRP) is a variant of vehicle routing problem (VRP) which describes various types of vehicles with different capacity to serve a set of customers with known geographical locations. This paper considers the optimal service deliveries of meals of a catering company located in Medan City, Indonesia. Due to the road condition as well as traffic, it is necessary for the company to use different type of vehicle to fulfill customers demand in time. The HVRP incorporates time dependency of travel times on the particular time of the day. The objective is to minimize the sum of the costs of travelling and elapsed time over the planning horizon. The problem can be modeled as a linear mixed integer program and we address a feasible neighbourhood search approach to solve the problem.
Wang, Junping; Ornek-Ballanco, Ceren; Xu, Jiahua; Yang, Weiguo; Yu, Xiaojun
2013-01-01
Intracellular delivery vehicles have been extensively investigated as these can serve as an effective tool in studying the cellular mechanism, by delivering functional protein to specific locations of the cells. In the current study, a polymer-lipid nanoparticle (PLN) system was developed as an intracellular delivery vehicle specifically targeting vinculin, a focal adhesion protein associated with cellular adhesive structures, such as focal adhesions and adherens junctions. The PLNs possessed an average size of 106 nm and had a positively charged surface. With a lower encapsulation efficiency 32% compared with poly(lactic-co-glycolic) acid (PLGA) nanoparticles (46%), the PLNs showed the sustained release profile of model drug BSA, while PLGA nanoparticles demonstrated an initial burst-release property. Cell-uptake experiments using mouse embryonic fibroblasts cultured in fibrin-fibronectin gels observed, under confocal microscope, that the anti-vinculin conjugated PLNs could successfully ship the cargo to the cytoplasm of fibroblasts, adhered to fibronectin-fibrin. With the use of cationic lipid, the unconjugated PLNs were shown to have high gene transfection efficiency. Furthermore, the unconjugated PLNs had nuclear-targeting capability in the absence of nuclear-localization signals. Therefore, the PLNs could be manipulated easily via different type of targeting ligands and could potentially be used as a powerful tool for cellular mechanism study, by delivering drugs to specific cellular organelles.
Autonomous self-navigating drug-delivery vehicles: from science fiction to reality.
Petrenko, Valery A
2017-12-01
Low efficacy of targeted nanomedicines in biological experiments enforced us to challenge the traditional concept of drug targeting and suggest a paradigm of 'addressed self-navigating drug-delivery vehicles,' in which affinity selection of targeting peptides and vasculature-directed in vivo phage screening is replaced by the migration selection, which explores ability of 'promiscuous' phages and their proteins to migrate through the tumor-surrounding cellular barriers, using a 'hub and spoke' delivery strategy, and penetrate into the tumor affecting the diverse tumor cell population. The 'self-navigating' drug-delivery paradigm can be used as a theoretical and technical platform in design of a novel generation of molecular medications and imaging probes for precise and personal medicine. [Formula: see text].
Branch-and-cut algorithms for the split delivery vehicle routing problem
Archetti, Claudia; Bianchessi, Nicola; Speranza, M. Grazia
2014-01-01
In this paper we present two exact branch-and-cut algorithms for the Split Delivery Vehicle Routing Problem (SDVRP) based on two relaxed formulations that provide lower bounds to the optimum. Procedures to obtain feasible solutions to the SDVRP from a feasible solution to the relaxed formulations
DEFF Research Database (Denmark)
Holm, R.; Jensen, I.H.M.; Sonnergaard, Jørn
2006-01-01
with the hard gelatin capsule. Three formulation variables, PEG200, a surfactant mixture, and an oil mixture, were included in the experimental design. The results of the mathematical analysis of the data demonstrated significant interactions among the formulation variables, and the desirability function......D-optimal design and the desirability function were applied to optimize a self-microemulsifying drug delivery system (SMEDDS). The optimized key parameters were the following: 1) particle size of the dispersed emulsion, 2) solubility of the drug in the vehicle, and 3) the vehicle compatibility...
Construction of a Nanodiamond–Tamoxifen Complex as a Breast Cancer Drug Delivery Vehicle
Directory of Open Access Journals (Sweden)
Linda-Lucila Landeros-Martínez
2016-01-01
Full Text Available According to the World Health Organization, breast cancer represents 16% of all cancer cases in women and is the second most common cancer. In the past decades, the mortality among patients with metastasis breast cancer has been reduced significantly via drug delivery by means of nanodiamond therapies, which are both biocompatible and scalable. In this study, we determined a theoretical pathway for the construction of a nanodiamond–tamoxifen complex that will act as a drug delivery vehicle for targeting tumor tissues of breast cancer. The tamoxifen pharmacophore was defined and the binding zone was identified for the electrostatic interaction between tamoxifen and a functionalized site of a nanodiamond particle allowing for attachment of the payload (this drug to the surface of the nanodiamond particle. In addition, an analysis of the intermolecular interaction between the nanodiamond and tamoxifen was conducted, showing three hydrogen bonds complying fully with Lipinski’s rule of five, which states that a compound should have five or fewer hydrogen bonds to be permeating and easily absorbed by the body (qualitative prediction. All calculations were performed using the conceptual Density Functional Theory with the M06 functional and the basis set 6-31G(d. The solvent effect has been taken into account by an implicit model, the conductor like polarizable continuum model.
Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery.
Tan, Kei X; Danquah, Michael K; Sidhu, Amandeep; Yon, Lau Sie; Ongkudon, Clarence M
2018-02-08
The search for smart delivery systems for enhanced pre-clinical and clinical pharmaceutical delivery and cell targeting continues to be a major biomedical research endeavor owing to differences in the physicochemical characteristics and physiological effects of drug molecules, and this affects the delivery mechanisms to elicit maximum therapeutic effects. Targeted drug delivery is a smart evolution essential to address major challenges associated with conventional drug delivery systems. These challenges mostly result in poor pharmacokinetics due to the inability of the active pharmaceutical ingredients to specifically act on malignant cells thus, causing poor therapeutic index and toxicity to surrounding normal cells. Aptamers are oligonucleotides with engineered affinities to bind specifically to their cognate targets. Aptamers have gained significant interests as effective targeting elements for enhanced therapeutic delivery as they can be generated to specifically bind to wide range of targets including proteins, peptides, ions, cells and tissues. Notwithstanding, effective delivery of aptamers as therapeutic vehicles is challenged by cell membrane electrostatic repulsion, endonuclease degradation, low pH cleavage, and binding conformation stability. The application of molecularly engineered biodegradable and biocompatible polymeric particles with tunable features such as surface area and chemistry, particulate size distribution and toxicity creates opportunities to develop smart aptamer-mediated delivery systems for controlled drug release. This article discusses opportunities for particulate aptamer-drug formulations to advance current drug delivery modalities by navigating active ingredients through cellular and biomolecular traffic to target sites for sustained and controlled release at effective therapeutic dosages while minimizing systemic cytotoxic effects. A proposal for a novel drug-polymer-aptamer-polymer (DPAP) design of aptamer-drug formulation with
Magnetotactic Bacterial Cages as Safe and Smart Gene Delivery Vehicles
Alsaiari, Shahad K.; Ezzedine, Alaa H.; Abdallah, Abdallah; Sougrat, Rachid; Khashab, Niveen M.
2016-01-01
In spite of the huge advances in the area of synthetic carriers, their efficiency still poorly compares to natural vectors. Herein, we report the use of unmodified magnetotactic bacteria as a guidable delivery vehicle for DNA functionalized gold nanoparticles (AuNPs). High cargo loading is established under anaerobic conditions (bacteria is alive) through endocytosis where AuNPs are employed as transmembrane proteins mimics (facilitate endocytosis) as well as imaging agents to verify and quantify loading and release. The naturally bio-mineralized magnetosomes, within the bacteria, induce heat generation inside bacteria through magnetic hyperthermia. Most importantly after exposing the system to air (bacteria is dead) the cell wall stays intact providing an efficient bacterial vessel. Upon incubation with THP-1 cells, the magnetotactic bacterial cages (MBCs) adhere to the cell wall and are directly engulfed through the phagocytic activity of these cells. Applying magnetic hyperthermia leads to the dissociation of the bacterial microcarrier and eventual release of cargo.
Magnetotactic Bacterial Cages as Safe and Smart Gene Delivery Vehicles
Alsaiari, Shahad K.
2016-07-27
In spite of the huge advances in the area of synthetic carriers, their efficiency still poorly compares to natural vectors. Herein, we report the use of unmodified magnetotactic bacteria as a guidable delivery vehicle for DNA functionalized gold nanoparticles (AuNPs). High cargo loading is established under anaerobic conditions (bacteria is alive) through endocytosis where AuNPs are employed as transmembrane proteins mimics (facilitate endocytosis) as well as imaging agents to verify and quantify loading and release. The naturally bio-mineralized magnetosomes, within the bacteria, induce heat generation inside bacteria through magnetic hyperthermia. Most importantly after exposing the system to air (bacteria is dead) the cell wall stays intact providing an efficient bacterial vessel. Upon incubation with THP-1 cells, the magnetotactic bacterial cages (MBCs) adhere to the cell wall and are directly engulfed through the phagocytic activity of these cells. Applying magnetic hyperthermia leads to the dissociation of the bacterial microcarrier and eventual release of cargo.
Enhancement of transdermal delivery of ibuprofen using microemulsion vehicle.
Hu, Liandong; Hu, Qiaofeng; Yang, Jianxue
2014-10-01
The objective of this study was to find a stable microemulsion vehicle for transdermal delivery of ibuprofen to improve the skin permeability. Microemulsion was prepared using different sorts of oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The effects of oleic acid and surfactant mixture on skin permeation of ibuprofen were evaluated with excised skins. The optimum formulation F3 consisting of 6% oleic acid, 30% Cremophor RH40/Transcutol P (2:1, w/w) and 59% water phase, showed a high permeation rate of 42.98 µg/cm(2)/hr. The mean droplet size of microemulsion was about 43 nm and no skin irritation signs were observed on the skin of rabbits. These results indicated that this novel microemulsion is a useful formulation for the transdermal delivery of ibuprofen.
Encapsulation of Curcumin in Self-Assembling Peptide Hydrogels as Injectable Drug Delivery Vehicles
Altunbas, Aysegul; Lee, Seung Joon; Rajasekaran, Sigrid A.; Schneider, Joel P.; Pochan, Darrin J.
2011-01-01
Curcumin, a hydrophobic polyphenol, is an extract of turmeric root with antioxidant, anti-inflammatory and anti-tumorigenic properties. Its lack of water solubility and relatively low bioavailability set major limitations for its therapeutic use. In this study, a self-assembling peptide hydrogel is demonstrated to be an effective vehicle for the localized delivery of curcumin over sustained periods of time. The curcumin-hydrogel is prepared in-situ where curcumin encapsulation within the hydrogel network is accomplished concurrently with peptide self-assembly. Physical and in vitro biological studies were used to demonstrate the effectiveness of curcumin-loaded β-hairpin hydrogels as injectable agents for localized curcumin delivery. Notably, rheological characterization of the curcumin loaded hydrogel before and after shear flow have indicated solid-like properties even at high curcumin payloads. In vitro experiments with a medulloblastoma cell line confirm that the encapsulation of the curcumin within the hydrogel does not have an adverse effect on its bioactivity. Most importantly, the rate of curcumin release and its consequent therapeutic efficacy can be conveniently modulated as a function of the concentration of the MAX8 peptide. PMID:21601921
Towards functional safety in drive-by-wire vehicles
Bergmiller, Peter Johannes
2015-01-01
This book presents approaches to address key challenges based on a vehicle level view and with a special emphasis on Drive-by-Wire systems. The design and testing of modern vehicle electronics are becoming more and more demanding due to increasing interdependencies among components and the safety criticality of tasks. The development towards Drive-by-Wire functionalities in vehicles with multiple actuators for vehicle control further increases the challenge. The book explicitly takes into account the interactions between components and aims at bridging the gap between the need to generate additional customer benefits and the effort to achieve functional safety. The book follows a twofold approach: on the one side, it presents a toolchain to support efficient further development of novel functionalities for Drive-by-Wire vehicles. The toolchain comprises appropriate software tools and scaled and full-scale experimental vehicles. On the other side, development towards functionally safe and flexible Drive-by-W...
Directory of Open Access Journals (Sweden)
Heungjo An
2018-05-01
Full Text Available While large construction sites have on-site loaders to handle heavy and large packages of bricks, small brick manufacturers employ a truck-mounted loader or sometimes deploy a loader truck to accompany normal brick delivery trucks to small construction sites lacking on-site loaders. It may be very challenging for small contractors to manage a sustainable delivery system that is both cost-effective and environmentally friendly. To address this issue, this paper proposes to solve a multi-trip vehicle loader routing problem by uniquely planning routes and schedules of several types of vehicles considering their synchronized operations at customer sites and multi trips. This paper also evaluates the sustainability of the developed model from both economic and environmental perspectives. Case studies based on small construction sites in the Middle East demonstrate applications of the proposed model to make the most economical plans for delivering bricks. Compared to the single-trip vehicle loader routing problem, the proposed model reduces, on average, 18.7% of the total delivery cost while increasing CO2 emission negligibly. The economic benefit is mainly achieved by reducing the required number of vehicles. Brick plant managers can use the proposed mathematical model to plan the most cost-effective delivery schedules sustainably while minimizing negative environmental effects.
Directory of Open Access Journals (Sweden)
Julia Rieck
2013-05-01
Full Text Available In reverse logistics networks, products (e.g., bottles or containers have to be transported from a depot to customer locations and, after use, from customer locations back to the depot. In order to operate economically beneficial, companies prefer a simultaneous delivery and pick-up service. The resulting Vehicle Routing Problem with Simultaneous Delivery and Pick-up (VRPSDP is an operational problem, which has to be solved daily by many companies. We present two mixed-integer linear model formulations for the VRPSDP, namely a vehicle-flow and a commodity-flow model. In order to strengthen the models, domain-reducing preprocessing techniques, and effective cutting planes are outlined. Symmetric benchmark instances known from the literature as well as new asymmetric instances derived from real-world problems are solved to optimality using CPLEX 12.1.
Split delivery vehicle routing problem with time windows: a case study
Latiffianti, E.; Siswanto, N.; Firmandani, R. A.
2018-04-01
This paper aims to implement an extension of VRP so called split delivery vehicle routing problem (SDVRP) with time windows in a case study involving pickups and deliveries of workers from several points of origin and several destinations. Each origin represents a bus stop and the destination represents either site or office location. An integer linear programming of the SDVRP problem is presented. The solution was generated using three stages of defining the starting points, assigning busses, and solving the SDVRP with time windows using an exact method. Although the overall computational time was relatively lengthy, the results indicated that the produced solution was better than the existing routing and scheduling that the firm used. The produced solution was also capable of reducing fuel cost by 9% that was obtained from shorter total distance travelled by the shuttle buses.
International Nuclear Information System (INIS)
Li, Yong-Yong; Li, Lan; Dong, Hai-Qing; Cai, Xiao-Jun; Ren, Tian-Bin
2013-01-01
PKKKRKV (Pro-Lys-Lys-Lys-Arg-Lys-Val, PV7), a seven amino acid peptide, has emerged as one of the primary nuclear localization signals that can be targeted into cell nucleus via the nuclear import machinery. Taking advantage of chemical diversity and biological activities of this short peptide sequence, in this study, Pluronic F127 nanomicelles engineered with nuclear localized functionality were successfully developed for intracellular drug delivery. These nanomicelles with the size ∼ 100 nm were self-assembled from F127 polymer that was flanked with two PV7 sequences at its both terminal ends. Hydrophobic anticancer drug doxorubicin (DOX) with inherent fluorescence was chosen as the model drug, which was found to be efficiently encapsulated into nanomicelles with the encapsulation efficiency at 72.68%. In comparison with the non-functionalized namomicelles, the microscopic observation reveals that PV7 functionalized nanomicelles display a higher cellular uptake, especially into the nucleus of HepG2 cells, due to the nuclear localization signal effects. Both cytotoxicity and apoptosis studies show that the DOX-loaded nanomicelles were more potent than drug nanomicelles without nuclear targeting functionality. It was thus concluded that PV7 functionalized nanomicelles could be a potentially alternative vehicle for nuclear targeting drug delivery. - Highlights: ► A new nuclear targeted drug delivery system based on micelles is developed. ► This micellar system features a core-shell structure with the size peaked at 100 nm. ► PV7, a short peptide sequence, is adopted as a nuclear targeting ligand. ► PV7 functionalized drug loaded micelles are more potent in killing tumor cells
Singh, Priya; Choudhury, Susobhan; Kulanthaivel, Senthilguru; Bagchi, Damayanti; Banerjee, Indranil; Ahmed, Saleh A; Pal, Samir Kumar
2018-02-01
The efficacy and toxicity of drugs depend not only on their potency but also on their ability to reach the target sites in preference to non-target sites. In this regards destabilization of delivery vehicles induced by light can be an effective strategy for enhancing drug delivery with spatial and temporal control. Herein we demonstrate that the photoinduced isomerization from closed (hydrophobic) to open isomeric form (hydrophilic) of a novel DHI encapsulated in liposome leads to potential light-controlled drug delivery vehicles. We have used steady state and picosecond resolved dynamics of a drug 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) incorporated in liposome to monitor the efficacy of destabilization of liposome in absence and presence UVA irradiation. Steady state and picosecond resolved polarization gated spectroscopy including the well-known strategy of solvation dynamics and Förster resonance energy transfer; reveal the possible mechanism out of various phenomena involved in destabilization of liposome. We have also investigated the therapeutic efficacy of doxorubicin (DOX) delivery from liposome to cervical cancer cell line HeLa. The FACS, confocal fluorescence microscopic and MTT assay studies reveal an enhanced cellular uptake of DOX leading to significant reduction in cell viability (∼40%) of HeLa followed by photoresponsive destabilization of liposome. Our studies successfully demonstrate that these DHI encapsulated liposomes have potential application as a smart photosensitive drug delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.
In-vehicle signing functions of an in-vehicle information system
Energy Technology Data Exchange (ETDEWEB)
Tufano, D.R.; Knee, H.E.; Spelt, P.F.
1996-04-01
The definition of In-Vehicle Signing (IVS) functions was guided by the principles of traffic engineering as they apply to the design and placement of roadway signs. Because of the dynamic and active nature of computing, communications, and display technology, IVS can fulfill the signing principles of traffic engineering in ways that have been impossible with conventional signage. Current signing technology represents a series of compromises of these principles, especially the data and equations contributing to the calculation of required sight distance. A number of conditions relevant to sight distance are quite variable, e.g.: vehicle speed, visibility, weather, and driver reaction time. However, conventional signing requires that there are fixed values of each variable for the determination of (e.g.) legibility distance. IVS, on the other hand, will be able to tailor the timing of sign presentation to the dynamically diverse variable values of all of these conditions. A clear, in-vehicle sign display, adaptive to ambient and driver conditions, will in fact obviate the entire issue of sign legibility. These capabilities, together with information filtering functions, will truly enhance the presentation of sign information to drivers. The development of IVS is a critical step in the development of an integrated In-Vehicle Information System (IVIS).
2015-01-01
solution approach that combines heuristic search and integer programming. Boudia et al. (2007) solved an SDVRP instance using a memetic algorithm with...Boudia, M., Prins, C., Reghioui, M., 2007. An effective memetic algorithm with population management for the split delivery vehicle routing problem
NREL/Industry Range-Extended Electric Vehicle for Package Delivery
Energy Technology Data Exchange (ETDEWEB)
Farrell, John T [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kelly, Kenneth J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Duran, Adam W [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Lammert, Michael P [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Miller, Eric S [National Renewable Energy Laboratory (NREL), Golden, CO (United States)
2018-01-15
Range-extended electric vehicle (EV) technology can be a viable option for reducing fuel consumption from medium-duty (MD) and heavy-duty (HD) engines by approximately 50 percent or more. Such engines have wide variations in use and duty cycles, however, and identifying the vocations/duty cycles most suitable for range-extended applications is vital for maximizing the potential benefits. This presentation provides information about NREL's research on range-extended EV technologies, with a focus on NREL's real-world data collection and analysis approach to identifying the vocations/duty cycles best suited for range-extender applications and to help guide related powertrain optimization and design requirements. The presentation also details NREL's drive cycle development process as it pertains to package delivery applications.
Exosomes as Drug Delivery Vehicles for Parkinson’s Disease Therapy
Haney, Matthew J.; Klyachko, Natalia L.; Zhao, Yuling; Gupta, Richa; Plotnikova, Evgeniya G.; He, Zhijian; Patel, Tejash; Piroyan, Aleksandr; Sokolsky, Marina; Kabanov, Alexander V.; Batrakova, Elena V.
2015-01-01
Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson’s disease (PD). Catalase was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze-thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100 - 200 nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders. PMID:25836593
2012-05-16
This Communications Data Delivery System Analysis Task 2 report describes and analyzes options for Vehicle to Vehicle (V2V) and Vehicle to Infrastructure (V2I) communications data delivery systems using various communication media (Dedicated Short Ra...
In-vehicle signing functions and systems concepts
Energy Technology Data Exchange (ETDEWEB)
Tufano, D.R.; Spelt, P.F.; Knee, H.E.
1996-03-01
This paper describes functional requirements and system concepts for an In-Vehicle Signing (IVS) system, which will bring information from roadway signs, signals, and pavement markings into the vehicle for presentation to the driver. Information filter functions will assure that the only messages displayed are those which are important to the driver and which apply. Display functions will optimize the presentation of the message to ambient conditions, driver preferences, the number of simultaneous messages, and the urgency of the message. Timing functions will display a sign as soon as it is needed, for the entire time that it applies, and only while it applies. IVS is one of the core components of an integrated In-Vehicle Information System, which will manage and fuse all driving-related information. Two different IVS system concepts have been investigated: one based on a map database, the other on beacon technology. This work is being conducted by the Oak Ridge National Laboratory for the US Federal Highway Administration as part of the Intelligent Transportation System Program.
Hybrid Electric Vehicle Publications | Transportation Research | NREL
Hybrid Electric Vehicle Publications Hybrid Electric Vehicle Publications The following technical papers, conference papers, and fact sheets provide information about NREL's hybrid electric fleet vehicle Class 8 Hybrid Electric Delivery Trucks. Mike Lammert. (2011) FedEx Delivery Trucks In-Use and Vehicle
Effects of Fuel Type and Fuel Delivery System on Pollutant Emissions of Pride and Samand Vehicles
Directory of Open Access Journals (Sweden)
Akbar Sarhadi
2017-04-01
Full Text Available This research was aimed to study the effect of the type of fuel delivery system (petrol, dedicated or bifuel, the type of consumed fuel (petrol or gas, the portion of consumed fuel and also the duration of dual-fuelling in producing carbon monoxide, carbon dioxide and unburned hydrocarbons from Pride and Samand. According to research objectives, data gathering from 2000 vehicles has been done by visiting Hafiz Vehicle Inspection Center every day for 2 months. The results of this survey indicated that although there is no significant difference between various fuel delivery systems in terms of producing the carbon monoxide, carbon dioxide and unburned hydrocarbons by Samand, considering the emission amount of carbon dioxide, the engine performance of Pride in bifuel and dedicated state in GTXI and 132 types is more unsatisfactory than that of petrol state by 0.3 and 0.4%, respectively. On the other hand, consuming natural gas increases the amount of carbon monoxide emission in dual- fuel Pride by 0.18% and decreases that in dual-fuel Samand by 1.2%, which signifies the better design of Samand in terms of fuel pumps, used kit type and other engine parts to use this alternative fuel compared to Pride. Since the portion of consumed fuel and also duration of dual-fuelling does not have a significant effect on the amount of output pollutants from the studied vehicles, it can be claimed that the output substances from the vehicle exhaust are more related to the vehicle’s condition than the fuel type.
Shah, Dhiral Ashwin
functional proteins can be delivered intracellularly in vitro using nanoparticles and used to target key signaling proteins and regulate cell signaling pathways. The same concept of naturally occurring protein-protein interactions can also be implemented to selectively bring intracellular protein targets in close proximity to proteasomal degradation machinery in cells and effect their depletion from the cellular compartments. This approach will be able to not only target entire pool of proteins to ubiquitination-mediated degradation, but also to specific sub-pools of posttranslationally modified proteins in the cell, provided peptides having distinct binding affinities are identified for posttranslational modifications. This system can then be tested for intracellular protein delivery using nanoparticle carriers to identify roles of different posttranslational modifications on the protein's activity. In future work, we propose to develop a cellular detection system, based on GFP complementation, which can be used to evaluate the efficiency of different protein delivery carriers to internalize proteins into the cell cytosol. We envision the application of nanoscale materials as intracellular protein delivery vehicles to target diverse cell signaling pathways at the posttranslational level, and subsequent metabolic manipulation, which may have interesting therapeutic properties and can potentially target stem cell fate.
Nature engineered diatom biosilica as drug delivery systems.
Uthappa, U T; Brahmkhatri, Varsha; Sriram, G; Jung, Ho-Young; Yu, Jingxian; Kurkuri, Nikita; Aminabhavi, Tejraj M; Altalhi, Tariq; Neelgund, Gururaj M; Kurkuri, Mahaveer D
2018-05-14
Diatoms, unicellular photosynthetic algae covered with siliceous cell wall, are also called frustule. These are the most potential naturally available materials for the development of cost-effective drug delivery systems because of their excellent biocompatibility, high surface area, low cost and ease of surface modification. Mesoporous silica materials such as MCM-41 and SBA-15 have been extensively used in drug delivery area. Their synthesis is challenging, time consuming, requires toxic chemicals and are energy intensive, making the entire process expensive and non-viable. Therefore, it is necessary to explore alternative materials. Surprisingly, nature has provided some exciting materials called diatoms; biosilica is one such a material that can be potentially used as a drug delivery vehicle. The present review focuses on different types of diatom species used in drug delivery with respect to their structural properties, morphology, purification process and surface functionalization. In this review, recent advances along with their limitations as well as the future scope to develop them as potential drug delivery vehicles are discussed. Copyright © 2018. Published by Elsevier B.V.
Lipophilic Polycation Vehicles Display High Plasmid DNA Delivery to Multiple Cell Types.
Wu, Yaoying; Smith, Adam E; Reineke, Theresa M
2017-08-16
A class of cationic poly(alkylamidoamine)s (PAAAs) containing lipophilic methylene linkers were designed and examined as in vitro plasmid DNA (pDNA) delivery agents. The PAAAs were synthesized via step-growth polymerization between a diamine monomer and each of four different diacid chloride monomers with varying methylene linker lengths, including glutaryl chloride, adipoyl chloride, pimeloyl chloride, and suberoyl chloride, which served to systematically increase the lipophilicity of the polymers. The synthesized polymers successfully complexed with pDNA in reduced serum medium at N/P ratios of 5 and greater, resulting in polyplexes with hydrodynamic diameters of approximately 1 μm. These polyplexes were tested for in vitro transgene expression and cytotoxicity using HDFa (human dermal fibroblast), HeLa (human cervical carcinoma), HMEC (human mammary epithelial), and HUVEC (human umbilical vein endothelial) cells. Interestingly, select PAAA polyplex formulations were found to be more effective than Lipofectamine 2000 at promoting transgene expression (GFP) while maintaining comparable or higher cell viability. Transgene expression was highest in HeLa cells (∼90% for most formulations) and lowest in HDFa cells (up to ∼20%) as measured by GFP fluorescence. In addition, the cytotoxicity of PAAA polyplex formulations was significantly increased as the molecular weight, N/P ratio, and methylene linker length were increased. The PAAA vehicles developed herein provide a new delivery vehicle design strategy of displaying attributes of both polycations and lipids, which show promise as a tunable scaffold for refining the structure-activity-toxicity profiles for future genome editing studies.
Directory of Open Access Journals (Sweden)
Xiaobing Gan
2012-01-01
Full Text Available This paper considers two additional factors of the widely researched vehicle routing problem with time windows (VRPTW. The two factors, which are very common characteristics in realworld, are uncertain number of vehicles and simultaneous delivery and pick-up service. Using minimization of the total transport costs as the objective of the extension VRPTW, a mathematic model is constructed. To solve the problem, an efficient multiswarm cooperative particle swarm optimization (MCPSO algorithm is applied. And a new encoding method is proposed for the extension VRPTW. Finally, comparing with genetic algorithm (GA and particle swarm optimization (PSO algorithm, the MCPSO algorithm performs best for solving this problem.
Calcium phosphate ceramics in drug delivery
Bose, Susmita; Tarafder, Solaiman; Edgington, Joe; Bandyopadhyay, Amit
2011-04-01
Calcium phosphate (CaP) particulates, cements and scaffolds have attracted significant interest as drug delivery vehicles. CaP systems, including both hydroxyapaptite and tricalcium phosphates, possess variable stoichiometry, functionality and dissolution properties which make them suitable for cellular delivery. Their chemical similarity to bone and thus biocompatibility, as well as variable surface charge density contribute to their controlled release properties. Among specific research areas, nanoparticle size, morphology, surface area due to porosity, and chemistry controlled release kinetics are the most active. This article discusses CaP systems in their particulate, cements, and scaffold forms for drug, protein, and growth factor delivery toward orthopedic and dental applications.
Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme
Energy Technology Data Exchange (ETDEWEB)
Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F.; Forte, Trudy M.
2006-06-14
This paper discribes a synthetic low density lipoprotein(LDL) made by complexing a 29 amino acid that consists of a lipid bindingdomain and the LDL receptor binding domain with a lipid microemulsion.The nano-LDL particles were intermdiate in size between LDL and HDL andbound to LDL receptors on GBM brain tumor cells. Synthetic nano-LDLuptake by GBM cells was LDL receptor specific and dependent on cellreceptor number. It is suggested that these synthetic particles can serveas a delivery vehicle for hydophobic anti-tumor drugs by targeting theLDL receptor.
Hakeem, Abdul; Duan, Ruixue; Zahid, Fouzia; Dong, Chao; Wang, Boya; Hong, Fan; Ou, Xiaowen; Jia, Yongmei; Lou, Xiaoding; Xia, Fan
2014-11-11
Herein, we report natural chitosan end-capped MCM-41 type MSNPs as novel, dual stimuli, responsive nano-vehicles for controlled anticancer drug delivery. The chitosan nanovalves tightly close the pores of the MSNPs to control premature cargo release under physiological conditions but respond to lysozyme and acidic media to release the trapped cargo.
In-vehicle information system functions
Energy Technology Data Exchange (ETDEWEB)
Tufano, D.R.; Spelt, P.F.; Knee, H.E.
1997-04-01
This paper describes the functional requirement for an In-Vehicle Information System (IVIS), which will manage and display all driving-related information from many sources. There are numerous information systems currently being fielded or developed (e.g., routing and navigation, collision avoidance). However, without a logical integration of all of the possible on-board information, there is a potential for overwhelming the driver. The system described in this paper will filter and prioritize information across all sources, and present it to the driver in a timely manner, within a unified interface. To do this, IVIS will perform three general functions: (1) interact with other, on-board information subsystems and the vehicle; (2) manage the information by filtering, prioritizing, and integrating it; and (3) interact with the driver, both in terms of displaying information to the driver and allowing the driver to input requests, goals and preferences. The functional requirements described in this paper have either been derived from these three high-level functions or are directly mandated by the overriding requirements for modularity and flexibility. IVIS will have to be able to accommodate different types of information subsystems, of varying level of sophistication. The system will also have to meet the diverse needs of different types of drivers (private, commercial, transit), who may have very different levels of expertise in using information systems.
EPA and the United Parcel Service (UPS) have developed a hydraulic hybrid delivery vehicle to explore and demonstrate the environmental benefits of the hydraulic hybrid for urban pick-up and delivery fleets.
Silica nanoparticles as vehicles for therapy delivery in neurological injury
Schenk, Desiree
Acrolein, a very reactive aldehyde, is a culprit in the biochemical cascade after primary, mechanical spinal cord injury (SCI), which leads to the destruction of tissue initially unharmed, referred to as "secondary injury". Additionally, in models of multiple sclerosis (MS) and some clinical research, acrolein levels are significantly increased. This aldehyde overwhelms the natural anti-oxidant system, reacts freely with proteins, and releases during lipid peroxidation (LPO), effectively regenerating its self. Due to its ability to make more copies of itself in the presence of tissue via lipid peroxidation, researchers believe that acrolein plays a role in the increased destruction of the central nervous system in both SCI and MS. Hydralazine, an FDA-approved hypertension drug, has been shown to scavenge acrolein, but its side effects and short half life at the appropriate dose for acrolein scavenging must be improved for beneficial clinical translation. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Nanoparticles made from silica provide distinct advantages. They form porous networks that can carry therapeutic molecules throughout the body. Therefore, a nanomedical approach has been designed using silica nanoparticles as a porous delivery vehicle hydralazine. The silica nanoparticles are formed in a one-step method that incorporates poly(ethylene) glycol (PEG), a stealth molecule, directly onto the nanoparticles. As an additional avenue for study, a natural product in green tea, epigallocatechin gallate (EGCG), has been explored for its ability to react with acrolein, disabling its reactive capabilities. Upon demonstration of attenuating acrolein, EGCG's delivery may also be improved using the nanomedical approach. The
International Nuclear Information System (INIS)
Zhao, Yang; Noori, Mehdi; Tatari, Omer
2016-01-01
Highlights: • Potential net present revenues of electric truck based V2G regulation services are investigated. • GHG emission mitigation of V2G regulation services provided by electric trucks are quantified. • The total cost of ownership and the life-cycle GHG emissions of electric trucks are also analyzed. • V2G regulation services for electric trucks could yield considerable revenues and GHG emission savings. - Abstract: Concerns regarding the fuel costs and climate change impacts associated with petroleum combustion are among the main driving factors for the adoption of electric vehicles. Future commercial delivery truck fleets may include Battery Electric Vehicles (BEVs) and Extended Range Electric Vehicles (EREVs); in addition to savings on fuel and maintenance costs, the introduction of these grid accessible electric vehicles will also provide fleet owners with possible Vehicle to Grid (V2G) opportunities. This study investigates the potential net present revenues and greenhouse gas (GHG) emission mitigation of V2G regulation services provided by electric trucks in a typical fleet. The total cost of ownership and the life-cycle GHG emissions of electric trucks are also analyzed and compared to those of traditional diesel trucks. To account for uncertainties, possible ranges for key parameters are considered instead of only considering fixed single data values for each parameter. The results of this research indicate that providing V2G regulation services for electric trucks could yield considerable additional revenues ($20,000–50,000) and significant GHG emission savings (approximately 300 ton CO_2) compared to conventional diesel trucks.
Teeples, Ronald; Glyer, David
1987-05-01
Both policy and technical analysis of water delivery systems have been based on cost functions that are inconsistent with or are incomplete representations of the neoclassical production functions of economics. We present a full-featured production function model of water delivery which can be estimated from a multiproduct, dual cost function. The model features implicit prices for own-water inputs and is implemented as a jointly estimated system of input share equations and a translog cost function. Likelihood ratio tests are performed showing that a minimally constrained, full-featured production function is a necessary specification of the water delivery operations in our sample. This, plus the model's highly efficient and economically correct parameter estimates, confirms the usefulness of a production function approach to modeling the economic activities of water delivery systems.
Functionalization of protein-based nanocages for drug delivery applications.
Schoonen, Lise; van Hest, Jan C M
2014-07-07
Traditional drug delivery strategies involve drugs which are not targeted towards the desired tissue. This can lead to undesired side effects, as normal cells are affected by the drugs as well. Therefore, new systems are now being developed which combine targeting functionalities with encapsulation of drug cargo. Protein nanocages are highly promising drug delivery platforms due to their perfectly defined structures, biocompatibility, biodegradability and low toxicity. A variety of protein nanocages have been modified and functionalized for these types of applications. In this review, we aim to give an overview of different types of modifications of protein-based nanocontainers for drug delivery applications.
The Effect of Mode of Delivery on Postpartum Sexual Functioning in Primiparous Women
Directory of Open Access Journals (Sweden)
Fatemeh Dabiri
2014-07-01
Full Text Available Objective: To evaluate the effect of mode of delivery on postpartum sexual functioning in primiparous women. Methods: In this cross-sectional descriptive study, 150 primiparous women in postpartum period, who attended the family planning or vaccination clinics, were enrolled for the study. Eighty-one had vaginal delivery with episiotomy and 69 had experienced cesarean section. Sexual function was evaluated by the Female Sexual Function Index within 3 and 6 months postpartum. Results: About 29% in vaginal delivery group and 37% in cesarean delivery group had resumed their sexual intercourses four weeks after delivery (p=0.280.There were no significant differences between mode of delivery and sexual functioning, including desire, arousal, lubrication, orgasm, satisfaction and pain. Conclusion: The present study showed that postpartum sexual functioning was not associated with the type of delivery.
Zhang, Ning; Zhao, Fenfang; Zou, Qianli; Li, Yongxin; Ma, Guanghui; Yan, Xuehai
2016-11-01
Tumor-responsive nanocarriers are highly valuable and demanded for smart drug delivery particularly in the field of photodynamic therapy (PDT), where a quick release of photosensitizers in tumors is preferred. Herein, it is demonstrated that protein-based nanospheres, prepared by the electrostatic assembly of proteins and polypeptides with intermolecular disulfide cross-linking and surface polyethylene glycol coupling, can be used as versatile tumor-responsive drug delivery vehicles for effective PDT. These nanospheres are capable of encapsulation of various photosensitizers including Chlorin e6 (Ce6), protoporphyrin IX, and verteporfin. The Chlorin e6-encapsulated nanospheres (Ce6-Ns) are responsive to changes in pH, redox potential, and proteinase concentration, resulting in multitriggered rapid release of Ce6 in an environment mimicking tumor tissues. In vivo fluorescence imaging results indicate that Ce6-Ns selectively accumulate near tumors and the quick release of Ce6 from Ce6-Ns can be triggered by tumors. In tumors the fluorescence of released Ce6 from Ce6-Ns is observed at 0.5 h postinjection, while in normal tissues the fluorescence appeared at 12 h postinjection. Tumor ablation is demonstrated by in vivo PDT using Ce6-Ns and the biocompatibility of Ce6-Ns is evident from the histopathology imaging, confirming the enhanced in vivo PDT efficacy and the biocompatibility of the assembled drug delivery vehicles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Bhirde, Ashwin A; Patel, Sachin; Sousa, Alioscka A; Patel, Vyomesh; Molinolo, Alfredo A; Ji, Youngmi; Leapman, Richard D; Gutkind, J Silvio; Rusling, James F
2010-12-01
To study the distribution and clearance of polyethylene glycol (PEG)-ylated single-walled carbon nanotube (SWCNTs) as drug delivery vehicles for the anticancer drug cisplatin in mice. PEG layers were attached to SWCNTs and dispersed in aqueous media and characterized using dynamic light scattering, scanning transmission electron microscopy and Raman spectroscopy. Cytotoxicity was assessed in vitro using Annexin-V assay, and the distribution and clearance pathways in mice were studied by histological staining and Raman spectroscopy. Efficacy of PEG-SWCNT-cisplatin for tumor growth inhibition was studied in mice. PEG-SWCNTs were efficiently dispersed in aqueous media compared with controls, and did not induce apoptosis in vitro. Hematoxylin and eosin staining, and Raman bands for SWCNTs in tissues from several vital organs from mice injected intravenously with nanotube bioconjugates revealed that control SWCNTs were lodged in lung tissue as large aggregates compared with the PEG-SWCNTs, which showed little or no accumulation. Characteristic SWCNT Raman bands in feces revealed the presence of bilary or renal excretion routes. Attachment of cisplatin on bioconjugates was visualized with Z-contrast scanning transmission electron microscopy. PEG-SWCNT-cisplatin with the attached targeting ligand EGF successfully inhibited growth of head and neck tumor xenografts in mice. PEG-SWCNTs, as opposed to control SWCNTs, form more highly dispersed delivery vehicles that, when loaded with both cisplatin and EGF, inhibit growth of squamous cell tumors.
Cooperative Control for Multiple Autonomous Vehicles Using Descriptor Functions
Directory of Open Access Journals (Sweden)
Marta Niccolini
2014-01-01
Full Text Available The paper presents a novel methodology for the control management of a swarm of autonomous vehicles. The vehicles, or agents, may have different skills, and be employed for different missions. The methodology is based on the definition of descriptor functions that model the capabilities of the single agent and each task or mission. The swarm motion is controlled by minimizing a suitable norm of the error between agents’ descriptor functions and other descriptor functions which models the entire mission. The validity of the proposed technique is tested via numerical simulation, using different task assignment scenarios.
Improved Ant Colony Optimization for Seafood Product Delivery Routing Problem
Directory of Open Access Journals (Sweden)
Baozhen Yao
2014-02-01
Full Text Available This paper deals with a real-life vehicle delivery routing problem, which is a seafood product delivery routing problem. Considering the features of the seafood product delivery routing problem, this paper formulated this problem as a multi-depot open vehicle routing problem. Since the multi-depot open vehicle routing problem is a very complex problem, a method is used to reduce the complexity of the problem by changing the multi-depot open vehicle routing problem into an open vehicle routing problem with a dummy central depot in this paper. Then, ant colony optimization is used to solve the problem. To improve the performance of the algorithm, crossover operation and some adaptive strategies are used. Finally, the computational results for the benchmark problems of the multi-depot vehicle routing problem indicate that the proposed ant colony optimization is an effective method to solve the multi-depot vehicle routing problem. Furthermore, the computation results of the seafood product delivery problem from Dalian, China also suggest that the proposed ant colony optimization is feasible to solve the seafood product delivery routing problem.
Hydraulic Hybrid Parcel Delivery Truck Deployment, Testing & Demonstration
Energy Technology Data Exchange (ETDEWEB)
Gallo, Jean-Baptiste [Calstart Incorporated, Pasadena, CA (United States)
2014-03-07
Although hydraulic hybrid systems have shown promise over the last few years, commercial deployment of these systems has primarily been limited to Class 8 refuse trucks. In 2005, the Hybrid Truck Users Forum initiated the Parcel Delivery Working Group including the largest parcel delivery fleets in North America. The goal of the working group was to evaluate and accelerate commercialization of hydraulic hybrid technology for parcel delivery vehicles. FedEx Ground, Purolator and United Parcel Service (UPS) took delivery of the world’s first commercially available hydraulic hybrid parcel delivery trucks in early 2012. The vehicle chassis includes a Parker Hannifin hydraulic hybrid drive system, integrated and assembled by Freightliner Custom Chassis Corp., with a body installed by Morgan Olson. With funding from the U.S. Department of Energy, CALSTART and its project partners assessed the performance, reliability, maintainability and fleet acceptance of three pre-production Class 6 hydraulic hybrid parcel delivery vehicles using information and data from in-use data collection and on-road testing. This document reports on the deployment of these vehicles operated by FedEx Ground, Purolator and UPS. The results presented provide a comprehensive overview of the performance of commercial hydraulic hybrid vehicles in parcel delivery applications. This project also informs fleets and manufacturers on the overall performance of hydraulic hybrid vehicles, provides insights on how the technology can be both improved and more effectively used. The key findings and recommendations of this project fall into four major categories: -Performance, -Fleet deployment, -Maintenance, -Business case. Hydraulic hybrid technology is relatively new to the market, as commercial vehicles have been introduced only in the past few years in refuse and parcel delivery applications. Successful demonstration could pave the way for additional purchases of hydraulic hybrid vehicles throughout the
Influence of microemulsions on cutaneous drug delivery
DEFF Research Database (Denmark)
Kreilgaard, Mads
2002-01-01
In attempt to increase cutaneous drug delivery, microemulsion vehicles have been more and more frequently employed over recent years. Microemulsion formulations have been shown to be superior for both transdermal and dermal delivery of particularly lipophilic compounds, but also hydrophilic...... compounds appear to benefit from application in microemulsions compared to conventional vehicles, like hydrogels, emulsions and liposomes. The favourable drug delivery properties of microemulsions appear to mainly be attributed to the excellent solubility properties. However, the vehicles may also act...... as penetration enhancers depending on the oil/surfactant constituents, which involves a risk of inducing local irritancy. The correlation between microemulsion structure/composition and drug delivery potential is not yet fully elucidated. However, a few studies have indicated that the internal structure...
Albumin–Polymer–Drug Conjugates: Long Circulating, High Payload Drug Delivery Vehicles
DEFF Research Database (Denmark)
Smith, Anton Allen Abbotsford; Zuwala, Kaja; Pilgram, Oliver
2016-01-01
Albumin is an exquisite tool of nature used in biomedicine to achieve long blood residence time for drugs, but the payload it can carry is typically limited to one molecule per protein. In contrast, synthetic macromolecular prodrugs contain multiple copies of drugs per polymer chain but offer only...... a marginal increase in the circulation lifetime of the drugs. We combine the benefits of the two platforms and at the same time overcome their respective limitations. Specifically, we develop the synthesis of albumin–polymer–drug conjugates to obtain long circulating, high payload drug delivery vehicles....... In vivo data validate that albumin endows the conjugate with a blood residence time similar to that of the protein and well exceeding that of the polymer. Therapeutic activity of the conjugates is validated using prodrugs of panobinostat, an HIV latency reversal agent, in which case the conjugates matched...
Directory of Open Access Journals (Sweden)
Dasa Cizkova
2018-03-01
Full Text Available It was recently shown that the conditioned medium (CM of mesenchymal stem cells can enhance viability of neural and glial cell populations. In the present study, we have investigated a cell-free approach via CM from rat bone marrow stromal cells (MScCM applied intrathecally (IT for spinal cord injury (SCI recovery in adult rats. Functional in vitro test on dorsal root ganglion (DRG primary cultures confirmed biological properties of collected MScCM for production of neurosphere-like structures and axon outgrowth. Afterwards, rats underwent SCI and were treated with IT delivery of MScCM or vehicle at postsurgical Days 1, 5, 9, and 13, and left to survive 10 weeks. Rats that received MScCM showed significantly higher motor function recovery, increase in spared spinal cord tissue, enhanced GAP-43 expression and attenuated inflammation in comparison with vehicle-treated rats. Spared tissue around the lesion site was infiltrated with GAP-43-labeled axons at four weeks that gradually decreased at 10 weeks. Finally, a cytokine array performed on spinal cord extracts after MScCM treatment revealed decreased levels of IL-2, IL-6 and TNFα when compared to vehicle group. In conclusion, our results suggest that molecular cocktail found in MScCM is favorable for final neuroregeneration after SCI.
Cascade Storage and Delivery System for a Multi Mission Space Exploration Vehicle (MMSEV)
Yagoda, Evan; Swickrath, Michael; Stambaugh, Imelda
2012-01-01
NASA is developing a Multi Mission Space Exploration Vehicle (MMSEV) for missions beyond Low Earth Orbit (LEO). The MMSEV is a pressurized vehicle used to extend the human exploration envelope for Lunar, Near Earth Object (NEO), and Deep Space missions. The Johnson Space Center is developing the Environmental Control and Life Support System (ECLSS) for the MMSEV. The MMSEV s intended use is to support longer sortie lengths with multiple Extra Vehicular Activities (EVAs) on a higher magnitude than any previous vehicle. This paper presents an analysis of a high pressure oxygen cascade storage and delivery system that will accommodate the crew during long duration Intra Vehicular Activity (IVA) and capable of multiple high pressure oxygen fills to the Portable Life Support System (PLSS) worn by the crew during EVAs. A cascade is a high pressure gas cylinder system used for the refilling of smaller compressed gas cylinders. Each of the large cylinders are filled by a compressor, but the cascade system allows small cylinders to be filled without the need of a compressor. In addition, the cascade system is useful as a "reservoir" to accommodate low pressure needs. A regression model was developed to provide the mechanism to size the cascade systems subject to constraints such as number of crew, extravehicular activity duration and frequency, and ullage gas requirements under contingency scenarios. The sizing routine employed a numerical integration scheme to determine gas compressibility changes during depressurization and compressibility effects were captured using the Soave-Redlich-Kwong (SRK) equation of state. A multi-dimensional nonlinear optimization routine was used to find the minimum cascade tank system mass that meets the mission requirements. The sizing algorithms developed in this analysis provide a powerful framework to assess cascade filling, compressor, and hybrid systems to design long duration vehicle ECLSS architecture. 1
HDL as a drug and nucleic acid delivery vehicle
Directory of Open Access Journals (Sweden)
Andras G Lacko
2015-10-01
Full Text Available This review is intended to evaluate the research findings and potential clinical applications of drug transport systems, developed based on the concepts of the structure/function and physiological role(s of high density lipoprotein=type nanoparticles. These macromolecules provide targeted transport of cholesteryl esters (a highly lipophilic payload in their natural/physiological environment. The property of accommodating highly water insoluble constituents in their core region enables HDL type nanoparticles to effectively transport hydrophobic drugs upon intravenous administration. Even though the application of reconstituted HDL in the treatment of a number of diseases is reviewed, the primary focus is on the application of HDL type drug delivery agents in cancer chemotherapy. The use of both native and synthetic HDL as drug delivery agents are compared to evaluate their respective potentials for commercial and clinical development. The current status and future perspectives for HDL type nanoparticles are discussed, including current obstacles and future applications in therapeutics.
Development of a lightweight electric urban delivery truck
Energy Technology Data Exchange (ETDEWEB)
Gillespie, G.; Martin, R.; Vader, S. [Unicell Ltd., Toronto, ON (Canada)
2007-07-15
A study was conducted to develop a lightweight urban parcel delivery vehicle that features a composite material, monocoque low-floor body and a zero-emission electric drive system. The long-term goal of project was to produce a vehicle with an energy efficiency that was nearly 90 per cent better than a conventional delivery vehicle. The objectives of the development phase were to complete the structural design of the composite, monocoque low-floor body. Electric drive options were explored to confirm the feasibility in terms of vehicle range, zero emissions and energy efficiency. This involved characterization of the vehicle duty cycle, development of a computer model of the electric powertrain, and simulations to confirm the vehicle's power and energy requirements. The design of the prototype was validated through testing in accordance with recognized vehicle performance tests and an in-service trial by Purolator Courier Ltd., a major Canadian courier service. Testing of the QuickSider delivery truck included vehicle dynamics, energy consumption, safety compliance, and in-service evaluation. No unacceptable stresses, deflections or resonances were identified in the structure. The vehicle's performance was found to be consistent with design expectations. Dynamometer tests have indicated that the ZEV range of the prototype is greater than the targeted 120 km. The overall energy efficiency of the vehicle was 50 per cent, as compared 11 per cent for a conventional diesel delivery truck. It was concluded that an overall energy efficiency of 75 per cent is achievable in production vehicles if improvements are made to the battery system, drive train, regenerative braking and auxiliary systems. 29 figs., 2 appendices.
Wen, Dongqi; Zhai, Wenjuan; Xiang, Sheng; Hu, Zhice; Wei, Tongchuan; Noll, Kenneth E
2017-11-01
Determination of the effect of vehicle emissions on air quality near roadways is important because vehicles are a major source of air pollution. A near-roadway monitoring program was undertaken in Chicago between August 4 and October 30, 2014, to measure ultrafine particles, carbon dioxide, carbon monoxide, traffic volume and speed, and wind direction and speed. The objective of this study was to develop a method to relate short-term changes in traffic mode of operation to air quality near roadways using data averaged over 5-min intervals to provide a better understanding of the processes controlling air pollution concentrations near roadways. Three different types of data analysis are provided to demonstrate the type of results that can be obtained from a near-roadway sampling program based on 5-min measurements: (1) development of vehicle emission factors (EFs) for ultrafine particles as a function of vehicle mode of operation, (2) comparison of measured and modeled CO 2 concentrations, and (3) application of dispersion models to determine concentrations near roadways. EFs for ultrafine particles are developed that are a function of traffic volume and mode of operation (free flow and congestion) for light-duty vehicles (LDVs) under real-world conditions. Two air quality models-CALINE4 (California Line Source Dispersion Model, version 4) and AERMOD (American Meteorological Society/U.S. Environmental Protection Agency Regulatory Model)-are used to predict the ultrafine particulate concentrations near roadways for comparison with measured concentrations. When using CALINE4 to predict air quality levels in the mixing cell, changes in surface roughness and stability class have no effect on the predicted concentrations. However, when using AERMOD to predict air quality in the mixing cell, changes in surface roughness have a significant impact on the predicted concentrations. The paper provides emission factors (EFs) that are a function of traffic volume and mode of
Kolesnikova, Tatiana A; Skirtach, Andre G; Möhwald, Helmuth
2013-01-01
Red blood cells (RBCs) and lipid-based carriers on the one hand and polymeric capsules on the other hand represent two of the most widely used carriers in drug delivery. Each class of these carriers has its own set of properties, specificity and advantages. Thorough comparative studies of such systems are reported here for the first time. In this review, RBCs are described in comparison with synthetic polymeric drug delivery vehicles using polyelectrolyte multilayer capsules as an example. Lipid-based composition of the shell in the former case is particularly attractive due to their inherent biocompatibility and flexibility of the carriers. On the other hand, synthetic approaches to fabrication of polyelectrolyte multilayer capsules permit manipulation of the permeability of their shell as well as tuning their composition, mechanical properties, release methods and targeting. In conclusion, properties of RBCs and polyelectrolyte multilayer capsules are reported here highlighting similarities and differences in their preparation and applications. In addition, their advantages and disadvantages are discussed.
Development of a Refined Space Vehicle Rollout Forcing Function
James, George; Tucker, Jon-Michael; Valle, Gerard; Grady, Robert; Schliesing, John; Fahling, James; Emory, Benjamin; Armand, Sasan
2016-01-01
For several decades, American manned spaceflight vehicles and the associated launch platforms have been transported from final assembly to the launch pad via a pre-launch phase called rollout. The rollout environment is rich with forced harmonics and higher order effects can be used for extracting structural dynamics information. To enable this utilization, processing tools are needed to move from measured and analytical data to dynamic metrics such as transfer functions, mode shapes, modal frequencies, and damping. This paper covers the range of systems and tests that are available to estimate rollout forcing functions for the Space Launch System (SLS). The specific information covered in this paper includes: the different definitions of rollout forcing functions; the operational and developmental data sets that are available; the suite of analytical processes that are currently in-place or in-development; and the plans and future work underway to solve two immediate problems related to rollout forcing functions. Problem 1 involves estimating enforced accelerations to drive finite element models for developing design requirements for the SLS class of launch vehicles. Problem 2 involves processing rollout measured data in near real time to understand structural dynamics properties of a specific vehicle and the class to which it belongs.
Multifunctional DNA-gold nanoparticles for targeted doxorubicin delivery.
Alexander, Colleen M; Hamner, Kristen L; Maye, Mathew M; Dabrowiak, James C
2014-07-16
In this report we describe the synthesis, characterization, and cytotoxic properties of DNA-capped gold nanoparticles having attached folic acid (FA), a thermoresponsive polymer (p), and/or poly(ethylene glycol) (PEG) oligomers that could be used to deliver the anticancer drug doxorubicin (DOX) in chemotherapy. The FA-DNA oligomer used in the construction of the delivery vehicle was synthesized through the reaction of the isolated folic acid N-hydroxysuccinimide ester with the amino-DNA and the conjugated DNA product was purified using high performance liquid chromatography (HPLC). This approach ultimately allowed control of the amount of FA attached to the surface of the delivery vehicle. Cytotoxicity studies using SK-N-SH neuroblastoma cells with drug loaded delivery vehicles were carried out using a variety of exposure times (1-48 h) and recovery times (1-72 h), and in order to access the effects of varying amounts of attached FA, in culture media deficient in FA. DOX loaded delivery vehicles having 50% of the DNA strands with attached FA were more cytotoxic than when all of the strands contained FA. Since FA stimulates cell growth, the reduced cytotoxicity of vehicles fully covered with FA suggests that the stimulatory effects of FA can more than compensate for the cytotoxic effects of the drug on the cell population. While attachment of hexa-ethylene glycol PEG(18) to the surface of the delivery vehicle had no effect on cytotoxicity, 100% FA plus the thermoresponsive polymer resulted in IC50 = 0.48 ± 0.01 for an exposure time of 24 h and a recovery time of 1 h, which is an order of magnitude more cytotoxic than free DOX. Confocal microscopic studies using fluorescence detection showed that SK-N-SH neuroblastoma cells exposed to DOX-loaded vehicles have drug accumulation inside the cell and, in the case of vehicles with attached FA and thermoresponsive polymer, the drug appears more concentrated. Since the biological target of DOX is DNA, the latter
Applications of nanodiamonds in drug delivery and catalysis.
Moosa, Basem; Fhayli, Karim; Li, Song; Julfakyan, Khatchatur; Ezzeddine, Alaa; Khashab, Niveen M
2014-01-01
The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles and imaging probes. Their ease of functionalization also led to the generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a controlled manner. The ample surface area of NDs allowed for a higher loading of not only small molecules but also macromolecules like genes and proteins. Recently, the unique surface of NDs has attracted more attention as catalyst support in a huge range of organic modification and C-C bond formation reactions. Herein, recent advances in the utilization of nanodiamonds as a drug delivery vehicle and catalytical support are highlighted and summarized to illustrate the potential and versatility of this cheap and commercially available nanomaterial.
Fu, Zhuo; Wang, Jiangtao
2018-01-01
In order to promote the development of low-carbon logistics and economize logistics distribution costs, the vehicle routing problem with split deliveries by backpack is studied. With the help of the model of classical capacitated vehicle routing problem, in this study, a form of discrete split deliveries was designed in which the customer demand can be split only by backpack. A double-objective mathematical model and the corresponding adaptive tabu search (TS) algorithm were constructed for solving this problem. By embedding the adaptive penalty mechanism, and adopting the random neighborhood selection strategy and reinitialization principle, the global optimization ability of the new algorithm was enhanced. Comparisons with the results in the literature show the effectiveness of the proposed algorithm. The proposed method can save the costs of low-carbon logistics and reduce carbon emissions, which is conducive to the sustainable development of low-carbon logistics. PMID:29747469
Xia, Yangkun; Fu, Zhuo; Tsai, Sang-Bing; Wang, Jiangtao
2018-05-10
In order to promote the development of low-carbon logistics and economize logistics distribution costs, the vehicle routing problem with split deliveries by backpack is studied. With the help of the model of classical capacitated vehicle routing problem, in this study, a form of discrete split deliveries was designed in which the customer demand can be split only by backpack. A double-objective mathematical model and the corresponding adaptive tabu search (TS) algorithm were constructed for solving this problem. By embedding the adaptive penalty mechanism, and adopting the random neighborhood selection strategy and reinitialization principle, the global optimization ability of the new algorithm was enhanced. Comparisons with the results in the literature show the effectiveness of the proposed algorithm. The proposed method can save the costs of low-carbon logistics and reduce carbon emissions, which is conducive to the sustainable development of low-carbon logistics.
Holden, Christopher A; Yuan, Quan; Yeudall, W Andrew; Lebman, Deborah A; Yang, Hu
2010-02-02
Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles. In particular, quantum dots and 5-(aminoacetamido) fluorescein-labeled polyamidoamine dendrimer G4.5, both of which were coated with amine-derivatized polyethylene glycol, were immobilized to the sodium periodate-treated surface of RAW264.7 macrophages through a transient Schiff base linkage. Further, a reducing agent, sodium cyanoborohydride, was applied to reduce Schiff bases to stable secondary amine linkages. The distribution of nanoparticles on the cell surface was confirmed by fluorescence imaging, and it was found to be dependent on the stability of the linkages coupling nanoparticles to the cell surface.
Periodic Heterogeneous Vehicle Routing Problem With Driver Scheduling
Mardiana Panggabean, Ellis; Mawengkang, Herman; Azis, Zainal; Filia Sari, Rina
2018-01-01
The paper develops a model for the optimal management of logistic delivery of a given commodity. The company has different type of vehicles with different capacity to deliver the commodity for customers. The problem is then called Periodic Heterogeneous Vehicle Routing Problem (PHVRP). The goal is to schedule the deliveries according to feasible combinations of delivery days and to determine the scheduling of fleet and driver and routing policies of the vehicles. The objective is to minimize the sum of the costs of all routes over the planning horizon. We propose a combined approach of heuristic algorithm and exact method to solve the problem.
Functionalized mesoporous silicon for targeted-drug-delivery.
Tabasi, Ozra; Falamaki, Cavus; Khalaj, Zahra
2012-10-01
The present work concerns a preliminary step in the production of anticancer drug loaded porous silicon (PSi) for targeted-drug-delivery applications. A successful procedure for the covalent attachment of folic acid, polyethylene glycol (PEG) and doxorubicin to hydrophilic mesoporous silicon layers is presented. A systematic approach has been followed to obtain the optimal composition of the N,N'-dicyclohexylcarbodiimide (DCC)/N-hydroxysuccimide (NHS) in dimethylsulfoxide (DMSO) solution for the surface activation process of the undecylenic acid (UD) grafted molecules to take place with minimal undesired byproduct formation. The effect of reactant concentration and kind of solvent (aqueous or DMSO) on the attachment of folic acid to the activated PSi layer has been investigated. The covalent attachment of the doxorubicin molecules to the PSi layer functionalized with folic acid and PEG is discussed. The drug release kinetics as a function of pH has been studied. The functionalized PSi particles show a high cytotoxicity compared to the equivalent amount of free drug. Cell toxicity tests show clearly that the incorporation of folate molecules increases substantially the toxicity of the loaded PSi particles. Accordingly this new functionalized PSi may be considered a proper candidate for targeted drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.
Mathematical Analysis of Vehicle Delivery Scale of Bike-Sharing Rental Nodes
Zhai, Y.; Liu, J.; Liu, L.
2018-04-01
Aiming at the lack of scientific and reasonable judgment of vehicles delivery scale and insufficient optimization of scheduling decision, based on features of the bike-sharing usage, this paper analyses the applicability of the discrete time and state of the Markov chain, and proves its properties to be irreducible, aperiodic and positive recurrent. Based on above analysis, the paper has reached to the conclusion that limit state (steady state) probability of the bike-sharing Markov chain only exists and is independent of the initial probability distribution. Then this paper analyses the difficulty of the transition probability matrix parameter statistics and the linear equations group solution in the traditional solving algorithm of the bike-sharing Markov chain. In order to improve the feasibility, this paper proposes a "virtual two-node vehicle scale solution" algorithm which considered the all the nodes beside the node to be solved as a virtual node, offered the transition probability matrix, steady state linear equations group and the computational methods related to the steady state scale, steady state arrival time and scheduling decision of the node to be solved. Finally, the paper evaluates the rationality and accuracy of the steady state probability of the proposed algorithm by comparing with the traditional algorithm. By solving the steady state scale of the nodes one by one, the proposed algorithm is proved to have strong feasibility because it lowers the level of computational difficulty and reduces the number of statistic, which will help the bike-sharing companies to optimize the scale and scheduling of nodes.
MATHEMATICAL ANALYSIS OF VEHICLE DELIVERY SCALE OF BIKE-SHARING RENTAL NODES
Directory of Open Access Journals (Sweden)
Y. Zhai
2018-04-01
Full Text Available Aiming at the lack of scientific and reasonable judgment of vehicles delivery scale and insufficient optimization of scheduling decision, based on features of the bike-sharing usage, this paper analyses the applicability of the discrete time and state of the Markov chain, and proves its properties to be irreducible, aperiodic and positive recurrent. Based on above analysis, the paper has reached to the conclusion that limit state (steady state probability of the bike-sharing Markov chain only exists and is independent of the initial probability distribution. Then this paper analyses the difficulty of the transition probability matrix parameter statistics and the linear equations group solution in the traditional solving algorithm of the bike-sharing Markov chain. In order to improve the feasibility, this paper proposes a "virtual two-node vehicle scale solution" algorithm which considered the all the nodes beside the node to be solved as a virtual node, offered the transition probability matrix, steady state linear equations group and the computational methods related to the steady state scale, steady state arrival time and scheduling decision of the node to be solved. Finally, the paper evaluates the rationality and accuracy of the steady state probability of the proposed algorithm by comparing with the traditional algorithm. By solving the steady state scale of the nodes one by one, the proposed algorithm is proved to have strong feasibility because it lowers the level of computational difficulty and reduces the number of statistic, which will help the bike-sharing companies to optimize the scale and scheduling of nodes.
Ex vivo cytosolic delivery of functional macromolecules to immune cells.
Directory of Open Access Journals (Sweden)
Armon Sharei
Full Text Available Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.
Applications of nanodiamonds in drug delivery and catalysis
Moosa, Basem
2014-01-01
The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles and imaging probes. Their ease of functionalization also led to the generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a controlled manner. The ample surface area of NDs allowed for a higher loading of not only small molecules but also macromolecules like genes and proteins. Recently, the unique surface of NDs has attracted more attention as catalyst support in a huge range of organic modification and C-C bond formation reactions. Herein, recent advances in the utilization of nanodiamonds as a drug delivery vehicle and catalytical support are highlighted and summarized to illustrate the potential and versatility of this cheap and commercially available nanomaterial. Copyright © 2014 American Scientific Publishers All rights reserved.
Nanoparticle functionalization for brain targeting drug delivery and diagnostic
DEFF Research Database (Denmark)
Gomes, Maria João; Mendes, Bárbara; Martins, Susana
2016-01-01
carriers to cross the BBB and achieve brain, and their functionalization strategies are described; and finally the delivery of nanoparticles to the target moiety, as diagnostics or therapeutics. Therefore, this chapter is focused on how the nanoparticle surface may be functionalized for drug delivery......Nanobiotechnology has been demonstrated to be an efficient tool for targeted therapy as well as diagnosis, with particular emphasis on brain tumor and neurodegenerative diseases. On this regard, the aim of this chapter is focused on engineered nanoparticles targeted to the brain, so that they have...... and diagnostics. Furthermore, it is also mentioned that some BBB targets were already used as transport mediators to central nervous system by functionalization on nanoparticles. It summarizes the nanoparticles potential in therapeutics and molecular targeting to BBB, and also an approach of the nanoparticle...
Safety assessment of automated vehicle functions by simulation-based fault injection
Juez, Garazi; Amparan, Estibaliz; Lattarulo, Ray; Rastelli, Joshue Perez; Ruiz, Alejandra; Espinoza, Huascar
2017-01-01
As automated driving vehicles become more sophisticated and pervasive, it is increasingly important to assure its safety even in the presence of faults. This paper presents a simulation-based fault injection approach (Sabotage) aimed at assessing the safety of automated vehicle functions. In particular, we focus on a case study to forecast fault effects during the model-based design of a lateral control function. The goal is to determine the acceptable fault detection interval for pe...
Polymer nanogels: a versatile nanoscopic drug delivery platform
Chacko, Reuben T.; Ventura, Judy; Zhuang, Jiaming; Thayumanavan, S.
2012-01-01
In this review we put the spotlight on crosslinked polymer nanogels, a promising platform that has the characteristics of an “ideal” drug delivery vehicle. Some of the key aspects of drug delivery vehicle design like stability, response to biologically relevant stimuli, passive targeting, active targeting, toxicity and ease of synthesis are discussed. We discuss several delivery systems in this light and highlight some examples of systems, which satisfy some or all of these design requirements. In particular, we point to the advantages that crosslinked polymeric systems bring to drug delivery. We review some of the synthetic methods of nanogel synthesis and conclude with the diverse applications in drug delivery where nanogels have been fruitfully employed. PMID:22342438
Tracked vehicles in hazardous environments
International Nuclear Information System (INIS)
Jones, S.; Walton, P.J.
1993-01-01
A programme of remote inspections has been conducted on the Magnox steel reactor pressure vessel at Trawsfynydd Power Station using climbing vehicles. Tracked remotely operated vehicles supported the inspection programme by assisting with the delivery and recovery of the climbing vehicles and facilitating the use of various accessory packages. This paper presents details of the support project, the tracked vehicles and of the uses made of them during the inspection programme. (author)
Supplier Cooperation in Drone Delivery
Sawadsitang, Suttinee; Niyato, Dusit; Siew, Tan Puay; Wang, Ping
2018-01-01
Recently, unmanned aerial vehicles (UAVs), also known as drones, has emerged as an efficient and cost-effective solution for package delivery. Especially, drones are expected to incur lower cost, and achieve fast and environment friendly delivery. While most of existing drone research concentrates on surveillance applications, few works studied the drone package delivery planning problem. Even so, the previous works only focus on the drone delivery planning of a single supplier. In this paper...
UAV Delivery Monitoring System
Directory of Open Access Journals (Sweden)
San Khin Thida
2018-01-01
Full Text Available UAV-based delivery systems are increasingly being used in the logistics field, particularly to achieve faster last-mile delivery. This study develops a UAV delivery system that manages delivery order assignments, autonomous flight operation, real time control for UAV flights, and delivery status tracking. To manage the delivery item assignments, we apply the concurrent scheduler approach with a genetic algorithm. The present paper describes real time flight data based on a micro air vehicle communication protocol (MAVLink. It also presents the detailed hardware components used for the field tests. Finally, we provide UAV component analysis to choose the suitable components for delivery in terms of battery capacity, flight time, payload weight and motor thrust ratio.
A Multi-Modality Mobility Concept for a Small Package Delivery UAV
Young, L. A.
2017-01-01
This paper will discuss a different approach to the typical notional small package delivery drone concept. Most delivery drone concepts employ a point-to-point aerial delivery CONOPS (Concept of Operations) from a warehouse directly to the front or back yards of a customers residence or a commercial office space. Instead, the proposed approach is somewhat analogous to current postal deliveries: a small aerial vehicle flies from a warehouse to designated neighborhood VTOL (Vertical Take-Off and Landing) landing spots where the aerial vehicle then converts to a "roadable" (ground-mobility) vehicle that then transits on sidewalks and/or bicycle paths till it arrives to the residence/office drop-off points. This concept and associated platform or vehicle will be referred in this paper as MICHAEL (Multimodal Intra-City Hauling and Aerial-Effected Logistics) concept. It is suggested that the MICHAEL concept potentially results in a more community friendly "delivery drone" approach.
Carboxylic acid-functionalized SBA-15 nanorods for gemcitabine delivery
International Nuclear Information System (INIS)
Bahrami, Zohreh; Badiei, Alireza; Ziarani, Ghodsi Mohammadi
2015-01-01
The present study deals with the functionalization of mesoporous silica nanoparticles as drug delivery systems. Mono, di, and tri amino-functionalized SBA-15 nanorods were synthesized by post-grafting method using (3-aminopropyl) triethoxysilane, N-(2-aminoethyl-)3- aminopropyltrimethoxysilane, and 3-[2-(2-aminoethylamino) ethylamino] propyl trimethoxysilane, respectively. The carboxylic acid derivatives of the amino-functionalized samples were obtained using succinic anhydride. Tminopropyltrimethoxysilanehe obtained modified materials were investigated as matrixes for the anticancer drug (gemcitabine) delivery. The prepared samples were characterized by SAXS, N 2 adsorption/desorption, SEM, transmission electron microscopy, thermogravimetric analysis, and FTIR and UV spectroscopies. The adsorption and release properties of all samples were studied. It was revealed that the adsorption capacity and release behavior of gemcitabine were highly dependent on the type of the introduced functional groups. The carboxylic acid-modified samples have higher loading content, due to the strong interaction with gemcitabine. The maximum content of deposited drug in the modified SBA-15 nanorods is close to 40 wt%. It was found that the surface functionalization leads toward significant decrease of the drug release rate. The carboxylic acid-functionalized samples have slower release rate in contrast with the amino-functionalized samples
Parsha, Kaushik; Mir, Osman; Satani, Nikunj; Yang, Bing; Guerrero, Waldo; Mei, Zhuyong; Cai, Chunyan; Chen, Peng R; Gee, Adrian; Hanley, Patrick J; Aronowski, Jaroslaw; Savitz, Sean I
2017-01-01
Extensive animal data indicate that mesenchymal stromal cells (MSCs) improve outcome in stroke models. Intra-arterial (IA) injection is a promising route of delivery for MSCs. Therapeutic effect of MSCs in stroke is likely based on the broad repertoire of secreted trophic and immunomodulatory cytokines produced by MSCs. We determined the differential effects of exposing MSCs to different types of clinically relevant vehicles, and/or different additives and passage through a catheter relevant to IA injections. MSCs derived from human bone marrow were tested in the following vehicles: 5% albumin (ALB), 6% Hextend (HEX) and 40% dextran (DEX). Each solution was tested (i) alone, (ii) with low-dose heparin, (iii) with 10% Omnipaque, or (iv) a combination of heparin and Omnipaque. Cells in vehicles were collected directly or passed through an IA catheter, and MSC viability and cytokine release profiles were assessed. Cell viability remained above 90% under all tested conditions with albumin being the highest at 97%. Viability was slightly reduced after catheter passage or exposure to heparin or Omnipaque. Catheter passage had little effect on MSC cytokine secretion. ALB led to increased release of angiogenic factors such as vascular endothelial growth factor compared with other vehicles, while HEX and DEX led to suppression of pro-inflammatory cytokines such as interleukin-6. However, when these three vehicles were subjected to catheter passage and/or exposure to additives, the cytokine release profile varied depending on the combination of conditions to which MSCs were exposed. Exposure of MSCs to certain types of vehicles or additives changes the profile of cytokine secretion. The activation phenotype of MSCs may therefore be affected by the vehicles used for these cells or the exposure to the adjuvants used in their administration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Metallothionein bioconjugates as delivery vehicles for bismuth-212 alpha particle therapy
International Nuclear Information System (INIS)
Macklis, R.M.; Morris, C.; Humm, J.; Hines, J.; Atcher, R.
1991-01-01
Metallothioneins (MTHs) are small cysteine-rich polypeptides that binds cationic metals at physiologic pH ranges through noncovalent -SH ligand interactions. Some leucine-rich renal MTHs have a particular avidity for bismuth. The authors have examined the ability of MTHs to selectively incorporate Bi-212, a short-lived high-energy alpha particle emitter currently under exploration as a potential therapeutic radiolabel for use in molecularly targeted cancer therapy. They find that under physiologic conditions, MTH will selectively incorporate Bi-212 after incubation with an equilibrium mixture of its upstream and downstream parents. The MTH moieties may be linked to tumor-binding macromolecules such as antibodies via thiolation reactions using SPDP, and the resultant Bismuth-avid molecules may be used either as primary delivery vehicles for the Bi-212 or as part of a 2-step release-and-catch isotope localization system in which the MTH-antibody conjugate is pre-localized at the tumor site and the radiometal is then administered and chelated in situ. They present the chemistry, dosimetry and potential clinical applications of this system
Emissions from light and medium goods vehicles in Denmark
DEFF Research Database (Denmark)
Jørgensen, Kaj
1996-01-01
The article analyses atmospheric pollution of light goods vehicles (i.e. freight vehicles lighter than 6 tonnes) and medium goods vehicles (i.e. 6-24 t delivery trucks) in Denmark, and evaluated the scope for emission reductions. Light goods vehicles are very inefficient vehicles, and moreover have...
Grizzli mobile systems and LPG delivery management; Grizzli mobile systems
Energy Technology Data Exchange (ETDEWEB)
Anon.
2000-07-01
Complete text of publication follows: Grizzli Mobile Systems (and its sister companies) specialists in data communications and system solutions, offer their complete management solution for LPG deliveries, right through from remote reading of the gas level in the tank, through route management, management of the delivery itself and finally on-site invoicing and payment. The system permits a supplier to really differentiate itself from its competitors in terms of customer service and control of its operations. Domestic gas tanks are often difficult to access; visual reading of the gauge is not always easy and often leads to the customer re-ordering in panic mode. The supplier has also to react in panic mode to the customer. Grizzli Mobile Systems has developed a radio module that is fitted to the gas tank that calls, at regular set intervals with the tank level to a Call Rider gateway plug. The Call Rider is a small box plugged into the regular telephone socket (also supplying multiple operator telephony and other home automation services). As soon as the gas level reaches a predetermined minimum level, this radio information is relayed via the Internet to the LPG supplier. The supplier can then arrange (in non-panic mode) to deliver gas to the customer, via conventional means or by use of an interactive radio display (attached to a refrigerator or similar by magnets) that communicates with the Call Rider by radio. Once a delivery date has been set, a Grizzli Mobile Systems' dispatch system, installed at the supplier's headquarters creates and transfers routes via GSM communications to its fleet of delivery vehicles. A main-frame mapping software provides real-time follow-up and status checks of the vehicles using the GPS functionality and imports data back from the vehicles and updates databases. The driver is also assisted in localizing delivery sites. Inside the cabin of the vehicle the driver has available a Fujitsu PenCentra pen computer, a Microsoft
Robust Predictive Functional Control for Flight Vehicles Based on Nonlinear Disturbance Observer
Directory of Open Access Journals (Sweden)
Yinhui Zhang
2015-01-01
Full Text Available A novel robust predictive functional control based on nonlinear disturbance observer is investigated in order to address the control system design for flight vehicles with significant uncertainties, external disturbances, and measurement noise. Firstly, the nonlinear longitudinal dynamics of the flight vehicle are transformed into linear-like state-space equations with state-dependent coefficient matrices. And then the lumped disturbances are considered in the linear structure predictive model of the predictive functional control to increase the precision of the predictive output and resolve the intractable mismatched disturbance problem. As the lumped disturbances cannot be derived or measured directly, the nonlinear disturbance observer is applied to estimate the lumped disturbances, which are then introduced to the predictive functional control to replace the unknown actual lumped disturbances. Consequently, the robust predictive functional control for the flight vehicle is proposed. Compared with the existing designs, the effectiveness and robustness of the proposed flight control are illustrated and validated in various simulation conditions.
Bioresponsive matrices in drug delivery
Directory of Open Access Journals (Sweden)
Ye George JC
2010-11-01
Full Text Available Abstract For years, the field of drug delivery has focused on (1 controlling the release of a therapeutic and (2 targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli.
Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.
Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed
2016-09-01
The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.
Exosomes as nanocarriers for siRNA delivery: paradigms and challenges.
Shahabipour, Fahimeh; Banach, Maciej; Sahebkar, Amirhossein
2016-12-01
Exosomes are nano-sized vesicles that facilitate intercellular communications through carrying genetic materials and functional biomolecules. Owing to their unique size and structure, exosomes have emerged as a useful tool to overcome the limitations of siRNA delivery. The use of exosomes as siRNA delivery vehicles lacks certain disadvantages of the existing foreign delivery systems such as viruses, polycationic polymers and liposomes, and introduces several advantages including inherent capacity to pass through biological barriers and escape from phagocytosis by the reticuloendothelial system, as well as being biocompatible, non-toxic, and immunologically inert. Different strategies have been employed to harness exosome-based delivery systems, including surface modification with targeting ligands, and using exosome-display technology, virus-modified exosomes, and exosome-mimetic vesicles. The present review provides a capsule summary of the recent advances and current challenges in the field of exosome-mediated siRNA delivery.
Energy Technology Data Exchange (ETDEWEB)
Ramroth, L. A.; Gonder, J. D.; Brooker, A. D.
2013-04-01
The National Renewable Energy Laboratory (NREL) validated diesel-conventional and diesel-hybrid medium-duty parcel delivery vehicle models to evaluate petroleum reductions and cost implications of hybrid and plug-in hybrid diesel variants. The hybrid and plug-in hybrid variants are run on a field data-derived design matrix to analyze the effect of drive cycle, distance, engine downsizing, battery replacements, and battery energy on fuel consumption and lifetime cost. For an array of diesel fuel costs, the battery cost per kilowatt-hour at which the hybridized configuration becomes cost-effective is calculated. This builds on a previous analysis that found the fuel savings from medium duty plug-in hybrids more than offset the vehicles' incremental price under future battery and fuel cost projections, but that they seldom did so under present day cost assumptions in the absence of purchase incentives. The results also highlight the importance of understanding the application's drive cycle specific daily distance and kinetic intensity.
The Relationship between Mode of Delivery and Sexual Function in Nulliparous Women
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Aytay Alesheikh
2016-07-01
Full Text Available Background & aim: Sexual activity is one of the most important aspects of a marital life. Childbirth is also a major event in the life of women, and the period of postpartum is a time of emotional upheaval. Since women believe that vaginal delivery could negatively affect their sexual function after childbirth, they tend to give birth through caesarean section. Therefore, this study aimed to evaluate the relationship between mode of delivery and sexual function in nulliparous women referred to healthcare centers in Mashhad, Iran. Methods: This correlational study was conducted on 450 nulliparous women, divided into two groups of vaginal delivery and cesarean section in 2014. Suubjects were selected via multistage sampling. Data collection tools included Female Sexual Function Index (FSFI, Depression, Anxiety and Stress scale (DASS-21, and Cassidy social support scale. Data was analyzed in SPSS version 16 using Spearman correlation coefficient and Mann-Whitney test, T-test, ANOVA, and Kruskal-Wallis. Moreover, general linear model was used to control confounding variables, and P-value of less than 0.05 was considered statistically significant. Results: Independent t-test results indicated that mean scores of sexual function in two groups of the study were 26.11±4.36 and 26.38±4.41, respectively, which revealed no statistically significant difference between the groups (P=0.509. Conclusion: No significant difference was observed between the vaginal delivery and caesarean section groups regarding sexual function. Therefore, it seems that cesarean section does not necessarily lead to pleasing sexual relationships in postpartum period compared to vaginal delivery.
Parallel Hybrid Vehicle Optimal Storage System
Bloomfield, Aaron P.
2009-01-01
A paper reports the results of a Hybrid Diesel Vehicle Project focused on a parallel hybrid configuration suitable for diesel-powered, medium-sized, commercial vehicles commonly used for parcel delivery and shuttle buses, as the missions of these types of vehicles require frequent stops. During these stops, electric hybridization can effectively recover the vehicle's kinetic energy during the deceleration, store it onboard, and then use that energy to assist in the subsequent acceleration.
Wang, Taoran; Xue, Jingyi; Hu, Qiaobin; Zhou, Mingyong; Chang, Chao; Luo, Yangchao
2017-06-05
The toxicity associated with concentrated synthetic surfactants and the poor stability at gastrointestinal condition are two major constraints for practical applications of solid lipid nanoparticles (SLN) as oral delivery vehicles. In this study, a synthetic surfactant-free and cross-linker-free method was developed to fabricate effective, safe, and ultra-stable lipid-polymer hybrid nanoparticles (LPN). Bovine serum albumin (BSA) and dextran varying in molecular weights were first conjugated through Maillard reaction and the conjugates were exploited to emulsify solid lipid by a solvent diffusion and sonication method. The multilayer structure was formed by self-assembly of BSA-dextran micelles to envelope solid lipid via a pH- and heating-induced facile process with simultaneous surface deposition of pectin. The efficiency of different BSA-dextran conjugates was systematically studied to prepare LPN with the smallest size, the most homogeneous distribution and the greatest stability. The molecular interactions were characterized by Fourier transform infrared and fluorescence spectroscopies. Both nano spray drying and freeze-drying methods were tested to produce spherical and uniform pectin-coated LPN powders that were able to re-assemble nanoscale structure when redispersed in water. The results demonstrated the promise of a synthetic surfactant- and cross-linker-free technique to prepare highly stable pectin-coated LPN from all natural biomaterials as potential oral delivery vehicles.
Congestion avoidance and break scheduling within vehicle routing
Kok, A.L.
2010-01-01
Vehicle routing is a complex daily task for businesses such as logistic service providers and distribution firms. Planners have to assign many orders to many vehicles and, for each vehicle, assign a delivery sequence. The objective is to minimize total transport costs. These costs typically include
Silk Electrogel Based Gastroretentive Drug Delivery System
Wang, Qianrui
Gastric cancer has become a global pandemic and there is imperative to develop efficient therapies. Oral dosing strategy is the preferred route to deliver drugs for treating the disease. Recent studies suggested silk electro hydrogel, which is pH sensitive and reversible, has potential as a vehicle to deliver the drug in the stomach environment. The aim of this study is to establish in vitro electrogelation e-gel based silk gel as a gastroretentive drug delivery system. We successfully extended the duration of silk e-gel in artificial gastric juice by mixing silk solution with glycerol at different ratios before the electrogelation. Structural analysis indicated the extended duration was due to the change of beta sheet content. The glycerol mixed silk e-gel had good doxorubicin loading capability and could release doxorubicin in a sustained-release profile. Doxorubicin loaded silk e-gels were applied to human gastric cancer cells. Significant cell viability decrease was observed. We believe that with further characterization as well as functional analysis, the silk e-gel system has the potential to become an effective vehicle for gastric drug delivery applications.
Cinnamate of inulin as a vehicle for delivery of colonic drugs.
López-Molina, Dorotea; Chazarra, Soledad; How, Chee Wun; Pruidze, Nikolov; Navarro-Perán, Enma; García-Cánovas, Francisco; García-Ruiz, Pedro Antonio; Rojas-Melgarejo, Francisco; Rodríguez-López, José Neptuno
2015-02-01
Colon diseases are difficult to treat because oral administrated drugs are absorbed at the stomach and intestine levels and they do not reach colon; in addition, intravenous administrated drugs are eliminated from the body before reaching colon. Inulin is a naturally occurring polysaccharide found in many plants. It consists of β 2-1 linked D-fructose molecules having a glucosyl unit at the reducing end. Various inulin and dextran hydrogels have been developed that serve as potential carrier for introduction of drugs into the colon. Because inulin is not absorbed in the stomach or in the small intestine, and inulin is degraded by colonic bacteria, drugs encapsulated in inulin-coated vesicles could be specifically liberated in the colon. Therefore, the use of inulin-coated vesicles could represent an advance for the treatment of colon diseases. Here, we study the use of a cinnamoylated derivative of chicory inulin as a vehicle for the controlled delivery of colonic drugs. The encapsulation of methotrexate in inulin vesicles and its release and activity was studied in colon cancer cells in cultures. Copyright © 2014 Elsevier B.V. All rights reserved.
Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems
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Feng Jiang
2015-10-01
Full Text Available Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX, are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.
Han, Shun; Shen, Jin-qiu; Gan, Yong; Geng, Hai-ming; Zhang, Xin-xin; Zhu, Chun-liu; Gan, Li
2010-01-01
Aim: To develop a novel vehicle based on cubosomes as an ophthalmic drug delivery system for flurbiprofen (FB) to reduce ocular irritancy and improve bioavailability. Methods: FB-loaded cubosomes were prepared using hot and high-pressure homogenization. Cubosomes were then characterized by particle size, zeta potential, encapsulation efficiency, particle morphology, inner cubic structure and in vitro release. Corneal permeation was evaluated using modified Franz-type cells. Ocular irritation was then evaluated using both the Draize method and histological examination. The ocular pharmacokinetics of FB was determined using microdialysis. Results: The particle size of each cubosome formulation was about 150 nm. A bicontinuous cubic phase of cubic P-type was determined using cryo-transmission electron microscopy (cryo-TEM) observation and small angle X-ray scattering (SAXS) analysis. In vitro corneal permeation study revealed that FB formulated in cubosomes exhibited 2.5-fold (F1) and 2.0-fold (F2) increase in Papp compared with FB PBS. In the ocular irritation test, irritation scores for each group were less than 2, indicating that all formulations exhibited excellent ocular tolerance. Histological examination revealed that neither the structure nor the integrity of the cornea was visibly affected after incubation with FB cubosomes. The AUC of FB administered as FB cubosome F2 was 486.36±38.93 ng·mL−1·min·μg−1, which was significantly higher than that of FB Na eye drops (P<0.01). Compared with FB Na eye drops, the Tmax of FB cubosome F2 was about 1.6-fold higher and the MRT was also significantly longer (P<0.001). Conclusion: This novel low-irritant vehicle based on cubosomes might be a promising system for effective ocular drug delivery. PMID:20686524
Waranis, R P; Sloan, K B
1987-08-01
A series of S6,9-bisacyloxymethyl-6-mercaptopurine (6,9-bis-6-MP) prodrug derivatives was synthesized and characterized. The solubilities of the derivatives in solvents (vehicles), which exhibited a wide range of polarities from water to oleic acid, were measured. The abilities of the prodrugs to deliver 6-mercaptopurine (6-MP) from the vehicles have also been determined, and experimental fluxes and permeability coefficients (Kp) have been calculated for a large number of prodrug: vehicle combinations. Generally the best prodrugs of the series in terms of delivering 6-MP, regardless of the vehicle, were the first two members--the bisacetyl- and the bispropionyloxymethyl-6-mercaptopurine prodrugs. This result has been attributed mainly to the increased water solubility of these two prodrugs compared with that of 6-MP and the other prodrugs, since all of the prodrugs are much more lipid soluble than 6-MP. For three vehicles--isopropyl myristate, propylene glycol, and water--there was a good correlation between log experimental Kp for the delivery of 6-MP by the prodrugs from those vehicles and the theoretical solubility parameters of the prodrugs. The stabilities of the bisacetyl-(2), bisproprionyl-(3), and bisbutyryloxymethyl-6-mercaptopurine (4) derivatives were determined in buffer and in buffer containing enzymes leached from the dermis. Prodrug 2 was more stable than 3 or 4 in the buffer containing the enzymes, while 4 was more stable than 2 or 3 in the plain buffer.
Borke, Tina; Najberg, Mathie; Ilina, Polina; Bhattacharya, Madhushree; Urtti, Arto; Tenhu, Heikki; Hietala, Sami
2018-01-01
Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Microencapsulated foods as a functional delivery vehicle for omega-3 fatty acids: a pilot study
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David Robert M
2009-05-01
Full Text Available Abstract It is well established that the ingestion of the omega-3 (N3 fatty acids docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA positively benefit a variety of health indices. Despite these benefits the actual intake of fish derived N3 is relatively small in the United States. The primary aim of our study was to examine a technology capable of delivering omega-3 fatty acids in common foods via microencapsulation (MicroN3 in young, healthy, active participants who are at low risk for cardiovascular disease. Accordingly, we randomized 20 participants (25.4 ± 6.2 y; 73.4 ± 5.1 kg to receive the double blind delivery of a placebo-matched breakfast meal (~2093 kJ containing MicroN3 (450–550 mg EPA/DHA during a 2-week pilot trial. Overall, we observed no differences in overall dietary macronutrient intake other than the N3 delivery during our treatment regimen. Post-test ANOVA analysis showed a significant elevation in mean (SE plasma DHA (91.18 ± 9.3 vs. 125.58 ± 11.3 umol/L; P
Ge, Shumin; Lin, Yuanyuan; Lu, Haoyang; Li, Qi; He, Jian; Chen, Bao; Wu, Chuanbin; Xu, Yuehong
2014-04-25
This project was carried out to exploit the feasibility of using microemulsion (ME) as an alternative carrier for percutaneous delivery econazole nitrate (ECN) and elucidate the underlying mechanism of permeation enhancement. The ME was developed based on Labrafil M 1944 Cs as oil phase, Solutol HS15 and Span 80 as surfactants, Transcutol P as cosurfactant and water as aqueous phase. The solubility of ECN was firstly determined for screening the ingredients of the system. Pseudo-ternary phase diagrams were constructed to formulate ME and select surfactant and cosurfactant. Central composite design-response surface methodology (CCD-RSM) was utilized to optimize the formulation of ME. The ECN loaded ME was characterized in terms of morphology, particle size and size distribution, pH value, refractive index, viscosity and conductivity, and storage stability of the ECN loaded ME was assayed. Percutaneous permeation of ECN from ME in vitro through rat skin was investigated in comparison with PBS aqueous suspension (1%, w/w), and results showed that ME enhanced drug retention in the skin and permeation through the skin, the enhancement of ME on skin deposition was further visualized through fluorescent-labeled ME by confocal laser scanning microscope (CLSM). The action mechanism of ME on improving percutaneous delivery was studied by performing a pretreatment test. It can speculate that ME does not simply behave as enhancer but it also acts as drug carrier. Furthermore, ME-skin interaction was elucidated through transmission electron microscope (TEM), and attenuated total reflectance fourier-transform infrared (ATR-FTIR). TEM was performed to visualize the micro morphological change of skin. ATR-FTIR was carried out to investigate the molecular vibrations of the components of stratum corneum (SC). The results indicate that the ME system may be a promising vehicle for percutaneous delivery of ECN. Copyright © 2014 Elsevier B.V. All rights reserved.
Dai, Juan; Long, Wei; Liang, Zhongping; Wen, Lu; Yang, Fan; Chen, Gang
2018-01-01
Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2 b (IFN α-2 b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37 °C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy.
Nanocomposite Hydrogels: 3D Polymer-Nanoparticle Synergies for On-Demand Drug Delivery.
Merino, Sonia; Martín, Cristina; Kostarelos, Kostas; Prato, Maurizio; Vázquez, Ester
2015-05-26
Considerable progress in the synthesis and technology of hydrogels makes these materials attractive structures for designing controlled-release drug delivery systems. In particular, this review highlights the latest advances in nanocomposite hydrogels as drug delivery vehicles. The inclusion/incorporation of nanoparticles in three-dimensional polymeric structures is an innovative means for obtaining multicomponent systems with diverse functionality within a hybrid hydrogel network. Nanoparticle-hydrogel combinations add synergistic benefits to the new 3D structures. Nanogels as carriers for cancer therapy and injectable gels with improved self-healing properties have also been described as new nanocomposite systems.
1983-01-01
Representative space based orbital transfer vehicles (OTV), ground based vehicle turnaround assessment, functional operational requirements and facilities, mission turnaround operations, a comparison of ground based versus space based tasks, activation of servicing facilities prior to IOC, fleet operations requirements, maintenance facilities, OTV servicing facilities, space station support requirements, and packaging for delivery are discussed.
Effects of vehicles and enhancers on transdermal delivery of clebopride.
Rhee, Yun-Seok; Huh, Jai-Yong; Park, Chun-Woong; Nam, Tae-Young; Yoon, Koog-Ryul; Chi, Sang-Cheol; Park, Eun-Seok
2007-09-01
The effects of vehicles and penetration enhancers on the skin permeation of clebopride were evaluated using Franz type diffusion cells fitted with excised rat dorsal skins. The binary vehicle system, diethylene glycol monoethyl ether/isopropyl myristate (40/60, w/w), significantly enhanced the skin permeation rate of clebopride. The skin permeation enhancers, oleic acid and ethanol when used in the binary vehicle system, resulted in relatively high clebopride skin permeation rates. A gel formulation consisting of 1.5% (w/w) clebopride, 5% (w/w) oleic acid, and 7% (w/w) gelling agent with the binary vehicle system resulted in a permeation rate of 28.90 microg/cm2/h. Overall, these results highlight the potential of clebopride formulation for the transdermal route.
Silica-Coated Liposomes for Insulin Delivery
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Neelam Dwivedi
2010-01-01
Full Text Available Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evident from Confocal Micro-Raman spectroscopy. Silica coat enhances the stability of insulin-loaded delivery vehicles. In vivo study shows that these silica coated formulations were biologically active in reducing glucose levels.
A high-density lipoprotein-mediated drug delivery system.
Mo, Zhong-Cheng; Ren, Kun; Liu, Xing; Tang, Zhen-Li; Yi, Guang-Hui
2016-11-15
High-density lipoprotein (HDL) is a comparatively dense and small lipoprotein that can carry lipids as a multifunctional aggregate in plasma. Several studies have shown that increasing the levels or improving the functionality of HDL is a promising target for treating a wide variety of diseases. Among lipoproteins, HDL particles possess unique physicochemical properties, including naturally synthesized physiological components, amphipathic apolipoproteins, lipid-loading and hydrophobic agent-incorporating characteristics, specific protein-protein interactions, heterogeneity, nanoparticles, and smaller size. Recently, the feasibility and superiority of using HDL particles as drug delivery vehicles have been of great interest. In this review, we summarize the structure, constituents, biogenesis, remodeling, and reconstitution of HDL drug delivery systems, focusing on their delivery capability, characteristics, applications, manufacturing, and drug-loading and drug-targeting characteristics. Finally, the future prospects are presented regarding the clinical application and challenges of using HDL as a pharmacodelivery carrier. Copyright © 2016 Elsevier B.V. All rights reserved.
International Nuclear Information System (INIS)
Rastogi, Lori; Kora, Aruna Jyothi; Arunachalam, J.
2012-01-01
A method for the production of highly stable gold nanoparticles (Au NP) was optimized using sodium borohydride as reducing agent and bovine serum albumin as capping agent. The synthesized nanoparticles were characterized using UV–visible spectroscopy, transmission electron microscopy, X‐ray diffraction (XRD) and dynamic light scattering techniques. The formation of gold nanoparticles was confirmed from the appearance of pink colour and an absorption maximum at 532 nm. These protein capped nanoparticles exhibited excellent stability towards pH modification and electrolyte addition. The produced nanoparticles were found to be spherical in shape, nearly monodispersed and with an average particle size of 7.8 ± 1.7 nm. Crystalline nature of the nanoparticles in face centered cubic structure is confirmed from the selected‐area electron diffraction and XRD patterns. The nanoparticles were functionalized with various amino-glycosidic antibiotics for utilizing them as drug delivery vehicles. Using Fourier transform infrared spectroscopy, the possible functional groups of antibiotics bound to the nanoparticle surface have been examined. These drug loaded nanoparticle solutions were tested for their antibacterial activity against Gram-negative and Gram-positive bacterial strains, by well diffusion assay. The antibiotic conjugated Au NP exhibited enhanced antibacterial activity, compared to pure antibiotic at the same concentration. Being protein capped and highly stable, these gold nanoparticles can act as effective carriers for drugs and might have considerable applications in the field of infection prevention and therapeutics. - Highlights: ► Method for NaBH 4 reduced and BSA capped gold nanoparticle was standardized. ► Nanoparticles were spherical and nearly monodispersed with a size of 7.8 nm. ► Nanoparticles are extremely stable towards pH modification and electrolyte addition. ► Antibiotic conjugated nanoparticles exhibited enhanced antibacterial activity
Lubis, Elita Sari
2016-01-01
Food delivery system is one various of geographical information systems (GIS) that can be applied through digitation process. The main case in food delivery service is the way to acquire shortest path and movement tracking of food delivery vehicle. Therefore, to accomplish the efficient food delivery system digitation process, it is needed to add facility of shortest path determination and food delivery vehicle tracking. This research uses A* shortest path algorithm to determine shortest path...
Evaluation of Urban Freight Deliveries using Microsimulation and Surrogate Safety Measures
2018-02-01
Freight deliveries on signalized urban streets are known to cause lane blockages during deliveries. When delivery vehicles block lanes of traffic near signalized intersections, the capacity of the intersection is affected. Current practice is for tra...
Flexible shape-memory scaffold for minimally invasive delivery of functional tissues
Montgomery, Miles; Ahadian, Samad; Davenport Huyer, Locke; Lo Rito, Mauro; Civitarese, Robert A.; Vanderlaan, Rachel D.; Wu, Jun; Reis, Lewis A.; Momen, Abdul; Akbari, Saeed; Pahnke, Aric; Li, Ren-Ke; Caldarone, Christopher A.; Radisic, Milica
2017-10-01
Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold’s shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved.
The Ariane Transfer Vehicle (ATV) system studies
Thomas, U.; Thirkettle, A.
1991-08-01
Two distinct concepts of the Ariane transfer vehicle (ATV) are compared which incorporate existing ATV technology and offer logistics delivery at competitive costs. One concept is based on the Ariane-5 upper stage and the Vehicle Equipment Bay, and the other does not include Ariane-5 functions so that existing upper-stage limitations can be eliminated. Both concepts are required to accomplish the same transport, rendezvous, and berthing maneuvers and allow for controlled destructive reentry. An ATV reference mission is outlined, and key ATV design drivers are listed which include safety requirements, debris protection, and propulsion criteria. The Ariane-5 upgrade is the most cost-effective design although the second design is more operationally efficient. The ATV can potentially be used to relieve the schedule of the shuttle flights required for building the Space Station Freedom.
Peptide-based soft materials as potential drug delivery vehicles.
Verma, Sandeep; Joshi, K B; Ghosh, Surajit
2007-11-01
Emerging concepts in the construction of nanostructures hold immense potential in the areas of drug delivery and targeting. Such nanoscopic assemblies/structures, similar to natural proteins and self-associating systems, may lead to the formation of programmable soft structures with expanded drug delivery options and the capability to circumvent first-pass metabolism. This article aims to illustrate key recent developments and innovative bioinspired design paradigms pertaining to peptide-containing self-assembled tubular and vesicular soft structures. Soft structures are composed of components that self-assemble to reveal diverse morphologies stabilized by weak, noncovalent interactions. Morphological properties of such structures and their ability to encapsulate drugs, biologicals and bioactive small molecules, with the promise of targeted delivery, are discussed.
Protein nanoparticles for therapeutic protein delivery.
Herrera Estrada, L P; Champion, J A
2015-06-01
Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.
Directory of Open Access Journals (Sweden)
Mohamed H. Abumaree
2012-01-01
Full Text Available We have fabricated surface-modified paclitaxel nanowires (SM-PNs with a precise diameter and an average length of 50 μm. The surface of these nanowires is coated with a monolayer of octadecylsiloxane (ODS, which prevents aggregation and enhances dispersivity in aqueous media. This system constitutes a novel drug delivery vehicle based on one-dimensional (1D nanostructures with a large drug to vehicle ratio. We assayed the cytotoxicity of different diameter SM-PNs (200, 80, 35, and 18 nm with U937 cells and compared their activity to microcrystalline paclitaxel. SM-PNs reduced U937 cell proliferation in culture followed by cell death. For the same amount of paclitaxel, different diameter SM-PNs displayed different cytotoxic effect at the same incubation time period. SM-PNs with 35 nm diameters were the most efficient in completely halting cell proliferation following the first 24 hours of treatment, associated with 42% cell death. SM-PNs with 18 nm diameters were least effective. These SM-PNs can be tailored to fit a certain treatment protocol by simply choosing the appropriate diameter.
Alternative Fuel Fleet Vehicle Evaluations | Transportation Research | NREL
delivery, transit, and freight vehicles. Although biodiesel is the most commonly used alternative fuel in Diesel and Biodiesel Renewable diesel is a conventional petroleum diesel substitute produced from alternative to conventional diesel and does not require any vehicle modifications. Biodiesel is an oxygenated
Fibrin glue as the cell-delivery vehicle for mesenchymal stromal cells in regenerative medicine.
Wu, Xiuwen; Ren, Jianan; Li, Jieshou
2012-05-01
The use of tissue-engineering techniques such as stem-cell therapy to renew injured tissues is a promising strategy in regenerative medicine. As a cell-delivery vehicle, fibrin glues (FG) facilitate cell attachment, growth and differentiation and, ultimately, tissue formation and organization by its three-dimensional structure. Numerous studies have provided evidence that stromal cells derived from bone marrow (bone marrow stromal cells; BMSC) and adipose tissue (adipose-derived stromal cells; ADSC) contain a population of adult multipotent mesenchymal stromal cells (MSC) and endothelial progenitor cells that can differentiate into several lineages. By combining MSC with FG, the implantation could take advantage of the mutual benefits. Researchers and physicians have pinned their hopes on stem cells for developing novel approaches in regenerative medicine. This review focuses on the therapeutic potential of MSC with FG in bone defect reconstruction, cartilage and tendon injury repair, ligament, heart and nerve regeneration, and, furthermore, wound healing.
Functionalized linear poly(amidoamine)s are efficient vectors for intracellular protein delivery
Coué, G.M.J.P.C.; Engbersen, Johannes F.J.
2011-01-01
An effective intracellular protein delivery system was developed based on functionalized linear poly(amidoamine)s (PAAs) that form self-assembled cationic nanocomplexes with oppositely charged proteins. Three differently functionalized PAAs were synthesized, two of these having repetitive disulfide
Directory of Open Access Journals (Sweden)
Ji-Hyun Yeom
Full Text Available Use of non-biological agents for mRNA delivery into living systems in order to induce heterologous expression of functional proteins may provide more advantages than the use of DNA and/or biological vectors for delivery. However, the low efficiency of mRNA delivery into live animals, using non-biological systems, has hampered the use of mRNA as a therapeutic molecule. Here, we show that gold nanoparticle-DNA oligonucleotide (AuNP-DNA conjugates can serve as universal vehicles for more efficient delivery of mRNA into human cells, as well as into xenograft tumors generated in mice. Injections of BAX mRNA loaded on AuNP-DNA conjugates into xenograft tumors resulted in highly efficient mRNA delivery. The delivered mRNA directed the efficient production of biologically functional BAX protein, a pro-apoptotic factor, consequently inhibiting tumor growth. These results demonstrate that mRNA delivery by AuNP-DNA conjugates can serve as a new platform for the development of safe and efficient gene therapy.
Delivery of Unmanned Aerial Vehicle Data
Ivancic, William D.; Sullivan, Donald V.
2011-01-01
To support much of NASA's Upper Atmosphere Research Program science, NASA has acquired two Global Hawk Unmanned Aerial Vehicles (UAVs). Two major missions are currently planned using the Global Hawk: the Global Hawk Pacific (GloPac) and the Genesis and Rapid Intensification Processes (GRIP) missions. This paper briefly describes GloPac and GRIP, the concept of operations and the resulting requirements and communication architectures. Also discussed are requirements for future missions that may use satellite systems and networks owned and operated by third parties.
Martinez, Andre P; Qamar, Bareera; Fuerst, Thomas R; Muro, Silvia; Andrianov, Alexander K
2017-06-12
A series of biodegradable drug delivery polymers with intrinsic multifunctionality have been designed and synthesized utilizing a polyphosphazene macromolecular engineering approach. Novel water-soluble polymers, which contain carboxylic acid and pyrrolidone moieties attached to an inorganic phosphorus-nitrogen backbone, were characterized by a suite of physicochemical methods to confirm their structure, composition, and molecular sizes. All synthesized polyphosphazenes displayed composition-dependent hydrolytic degradability in aqueous solutions at neutral pH. Their formulations were stable at lower temperatures, potentially indicating adequate shelf life, but were characterized by accelerated degradation kinetics at elevated temperatures, including 37 °C. It was found that synthesized polyphosphazenes are capable of environmentally triggered self-assembly to produce nanoparticles with narrow polydispersity in the size range of 150-700 nm. Protein loading capacity of copolymers has been validated via their ability to noncovalently bind avidin without altering biological functionality. Acid-induced membrane-disruptive activity of polyphosphazenes has been established with an onset corresponding to the endosomal pH range and being dependent on polymer composition. The synthesized polyphosphazenes facilitated cell-surface interactions followed by time-dependent, vesicular-mediated, and saturable internalization of a model protein cargo into cancer cells, demonstrating the potential for intracellular delivery.
Liposome-based Formulation for Intracellular Delivery of Functional Proteins
Directory of Open Access Journals (Sweden)
Benoît Chatin
2015-01-01
Full Text Available The intracellular delivery of biologically active protein represents an important emerging strategy for both fundamental and therapeutic applications. Here, we optimized in vitro delivery of two functional proteins, the β-galactosidase (β-gal enzyme and the anti-cytokeratin8 (K8 antibody, using liposome-based formulation. The guanidinium-cholesterol cationic lipid bis (guanidinium-tren-cholesterol (BGTC (bis (guanidinium-tren-cholesterol combined to the colipid dioleoyl phosphatidylethanolamine (DOPE (dioleoyl phosphatidylethanolamine was shown to efficiently deliver the β-gal intracellularly without compromising its activity. The lipid/protein molar ratio, protein amount, and culture medium were demonstrated to be key parameters affecting delivery efficiency. The protein itself is an essential factor requiring selection of the appropriate cationic lipid as illustrated by low K8 binding activity of the anti-K8 antibody using guanidinium-based liposome. Optimization of various lipids led to the identification of the aminoglycoside lipid dioleyl succinyl paromomycin (DOSP associated with the imidazole-based helper lipid MM27 as a potent delivery system for K8 antibody, achieving delivery in 67% of HeLa cells. Cryo-transmission electron microscopy showed that the structure of supramolecular assemblies BGTC:DOPE/β-gal and DOSP:MM27/K8 were different depending on liposome types and lipid/protein molar ratio. Finally, we observed that K8 treatment with DOSP:MM27/K8 rescues the cyclic adenosine monophosphate (cAMP-dependent chloride efflux in F508del-CFTR expressing cells, providing a new tool for the study of channelopathies.
Directory of Open Access Journals (Sweden)
M. Dumitriu
2015-11-01
Full Text Available The paper herein focuses on the dynamic response of a two-bogie vehicle to the excitations derived from the track vertical irregularities. The symmetrical and antisymmetrical modes due from the bounce and pitch motions of the axles’ planes in the two bogies are being considered. The analysis of the dynamic response in the vehicle relies on the response functions in three reference points of the carbody, composed by means of these response functions to the symmetrical and antisymmetrical excitation modes. Similarly, the dynamic response of the vehicle to the track stochastic irregularities is examined and expressed as a power spectral density of the carbody vertical acceleration and the root mean square of the acceleration and the index of the partial comfort to the vertical vibrations is calculated. The paper is structured into two parts. The Part I includes all the theoretical elements required for the analysis of the dynamic response in the vehicle, while Part II introduces the results of the numerical analysis.
Directory of Open Access Journals (Sweden)
Jiyoon Park
2018-03-01
Full Text Available Unmanned aerial vehicles (UAV, drones used as delivery vehicles have received increasing attention due to their mobility and accessibility to remote areas. The purpose of this study is to evaluate the environmental impacts of drone versus motorcycle delivery and to compare the expected environmental improvements due to drone delivery in urban and rural areas. In addition, the potential environmental contributions of electric motorcycles were assessed to determine the effects of introducing this new type of vehicle. Changes in the national electricity generation plan were also examined. The results showed that global warming potential (GWP per 1 km delivery by drone was one-sixth that of motorcycle delivery, and the particulates produced by drone delivery were half that of motorcycle delivery. The actual environmental impact reduction in consideration of the delivery distance was 13 times higher in a rural area than in an urban area. Increasing the use of environmentally friendly electricity systems, such as solar and wind power, would further enhance the environmental effects of a drone delivery system.
Plasmid DNA Delivery: Nanotopography Matters.
Song, Hao; Yu, Meihua; Lu, Yao; Gu, Zhengying; Yang, Yannan; Zhang, Min; Fu, Jianye; Yu, Chengzhong
2017-12-20
Plasmid DNA molecules with unique loop structures have widespread bioapplications, in many cases relying heavily on delivery vehicles to introduce them into cells and achieve their functions. Herein, we demonstrate that control over delicate nanotopography of silica nanoparticles as plasmid DNA vectors has significant impact on the transfection efficacy. For silica nanoparticles with rambutan-, raspberry-, and flower-like morphologies composed of spike-, hemisphere-, and bowl-type subunit nanotopographies, respectively, the rambutan-like nanoparticles with spiky surfaces demonstrate the highest plasmid DNA binding capability and transfection efficacy of 88%, higher than those reported for silica-based nanovectors. Moreover, it is shown that the surface spikes of rambutan nanoparticles provide a continuous open space to bind DNA chains via multivalent interactions and protect the gene molecules sheltered in the spiky layer against nuclease degradation, exhibiting no significant transfection decay. This unique protection feature is in great contrast to a commercial transfection agent with similar transfection performance but poor protection capability against enzymatic cleavage. Our study provides new understandings in the rational design of nonviral vectors for efficient gene delivery.
Functionalized nanoparticles for AMF-induced gene and drug delivery
Biswas, Souvik
The properties and broad applications of nano-magnetic colloids have generated much interest in recent years. Specially, Fe3O4 nanoparticles have attracted a great deal of attention since their magnetic properties can be used for hyperthermia treatment or drug targeting. For example, enhanced levels of intracellular gene delivery can be achieved using Fe3O4 nano-vectors in the presence of an external magnetic field, a process known as 'magnetofection'. The low cytotoxicity, tunable particle size, ease of surface functionalization, and ability to generate thermal energy using an external alternating magnetic field (AMF) are properties have propelled Fe3O4 research to the forefront of nanoparticle research. The strategy of nanoparticle-mediated, AMF-induced heat generation has been used to effect intracellular hyperthermia. One application of this 'magnetic hyperthermia' is heat activated local delivery of a therapeutic effector (e.g.; drug or polynucleotide). This thesis describes the development of a magnetic nano-vector for AMF-induced, heat-activated pDNA and small molecule delivery. The use of heat-inducible vectors, such as heat shock protein ( hsp) genes, is a promising mode of gene therapy that would restrict gene expression to a local region by focusing a heat stimulus only at a target region. We thus aimed to design an Fe3O4 nanoparticle-mediated gene transfer vehicle for AMF-induced localized gene expression. We opted to use 'click' oximation techniques to assemble the magnetic gene transfer vector. Chapter 2 describes the synthesis, characterization, and transfection studies of the oxime ether lipid-based nano-magnetic vectors MLP and dMLP. The synthesis and characterization of a novel series of quaternary ammonium aminooxy reagents (2.1--2.4) is described. These cationic aminooxy compounds were loaded onto nanoparticles for ligation with carbonyl groups and also to impart a net positive charge on the nanoparticle surface. Our studies indicated that the
Mout, Rubul; Rotello, Vincent M
2017-10-20
In this protocol, engineered Cas9-ribonucleoprotein (Cas9 protein and sgRNA, together called Cas9-RNP) and gold nanoparticles are used to make nanoassemblies that are employed to deliver Cas9-RNP into cell cytoplasm and nucleus. Cas9 protein is engineered with an N-terminus glutamic acid tag (E-tag or En, where n = the number of glutamic acid in an E-tag and usually n = 15 or 20), C-terminus nuclear localizing signal (NLS), and a C-terminus 6xHis-tag. [Cas9En hereafter] To use this protocol, the first step is to generate the required materials (gold nanoparticles, recombinant Cas9En, and sgRNA). Laboratory-synthesis of gold nanoparticles can take up to a few weeks, but can be synthesized in large batches that can be used for many years without compromising the quality. Cas9En can be cloned from a regular SpCas9 gene (Addgene plasmid id = 47327), and expressed and purified using standard laboratory procedures which are not a part of this protocol. Similarly, sgRNA can be laboratory-synthesized using in vitro transcription from a template gene (Addgene plasmid id = 51765) or can be purchased from various sources. Once these materials are ready, it takes about ~30 min to make the Cas9En-RNP complex and 10 min to make the Cas9En-RNP/nanoparticles nanoassemblies, which are immediately used for delivery (Figure 1). Complete delivery (90-95% cytoplasmic and nuclear delivery) is achieved in less than 3 h. Follow-up editing experiments require additional time based on users' need. Synthesis of arginine functionalized gold nanoparticles (ArgNPs) (Yang et al ., 2011), expression of recombinant Cas9En, and in vitro synthesis of sgRNA is reported elsewhere (Mout et al ., 2017). We report here only the generation of the delivery vehicle i.e. , the fabrication of Cas9En-RNP/ArgNPs nanoassembly.
Evaluation of synthetic zeolites as oral delivery vehicle for anti-inflammatory drugs
Directory of Open Access Journals (Sweden)
Elham Khodaverdi
2014-05-01
Full Text Available Objective(s: In this research, zeolite X and zeolite Y were used as vehicle to prepare intestine targeted oral delivery systems of indomethacin and ibuprofen. Materials and Methods: A soaking procedure was implemented to encapsulate indomethacin or ibuprofen within synthetic zeolites. Gravimetric methods and IR spectra of prepared formulations were used to assess drug loading efficiencies into zeolite structures. Scanning Electron Microscopy (SEM was also utilized to determine morphologies changes in synthetic zeolites after drug loading. At the next stage, dissolution studies were used to predict the in vivo performance of prepared formulations at HCl 0.1 N and PBS pH 6.5 as simulated gastric fluid (SGF and simulated intestine fluid (SIF, respectively. Results: Drug loadings of prepared formulations was determined between 24-26 % w/w. Dissolution tests at SGF were shown that zeolites could retain acidic model drugs in their porous structures and can be able to limit their release into the stomach. On the other hand, all prepared formulations completely released model drugs during 3 hr in simulated intestine fluid. Conclusion: Obtained results indicated zeolites could potentially be able to release indomethacin and ibuprofen in a sustained and controlled manner and reduced adverse effects commonly accompanying oral administrations of NSAIDs.
Directory of Open Access Journals (Sweden)
Liang G
2018-01-01
Full Text Available Gaofeng Liang,1,2,* Shu Kan,2,* Yanliang Zhu,3 Shuying Feng,1 Wenpo Feng,1 Shegan Gao1,4 1Medical College, Henan University of Science and Technology, Luoyang, China; 2Department of Biomedical Engineering, University of California Berkeley, California, CA, USA; 3State Key laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 4Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China *These authors contributed equally to this work Introduction: Exosomes are closed-membrane nanovesicles that are secreted by a variety of cells and exist in most body fluids. Recent studies have demonstrated the potential of exosomes as natural vehicles that target delivery of functional small RNA and chemotherapeutics to diseased cells. Methods: In this study, we introduce a new approach for the targeted delivery of exosomes loaded with functional miR-26a to scavenger receptor class B type 1-expressing liver cancer cells. The tumor cell-targeting function of these engineered exosomes was introduced by expressing in 293T cell hosts, the gene fusion between the transmembrane protein of CD63 and a sequence from Apo-A1. The exosomes harvested from these 293T cells were loaded with miR-26a via electroporation. Results: The engineered exosomes were shown to bind selectively to HepG2 cells via the scavenger receptor class B type 1–Apo-A1 complex and then internalized by receptor-mediated endocytosis. The release of miR-26a in exosome-treated HepG2 cells upregulated miR-26a expression and decreased the rates of cell migration and proliferation. We also presented evidence that suggest cell growth was inhibited by miR-26a-mediated decreases in the amounts of key proteins that regulate the cell cycle. Conclusion: Our gene delivery strategy can be adapted to treat a broad spectrum of cancers by expressing proteins on the surface of mi
Assessment of Extension Service Delivery on Improved Cassava ...
African Journals Online (AJOL)
Extension service delivery is too often merely seen as a vehicle for spreading scientific and technical progress and technology transfer. In the real sense, however, dissemination of knowledge is not a one way affair from scientists to producers. The study was conducted to assess extension service delivery on improved ...
Tu, Ting-Yu; Yang, Shu-Jyuan; Wang, Chung-Hao; Lee, Shin-Yu; Shieh, Ming-Jium
2018-02-01
Drug delivery systems combined multimodal therapy strategies are very promising in cancer theranostic applications. In this work, a new drug-delivery vehicles based on human serum albumin (HSA)-coated gold nanorods (GNR/PSS/HSA NPs) was developed. The success of coating was verified by transmission electron microscopy (TEM), zeta potential and fourier transform infrared spectroscopy (FTIR). Furthermore, it is demonstrated that doxorubicin (DOX) is successfully loaded among multilayered gold nanorods by the electrostatic and hydrophobic force, and DOX@GNR/PSS/HSA NPs were highly biocompatible and stable in various physiological solutions. The NPs possess strong absorbance in nearinfrared (NIR) region, and high photothermal conversion efficiency for outstanding photothermal therapy applications. A bimodal drug release triggered by proteinase or NIR irradiation has been revealed, resulting in a significant chemotherapeutic effect in tumor sites because of the preferential drug accumulation and triggered release. Importantly, the in vitro and in vivo experiments demonstrated that DOX@GNR/PSS/HSA NPs, which combined photothermal and chemotherapy for cancer therapy, revealing a remarkably superior synergistic anticancer effect over either monotherapy. All these results suggested a considerable potential of DOX@GNR/PSS/HSA NPs nano-platform for antitumor therapy.
Ryazantsev, V.; Mezentsev, N.; Zakharov, A.
2018-02-01
This paper is dedicated to a solution of the issue of synthesis of the vehicle longitudinal dynamics control functions (acceleration and deceleration control) based on the element base of the vehicle active safety system (ESP) - driverless vehicle development tool. This strategy helps to reduce time and complexity of integration of autonomous motion control systems (AMCS) into the vehicle architecture and allows direct control of actuators ensuring the longitudinal dynamics control, as well as reduction of time for calibration works. The “vehicle+wheel+road” longitudinal dynamics control is complicated due to the absence of the required prior information about the control object. Therefore, the control loop becomes an adaptive system, i.e. a self-adjusting monitoring system. Another difficulty is the driver’s perception of the longitudinal dynamics control process in terms of comfort. Traditionally, one doesn’t pay a lot of attention to this issue within active safety systems, and retention of vehicle steerability, controllability and stability in emergency situations are considered to be the quality criteria. This is mainly connected to its operational limits, since it is activated only in critical situations. However, implementation of the longitudinal dynamics control in the AMCS poses another challenge for the developers - providing the driver with comfortable vehicle movement during acceleration and deceleration - while the possible highest safety level in terms of the road grip is provided by the active safety system (ESP). The results of this research are: universal active safety system - AMCS interaction interface; block diagram for the vehicle longitudinal acceleration and deceleration control as one of the active safety system’s integrated functions; ideology of adaptive longitudinal dynamics control, which enables to realize the deceleration and acceleration requested by the AMCS; algorithms synthesised; analytical experiments proving the
Principles of topical treatment: advancement in gel vehicle technology.
Feldman, Steven R
2014-04-01
Topical treatment is a pillar of dermatologic practice. The delivery of drug by a topical vehicle is dependent on complex physical chemistry and on how well patients apply the product. The potency of topical agents is not solely dependent on the concentration of active drug in the vehicle. A corticosteroid molecule may have vastly different potency depending on what vehicle is used to deliver it. Similarly, a new gel vehicle is able to deliver considerably more active antifungal than an older vehicle technology and may represent a promising vehicle for other novel formulations. The use of new vehicles can provide more effective means for treating patients with skin disease.
Repair costs and the intensity of vehicle use
Directory of Open Access Journals (Sweden)
Paweł DROŹDZIEL
2013-01-01
Full Text Available This paper presents correlation analyses of real-life data associated with the intensity of use of vehicles and the costs of replacement of operating materials and components performed in a three-year period for delivery vans, which was operated by the Poczta Polska (Polish Mail delivery office in Lublin.
International Nuclear Information System (INIS)
Panwar, Nishtha; Yang, Chengbin; Yin, Feng; Chuan, Tjin Swee; Yong, Ken-Tye; Yoon, Ho Sup
2015-01-01
RNA interference (RNAi)-based gene silencing possesses great ability for therapeutic intervention in pancreatic cancer. Among various oncogene mutations, Interleukin-8 (IL-8) gene mutations are found to be overexpressed in many pancreatic cell lines. In this work, we demonstrate IL-8 gene silencing by employing an RNAi-based gene therapy approach and this is achieved by using gold nanorods (AuNRs) for efficient delivery of IL-8 small interfering RNA (siRNA) to the pancreatic cell lines of MiaPaCa-2 and Panc-1. Upon comparing to Panc-1 cells, we found that the dominant expression of the IL-8 gene in MiaPaCa-2 cells resulted in an aggressive behavior towards the processes of cell invasion and metastasis. We have hence investigated the suitability of using AuNRs as novel non-viral nanocarriers for the efficient uptake and delivery of IL-8 siRNA in realizing gene knockdown of both MiaPaCa-2 and Panc-1 cells. Flow cytometry and fluorescence imaging techniques have been applied to confirm transfection and release of IL-8 siRNA. The ratio of AuNRs and siRNA has been optimized and transfection efficiencies as high as 88.40 ± 2.14% have been achieved. Upon successful delivery of IL-8 siRNA into cancer cells, the effects of IL-8 gene knockdown are quantified in terms of gene expression, cell invasion, cell migration and cell apoptosis assays. Statistical comparative studies for both MiaPaCa-2 and Panc-1 cells are presented in this work. IL-8 gene silencing has been demonstrated with knockdown efficiencies of 81.02 ± 10.14% and 75.73 ± 6.41% in MiaPaCa-2 and Panc-1 cells, respectively. Our results are then compared with a commercial transfection reagent, Oligofectamine, serving as positive control. The gene knockdown results illustrate the potential role of AuNRs as non-viral gene delivery vehicles for RNAi-based targeted cancer therapy applications. (paper)
National Research Council Canada - National Science Library
Booher, Shawn K
2005-01-01
...) to the Vehicle Operations section (LGRVO). The motivation of this initiative, more specifically referred to as Supply/Transportation Reengineering, was to streamline similar processes, and to effectively and efficiently utilize resources...
Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles
Balivada, Sivasai
Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V
Modular Energy Storage System for Alternative Energy Vehicles
Energy Technology Data Exchange (ETDEWEB)
Thomas, Janice [Magna Electronics Inc., Auburn Hills, MI (United States); Ervin, Frank [Magna Electronics Inc., Auburn Hills, MI (United States)
2012-05-15
An electrical vehicle environment was established to promote research and technology development in the area of high power energy management. The project incorporates a topology that permits parallel development of an alternative energy delivery system and an energy storage system. The objective of the project is to develop technologies, specifically power electronics, energy storage electronics and controls that provide efficient and effective energy management between electrically powered devices in alternative energy vehicles plugin electric vehicles, hybrid vehicles, range extended vehicles, and hydrogen-based fuel cell vehicles. In order to meet the project objectives, the Vehicle Energy Management System (VEMS) was defined and subsystem requirements were obtained. Afterwards, power electronics, energy storage electronics and controls were designed. Finally, these subsystems were built, tested individually, and integrated into an electric vehicle system to evaluate and optimize the subsystems performance. Phase 1 of the program established the fundamental test bed to support development of an electrical environment ideal for fuel cell application and the mitigation of many shortcomings of current fuel cell technology. Phase 2, continued development from Phase 1, focusing on implementing subsystem requirements, design and construction of the energy management subsystem, and the integration of this subsystem into the surrogate electric vehicle. Phase 2 also required the development of an Alternative Energy System (AES) capable of emulating electrical characteristics of fuel cells, battery, gen set, etc. Under the scope of the project, a boost converter that couples the alternate energy delivery system to the energy storage system was developed, constructed and tested. Modeling tools were utilized during the design process to optimize both component and system design. This model driven design process enabled an iterative process to track and evaluate the impact
Comparative costs and benefits of hydrogen vehicles
Energy Technology Data Exchange (ETDEWEB)
Berry, G.D. [Lawrence Livermore National Lab., CA (United States)
1996-10-01
The costs and benefits of hydrogen as a vehicle fuel are compared to gasoline, natural gas, and battery-powered vehicles. Costs, energy, efficiency, and tail-pipe and full fuel cycle emissions of air pollutants and greenhouse gases were estimated for hydrogen from a broad range of delivery pathways and scales: from individual vehicle refueling systems to large stations refueling 300 cars/day. Hydrogen production from natural gas, methanol, and ammonia, as well as water electrolysis based on alkaline or polymer electrolytes and steam electrolysis using solid oxide electrolytes are considered. These estimates were compared to estimates for competing fuels and vehicles, and used to construct oil use, air pollutant, and greenhouse gas emission scenarios for the U.S. passenger car fleet from 2005-2050. Fuel costs need not be an overriding concern in evaluating the suitability of hydrogen as a fuel for passenger vehicles. The combined emissions and oil import reduction benefits of hydrogen cars are estimated to be significant, valued at up to {approximately}$400/yr for each hydrogen car when primarily clean energy sources are used for hydrogen production. These benefits alone, however, become tenuous as the basis supporting a compelling rationale for hydrogen fueled vehicles, if efficient, advanced fossil-fuel hybrid electric vehicles (HEV`s) can achieve actual on-road emissions at or below ULEV standards in the 2005-2015 timeframe. It appears a robust rationale for hydrogen fuel and vehicles will need to also consider unique, strategic, and long-range benefits of hydrogen vehicles which can be achieved through the use of production, storage, delivery, and utilization methods for hydrogen which are unique among fuels: efficient use of intermittent renewable energy sources, (e,g, wind, solar), small-scale feasibility, fuel production at or near the point of use, electrolytic production, diverse storage technologies, and electrochemical conversion to electricity.
The pickup and delivery problem with cross-docking opportunity
DEFF Research Database (Denmark)
Petersen, Hanne Løhmann; Røpke, Stefan
2011-01-01
delivery by one truck, or by being picked up and transported to the cross-dock by one vehicle, and subsequently delivered at its final destination by another vehicle. Handling times at customers sites and terminal are given. A typical daily instance includes 500-1,000 requests. We solve the problem using...
Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview.
Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Graça
2017-05-01
In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.
Multi-functional Electric Module for a Vehicle
Bluethmann, William J. (Inventor); Waligora, Thomas M. (Inventor); Fraser-Chanpong, Nathan (Inventor); Reed, Ryan (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Spain, Ivan (Inventor); Dawson, Andrew D. (Inventor); Figuered, Joshua M. (Inventor); Herrera, Eduardo (Inventor); Markee, Mason M. (Inventor)
2015-01-01
A multi-functional electric module (eModule) is provided for a vehicle having a chassis, a master controller, and a drive wheel having a propulsion-braking module. The eModule includes a steering control assembly, mounting bracket, propulsion control assembly, brake controller, housing, and control arm. The steering control assembly includes a steering motor controlled by steering controllers in response to control signals from the master controller. A mounting feature of the bracket connects to the chassis. The propulsion control assembly and brake controller are in communication with the propulsion-braking module. The control arm connects to the lower portion and contains elements of a suspension system, with the control arm being connectable to the drive wheel via a wheel input/output block. The controllers are responsive to the master controller to control a respective steering, propulsion, and braking function. The steering motor may have a dual-wound stator with windings controlled via the respective steering controllers.
Automated Guided Vehicle For Phsically Handicapped People - A Cost Effective Approach
Kumar, G. Arun, Dr.; Sivasubramaniam, Mr. A.
2017-12-01
Automated Guided vehicle (AGV) is like a robot that can deliver the materials from the supply area to the technician automatically. This is faster and more efficient. The robot can be accessed wirelessly. A technician can directly control the robot to deliver the components rather than control it via a human operator (over phone, computer etc. who has to program the robot or ask a delivery person to make the delivery). The vehicle is automatically guided through its ways. To avoid collisions a proximity sensor is attached to the system. The sensor senses the signals of the obstacles and can stop the vehicle in the presence of obstacles. Thus vehicle can avoid accidents that can be very useful to the present industrial trend and material handling and equipment handling will be automated and easy time saving methodology.
siRNA delivery with lipid-based systems
DEFF Research Database (Denmark)
Foged, Camilla
2012-01-01
A key hurdle for the further development of RNA interference (RNAi) therapeutics like small interfering RNA (siRNA) is their safe and effective delivery. Lipids are promising and versatile carriers because they are based on Nature's own building blocks and can be provided with properties which......RNA into more hydrophobic lipoplexes, which promote passage of the siRNA across cellular membrane barriers, especially when lipids are added that facilitate membrane fusion. Despite these attractive features, siRNA delivery vehicles are facing a number of challenges such as the limited delivery efficiency...
Lipoamino acid-based micelles as promising delivery vehicles for monomeric amphotericin B.
Serafim, Cláudia; Ferreira, Inês; Rijo, Patrícia; Pinheiro, Lídia; Faustino, Célia; Calado, António; Garcia-Rio, Luis
2016-01-30
Lipoamino acid-based micelles have been developed as delivery vehicles for the hydrophobic drug amphotericin B (AmB). The micellar solubilisation of AmB by a gemini lipoamino acid (LAA) derived from cysteine and its equimolar mixtures with the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC), as well as the aggregation sate of the drug in the micellar systems, was studied under biomimetic conditions (phosphate buffered-saline, pH 7.4) using UV-vis spectroscopy. Pure surfactant systems and equimolar mixtures were characterized by tensiometry and important parameters were determined, such as critical micelle concentration (CMC), surface tension at the CMC (γCMC), maximum surface excess concentration (Γmax), and minimum area occupied per molecule at the water/air interface (Amin). Rheological behaviour from viscosity measurements at different shear rates was also addressed. Solubilisation capacity was quantified in terms of molar solubilisation ratio (χ), micelle-water partition coefficient (KM) and Gibbs energy of solubilisation (ΔGs°). Formulations of AmB in micellar media were compared in terms of drug loading, encapsulation efficiency, aggregation state of AmB and in vitro antifungal activity against Candida albicans. The LAA-containing micellar systems solubilise AmB in its monomeric and less toxic form and exhibit in vitro antifungal activity comparable to that of the commercial formulation Fungizone. Copyright © 2015 Elsevier B.V. All rights reserved.
2013-04-30
This report discusses light-vehicle crash countermeasure profiles and functions for five target pre-crash scenario groups based on vehicle-to-vehicle (V2V) communications. Target pre-crash scenario groups include rear-end, lane change, opposite direc...
Theodoropoulos, Dimitrios; Rova, Aikaterini; Smith, James R; Barbu, Eugen; Calabrese, Gianpiero; Vizirianakis, Ioannis S; Tsibouklis, John; Fatouros, Dimitrios G
2013-11-15
Liposomes of phosphatidylcholine or of dimyristoylphosphatidylcholine that incorporate bis-nido-carborane dequalinium salt are stable in physiologically relevant media and have in vitro toxicity profiles that appear to be compatible with potential therapeutic applications. These features render the structures suitable candidate boron-delivery vehicles for evaluation in the boron neutron capture therapy of cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.
Ultrasound-Mediated Drug/Gene Delivery in Solid Tumor Treatment
Directory of Open Access Journals (Sweden)
Yufeng Zhou
2013-01-01
Full Text Available Ultrasound is an emerging modality for drug delivery in chemotherapy. This paper reviews this novel technology by first introducing the designs and characteristics of three classes of drug/gene vehicles, microbubble (including nanoemulsion, liposomes, and micelles. In comparison to conventional free drug, the targeted drug-release and delivery through vessel wall and interstitial space to cancerous cells can be activated and enhanced under certain sonication conditions. In the acoustic field, there are several reactions of these drug vehicles, including hyperthermia, bubble cavitation, sonoporation, and sonodynamics, whose physical properties are illustrated for better understanding of this approach. In vitro and in vivo results are summarized, and future directions are discussed. Altogether, ultrasound-mediated drug/gene delivery under imaging guidance provides a promising option in cancer treatment with enhanced agent release and site specificity and reduced toxicity.
Directory of Open Access Journals (Sweden)
Tian Wu
2014-11-01
Full Text Available This paper presents a model for the projection of Chinese vehicle stocks and road vehicle energy demand through 2050 based on low-, medium-, and high-growth scenarios. To derive a gross-domestic product (GDP-dependent Gompertz function, Chinese GDP is estimated using a recursive dynamic Computable General Equilibrium (CGE model. The Gompertz function is estimated using historical data on vehicle development trends in North America, Pacific Rim and Europe to overcome the problem of insufficient long-running data on Chinese vehicle ownership. Results indicate that the number of projected vehicle stocks for 2050 is 300, 455 and 463 million for low-, medium-, and high-growth scenarios respectively. Furthermore, the growth in China’s vehicle stock will increase beyond the inflection point of Gompertz curve by 2020, but will not reach saturation point during the period 2014–2050. Of major road vehicle categories, cars are the largest energy consumers, followed by trucks and buses. Growth in Chinese vehicle demand is primarily determined by per capita GDP. Vehicle saturation levels solely influence the shape of the Gompertz curve and population growth weakly affects vehicle demand. Projected total energy consumption of road vehicles in 2050 is 380, 575 and 586 million tonnes of oil equivalent for each scenario.
A delivery transfer function (DTF) analysis for helical tomotherapy
International Nuclear Information System (INIS)
Kissick, Michael W; Mackie, Thomas Rockwell; Jeraj, Robert
2007-01-01
The previous theoretical work of a delivery transfer function (DTF) in radiotherapy is expanded to include the unique intensity modulation method of helical tomotherapy. In addition to the collimation of each beamlet, and the Gaussian scatter convolution spreading of the dose that other radiotherapy units have, helical tomotherapy uses 51 small arcs of varying lengths to adjust the intensity. The blurring from these arcs is not taken into account during treatment planning. A theoretical DTF is constructed, and a calculation is performed which includes this unique source motion in relation to the other DTF components. Various typical delivery parameters are used to generate resolution maps for a constant intensity projection. Near the isocenter, the transverse (to a given beam direction) blurring is small but at larger radii (>6 cm), the source blurring dominates over leaf size. For most clinical situations, this inherent source motion blurring is expected to be negligible
Seaweed Polysaccharide-Based Nanoparticles: Preparation and Applications for Drug Delivery
Directory of Open Access Journals (Sweden)
Jayachandran Venkatesan
2016-01-01
Full Text Available In recent years, there have been major advances and increasing amounts of research on the utilization of natural polymeric materials as drug delivery vehicles due to their biocompatibility and biodegradability. Seaweed polysaccharides are abundant resources and have been extensively studied for several biological, biomedical, and functional food applications. The exploration of seaweed polysaccharides for drug delivery applications is still in its infancy. Alginate, carrageenan, fucoidan, ulvan, and laminarin are polysaccharides commonly isolated from seaweed. These natural polymers can be converted into nanoparticles (NPs by different types of methods, such as ionic gelation, emulsion, and polyelectrolyte complexing. Ionic gelation and polyelectrolyte complexing are commonly employed by adding cationic molecules to these anionic polymers to produce NPs of a desired shape, size, and charge. In the present review, we have discussed the preparation of seaweed polysaccharide-based NPs using different types of methods as well as their usage as carriers for the delivery of various therapeutic molecules (e.g., proteins, peptides, anti-cancer drugs, and antibiotics. Seaweed polysaccharide-based NPs exhibit suitable particle size, high drug encapsulation, and sustained drug release with high biocompatibility, thereby demonstrating their high potential for safe and efficient drug delivery.
Energy Technology Data Exchange (ETDEWEB)
Duran, Adam W [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kelly, Kenneth J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kresse, John [Cummins; Li, Ke [Cummins
2018-04-03
When developing and designing new technology for integrated vehicle systems deployment, standard cycles have long existed for chassis dynamometer testing and tuning of the powertrain. However, to this day with recent developments and advancements in plug-in hybrid and battery electric vehicle technology, no true 'work day' cycles exist with which to tune and measure energy storage control and thermal management systems. To address these issues and in support of development of a range-extended pickup and delivery Class 6 commercial vehicle, researchers at the National Renewable Energy Laboratory in collaboration with Cummins analyzed 78,000 days of operational data captured from more than 260 vehicles operating across the United States to characterize the typical daily performance requirements associated with Class 6 commercial pickup and delivery operation. In total, over 2.5 million miles of real-world vehicle operation were condensed into a pair of duty cycles, an 80-mile cycle and a 100-mile cycle representative of the daily operation of U.S. class 3-6 commercial pickup and delivery trucks. Using novel machine learning clustering methods combined with mileage-based weighting, these composite representative cycles correspond to 90th and 95th percentiles for daily vehicle miles traveled by the vehicles observed. In addition to including vehicle speed vs time drive cycles, in an effort to better represent the environmental factors encountered by pickup and delivery vehicles operating across the United States, a nationally representative grade profile and key status information were also appended to the speed vs. time profiles to produce a 'work day' cycle that captures the effects of vehicle dynamics, geography, and driver behavior which can be used for future design, development, and validation of technology.
Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin
Directory of Open Access Journals (Sweden)
Ranjit Kumar Harwansh
2011-12-01
Full Text Available The present investigation aims to evaluate an isotropic and thermodynamically stable nanoemulsion formulation for transdermal delivery of glycyrrhizin (GZ, with minimum surfactant and cosurfactant (Smix concentrations that could improve its solubility, permeation enhancement, and stability. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared using soyabean oil as oil, Span 80, Brij 35 as a surfactant and isopropyl alcohol as a cosurfactant. Nanoemulsion formulations that passed the thermodynamic stability tests were characterized for pH, viscosity and droplet size using a transmission electron microscopy. The transdermal ability of glycyrrhizin through human cadaver skin was determined using Franz diffusion cells. The in vitro skin permeation profile of the optimized nanoemulsion formulation (NE2 was compared to that of conventional gel. A significant increase in permeability parameters such as steady-state flux (Jss and permeability coefficient (Kp was observed in the optimized nanoemulsion formulation (NE2, which consisted of 1% wt/wt of mono ammonium glycyrrhizinate (MAG, 32.4% Span 80, 3.7% Brij 35, 10% isopropyl alcohol, 46.5% soyabean oil and 6.4% distilled water. No obvious skin irritation was observed for the studied nanoemulsion formulation (NE2 or the gel. The results indicated that nanoemulsions are promising vehicles for transdermal delivery of glycyrrhizin through human cadaver skin, without the use of additional permeation enhancers, because excipients of nanoemulsions act as permeation enhancers themselves.O objetivo da investigação é avaliar uma nanoemulsão isotrópica termodinamicamente estável para a administração transdérmica da glicirrizina (GZ, com concentrações mínimas de tensoativo e co-tensoativo (Smix, que poderiam melhorar a sua solubilidade, a permeação e a estabilidade. Os diagramas pseudo-ternários de fase foram desenvolvidos e diversas nanoemulsões foram
Jiyoon Park; Solhee Kim; Kyo Suh
2018-01-01
Unmanned aerial vehicles (UAV, drones) used as delivery vehicles have received increasing attention due to their mobility and accessibility to remote areas. The purpose of this study is to evaluate the environmental impacts of drone versus motorcycle delivery and to compare the expected environmental improvements due to drone delivery in urban and rural areas. In addition, the potential environmental contributions of electric motorcycles were assessed to determine the effects of introducing t...
A targeted drug delivery system based on dopamine functionalized nano graphene oxide
Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim
2017-01-01
The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.
Papastefanaki, Florentia; Jakovcevski, Igor; Poulia, Nafsika; Djogo, Nevena; Schulz, Florian; Martinovic, Tamara; Ciric, Darko; Loers, Gabrielle; Vossmeyer, Tobias; Weller, Horst; Schachner, Melitta; Matsas, Rebecca
2015-06-01
Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.
Energy Technology Data Exchange (ETDEWEB)
Ragatz, A.; Duran, A.; Thornton, M.; Walkowicz, K.
2014-04-02
This presentation discusses the results of emissions testing for medium-duty conventional and diesel-electric hybrid vehicles. Testing was based on a field evaluation approach that utilized the Fleet DNA drive cycle database and NREL’s Renewable Fuels and Lubricants (ReFUEL) Laboratory chassis dynamometer. Vehicles tested included parcel delivery (Class 6 step vans), beverage delivery (Class 8 tractors), and parcel delivery (Class 7 box trucks) vehicles, all with intended service class medium/heavy heavy-duty diesel (MHDD).
Results for fuel economy and tailpipe NOx emissions included: diesel hybrid electric vehicles showed an average fuel economy advantage on identified test cycles: Class 6 Step Vans: 26%; Class 7 Box Trucks: 24.7%; Class 8 Tractors: 17.3%. Vehicle miles traveled is an important factor in determining total petroleum and CO2 displacement. Higher NOx emissions were observed over some test cycles: highly drive cycle dependent; engine-out differences may result from different engine operating point; and selective catalyst reduction temperature may play a role, but does not explain the whole story.
Filled carbon nanotubes in biomedical imaging and drug delivery.
Martincic, Markus; Tobias, Gerard
2015-04-01
Carbon nanotubes have been advocated as promising candidates in the biomedical field in the areas of diagnosis and therapy. In terms of drug delivery, the use of carbon nanotubes can overcome some limitations of 'free' drugs by improving the formulation of poorly water-soluble drugs, allowing targeted delivery and even enabling the co-delivery of two or more drugs for combination therapy. Two different approaches are currently being explored for the delivery of diagnostic and therapeutic agents by carbon nanotubes, namely attachment of the payload to the external sidewalls or encapsulation into the inner cavities. Although less explored, the latter confers additional stability to the chosen diagnostic or therapeutic agents, and leaves the backbone structure of the nanotubes available for its functionalization with dispersing and targeting moieties. Several drug delivery systems and diagnostic agents have been developed in the last years employing the inner tubular cavities of carbon nanotubes. The research discussed in this review focuses on the use of carbon nanotubes that contain in their interior drug molecules and diagnosis-related compounds. The approaches employed for the development of such nanoscale vehicles along with targeting and releasing strategies are discussed. The encapsulation of both biomedical contrast agents and drugs inside carbon nanotubes is further expanding the possibilities to allow an early diagnosis and treatment of diseases.
Pang, Chi Ting; Ammit, Alaina J; Ong, Yu Qing Elysia; Wheate, Nial J
2017-11-01
Novel para-sulfonatocalix[4]arene (sCX[4]) and polyamidoamine (PAMAM) dendrimer nanocomplexes were evaluated as delivery vehicles for the platinum anticancer agent [(1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] chloride (PHENSS). Different ratios of sCX[4] to PHENSS were tested for their compatibility, with a ratio of 6:1 sCX[4]:PHENSS having the best solubility. The loading of sCX[4], and sCX[4]-bound PHENSS, onto three different generations of PAMAM dendrimers (G3.0-5.0) was examined using UV-visible spectrophotometry. The quantity of sCX[4] bound was found to increase exponentially with dendrimer size: G3, 15 sCX[4] molecules per dendrimer; G4, 37; and G5, 78. Similarly, the loading of sCX[4]-bound PHENSS also increased with increasing dendrimer size: G3, 7 PHENSS molecules per dendrimer; G4, 14; and G5, 28.5. The loading of sCX[4]-bound PHENSS molecules is significantly lower when compared with that of sCX[4], which indicates that less than half of the binding sites were occupied (45, 44, and 44%, respectively). By 1 H NMR and UV-vis analysis, the nanocomplex was found to be stable in NaCl solutions at concentrations up to 150mM. While PHENSS is more active in vitro than cisplatin against the human breast cancer cell line, MCF-7, delivery of PHENSS using the sCX[4]-dendrimer nanocomplexes, regardless of dendrimer generation, had little effect on PHENSS cytotoxicity. The results of this study may have application in the delivery of a variety of small molecule metal-based drugs for which chemical conjugation to a nanoparticle is undesired or not feasible. Copyright © 2017 Elsevier Inc. All rights reserved.
Magnetic nanoparticles: A multifunctional vehicle for modern theranostics.
Angelakeris, M
2017-06-01
Magnetic nanoparticles provide a unique multifunctional vehicle for modern theranostics since they can be remotely and non-invasively employed as imaging probes, carrier vectors and smart actuators. Additionally, special delivery schemes beyond the typical drug delivery such as heat or mechanical stress may be magnetically triggered to promote certain cellular pathways. To start with, we need magnetic nanoparticles with several well-defined and reproducible structural, physical, and chemical features, while bio-magnetic nanoparticle design imposes several additional constraints. Except for the intrinsic requirement for high quality of magnetic properties in order to obtain the maximum efficiency with the minimum dose, the surface manipulation of the nanoparticles is a key aspect not only for transferring them from the growth medium to the biological environment but also to bind functional molecules that will undertake specific targeting, drug delivery, cell-specific monitoring and designated treatment without sparing biocompatibility and sustainability in-vivo. The ability of magnetic nanoparticles to interact with matter at the nanoscale not only provides the possibility to ascertain the molecular constituents of a disease, but also the way in which the totality of a biological function may be affected as well. The capacity to incorporate an array of structural and chemical functionalities onto the same nanoscale architecture also enables more accurate, sensitive and precise screening together with cure of diseases with significant pathological heterogeneity such as cancer. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader. Copyright © 2017 Elsevier B.V. All rights reserved.
Liu, Gang; Wang, Zhiyong; Lee, Seulki; Ai, Hua; Chen, Xiaoyuan
2012-01-01
With the rapid development of nanotechnology, inorganic magnetic nanoparticles, especially iron oxide nanoparticles (IOs), have emerged as great vehicles for biomedical diagnostic and therapeutic applications. In order to rationally design IO-based gene delivery nanovectors, surface modification is essential and determines the loading and release of the gene of interest. Here we highlight the basic concepts and applications of nonviral gene delivery vehicles based on low molecular weight N-al...
Intranasal delivery of antiviral siRNA.
Barik, Sailen
2011-01-01
Intranasal administration of synthetic siRNA is an effective modality of RNAi delivery for the prevention and therapy of respiratory diseases, including pulmonary infections. Vehicles used for nasal siRNA delivery include established as well as novel reagents, many of which have been recently optimized. In general, they all promote significant uptake of siRNA into the lower respiratory tract, including the lung. When properly designed and optimized, these siRNAs offer significant protection against respiratory viruses such as influenza virus, parainfluenza virus and respiratory syncytial virus (RSV). Nasally administered siRNA remains within the lung and does not access systemic blood flow, as judged by its absence in other major organs such as liver, heart, kidney, and skeletal muscle. Adverse immune reaction is generally not encountered, especially when immunogenic and/or off-target siRNA sequences and toxic vehicles are avoided. In fact, siRNA against RSV has entered Phase II clinical trials in human with promising results. Here, we provide a standardized procedure for using the nose as a specific route for siRNA delivery into the lung of laboratory animals. It should be clear that this simple and efficient system has enormous potential for therapeutics.
Suthikarnnarunai, N.; Olinick, E.
2009-01-01
We present a case study on the application of techniques for solving the Vehicle Routing Problem (VRP) to improve the transportation service provided by the University of The Thai Chamber of Commerce to its staff. The problem is modeled as VRP with time windows, split deliveries, and a mixed fleet. An exact algorithm and a heuristic solution procedure are developed to solve the problem and implemented in the AMPL modeling language and CPLEX Integer Programming solver. Empirical results indicate that the heuristic can find relatively good solutions in a small fraction of the time required by the exact method. We also perform sensitivity analysis and find that a savings in outsourcing cost can be achieved with a small increase in vehicle capacity.
Hydrogen vehicle fueling station
Energy Technology Data Exchange (ETDEWEB)
Daney, D.E.; Edeskuty, F.J.; Daugherty, M.A. [Los Alamos National Lab., NM (United States)] [and others
1995-09-01
Hydrogen fueling stations are an essential element in the practical application of hydrogen as a vehicle fuel, and a number of issues such as safety, efficiency, design, and operating procedures can only be accurately addressed by a practical demonstration. Regardless of whether the vehicle is powered by an internal combustion engine or fuel cell, or whether the vehicle has a liquid or gaseous fuel tank, the fueling station is a critical technology which is the link between the local storage facility and the vehicle. Because most merchant hydrogen delivered in the US today (and in the near future) is in liquid form due to the overall economics of production and delivery, we believe a practical refueling station should be designed to receive liquid. Systems studies confirm this assumption for stations fueling up to about 300 vehicles. Our fueling station, aimed at refueling fleet vehicles, will receive hydrogen as a liquid and dispense it as either liquid, high pressure gas, or low pressure gas. Thus, it can refuel any of the three types of tanks proposed for hydrogen-powered vehicles -- liquid, gaseous, or hydride. The paper discusses the fueling station design. Results of a numerical model of liquid hydrogen vehicle tank filling, with emphasis on no vent filling, are presented to illustrate the usefulness of the model as a design tool. Results of our vehicle performance model illustrate our thesis that it is too early to judge what the preferred method of on-board vehicle fuel storage will be in practice -- thus our decision to accommodate all three methods.
Inclusion bodies as potential vehicles for recombinant protein delivery into epithelial cells
2012-01-01
Background We present the potential of inclusion bodies (IBs) as a protein delivery method for polymeric filamentous proteins. We used as cell factory a strain of E. coli, a conventional host organism, and keratin 14 (K14) as an example of a complex protein. Keratins build the intermediate filament cytoskeleton of all epithelial cells. In order to build filaments, monomeric K14 needs first to dimerize with its binding partner (keratin 5, K5), which is then followed by heterodimer assembly into filaments. Results K14 IBs were electroporated into SW13 cells grown in culture together with a “reporter” plasmid containing EYFP labeled keratin 5 (K5) cDNA. As SW13 cells do not normally express keratins, and keratin filaments are built exclusively of keratin heterodimers (i.e. K5/K14), the short filamentous structures we obtained in this study can only be the result of: a) if both IBs and plasmid DNA are transfected simultaneously into the cell(s); b) once inside the cells, K14 protein is being released from IBs; c) released K14 is functional, able to form heterodimers with EYFP-K5. Conclusions Soluble IBs may be also developed for complex cytoskeletal proteins and used as nanoparticles for their delivery into epithelial cells. PMID:22624805
In-vehicle human factors for integrated multi-function systems: Making ITS user-friendly
Energy Technology Data Exchange (ETDEWEB)
Spelt, P.F.; Scott, S.
1998-04-01
As more and more Intelligent Transportation System in-vehicle equipment enters the general consumer market, the authors are about to find out how different design engineers are from ordinary drivers. Driver information systems are being developed and installed in vehicles at an ever-increasing rate. These systems provide information on diverse topics of concern and convenience to the driver, such as routing and navigation, emergency and collision warnings, and a variety of motorists services, or yellow pages functions. Most of these systems are being developed and installed in isolation from each other, with separate means of gathering the information and of displaying it to the driver. The current lack of coordination among on-board systems threatens to create a situation in which different messages on separate displays will be competing with each other for the drivers attention. Urgent messages may go unnoticed, and the number of messages may distract the driver from the most critical task of controlling the vehicle. Thus, without good human factors design and engineering for integrating multiple systems in the vehicle, consumers may find ITS systems confusing and frustrating to use. The current state of the art in human factors research and design for in-vehicle systems has a number of fundamental gaps. Some of these gaps were identified during the Intelligent Vehicle Initiative Human Factors Technology Workshop, sponsored by the US Department of Transportation, in Troy, Michigan, December 10--11, 1997. One task for workshop participants was to identify needed research areas or topics relating to in-vehicle human factors. The top ten unmet research needs from this workshop are presented. Many of these gaps in human factors research knowledge indicate the need for standardization in the functioning of interfaces for safety-related devices such as collision avoidance systems (CAS) and adaptive cruise controls (ACC). Such standards and guidelines will serve to make
Artificial Virus as Trump-card to Resolve Exigencies in Targeted Gene Delivery.
Ajithkumar, K C; Pramod, Kannissery
2018-01-01
Viruses are potent pathogens that can effectively deliver the genetic material to susceptible host cells. This capability is beneficially utilized to successfully deliver the genetic material. However, the use of virus mediated gene delivery is considered divisive, because the potentially replicable genomes recombine or integrate with the cell DNA resulting in immunogenicity, ranging from inflammation to death. Thus, the need for potentially effective non-viral gene delivery vehicles arises. Non-viral vectors, protein only particles and virus like particles (VLP) can be constructed which contain all the necessary functional moieties. These resemble viruses and are called artificial or synthetic virus. The artificial virus eliminates the disadvantages of viral vectors but retain the beneficial effects of the viruses. Need for further functionalization can be avoided by this approach because incorporation of requisite agents such as cell ligands, membrane active peptides, etc. into proteins is possible. The protein- DNA complexes resemble bacterial inclusion bodies. Nucleic acids influence conformation of protein units which subsequently result in cell uptake and finally to the cell nucleus. Such tunable systems mimic the activities of infected viruses and are used for the safe and effective delivery of drugs and genetic material in gene therapy. The versatility, stability and biocompatible nature of artificial virus along with high transfection efficacy have made it favorite for gene delivery purposes, in addition to being useful for various biomedical and drug delivery applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Routing strategies for efficient deployment of alternative fuel vehicles for freight delivery.
2017-02-01
With increasing concerns on environmental issues, recent research on Vehicle Routing Problems : (VRP) has added new factors such as greenhouse gas emissions and alternative fuel vehicles into : the models. In this report, we consider one such promisi...
Metabolic approaches to enhance transdermal drug delivery. 1. Effect of lipid synthesis inhibitors.
Tsai, J C; Guy, R H; Thornfeldt, C R; Gao, W N; Feingold, K R; Elias, P M
1996-06-01
The intercellular domains of the stratum corneum, which contain a mixture of cholesterol, free fatty acids, and ceramides, mediate both the epidermal permeability barrier and the transdermal delivery of both lipophilic and hydrophilic molecules. Prior studies have shown that each of the three key lipid classes is required for normal barrier function. For example, selective inhibition of either cholesterol, fatty acid, or ceramide synthesis in the epidermis delays barrier recovery rates after barrier perturbation of hairless mouse skin in vivo. In this study, we investigated the potential of certain inhibitors of lipid synthesis to enhance the transdermal delivery of lidocaine or caffeine as a result of their capacity to perturb barrier homeostasis. After acetone disruption of the barrier, the extent of lidocaine delivery and the degree of altered barrier function paralleled each other. Moreover, the further alteration in barrier function produced by either the fatty acid synthesis inhibitor 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), the cholesterol synthesis inhibitor fluvastatin (FLU), or cholesterol sulfate (CS) resulted in a further increase in lidocaine absorption. Furthermore, coapplications of TOFA and CS together caused an additive increase in lidocaine uptake. Finally, a comparable increase in drug delivery occurred when the barrier was disrupted initially with DMSO instead of acetone; coapplications of TOFA and FLU together again delayed barrier recovery and increased drug delivery by about 8-fold vs delivery from a standard enhancing vehicle. Whereas these metabolic inhibitors also variably increased the octanol/water partitioning of the drugs studied (perhaps via complexion or pH alterations), physicochemical effects of the inhibitors alone did not alter drug uptake in intact skin; i.e., passive mechanisms alone cannot account for the net increase in drug delivery. Our results show that modulations of epidermal lipid biosynthesis, following
Directory of Open Access Journals (Sweden)
Haran Yogasundaram
2012-01-01
Full Text Available Developing vehicles for the delivery of therapeutic molecules, like siRNA, is an area of active research. Nanoparticles composed of bovine serum albumin, stabilized via the adsorption of poly-L-lysine (PLL, have been shown to be potentially inert drug-delivery vehicles. With the primary goal of reducing nonspecific protein adsorption, the effect of using comb-type structures of poly(ethylene glycol (1 kDa, PEG units conjugated to PLL (4.2 and 24 kDa on BSA-NP properties, apparent siRNA release rate, cell viability, and cell uptake were evaluated. PEGylated PLL coatings resulted in NPs with ζ-potentials close to neutral. Incubation with platelet-poor plasma showed the composition of the adsorbed proteome was similar for all systems. siRNA was effectively encapsulated and released in a sustained manner from all NPs. With 4.2 kDa PLL, cellular uptake was not affected by the presence of PEG, but PEG coating inhibited uptake with 24 kDa PLL NPs. Moreover, 24 kDa PLL systems were cytotoxic and this cytotoxicity was diminished upon PEG incorporation. The overall results identified a BSA-NP coating structure that provided effective siRNA encapsulation while reducing ζ-potential, protein adsorption, and cytotoxicity, necessary attributes for in vivo application of drug-delivery vehicles.
Kulkarni, Bhagyashree; Surnar, Bapurao; Jayakannan, Manickam
2016-03-14
Multipurpose polymer nanoscaffolds for cellular imaging and delivery of anticancer drug are urgently required for the cancer therapy. The present investigation reports a new polymer drug delivery concept based on biodegradable polycaprolactone (PCL) and highly luminescent π-conjugated fluorophore as dual functional nanocarrier for cellular imaging and delivery vehicles for anticancer drug to cancer cells. To accomplish this goal, a new substituted caprolactone monomer was designed, and it was subjected to ring opening polymerization using a blue luminescent bishydroxyloligo-phenylenevinylene (OPV) fluorophore as an initiator. A series of A-B-A triblock copolymer building blocks with a fixed OPV π-core and variable chain biodegradable PCL arm length were tailor-made. These triblocks self-assembled in organic solvents to produce well-defined helical nanofibers, whereas in water they produced spherical nanoparticles (size ∼150 nm) with blue luminescence. The hydrophobic pocket of the polymer nanoparticle was found to be an efficient host for loading water insoluble anticancer drug such as doxorubicin (DOX). The photophysical studies revealed that there was no cross-talking between the OPV and DOX chromophores, and their optical purity was retained in the nanoparticle assembly for cellular imaging. In vitro studies revealed that the biodegradable PCL arm was susceptible to enzymatic cleavage at the intracellular lysosomal esterase under physiological conditions to release the loaded drugs. The nascent nanoparticles were found to be nontoxic to cancer cells, whereas the DOX-loaded nanoparticles accomplished more than 80% killing in HeLa cells. Confocal microscopic analysis confirmed the cell penetrating ability of the blue luminescent polymer nanoparticles and their accumulation preferably in the cytoplasm. The DOX loaded red luminescent polymer nanoparticles were also taken up by the cells, and the drug was found to be accumulated at the perinuclear environment
Yosemite Waters Vehicle Evaluation Report: Final Results
Energy Technology Data Exchange (ETDEWEB)
Eudy, L.; Barnitt, R.; Alleman, T. L.
2005-08-01
Document details the evaluation of Fischer-Tropsch diesel, a gas-to-liquid fuel, in medium-duty delivery vehicles at Yosemite Waters. The study was conducted by NREL at the company's Fullerton, California, bottling headquarters.
Oral transmucosal delivery of naratriptan.
Sattar, Mohammed; Lane, Majella E
2016-11-30
Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the treatment of migraine and is available in tablet dosage forms for oral administration. Buccal drug delivery offers a number of advantages compared with conventional oral delivery including rapid absorption, avoidance of first pass metabolism and improved patient compliance. We have previously prepared and characterised the base form of NAR and shown that it has more favourable properties for buccal delivery compared with NAR.HCl. This study describes the design and evaluation of a range of formulations for oral transmucosal delivery of NAR base. Permeation studies were conducted using excised porcine buccal tissue mounted in Franz cells. Of the neat solvents examined, Transcutol ® P (TC) showed the greatest enhancement effects and was the vehicle in which NAR was most soluble. The mechanisms by which TC might promote permeation were further probed using binary systems containing TC with either buffer or Miglyol 812 ® (MG). Mass balance studies were also conducted for these systems. The permeation of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC appears to promote enhanced membrane permeation of NAR because of its rapid uptake into the buccal tissue. Synergistic enhancement of buccal permeation was observed when TC was combined with MG and this is attributed to the increased thermodynamic activity of NAR in these formulations. Significantly enhanced permeation of NAR was achieved for TC:MG and this was also associated with less TC remaining on the tissue or in the tissue at the end of the experiment. To our knowledge this is the first report where both enhancer and active have been monitored in buccal permeation studies. The findings underline the importance of understanding the fate of vehicle components for rational formulation design of buccal delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.
An operating system for future aerospace vehicle computer systems
Foudriat, E. C.; Berman, W. J.; Will, R. W.; Bynum, W. L.
1984-01-01
The requirements for future aerospace vehicle computer operating systems are examined in this paper. The computer architecture is assumed to be distributed with a local area network connecting the nodes. Each node is assumed to provide a specific functionality. The network provides for communication so that the overall tasks of the vehicle are accomplished. The O/S structure is based upon the concept of objects. The mechanisms for integrating node unique objects with node common objects in order to implement both the autonomy and the cooperation between nodes is developed. The requirements for time critical performance and reliability and recovery are discussed. Time critical performance impacts all parts of the distributed operating system; e.g., its structure, the functional design of its objects, the language structure, etc. Throughout the paper the tradeoffs - concurrency, language structure, object recovery, binding, file structure, communication protocol, programmer freedom, etc. - are considered to arrive at a feasible, maximum performance design. Reliability of the network system is considered. A parallel multipath bus structure is proposed for the control of delivery time for time critical messages. The architecture also supports immediate recovery for the time critical message system after a communication failure.
Vehicle Development Laboratory
Federal Laboratory Consortium — FUNCTION: Supports the development of prototype deployment platform vehicles for offboard countermeasure systems.DESCRIPTION: The Vehicle Development Laboratory is...
Hydrogen storage and delivery system development: Analysis
Energy Technology Data Exchange (ETDEWEB)
Handrock, J.L. [Sandia National Labs., Livermore, CA (United States)
1996-10-01
Hydrogen storage and delivery is an important element in effective hydrogen utilization for energy applications and is an important part of the FY1994-1998 Hydrogen Program Implementation Plan. This project is part of the Field Work Proposal entitled Hydrogen Utilization in Internal Combustion Engines (ICE). The goal of the Hydrogen Storage and Delivery System Development Project is to expand the state-of-the-art of hydrogen storage and delivery system design and development. At the foundation of this activity is the development of both analytical and experimental evaluation platforms. These tools provide the basis for an integrated approach for coupling hydrogen storage and delivery technology to the operating characteristics of potential hydrogen energy use applications. Results of the analytical model development portion of this project will be discussed. Analytical models have been developed for internal combustion engine (ICE) hybrid and fuel cell driven vehicles. The dependence of hydride storage system weight and energy use efficiency on engine brake efficiency and exhaust temperature for ICE hybrid vehicle applications is examined. Results show that while storage system weight decreases with increasing engine brake efficiency energy use efficiency remains relatively unchanged. The development, capability, and use of a recently developed fuel cell vehicle storage system model will also be discussed. As an example of model use, power distribution and control for a simulated driving cycle is presented. Model calibration results of fuel cell fluid inlet and exit temperatures at various fuel cell idle speeds, assumed fuel cell heat capacities, and ambient temperatures are presented. The model predicts general increases in temperature with fuel cell power and differences between inlet and exit temperatures, but under predicts absolute temperature values, especially at higher power levels.
Visiting Vehicle Ground Trajectory Tool
Hamm, Dustin
2013-01-01
The International Space Station (ISS) Visiting Vehicle Group needed a targeting tool for vehicles that rendezvous with the ISS. The Visiting Vehicle Ground Trajectory targeting tool provides the ability to perform both realtime and planning operations for the Visiting Vehicle Group. This tool provides a highly reconfigurable base, which allows the Visiting Vehicle Group to perform their work. The application is composed of a telemetry processing function, a relative motion function, a targeting function, a vector view, and 2D/3D world map type graphics. The software tool provides the ability to plan a rendezvous trajectory for vehicles that visit the ISS. It models these relative trajectories using planned and realtime data from the vehicle. The tool monitors ongoing rendezvous trajectory relative motion, and ensures visiting vehicles stay within agreed corridors. The software provides the ability to update or re-plan a rendezvous to support contingency operations. Adding new parameters and incorporating them into the system was previously not available on-the-fly. If an unanticipated capability wasn't discovered until the vehicle was flying, there was no way to update things.
Electric and hybrid vehicle program. Quarterly report, January-February-March 1981
Energy Technology Data Exchange (ETDEWEB)
1981-05-01
Highlights of program developments are discussed, and ETV-1 test results are described. The temperature effects on lead-acid battery performance from 27 to 55/sup 0/C are reported, and the status of demonstration electric vehicle orders and deliveries is summarized. The certification and testing status of demonstration project vehicles is outlined, and a personnel directory for the DOE Electric and Hybrid Vehicle Program is included. (WHK)
International Nuclear Information System (INIS)
Duarte, G.O.; Gonçalves, G.A.; Baptista, P.C.; Farias, T.L.
2015-01-01
Highlights: • Innovative methodology to estimate VSP fuel consumption based on public available data. • Model validation with accurate fuel consumption results (absolute deviation from 4.7% to 9.2%). • Best-selling vehicles in Portugal case study was developed for different driving cycles. - Abstract: A method to perform the energy characterization of a vehicle according to the specific power required while driving was developed using public vehicle certification data. Using a portable emission measurement system, fuel consumption was quantified in a second-by-second basis under on-road conditions for 19 vehicles (spark-ignition, compression-ignition and hybrids). This data allowed building generic curves of fuel consumption as a function of the specific power, according to Vehicle Specific Power methodology. Comparing on-road measurements and the model estimates, a R 2 higher than 0.9 for conventional and hybrid vehicles was obtained regarding modal fuel consumption. Comparing the fuel consumption measured on the drive cycles performed by each vehicle and the correspondent estimates, an absolute deviation of 9.2% ± 9.2% was found for conventional vehicles and 4.7% ± 1.8% for hybrids vehicles. This methodology was validated and applied to estimate the energy impacts of the best-selling vehicles in Portugal for different driving cycles. This prompt method, that does not require vehicle monitoring, can estimate curves of fuel consumption in g/s, as a function of specific power, which allows quantifying the absolute fuel use for any driving cycle
Directory of Open Access Journals (Sweden)
Maryam Ashouri
2017-07-01
Full Text Available Vehicle routing problem (VRP is a Nondeterministic Polynomial Hard combinatorial optimization problem to serve the consumers from central depots and returned back to the originated depots with given vehicles. Furthermore, two of the most important extensions of the VRPs are the open vehicle routing problem (OVRP and VRP with simultaneous pickup and delivery (VRPSPD. In OVRP, the vehicles have not return to the depot after last visit and in VRPSPD, customers require simultaneous delivery and pick-up service. The aim of this paper is to present a combined effective ant colony optimization (CEACO which includes sweep and several local search algorithms which is different with common ant colony optimization (ACO. An extensive numerical experiment is performed on benchmark problem instances addressed in the literature. The computational result shows that suggested CEACO approach not only presented a very satisfying scalability, but also was competitive with other meta-heuristic algorithms in the literature for solving VRP, OVRP and VRPSPD problems. Keywords: Meta-heuristic algorithms, Vehicle Routing Problem, Open Vehicle Routing Problem, Simultaneously Pickup and Delivery, Ant Colony Optimization.
Directory of Open Access Journals (Sweden)
Gazi Mohammad Hasan Jamil
2014-08-01
Full Text Available Abstract. With the rising costs of gasoline, many vehicle owners are looking for alternatives of it. Compressed natural gas (CNG has been tested for this very purpose in some countries and found as a better alternative so far. CNG comes from country’s natural resources and it is clean and less costly to use. This paper is mainly an analysis of the potential benefits of using natural gas as a transportation fuel by the service delivery industries. It will examine CNG’s potential contribution in reducing delivery and vehicle maintenance cost, saving money in the long run projects, improving fuel efficiency, enhancing physical safety and assuring environment friendly emissions of carbon monoxide or reactive gases for the service delivery industries.Keywords: Compressed natural gas (CNG, Service Delivery, Fossil fuel, Global warming, Competitiveness
Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines.
Démoulins, Thomas; Milona, Panagiota; Englezou, Pavlos C; Ebensen, Thomas; Schulze, Kai; Suter, Rolf; Pichon, Chantal; Midoux, Patrick; Guzmán, Carlos A; Ruggli, Nicolas; McCullough, Kenneth C
2016-04-01
Self-amplifying replicon RNA (RepRNA) are large molecules (12-14 kb); their self-replication amplifies mRNA template numbers, affording several rounds of antigen production, effectively increasing vaccine antigen payloads. Their sensitivity to RNase-sensitivity and inefficient uptake by dendritic cells (DCs) - absolute requirements for vaccine design - were tackled by condensing RepRNA into synthetic, nanoparticulate, polyethylenimine (PEI)-polyplex delivery vehicles. Polyplex-delivery formulations for small RNA molecules cannot be transferred to RepRNA due to its greater size and complexity; the N:P charge ratio and impact of RepRNA folding would influence polyplex condensation, post-delivery decompaction and the cytosolic release essential for RepRNA translation. Polyplex-formulations proved successful for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid to DCs. Cytosolic translocation was facilitated, leading to RepRNA translation. This efficacy was confirmed in vivo, inducing both humoral and cellular immune responses. Accordingly, this paper describes the first PEI-polyplexes providing efficient delivery of the complex and large, self-amplifying RepRNA vaccines. The use of self-amplifying replicon RNA (RepRNA) to increase vaccine antigen payloads can potentially be useful in effective vaccine design. Nonetheless, its use is limited by the degradation during the uptake process. Here, the authors attempted to solve this problem by packaging RepRNA using polyethylenimine (PEI)-polyplex delivery vehicles. The efficacy was confirmed in vivo by the appropriate humoral and cellular immune responses. This novel delivery method may prove to be very useful for future vaccine design. Copyright © 2015 Elsevier Inc. All rights reserved.
The Impact of Timing and Dose of Rehabilitation Delivery on Functional Recovery of Stroke Patients
Directory of Open Access Journals (Sweden)
Hsiu-Chen Huang
2009-05-01
Conclusion: There is a dose-dependent effect of rehabilitation on functional improvement of stroke patients for the first 6 months post-stroke, and earlier delivery of rehabilitation has lasting effects on the functional recovery of stroke patients up to 1 year.
Non-viral Nucleic Acid Delivery Strategies to the Central Nervous System
Directory of Open Access Journals (Sweden)
James-Kevin Tan
2016-11-01
Full Text Available With an increased prevalence and understanding of central nervous system injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore the in vivo challenges hindering non-viral nucleic acid delivery to the central nervous system and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection, and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstrated in vivo gene transfer to the central nervous system are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for central nervous system applications and will ultimately bring non-viral vectors closer to clinical application.
Directory of Open Access Journals (Sweden)
Sandeep Kumar
2015-08-01
Full Text Available Abstract Multi-hop data delivery through vehicular ad hoc networks is complicated by the fact that vehicular networks are highly mobile and frequently disconnected. To address this issue the idea of helper node is opted where a moving vehicles carries the packet until a new vehicle moves into its vicinity and forwards the packet. Different from existing helper node solution use of the predicable vehicle mobility is made which is limited by the traffic pattern and the road layout. Based on the existing traffic pattern a vehicle can find the next road to forward packet a vehicle can find the next road to forward the packet to reduce the delay. Several vehicle-assisted date delievery VADD protocol is proposed to forward the packet to the best road with the road with the lowest data delivery delay. Experiment results are used to evaluate the proposed solutions. Results show that the proposed VADD protocol outperform existing solution in terms of packet delivery ratio data packet delay and protocol overhead. Among the proposed VADD protocols the Hybrid probe HVADD protocol has much better performance. In this Solution the helper node technique is provider with which the helper node will contain destination node path and the path in routine table continuously changes with the help of helper node technique.
Parlak, Cemal; Alver, Özgür
2017-06-01
Amantadine is a well-known drug for its treatment effect on Parkinson's disease and influenza infection or hepatitis. Heteroatom doped fullerenes have been extensively examined for their possible usage in sensor technology and medical applications as drug delivery vehicles. In this research, pristine and B, Al, Si, Ga, Ge doped C60 fullerenes and their interaction with amantadine drug molecule were investigated based on the density functional theory calculations. Findings suggest that doped C60 fullerenes might be used to detect the presence of amantadine and they might be used as drug delivery vehicles because of their moderately high adsorption energies with amantadine.
Medium- and Heavy-Duty Vehicle Duty Cycles for Electric Powertrains
Energy Technology Data Exchange (ETDEWEB)
Kelly, Kenneth; Bennion, Kevin; Miller, Eric; Prohaska, Bob
2016-03-02
NREL's Fleet Test and Evaluation group has extensive in-use vehicle data demonstrating the importance of understanding the vocational duty cycle for appropriate sizing of electric vehicle (EV) and power electronics components for medium- and heavy-duty EV applications. This presentation includes an overview of recent EV fleet evaluation projects that have valuable in-use data that can be leveraged for sub-system research, analysis, and validation. Peak power and power distribution data from in-field EVs are presented for four different vocations, including class 3 delivery vans, class 6 delivery trucks, class 8 transit buses, and class 8 port drayage trucks, demonstrating the impacts of duty cycle on performance requirements.
Applications of nanodiamonds in drug delivery and catalysis
Moosa, Basem; Fhayli, Karim; Li, Song; Julfakyan, Khachatur; Ezzeddine, Alaa; Khashab, Niveen M.
2014-01-01
The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles
Kinetics of lipid-nanoparticle-mediated intracellular mRNA delivery and function
Zhdanov, Vladimir P.
2017-10-01
mRNA delivery into cells forms the basis for one of the new and promising ways to treat various diseases. Among suitable carriers, lipid nanoparticles (LNPs) with a size of about 100 nm are now often employed. Despite high current interest in this area, the understanding of the basic details of LNP-mediated mRNA delivery and function is limited. To clarify the kinetics of mRNA release from LNPs, the author uses three generic models implying (i) exponential, (ii) diffusion-controlled, and (iii) detachment-controlled kinetic regimes, respectively. Despite the distinct differences in these kinetics, the associated transient kinetics of mRNA translation to the corresponding protein and its degradation are shown to be not too sensitive to the details of the mRNA delivery by LNPs (or other nanocarriers). In addition, the author illustrates how this protein may temporarily influence the expression of one gene or a few equivalent genes. The analysis includes positive or negative regulation of the gene transcription via the attachment of the protein without or with positive or negative feedback in the gene expression. Stable, bistable, and oscillatory schemes have been scrutinized in this context.
Implications of Functional Capacity Loss and Fatality for Vehicle Safety Prioritization.
McMurry, Timothy L; Sherwood, Chris; Poplin, Gerald S; Seguí-Gómez, María; Crandall, Jeff
2015-01-01
We investigate the use of the Functional Capacity Index (FCI) as a tool for establishing vehicle safety priorities by comparing the life year burden of injuries to the burden of fatality in frontal and side automotive crashes. We demonstrate FCI's utility by investigating in detail the resulting disabling injuries and their life year costs. We selected occupants in the 2000-2013 NASS-CDS database involved in frontal and side crashes, merged their injuries with FCI, and then used the merged data to estimate each occupant's overall functional loss. Lifetime functional loss was assessed by combining this measure of impairment with the occupants' expected future life spans, estimated from the Social Security Administration's Actuarial Life Table. Frontal crashes produce a large number of disabling injuries, particularly to the lower extremities. In our population, these crashes are estimated to account for approximately 400,000 life years lost to disability in comparison with 500,000 life years lost to fatality. Victims of side crashes experienced a higher rate of fatality but a significantly lower rate of disabling injury (0.3 vs. 1.0%), resulting in approximately 370,000 life years lost to fatality versus 50,000 life years lost to disability. The burden of disabling injuries to car crash survivors should be considered when setting vehicle safety design priorities. In frontal crashes this burden in life years is similar to the burden attributable to fatality.
Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems
Directory of Open Access Journals (Sweden)
Kaur R
2013-01-01
Full Text Available Randeep Kaur, Ildiko BadeaDrug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaAbstract: Detonation nanodiamonds (NDs are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.Keywords: dispersion, surface functionalization, toxicity, carriers, fluorescence, light scattering
Energy Technology Data Exchange (ETDEWEB)
Nielsen, L.H.; Joergensen, K.
2000-04-01
The aim of the project is to analyse energy, environmental and economic aspects of integrating electric vehicles in the future Danish energy system. Consequences of large-scale utilisation of electric vehicles are analysed. The aim is furthermore to illustrate the potential synergistic interplay between the utilisation of electric vehicles and large-scale utilisation of fluctuating renewable energy resources, such as wind power. Economic aspects for electric vehicles interacting with a liberalised electricity market are analysed. The project focuses on battery electric vehicles and fuel cell vehicles based on hydrogen. Based on assumptions on the future technical development for battery electric vehicles, fuel cell vehicles on hydrogen, and for the conventional internal combustion engine vehicles, scenarios are set up to reflect expected options for the long-term development of road transport vehicles. Focus is put on the Danish fleet of passenger cars and delivery vans. The scenario analysis includes assumptions on market potential developments and market penetration for the alternative vehicles. Vehicle replacement rates in the Danish transport fleet and the size of fleet development are based on data from The Danish Road Directorate. The electricity supply system development assumed is based on the Danish energy plan, Energy 21, The Plan scenario. The time horizon of the analysis is year 2030. Results from the scenario analysis include the time scales involved for the potential transition towards electricity based vehicles, the fleet composition development, the associated developments in transport fuel consumption and fuel substitution, and the potential CO{sub 2}-emission reduction achievable in the overall transport and power supply system. Detailed model simulations, on an hourly basis, have furthermore been carried out for year 2005 that address potential electricity purchase options for electric vehicles in the context of a liberalised electricity market
International Nuclear Information System (INIS)
Nielsen, L.H.; Joergensen, K.
2000-04-01
The aim of the project is to analyse energy, environmental and economic aspects of integrating electric vehicles in the future Danish energy system. Consequences of large-scale utilisation of electric vehicles are analysed. The aim is furthermore to illustrate the potential synergistic interplay between the utilisation of electric vehicles and large-scale utilisation of fluctuating renewable energy resources, such as wind power. Economic aspects for electric vehicles interacting with a liberalised electricity market are analysed. The project focuses on battery electric vehicles and fuel cell vehicles based on hydrogen. Based on assumptions on the future technical development for battery electric vehicles, fuel cell vehicles on hydrogen, and for the conventional internal combustion engine vehicles, scenarios are set up to reflect expected options for the long-term development of road transport vehicles. Focus is put on the Danish fleet of passenger cars and delivery vans. The scenario analysis includes assumptions on market potential developments and market penetration for the alternative vehicles. Vehicle replacement rates in the Danish transport fleet and the size of fleet development are based on data from The Danish Road Directorate. The electricity supply system development assumed is based on the Danish energy plan, Energy 21, The Plan scenario. The time horizon of the analysis is year 2030. Results from the scenario analysis include the time scales involved for the potential transition towards electricity based vehicles, the fleet composition development, the associated developments in transport fuel consumption and fuel substitution, and the potential CO 2 -emission reduction achievable in the overall transport and power supply system. Detailed model simulations, on an hourly basis, have furthermore been carried out for year 2005 that address potential electricity purchase options for electric vehicles in the context of a liberalised electricity market. The
Field Evaluation of Medium-Duty Plug-in Electric Delivery Trucks
Energy Technology Data Exchange (ETDEWEB)
Prohaska, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States); Simpson, Mike [National Renewable Energy Lab. (NREL), Golden, CO (United States); Ragatz, Adam [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kelly, Kenneth [National Renewable Energy Lab. (NREL), Golden, CO (United States); Smith, Kandler [National Renewable Energy Lab. (NREL), Golden, CO (United States); Walkowicz, Kevin [National Renewable Energy Lab. (NREL), Golden, CO (United States)
2016-12-01
This report focuses on medium-duty electric delivery vehicles operated by Frito-Lay North America (FLNA) at its Federal Way, Washington, distribution center. The 100% electric drive system is an alternative to conventional diesel delivery trucks and reduces both energy consumption and carbon dioxide (CO2) emissions. The vehicles' drive cycles and operation are analyzed and compared to demonstrate the importance of matching specific electric vehicle (EV) technologies to the appropriate operational duty cycle. The results of this analysis show that the Smith Newton EVs demonstrated a 68% reduction in energy consumption over the data reporting period compared to the conventional diesel vehicles, as well as a 46.4% reduction in CO2 equivalent emissions based on the local energy generation source. In addition to characterizing the in-use performance of the EVs compared to the conventional diesels, detailed facility load data were collected at the main building power feed as well as from each of the 10 EV chargers to better understand the broader implications associated with commercial EV deployment. These facility loads were incorporated into several modeling scenarios to demonstrate the potential benefits of integrating onsite renewables.
Medium-Duty Plug-in Electric Delivery Truck Fleet Evaluation
Energy Technology Data Exchange (ETDEWEB)
Prohaska, Robert; Ragatz, Adam; Simpson, Mike; Kelly, Kenneth
2016-06-29
In this paper, the authors present an overview of medium-duty electric vehicle (EV) operating behavior based on in-use data collected from Smith Newton electric delivery vehicles and compare their performance and operation to conventional diesel trucks operating in the same fleet. The vehicles' drive cycles and operation are analyzed and compared to demonstrate the importance of matching specific EV technologies to the appropriate operational duty cycle. The results of this analysis show that the Smith Newton EVs demonstrated a 68% reduction in energy consumption over the data reporting period compared to the conventional diesel vehicles, as well as a 46.4% reduction in carbon dioxide equivalent emissions based on the local energy generation source.
Chen, Jiajia; Zhao, Pan; Liang, Huawei; Mei, Tao
2014-09-18
The autonomous vehicle is an automated system equipped with features like environment perception, decision-making, motion planning, and control and execution technology. Navigating in an unstructured and complex environment is a huge challenge for autonomous vehicles, due to the irregular shape of road, the requirement of real-time planning, and the nonholonomic constraints of vehicle. This paper presents a motion planning method, based on the Radial Basis Function (RBF) neural network, to guide the autonomous vehicle in unstructured environments. The proposed algorithm extracts the drivable region from the perception grid map based on the global path, which is available in the road network. The sample points are randomly selected in the drivable region, and a gradient descent method is used to train the RBF network. The parameters of the motion-planning algorithm are verified through the simulation and experiment. It is observed that the proposed approach produces a flexible, smooth, and safe path that can fit any road shape. The method is implemented on autonomous vehicle and verified against many outdoor scenes; furthermore, a comparison of proposed method with the existing well-known Rapidly-exploring Random Tree (RRT) method is presented. The experimental results show that the proposed method is highly effective in planning the vehicle path and offers better motion quality.
Modified biomolecule as potential vehicle for buccal delivery of doxepin.
Laffleur, Flavia; Zilio, Martina; Shuwisitkul, Duangratana
2016-10-01
Doxepin is a traditional tricyclic antidepressant with analgesic and anesthetic properties when applied topically to the mucosa. Doxepin is one approach in treating insomnia and depression in Parkinson's disease. Patients with Parkinson's disease suffer difficulties in swallowing. Therefore, it was the aim of this study to develop a buccal-adhesive delivery system. Pectin was modified with cysteine. Stability assays in form of disintegration assay according to the Ph.Eur were performed. Furthermore, bioadhesiveness on buccal mucosa was investigated incorporating the drug doxepin. The adhesiveness was improved 1.4-fold and revealed a sustained release over 3 h. Taking these findings into account, the modifications render this designed excipient fruitful for buccal delivery.
The combination of chemotherapy and radiotherapy towards more efficient drug delivery.
Cao, Wei; Gu, Yuwei; Meineck, Myriam; Xu, Huaping
2014-01-01
Research on anticancer therapies has advanced significantly in recent years. New therapeutic platforms that can further improve the health of patients are still highly demanded. We propose the idea of combining regular chemotherapy with radiation therapy to minimize side effects as well as increase drug-delivery efficiency. In this Focus Review, we seek to provide an overview of recent advances that can combine chemotherapy and radiotherapy. We begin by reviewing the current state of systems that can combine chemotherapy and gamma radiation. Among them, diselenide-containing polymers are highlighted as sensitive drug-delivery vehicles that can disassemble under gamma radiation. Then X-ray responsive materials as promising alternative systems are summarized, including X-ray responsive drug-delivery vehicles, prodrugs that can be activated by X-rays, and radiation-site-targeting systems. Finally, we describe strategies that involve phototherapies. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Fire Detection Tradeoffs as a Function of Vehicle Parameters
Urban, David L.; Dietrich, Daniel L.; Brooker, John E.; Meyer, Marit E.; Ruff, Gary A.
2016-01-01
Fire survivability depends on the detection of and response to a fire before it has produced an unacceptable environment in the vehicle. This detection time is the result of interplay between the fire burning and growth rates; the vehicle size; the detection system design; the transport time to the detector (controlled by the level of mixing in the vehicle); and the rate at which the life support system filters the atmosphere, potentially removing the detected species or particles. Given the large differences in critical vehicle parameters (volume, mixing rate and filtration rate) the detection approach that works for a large vehicle (e.g. the ISS) may not be the best choice for a smaller crew capsule. This paper examines the impact of vehicle size and environmental control and life support system parameters on the detectability of fires in comparison to the hazard they present. A lumped element model was developed that considers smoke, heat, and toxic product release rates in comparison to mixing and filtration rates in the vehicle. Recent work has quantified the production rate of smoke and several hazardous species from overheated spacecraft polymers. These results are used as the input data set in the lumped element model in combination with the transport behavior of major toxic products released by overheating spacecraft materials to evaluate the necessary alarm thresholds to enable appropriate response to the fire hazard.
2015-09-28
buoyant underwater vehicle with an interior space in which a length of said underwater vehicle is equal to one tenth of the acoustic wavelength...underwater vehicle with an interior space in which a length of said underwater vehicle is equal to one tenth of the acoustic wavelength; an...unmanned underwater vehicle that can function as an acoustic vector sensor. (2) Description of the Prior Art [0004] It is known that a propagating
Statistical analysis of vehicle loads measured with three different vehicle weighing devices
CSIR Research Space (South Africa)
Mkhize, ZQP
2005-07-01
Full Text Available MEASURED WITH THREE DIFFERENT VEHICLE WEIGHING DEVICES Z Q P MKHIZE and M DE BEER CSIR Transportek, PO Box 395, Pretoria, 0001 ABSTRACT This study introduces a new scale for weighing individual tyres of slow moving vehicles. The new technology... that vehicles exert on pavements plays a vital part in the deterioration of the structural and functional capacity of the road. It also influences the safety of the vehicles, especially when vehicles are operated under overloaded and/or inappropriately loaded...
Delivery of Gemcitabine Prodrugs Employing Mesoporous Silica Nanoparticles
Directory of Open Access Journals (Sweden)
Alessio Malfanti
2016-04-01
Full Text Available In this paper, mesoporous silica nanoparticles (MSNs were studied as vehicles for the delivery of the antitumoral drug gemcitabine (GEM and of its 4-(N-acyl derivatives, (4-(N-valeroyl-(C5GEM, 4-(N-lauroyl-(C12GEM and 4-(N-stearoyl-gemcitabine (C18GEM. The loading of the GEM lipophilic prodrugs on MSNs was explored with the aim to obtain both a physical and a chemical protection of GEM from rapid plasmatic metabolization. For this purpose, MSNs as such or with grafted aminopropyl and carboxyethyl groups were prepared and characterized. Then, their different drug loading capacity in relation to the nature of the functional group was evaluated. In our experimental conditions, GEM was not loaded in any MSNs, while C12GEM was the most efficiently encapsulated and employed for further evaluation. The results showed that loading capacity increased with the presence of functional groups on the nanoparticles; similarly, the presence of functional groups on MSNs’ surface influenced the drug release profile. Finally, the cytotoxicity of the different preparations was evaluated and data showed that C12GEM loaded MSNs are less cytotoxic than the free drug with an activity that increased with the incubating time, indicating that all these systems are able to release the drug in a controlled manner. Altogether, the results demonstrate that these MSNs could be an interesting system for the delivery of anticancer drugs.
Singh, N Dolendro; Ding, Yi; Daniell, Henry
2009-01-01
Many vaccine antigens and biopharmaceutical proteins have been expressed at high levels via the chloroplast genome and their functionality has been evaluated using in vitro assays in cell cultures (i.e., macrophage lysis assay, inhibition of vesicular stomatitis virus-induced cytopathicity in baby hamster kidney cells, or inhibition of human HIV infection in TZM-BL cells) as well as protection after challenge with bacterial or viral pathogens or antitumor assays or delay the onset of insulitis in suitable animal models. Production of therapeutic proteins in chloroplasts eliminates the expensive fermentation technology. Moreover, oral delivery of chloroplast-derived therapeutic proteins eliminates expensive purification steps, cold storage, cold transportation, and delivery via sterile needles, thereby further decreasing their cost. In this chapter, we describe detailed protocols for chloroplast transformation including the construction of chloroplast transformation vectors, delivery of DNA into plant cells using particle bombardment, selection and regeneration of transformants by tissue culture, confirmation of transgene integration into the chloroplast genome and homoplasmy, evaluation of foreign gene expression, purification of foreign protein, or oral delivery via bioencapsulation, functional evaluation using in vitro and in vivo assays, and evaluation of immunity after challenge with pathogens in suitable animal models.
Optimal Routing for Heterogeneous Fixed Fleets of Multicompartment Vehicles
Wang, Qian; Ji, Qingkai; Chiu, Chun-Hung
2014-01-01
We present a metaheuristic called the reactive guided tabu search (RGTS) to solve the heterogeneous fleet multicompartment vehicle routing problem (MCVRP), where a single vehicle is required for cotransporting multiple customer orders. MCVRP is commonly found in delivery of fashion apparel, petroleum distribution, food distribution, and waste collection. In searching the optimum solution of MCVRP, we need to handle a large amount of local optima in the solution spaces. To overcome this proble...
International Nuclear Information System (INIS)
Farmanzadeh, Davood; Ghazanfary, Samereh
2014-01-01
Graphical abstract: - Highlights: • Solvation energies show that the BNNTs/amino acids complex stabilizes in presence of solvent. • The adsorption process is sensitive to the external electric field. • The electric field is a suitable method for adsorption and storage of amino acids on BNNTs. - Abstract: The interaction of Glu (Glutamic acid), Lys (Lysine), Gly (Glycine) and Ser (Serine) amino acids with different polarities and (9, 0) zigzag single-wall boron nitride nanotubes (BNNTs) with various lengths in the presence and absence of external electric field (EF) in gas and solvent phases, are studied using density functional theory. It is found that interaction of Glu, Lys, Gly and Ser amino acids with BNNTs in both phases is energetically favorable. From solvation energy calculations, it can be seen that the BNNTs/amino acid complex dissolution in water is spontaneous. The adsorption energies and quantum molecular descriptors changed in the presence of external EF. Therefore, the study of BNNTs/amino acid complex under influence of external electric field is very important in proposing or designing new drug delivery systems in the presence of external EF. Results indicate that Glu, Lys, Gly and Ser amino acids can be adsorbed considerably on the BNNTs in the existence of external electric field. Our results showed that the BNNTs can act as a suitable drug delivery vehicle of Glu, Lys, Gly and Ser amino acids within biological systems and strength of adsorption and rate of drug release can be controlled by the external EF
Optimization of a truck-drone in tandem delivery network using K-means and genetic algorithm
Mourelo Ferrandez, Sergio; Harbison, Timothy; Webwer, Troy; Sturges, Robert; Rich, Robert
2016-01-01
Purpose: The purpose of this paper is to investigate the effectiveness of implementing unmanned aerial delivery vehicles in delivery networks. We investigate the notion of the reduced overall delivery time and energy for a truck-drone network by comparing the in-tandem system with a stand-alone delivery effort. The objectives are (1) to investigate the time and energy associated to a truck-drone delivery network compared to standalone truck or drone, (2) to propose an optimizat...
Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells
Hindriksen, Sanne; Bramer, Arne J; Truong, My Anh; Vromans, Martijn J M; Post, Jasmin B; Verlaan-Klink, Ingrid; Snippert, Hugo J; Lens, Susanne M A; Hadders, Michael A
2017-01-01
The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited
Williams, Alwyn; Kane, Daniel A; Ewing, Patrick M; Atwood, Lesley W; Jilling, Andrea; Li, Meng; Lou, Yi; Davis, Adam S; Grandy, A Stuart; Huerd, Sheri C; Hunter, Mitchell C; Koide, Roger T; Mortensen, David A; Smith, Richard G; Snapp, Sieglinde S; Spokas, Kurt A; Yannarell, Anthony C; Jordan, Nicholas R
2016-01-01
There is increasing global demand for food, bioenergy feedstocks and a wide variety of bio-based products. In response, agriculture has advanced production, but is increasingly depleting soil regulating and supporting ecosystem services. New production systems have emerged, such as no-tillage, that can enhance soil services but may limit yields. Moving forward, agricultural systems must reduce trade-offs between production and soil services. Soil functional zone management (SFZM) is a novel strategy for developing sustainable production systems that attempts to integrate the benefits of conventional, intensive agriculture, and no-tillage. SFZM creates distinct functional zones within crop row and inter-row spaces. By incorporating decimeter-scale spatial and temporal heterogeneity, SFZM attempts to foster greater soil biodiversity and integrate complementary soil processes at the sub-field level. Such integration maximizes soil services by creating zones of 'active turnover', optimized for crop growth and yield (provisioning services); and adjacent zones of 'soil building', that promote soil structure development, carbon storage, and moisture regulation (regulating and supporting services). These zones allow SFZM to secure existing agricultural productivity while avoiding or minimizing trade-offs with soil ecosystem services. Moreover, the specific properties of SFZM may enable sustainable increases in provisioning services via temporal intensification (expanding the portion of the year during which harvestable crops are grown). We present a conceptual model of 'virtuous cycles', illustrating how increases in crop yields within SFZM systems could create self-reinforcing feedback processes with desirable effects, including mitigation of trade-offs between yield maximization and soil ecosystem services. Through the creation of functionally distinct but interacting zones, SFZM may provide a vehicle for optimizing the delivery of multiple goods and services in
Directory of Open Access Journals (Sweden)
Alwyn eWilliams
2016-02-01
Full Text Available There is increasing global demand for food, bioenergy feedstocks and a wide variety of bio-based products. In response, agriculture has advanced production, but is increasingly depleting soil regulating and supporting ecosystem services. New production systems have emerged, such as no-tillage, that can enhance soil services but may limit yields. Moving forward, agricultural systems must reduce trade-offs between production and soil services. Soil functional zone management (SFZM is a novel strategy for developing sustainable production systems that attempts to integrate the benefits of conventional, intensive agriculture and no-tillage. SFZM creates distinct functional zones within crop row and inter-row spaces. By incorporating decimetre-scale spatial and temporal heterogeneity, SFZM attempts to foster greater soil biodiversity and integrate complementary soil processes at the sub-field level. Such integration maximizes soil services by creating zones of ‘active turnover’, optimized for crop growth and yield (provisioning services; and adjacent zones of ‘soil building’, that promote soil structure development, carbon storage and moisture regulation (regulating and supporting services. These zones allow SFZM to secure existing agricultural productivity while avoiding or minimizing trade-offs with soil ecosystem services. Moreover, the specific properties of SFZM may enable sustainable increases in provisioning services via temporal intensification (expanding the portion of the year during which harvestable crops are grown. We present a conceptual model of ‘virtuous cycles’, illustrating how increases in crop yields within SFZM systems could create self-reinforcing feedback processes with desirable effects, including mitigation of trade-offs between yield maximization and soil ecosystem services. Through the creation of functionally distinct but interacting zones, SFZM may provide a vehicle for optimizing the delivery of multiple
16 CFR 309.15 - Posting of non-liquid alternative vehicle fuel rating.
2010-01-01
... rating. (a) If you are a retailer who offers for sale or sells non-liquid alternative vehicle fuel (other... fuel. If you are a retailer who offers for sale or sells electricity to consumers through an electric... vehicle fuel dispensing system, either by letter or on the delivery ticket or other paper, or by a...
Directory of Open Access Journals (Sweden)
Kh. Broumandfar
2012-04-01
Full Text Available Background: Desirable sexual function has an important role in strengthening the marital life of the couples. Sexual disorders can cause mental pressure and affect quality of life and marital relationship. Methods: This was a descriptive correlation study in one group and one phase covering multivariables. The study sample included 384 women after delivery period that had the following inclusion criteria: the age of at least 18 years, delivery in 38-42 pregnancy weeks, primiparous and multiparous women, living in the city, single pregnancy, and twelve months elapsed from the delivery. The required data such demographic, marital satisfaction and sexual function index were collected through reporting questionnaire. The data were analyzed using descriptive and inferential statistical methods using software SPSS. Results: The findings of the study indicated that the most prevalent disorder of the sexual relationship in postpartum was dyspareunia and the least prevalent was the sexual desire. There was no significant association between sexual function and, age, education degree , body mass index ,body size and job, but there was a significant association for other factors such as the economic, residence and marital satisfaction (p<0.01. Conclusion: It is recommended that sexual problems after delivery be placed on the list of health teaching issues to pass easily this period of time. Women should be assured that these problems gradually would be improved and they should learn using proper techniques to decrease dyspareunia which is a sexual disorder in postpartum period.
Frank, Andrew A.
1984-01-01
A control system and method for a power delivery system, such as in an automotive vehicle, having an engine coupled to a continuously variable ratio transmission (CVT). Totally independent control of engine and transmission enable the engine to precisely follow a desired operating characteristic, such as the ideal operating line for minimum fuel consumption. CVT ratio is controlled as a function of commanded power or torque and measured load, while engine fuel requirements (e.g., throttle position) are strictly a function of measured engine speed. Fuel requirements are therefore precisely adjusted in accordance with the ideal characteristic for any load placed on the engine.
Modeling of electric vehicle battery for vehicle-to-grid applications
DEFF Research Database (Denmark)
Pang, Ying; Brady, Cormac; Pellegrino, Giustino
2013-01-01
Electric vehicle battery models are essential when performing analysis of EV systems. The battery package of electric vehicles is complicated and unpredictable because of its chemical based functioning. In this paper, a battery model is presented with a number of internal and external factors taken...
Automated driving and autonomous functions on road vehicles
Gordon, T. J.; Lidberg, M.
2015-07-01
In recent years, road vehicle automation has become an important and popular topic for research and development in both academic and industrial spheres. New developments have received extensive coverage in the popular press, and it may be said that the topic has captured the public imagination. Indeed, the topic has generated interest across a wide range of academic, industry and governmental communities, well beyond vehicle engineering; these include computer science, transportation, urban planning, legal, social science and psychology. While this follows a similar surge of interest - and subsequent hiatus - of Automated Highway Systems in the 1990s, the current level of interest is substantially greater, and current expectations are high. It is common to frame the new technologies under the banner of 'self-driving cars' - robotic systems potentially taking over the entire role of the human driver, a capability that does not fully exist at present. However, this single vision leads one to ignore the existing range of automated systems that are both feasible and useful. Recent developments are underpinned by substantial and long-term trends in 'computerisation' of the automobile, with developments in sensors, actuators and control technologies to spur the new developments in both industry and academia. In this paper, we review the evolution of the intelligent vehicle and the supporting technologies with a focus on the progress and key challenges for vehicle system dynamics. A number of relevant themes around driving automation are explored in this article, with special focus on those most relevant to the underlying vehicle system dynamics. One conclusion is that increased precision is needed in sensing and controlling vehicle motions, a trend that can mimic that of the aerospace industry, and similarly benefit from increased use of redundant by-wire actuators.
Intelligent Vehicle Health Management
Paris, Deidre E.; Trevino, Luis; Watson, Michael D.
2005-01-01
As a part of the overall goal of developing Integrated Vehicle Health Management systems for aerospace vehicles, the NASA Faculty Fellowship Program (NFFP) at Marshall Space Flight Center has performed a pilot study on IVHM principals which integrates researched IVHM technologies in support of Integrated Intelligent Vehicle Management (IIVM). IVHM is the process of assessing, preserving, and restoring system functionality across flight and ground systems (NASA NGLT 2004). The framework presented in this paper integrates advanced computational techniques with sensor and communication technologies for spacecraft that can generate responses through detection, diagnosis, reasoning, and adapt to system faults in support of INM. These real-time responses allow the IIVM to modify the affected vehicle subsystem(s) prior to a catastrophic event. Furthermore, the objective of this pilot program is to develop and integrate technologies which can provide a continuous, intelligent, and adaptive health state of a vehicle and use this information to improve safety and reduce costs of operations. Recent investments in avionics, health management, and controls have been directed towards IIVM. As this concept has matured, it has become clear the INM requires the same sensors and processing capabilities as the real-time avionics functions to support diagnosis of subsystem problems. New sensors have been proposed, in addition, to augment the avionics sensors to support better system monitoring and diagnostics. As the designs have been considered, a synergy has been realized where the real-time avionics can utilize sensors proposed for diagnostics and prognostics to make better real-time decisions in response to detected failures. IIVM provides for a single system allowing modularity of functions and hardware across the vehicle. The framework that supports IIVM consists of 11 major on-board functions necessary to fully manage a space vehicle maintaining crew safety and mission
Assessment of Beta-Cell Function During Pregnancy and after Delivery
Directory of Open Access Journals (Sweden)
Genova M. P.
2014-06-01
Full Text Available The aim of the present study was to assess β-cell function using homeostasis model (HOMA-B and disposition index (DI in pregnant women with/without gestational diabetes, and after delivery. A total of 102 pregnant women between 24-28 gestational weeks (53 with gestational diabetes mellitus (GDM and 49 with normal glucose tolerance (NGT and 22 GDM postpartum women (8-12 weeks after delivery were included in the study. All postpartum women had a history of GDM. HOMA indexes (insulin resistance - HOMA-IR and HOMA-B for assessing β-cell function were calculated from fasting glucose and insulin concentrations. To estimate insulin secretion independent of insulin sensitivity, DI was calculated using glucose and insulin levels at 0 and 60 min during the course of a 2 h 75g oral glucose tolerance test (OGTT. In GDM pregnant women HOMA-B was significantly lower compared to NGT women (p = 0.017, but there was no significant difference compared to women after birth (NS. There was difference between NGT and postpartum women (p < 0.05. DI was significantly lower for GDM pregnant women in comparison to NGT and postpartum women (p < 0.0001; p = 0.011, between NGT and women after birth (p < 0.04. In our study, comparison of НОМА-В in NGT and GDM pregnant women demonstrated that the OR of developing GDM was 0.989 (95% CI, 0.980-0.998, P = 0.013, and comparison of DI in healthy pregnant and GDM showed that the OR of developing GDM was 0.967 (95% CI, 0.947-0.988, P = 0.002. Therefore, HOMA-B and DI appear to be protective factors in the risk of developing GDM. According to our results, assessment of β-cell function, using HOMA-B and DI, showed that they are lower in GDM than NGT group and postpartum women. It is important to note that HOMA-B did not show significant difference between GDM pregnant and women after delivery with a history for GDM. We assume that pregnant women with GDM have a pancreatic β-cell defect that remains after birth. These women
Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems.
Kaur, Randeep; Badea, Ildiko
2013-01-01
Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.
Energy Technology Data Exchange (ETDEWEB)
Pohl, Hans
2013-03-15
The report presents results from an international survey covering the status and development of tractionary fuel cells. Interviews, study visits, reports, journals, media coverage and participation in IEA Advanced Fuel Cells Annex 26 have served as main sources of information. The development in Korea has been devoted particular attention this period. The report covers the development during the second part of 2011 and the whole 2012. The transport sector must change to provide mobility for people and goods in a long-term sustainable way. Fuel cell technology offers an important opportunity for the vehicle manufacturer and the vehicle user to maintain the same level of performance, comfort and versatility without compromising the sustainability requirements. Fuel cell vehicles typically use polymer electrolyte fuel cells (PEFC) and pressurized hydrogen. They also use tractionary batteries for about the same reasons as other hybrid electric vehicles. For commercial vehicles fuel cells are developed for the production of auxiliary power, to be used when the vehicles are parked, for example. Until 2015, Hyundai aims at making up to 1,000 fuel cell vehicles. After 2015 the plan is for several thousand every year. Until 2025, Hyundai aims at a total delivery of more than 100,000 fuel cell vehicles and the technology is then expected to be fully competitive. A roadmap shows that Korea until 2015 has established 43 and until 2030, a total of 500 hydrogen refuelling stations are indicated. The Skaane Region has carried out the first Swedish procurement of fuel cell vehicles. Two Hyundai iX35 FCEV were purchased for delivery 2013. In addition, the city of Copenhagen has purchased 15 such vehicles. During the next few years three hydrogen refuelling stations will be established in the Copenhagen area. January 2012, the California Air Resources Board decided the new set of regulations Advanced Clean Cars. It comprises three parts; tailpipe emissions and greenhouse gases, Zero
Yanes, Rolando Eduardo
Mesoporous silica nanoparticles (MSNs) are attractive drug delivery vehicle candidates due to their biocompatibility, stability, high surface area and efficient cellular uptake. In this dissertation, I discuss three aspects of MSNs' cellular behavior. First, MSNs are targeted to primary and metastatic cancer cell lines, then their exocytosis from cancer cells is studied, and finally they are used to recover intracellular proteins. Targeting of MSNs to primary cancer cells is achieved by conjugating transferrin on the surface of the mesoporous framework, which resulted in enhancement of nanoparticle uptake and drug delivery efficacy in cells that overexpress the transferrin receptor. Similarly, RGD peptides are used to target metastatic cancer cell lines that over-express integrin alphanubeta3. A circular RGD peptide is bound to the surface of MSNs and the endocytosis and cell killing efficacy of camptothecin loaded nanoparticles is significantly improved in cells that express the target receptor. Besides targeting, I studied the ultimate fate of phosphonate coated mesoporous silica nanoparticles inside cells. I discovered that the nanoparticles are exocytosed from cells through lysosomal exocytosis. The nanoparticles are exocytosed in intact form and the time that they remain inside the cells is affected by the surface properties of the nanoparticles and the type of cells. Cells that have a high rate of lysosomal exocytosis excrete the nanoparticles rapidly, which makes them more resistant to drug loaded nanoparticles because the amount of drug that is released inside the cell is limited. When the exocytosis of MSNs is inhibited, the cell killing efficacy of nanoparticles loaded with camptothecin is enhanced. The discovery that MSNs are exocytosed by cells led to a study to determine if proteins could be recovered from the exocytosed nanoparticles. The procedure to isolate exocytosed zinc-doped iron core MSNs and identify the proteins bound to them was developed
Postupalenko, Viktoriia; Desplancq, Dominique; Orlov, Igor; Arntz, Youri; Spehner, Danièle; Mely, Yves; Klaholz, Bruno P; Schultz, Patrick; Weiss, Etienne; Zuber, Guy
2015-09-01
Recombinant proteins with cytosolic or nuclear activities are emerging as tools for interfering with cellular functions. Because such tools rely on vehicles for crossing the plasma membrane we developed a protein delivery system consisting in the assembly of pyridylthiourea-grafted polyethylenimine (πPEI) with affinity-purified His-tagged proteins pre-organized onto a nickel-immobilized polymeric guide. The guide was prepared by functionalization of an ornithine polymer with nitrilotriacetic acid groups and shown to bind several His-tagged proteins. Superstructures were visualized by electron and atomic force microscopy using 2 nm His-tagged gold nanoparticles as probes. The whole system efficiently carried the green fluorescent protein, single-chain antibodies or caspase 3, into the cytosol of living cells. Transduction of the protease caspase 3 induced apoptosis in two cancer cell lines, demonstrating that this new protein delivery method could be used to interfere with cellular functions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Hu, Weihua; Wang, Jing; He, Xiangfeng; Zhang, Hongyi; Yu, Fangliu; Jiang, Longwei; Chen, Dengyu; Chen, Junsong; Dou, Jun
2011-01-01
Ovarian cancer causes more deaths than any other cancer of the female reproductive system, and its overall cure rate remains low. The present study investigated human umbilical blood mononuclear cell (UBMC)-derived mesenchymal stem cells (UBMC-MSCs) as interleukin-21 (IL-21) gene delivery vehicles for ovarian cancer therapy in nude mice. MSCs were isolated from UBMCs and the expanded cells were phenotyped by flow cytometry. Cultured UBMCs were differentiated into osteocytes and adipocytes using appropriate media and then the UBMC-MSCs were transfected with recombinant pIRES2-IL-21-enhancement green fluorescent protein. UBMC-MSCs expressing IL-21 were named as UBMC-MSC-IL-21. Mice with A2780 ovarian cancer were treated with UBMC-MSC-IL-21 intravenously, and the therapeutic efficacy was evaluated by the tumor volume and mouse survival. To address the mechanism of UBMC-MSC-IL-21 against ovarian cancer, the expression of IL-21, natural killer glucoprotein 2 domain and major histocompatibility complex class I chain-related molecules A/B were detected in UBMC-MSC-IL-21 and in the tumor sites. Interferon-γ-secreting splenocyte numbers and natural killer cytotoxicity were significantly increased in the UBMC-MSC-IL-21-treated mice as compared with the UBMC-MSCs or the UBMC-MSC-mock plasmid-treated mice. Most notably, tumor growth was delayed and survival was prolonged in ovarian-cancer-bearing mice treated with UBMC-MSC-IL-21. Our data provide important evidence that UBMC-MSCs can serve as vehicles for IL-21 gene delivery and inhibit the established tumor. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.
A Rich Vehicle Routing Problem with Multiple Trips and Driver Shifts
Arda, Yasemin; Crama, Yves; Kucukaydin, Hande; Talla Nobibon, Fabrice
2012-01-01
This study is concerned with a rich vehicle routing problem (RVRP) encountered at a Belgian transportation company in charge of servicing supermarkets and hypermarkets belonging to a franchise. The studied problem can be classified as a one-to-many-to-one pick-up and delivery problem, where there is a single depot from which all delivery customers are served and to which every pick-up demand must be carried back (Gutiérrez-Jarpa et al., 2010). The delivery and backhaul customers are considere...
The split delivery capacitated team orienteering problem
Archetti, C.; Bianchessi, N.; Speranza, M. G.; Hertz, A.
2014-01-01
In this article, we study the capacitated team orienteering problem where split deliveries are allowed. A set of potential customers is given, each associated with a demand and a profit. The set of customers to be served by a fleet of capacitated vehicles has to be identified in such a way that the
Fuel cell mining vehicles: design, performance and advantages
International Nuclear Information System (INIS)
Betournay, M.C.; Miller, A.R.; Barnes, D.L.
2003-01-01
The potential for using fuel cell technology in underground mining equipment was discussed with reference to the risks associated with the operation of hydrogen vehicles, hydrogen production and hydrogen delivery systems. This paper presented some of the initiatives for mine locomotives and fuel cell stacks for underground environments. In particular, it presents the test results of the first applied industrial fuel cell vehicle in the world, a mining and tunneling locomotive. This study was part of an international initiative managed by the Fuel Cell Propulsion Institute which consists of several mining companies, mining equipment manufacturers, and fuel cell technology developers. Some of the obvious benefits of fuel cells for underground mining operations include no exhaust gases, lower electrical costs, significantly reduced maintenance, and lower ventilation costs. Another advantage is that the technology can be readily automated and computer-based for tele-remote operations. This study also quantified the cost and operational benefits associated with fuel cell vehicles compared to diesel vehicles. It is expected that higher vehicle productivity could render fuel cell underground vehicles cost-competitive. 6 refs., 1 tab
Functional design of heat exchange for pneumatic vehicles
Xu, Z. G.; Yang, D. Y.; Shen, W. D.; Liu, T. T.
2017-10-01
With the increasingly serious environmental problems, especially the impact of fog and haze, the development of air powered vehicles has become an important research direction of new energy vehicles. Quadrature test was done with different materials, i.e. stainless steel and aluminum alloy, at different inlet pressures, using different expansion gases, i.e. air, CO2, for heat exchanging properties for pneumatic vehicles. The mathematics as well as simulation methods are used to analyze the different heat exchanging effects in the multistage cylinder. The research results showed that the stainless steel has better effects in heat exchanging than Aluminum Alloy; the intake pressure has little effect on CO2 than the air in heat exchanging effect. CO2 is better in heat exchanging than air.
Communications data delivery system analysis : public workshop read-ahead document.
2012-04-09
This document presents an overview of work conducted to date around development and analysis of communications data delivery systems for : supporting transactions in the connected vehicle environment. It presents the results of technical analysis of ...
Functional Hybrid Biomaterials based on Peptide-Polymer Conjugates for Nanomedicine
Shu, Jessica Yo
, biological evaluations were performed to investigate the potential of micelles as drug delivery vehicles. In vitro cell studies demonstrated that the micelles can be used as a delivery vehicle to tailor the cellular uptake, time release, and intracellular trafficking of drugs. In vivo biodistribution and pharmacokinetic experiments showed long blood circulation. This work demonstrates that peptide-polymer conjugates can be used as building blocks to generate hierarchical functional nanostructures with a wide range of applications, only one of which is drug delivery.
T cells enhance gold nanoparticle delivery to tumors in vivo
Kennedy, Laura C.; Bear, Adham S.; Young, Joseph K.; Lewinski, Nastassja A.; Kim, Jean; Foster, Aaron E.; Drezek, Rebekah A.
2011-12-01
Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.
International Nuclear Information System (INIS)
Sena, P.A.
1986-01-01
The ground vehicle is one of the most effective tools available to an adversary force. Vehicles can be used to penetrate many types of perimeter barriers, transport equipment and personnel rapidly over long distances, and deliver large amounts of explosives directly to facilities in suicide missions. The function of a vehicle barrier system is to detain or disable a defined threat vehicle at a selected distance from a protected facility. Numerous facilities are installing, or planning to install, vehicle barrier systems and many of these facilities are requesting guidance to do so adequately. Therefore, vehicle barriers are being evaluated to determine their stopping capabilities so that systems can be designed that are both balanced and capable of providing a desired degree of protection. Equally important, many of the considerations that should be taken into account when establishing a vehicle barrier system have been identified. These considerations which pertain to site preparation, barrier selection, system integration and operation, and vehicle/barrier interaction, are discussed in this paper
Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong
2017-12-01
Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.
Implementing electric vehicles in urban distribution: A discrete event simulation
Lebeau, Philippe; Macharis, Cathy; Mierlo, Joeri Van; Maes, Guillaume
2013-01-01
Urban freight transport becomes increasingly important with the development of cities. However, it generates also inefficiencies on social, economic and environmental aspects. A possible solution is the use of urban distribution centres in order to rationalise the deliveries and to operate the last miles with clean vehicles. Electric vehicles are gaining attention lately but some barriers remain. Since costs barriers were already investigated, the paper aimed at evaluating the difference of p...
Exosomes: Nanoparticulate tools for RNA interference and drug delivery.
Shahabipour, Fahimeh; Barati, Nastaran; Johnston, Thomas P; Derosa, Giuseppe; Maffioli, Pamela; Sahebkar, Amirhossein
2017-07-01
Exosomes are naturally occurring extracellular vesicles released by most mammalian cells in all body fluids. Exosomes are known as key mediators in cell-cell communication and facilitate the transfer of genetic and biochemical information between distant cells. Structurally, exosomes are composed of lipids, proteins, and also several types of RNAs which enable these vesicles to serve as important disease biomarkers. Moreover, exosomes have emerged as novel drug and gene delivery tools owing to their multiple advantages over conventional delivery systems. Recently, increasing attention has been focused on exosomes for the delivery of drugs, including therapeutic recombinant proteins, to various target tissues. Exosomes are also promising vehicles for the delivery of microRNAs and small interfering RNAs, which is usually hampered by rapid degradation of these RNAs, as well as inefficient tissue specificity of currently available delivery strategies. This review highlights the most recent accomplishments and trends in the use of exosomes for the delivery of drugs and therapeutic RNA molecules. © 2017 Wiley Periodicals, Inc.
Full truckload vehicle routing problem with profits
Directory of Open Access Journals (Sweden)
Jian Li
2014-04-01
Full Text Available A new variant of the full truckload vehicle routing problem is studied. In this problem there are more than one delivery points corresponding to the same pickup point, and one order is allowed to be served several times by the same vehicle or different vehicles. For the orders which cannot be assigned because of resource constraint, the logistics company outsources them to other logistics companies at a certain cost. To maximize its profits, logistics company decides which to be transported by private fleet and which to be outsourced. The mathematical model is constructed for the problem. Since the problem is NP-hard and it is difficult to solve the large-scale problems with an exact algorithm, a hybrid genetic algorithm is proposed. Computational results show the effectiveness of the hybrid genetic algorithm.
Advanced Space Transportation Concepts and Propulsion Technologies for a New Delivery Paradigm
Robinson, John W.; McCleskey, Carey M.; Rhodes, Russel E.; Lepsch, Roger A.; Henderson, Edward M.; Joyner, Claude R., III; Levack, Daniel J. H.
2013-01-01
This paper describes Advanced Space Transportation Concepts and Propulsion Technologies for a New Delivery Paradigm. It builds on the work of the previous paper "Approach to an Affordable and Productive Space Transportation System". The scope includes both flight and ground system elements, and focuses on their compatibility and capability to achieve a technical solution that is operationally productive and also affordable. A clear and revolutionary approach, including advanced propulsion systems (advanced LOX rich booster engine concept having independent LOX and fuel cooling systems, thrust augmentation with LOX rich boost and fuel rich operation at altitude), improved vehicle concepts (autogeneous pressurization, turbo alternator for electric power during ascent, hot gases to purge system and keep moisture out), and ground delivery systems, was examined. Previous papers by the authors and other members of the Space Propulsion Synergy Team (SPST) focused on space flight system engineering methods, along with operationally efficient propulsion system concepts and technologies. This paper continues the previous work by exploring the propulsion technology aspects in more depth and how they may enable the vehicle designs from the previous paper. Subsequent papers will explore the vehicle design, the ground support system, and the operations aspects of the new delivery paradigm in greater detail.
Prausnitz, Mark R.; Langer, Robert
2009-01-01
Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767
Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform
Energy Technology Data Exchange (ETDEWEB)
Fischer, Nicholas O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Weilhammer, Dina R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Dunkle, Alexis [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Thomas, Cynthia [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Hwang, Mona [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Corzett, Michele [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Lychak, Cheri [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Mayer, Wasima [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Urbin, Salustra [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Collette, Nicole [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Chiun Chang, Jiun [Univ. of California, Merced, CA (United States). School of Natural Sciences; Loots, Gabriela G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Univ. of California, Merced, CA (United States). School of Natural Sciences; Rasley, Amy [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Blanchette, Craig D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division; Ceña, Valentin [Univ. of Castilla-La Mancha, Real (Spain)
2014-03-27
Nanoparticles hold great promise for the delivery of therapeutics, yet limitations remain with regards to the use of these nanosystems for efficient long-lasting targeted delivery of therapeutics, including imparting functionality to the platform, in vivo stability, drug entrapment efficiency and toxicity. In order to begin to address these limitations, we evaluated the functionality, stability, cytotoxicity, toxicity, immunogenicity and in vivo biodistribution of nanolipoprotein particles (NLPs), which are mimetics of naturally occurring high-density lipoproteins (HDLs). We also found that a wide range of molecules could be reliably conjugated to the NLP, including proteins, single-stranded DNA, and small molecules. The NLP was also found to be relatively stable in complex biological fluids and displayed no cytotoxicity in vitro at doses as high as 320 µg/ml. In addition, we observed that in vivo administration of the NLP daily for 14 consecutive days did not induce significant weight loss or result in lesions on excised organs. Furthermore, the NLPs did not display overt immunogenicity with respect to antibody generation. Finally, the biodistribution of the NLP in vivo was found to be highly dependent on the route of administration, where intranasal administration resulted in prolonged retention in the lung tissue. Though only a select number of NLP compositions were evaluated, the findings of this study suggest that the NLP platform holds promise for use as both a targeted and non-targeted in vivo delivery vehicle for a range of therapeutics.
Wood, Matthew D; MacEwan, Matthew R; French, Alexander R; Moore, Amy M; Hunter, Daniel A; Mackinnon, Susan E; Moran, Daniel W; Borschel, Gregory H; Sakiyama-Elbert, Shelly E
2010-08-15
Glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) have both been shown to enhance peripheral nerve regeneration following injury and target different neuronal populations. The delivery of either growth factor at the site of injury may, therefore, result in quantitative differences in motor nerve regeneration and functional recovery. In this study we evaluated the effect of affinity-based delivery of GDNF or NGF from fibrin-filled nerve guidance conduits (NGCs) on motor nerve regeneration and functional recovery in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated consisting of GDNF or NGF and the affinity-based delivery system (DS) within NGCs, control groups excluding the DS and/or growth factor, and nerve isografts. Groups with growth factor in the conduit demonstrated equivalent or superior performance in behavioral tests and relative muscle mass measurements compared to isografts at 12 weeks. Additionally, groups with GDNF demonstrated greater specific twitch and tetanic force production in extensor digitorum longus (EDL) muscle than the isograft control, while groups with NGF produced demonstrated similar force production compared to the isograft control. Assessment of motor axon regeneration by retrograde labeling further revealed that the number of ventral horn neurons regenerating across NGCs containing GDNF and NGF DS was similar to the isograft group and these counts were greater than the groups without growth factor. Overall, the GDNF DS group demonstrated superior functional recovery and equivalent motor nerve regeneration compared to the isograft control, suggesting it has potential as a treatment for motor nerve injury.
Chemical functionalization of hyaluronic acid for drug delivery applications
Energy Technology Data Exchange (ETDEWEB)
Vasi, Ana-Maria [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); Popa, Marcel Ionel, E-mail: mipopa@ch.tuiasi.ro [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); Butnaru, Maria [“Grigore T. Popa” University of Medicine Pharmacy, Faculty of Medical Bioengineering, 9-13 Kogalniceanu Street, 700454 Iasi (Romania); Dodi, Gianina [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); SCIENT — Research Center for Instrumental Analysis, S.C. CROMATEC PLUS, 18 Sos. Cotroceni, 060114 Bucharest (Romania); Verestiuc, Liliana [“Grigore T. Popa” University of Medicine Pharmacy, Faculty of Medical Bioengineering, 9-13 Kogalniceanu Street, 700454 Iasi (Romania)
2014-05-01
Functionalized hyaluronic acid (HA) derivatives were obtained by ring opening mechanism of maleic anhydride (MA). FTIR and H{sup 1} NMR spectroscopy were used to confirm the chemical linkage of MA on the hyaluronic acid chains. Thermal analysis (TG-DTG and DSC) and GPC data for the new products revealed the formation of new functional groups, without significant changes in molecular weight and thermal stability. New gels based on hyaluronic acid modified derivatives were obtained by acrylic acid copolymerization in the presence of a redox initiation system. The resulted circular and interconnected pores of the gels were visualized by SEM. The release profiles of an ophthalmic model drug, pilocarpine from tested gels were studied in simulated media. Evaluation of the cytotoxicity and cell proliferation properties indicates the potential of the new systems to be used in contact with biological media in drug delivery applications. - Highlights: • New functionalized hyaluronic acid was prepared by ring opening of maleic anhydride. • Gels with circular pores based on acrylic acid copolymerization were formulated. • In vitro drug loading/release profile was evaluated in simulated ophthalmic media. • The cytotoxicity indicates the potential of derivatives to be used in vivo.
alpha-MSH and Org.2766 in peripheral nerve regeneration: different routes of delivery.
Van der Zee, C E; Brakkee, J H; Gispen, W H
1988-03-15
The efficacy of melanocortins (alpha-MSH and an ACTH-(4-9) analog, Org.2766) in accelerating functional recovery from sciatic nerve damage following various types of subcutaneous and oral administration was assessed in the rat. Furthermore, the effectiveness of the local delivery of melanocortins to the site of injury was examined. An accelerated recovery was evident following subcutaneous constant delivery of Org.2766 from an osmotic mini-pump and from biodegradable polymere microspheres, and was as effective as repeated subcutaneous injections of alpha-MSH or Org.2766. Oral administration of Org.2766 was ineffective. Local application of Org.2766, achieved by wrapping a peptide-impregnated biodegradable gelatine foam matrix around the site of injury, facilitated recovery as well. The biodegradable microspheres and gelatine foam matrix may be of importance in eventual clinical use as effective vehicles for administration of melanocortins in the treatment of peripheral nerve damage.
Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery.
Sajeesh, S; Vauthier, C; Gueutin, C; Ponchel, G; Sharma, Chandra P
2010-08-01
In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system. Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles. The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions. Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated. Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles. PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue. Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles. From these studies thiolation of hydrogel microparticles seems to be a promising approach to improve oral delivery of proteins/peptides. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
In vitro and in vivo delivery of therapeutic proteins using cell penetrating peptides.
Bolhassani, Azam; Jafarzade, Behnaz Sadat; Mardani, Golnaz
2017-01-01
The failure of proteins to penetrate mammalian cells or target tumor cells restricts their value as therapeutic tools in a variety of diseases such as cancers. Recently, protein transduction domains (PTDs) or cell penetrating peptides (CPPs) have been shown to promote the delivery of therapeutic proteins or peptides into live cells. The successful delivery of proteins mainly depends on their physicochemical properties. Although, linear cell penetrating peptides are one of the most effective delivery vehicles; but currently, cyclic CPPs has been developed to potently transport bioactive full-length proteins into cells. Up to now, several small protein transduction domains from viral proteins including Tat or VP22 could be fused to other peptides or proteins to entry them in various cell types at a dose-dependent approach. A major disadvantage of PTD-fusion proteins is primary uptake into endosomal vesicles leading to inefficient release of the fusion proteins into the cytosol. Recently, non-covalent complex formation (Chariot) between proteins and CPPs has attracted a special interest to overcome some delivery limitations (e.g., toxicity). Many preclinical and clinical trials of CPP-based delivery are currently under evaluation. Generally, development of more efficient protein transduction domains would significantly increase the potency of protein therapeutics. Moreover, the synergistic or combined effects of CPPs with other delivery systems for protein/peptide drug delivery would promote their therapeutic effects in cancer and other diseases. In this review, we will describe the functions and implications of CPPs for delivering the therapeutic proteins or peptides in preclinical and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.
DNA origami as an in vivo drug delivery vehicle for cancer therapy.
Zhang, Qian; Jiang, Qiao; Li, Na; Dai, Luru; Liu, Qing; Song, Linlin; Wang, Jinye; Li, Yaqian; Tian, Jie; Ding, Baoquan; Du, Yang
2014-07-22
Many chemotherapeutics used for cancer treatments encounter issues during delivery to tumors in vivo and may have high levels of systemic toxicity due to their nonspecific distribution. Various materials have been explored to fabricate nanoparticles as drug carriers to improve delivery efficiency. However, most of these materials suffer from multiple drawbacks, such as limited biocompatibility and inability to engineer spatially addressable surfaces that can be utilized for multifunctional activity. Here, we demonstrate that DNA origami possessed enhanced tumor passive targeting and long-lasting properties at the tumor region. Particularly, the triangle-shaped DNA origami exhibits optimal tumor passive targeting accumulation. The delivery of the known anticancer drug doxorubicin into tumors by self-assembled DNA origami nanostructures was performed, and this approach showed prominent therapeutic efficacy in vivo. The DNA origami carriers were prepared through the self-assembly of M13mp18 phage DNA and hundreds of complementary DNA helper strands; the doxorubicin was subsequently noncovalently intercalated into these nanostructures. After conducting fluorescence imaging and safety evaluation, the doxorubicin-containing DNA origami exhibited remarkable antitumor efficacy without observable systemic toxicity in nude mice bearing orthotopic breast tumors labeled with green fluorescent protein. Our results demonstrated the potential of DNA origami nanostructures as innovative platforms for the efficient and safe drug delivery of cancer therapeutics in vivo.
Ross, Hans-Leo
2016-01-01
This book highlights the current challenges for engineers involved in product development and the associated changes in procedure they make necessary. Methods for systematically analyzing the requirements for safety and security mechanisms are described using examples of how they are implemented in software and hardware, and how their effectiveness can be demonstrated in terms of functional and design safety are discussed. Given today’s new E-mobility and automated driving approaches, new challenges are arising and further issues concerning “Road Vehicle Safety” and “Road Traffic Safety” have to be resolved. To address the growing complexity of vehicle functions, as well as the increasing need to accommodate interdisciplinary project teams, previous development approaches now have to be reconsidered, and system engineering approaches and proven management systems need to be supplemented or wholly redefined. The book presents a continuous system development process, starting with the basic requiremen...
Sampaio Oliveira, A.H.; Urrutia, S.
2017-01-01
In this paper, we consider the pickup and delivery traveling salesman problem with multiple stacks in which a single vehicle must serve a set of customer requests defined by a pair of pickup and delivery destinations of an item. The vehicle contains a fixed number of stacks, where each item is
Operator Informational Needs for Multiple Autonomous Small Vehicles
Trujillo, Anna C.; Fan, Henry; Cross, Charles D.; Hempley, Lucas E.; Cichella, Venanzio; Puig-Navarro, Javier; Mehdi, Syed Bilal
2015-01-01
With the anticipated explosion of small unmanned aerial vehicles, it is highly likely that operators will be controlling fleets of autonomous vehicles. To fulfill the promise of autonomy, vehicle operators will not be concerned with manual control of the vehicle; instead, they will deal with the overall mission. Furthermore, the one operator to many vehicles is becoming a constant meme with various industries including package delivery, search and rescue, and utility companies. In order for an operator to concurrently control several vehicles, his station must look and behave very differently than the current ground control station instantiations. Furthermore, the vehicle will have to be much more autonomous, especially during non-normal operations, in order to accommodate the knowledge deficit or the information overload of the operator in charge of several vehicles. The expected usage increase of small drones requires presenting the operational information generated by a fleet of heterogeneous autonomous agents to an operator. NASA Langley Research Center's Autonomy Incubator has brought together researchers in various disciplines including controls, trajectory planning, systems engineering, and human factors to develop an integrated system to study autonomy issues. The initial human factors effort is focusing on mission displays that would give an operator the overall status of all autonomous agents involved in the current mission. This paper will discuss the specifics of the mission displays for operators controlling several vehicles.
Nadiminti, Pavani P; Dong, Yao D; Sayer, Chad; Hay, Phillip; Rookes, James E; Boyd, Ben J; Cahill, David M
2013-03-13
Agrochemical spray formulations applied to plants are often mixed with surfactants that facilitate delivery of the active ingredient. However, surfactants cause phytotoxicity and off-target effects in the environment. We propose the use of nanostructured liquid crystalline particles (NLCP) as an alternative to surfactant-based agrochemical delivery. For this, we have compared the application of commercial surfactants, di (2-ethylhexyl) sulfosuccinate and alkyl dimethyl betaine, with NLCP made from phytantriol, at concentrations of 0.1%, 1% and 5% on the adaxial surface of leaves of four plant species Ttriticum aestivum (wheat), Zea mays (maize), Lupinus angustifolius (lupin), and Arabidopsis thaliana. In comparison with the application of surfactants there was less phytotoxicity on leaves of each species following treatment with NLCP. Following treatment of leaves with NLCP analysis of cuticular wax micromorphology revealed less wax solubilization in the monocot species. The results clearly show that there are advantages in the use of NLCP rather than surfactants for agrochemical delivery.
Carrier-free, functionalized pure drug nanorods as a novel cancer-targeted drug delivery platform
International Nuclear Information System (INIS)
Li Yanan; An Feifei; Zhang Xiaohong; Yang Yinlong; Liu Zhuang; Zhang Xiujuan
2013-01-01
A one-dimensional drug delivery system (1D DDS) is highly attractive since it has distinct advantages such as enhanced drug efficiency and better pharmacokinetics. However, drugs in 1D DDSs are all encapsulated in inert carriers, and problems such as low drug loading content and possible undesirable side effects caused by the carriers remain a serious challenge. In this paper, a novel, carrier-free, pure drug nanorod-based, tumor-targeted 1D DDS has been developed. Drugs are first prepared as nanorods and then surface functionalized to achieve excellent water dispersity and stability. The resulting drug nanorods show enhanced internalization rates mainly through energy-dependent endocytosis, with the shape-mediated nanorod (NR) diffusion process as a secondary pathway. The multiple endocytotic mechanisms lead to significantly improved drug efficiency of functionalized NRs with nearly ten times higher cytotoxicity than those of free molecules and unfunctionalized NRs. A targeted drug delivery system can be readily achieved through surface functionalization with targeting group linked amphipathic surfactant, which exhibits significantly enhanced drug efficacy and discriminates between cell lines with high selectivity. These results clearly show that this tumor-targeting DDS demonstrates high potential toward specific cancer cell lines. (paper)
A hybrid life cycle assessment of the vehicle-to-grid application in light duty commercial fleet
International Nuclear Information System (INIS)
Zhao, Yang; Tatari, Omer
2015-01-01
The vehicle-to-grid system is an approach utilizing the idle battery capacity of electric vehicles while they are parked to provide supplementary energy to the power grid. As electrification continues in light duty vehicle fleets, the application of vehicle-to-grid systems for commercial delivery truck fleets can provide extra revenue for fleet owners, and also has significant potential for reducing greenhouse gas emissions from the electricity generation sector. In this study, an economic input–output based hybrid life cycle assessment is conducted to analyze the potential greenhouse gas emissions emission savings from the use of the vehicle-to-grid system, as well as the possible emission impacts caused by battery degradation. A Monte Carlo simulation was performed to address the uncertainties that lie in the electricity exchange amount of the vehicle-to-grid service as well as the battery life of the electric vehicles. The results of this study showed that extended range electric vehicles and battery electric vehicles are both viable regulation service providers for saving greenhouse gas emissions from electricity generation if the battery wear-out from regulation services is assumed to be minimal, but the vehicle-to-grid system becomes less attractive at higher battery degradation levels. - Highlights: • The commercial delivery trucks are studied as vehicle-to-grid service providers. • Hybrid life cycle assessment is conducted to evaluate emission mitigation. • Battery degradation level and corresponding emissions and cost are evaluated. • Vehicle-to-grid service is shown to have significant emission saving effect.
Energy Technology Data Exchange (ETDEWEB)
Stephens, T. S. [Argonne National Lab. (ANL), Argonne, IL (United States); Taylor, C. H. [TA Engineering, Inc., Catonsville, MD (United States); Moore, J. S. [TA Engineering, Inc., Catonsville, MD (United States); Ward, J. [United States Department of Energy, Washington, DC (United States). Office of Energy Efficiency and Renewable Energy
2016-02-23
Under a diverse set of programs, the Vehicle Technologies and Fuel Cell Technologies offices of DOE’s Office of Energy Efficiency and Renewable Energy invest in research, development, demonstration, and deployment of advanced vehicle, hydrogen production, delivery and storage, and fuel cell technologies. This report estimates the benefits of successfully developing and deploying these technologies (a “Program Success” case) relative to a base case (the “No Program” case). The Program Success case represents the future with completely successful deployment of Vehicle Technologies Office (VTO) and Fuel Cell Technologies Office (FCTO) technologies. The No Program case represents a future in which there is no contribution after FY 2016 by the VTO or FCTO to these technologies. The benefits of advanced vehicle, hydrogen production, delivery and storage, and fuel cell technologies were estimated on the basis of differences in fuel use, primary energy use, and greenhouse gas (GHG) emissions from light-, medium- and heavy-duty vehicles, including energy and emissions from fuel production, between the base case and the Program Success case. Improvements in fuel economy of various vehicle types, growth in the stock of fuel cell vehicles and other advanced technology vehicles, and decreased GHG intensity of hydrogen production and delivery in the Program Success case over the No Program case were projected to result in savings in petroleum use and GHG emissions. Benefits were disaggregated by individual program technology areas, which included the FCTO program and the VTO subprograms of batteries and electric drives; advanced combustion engines; fuels and lubricants; materials (for reduction in vehicle mass, or “lightweighting”); and, for medium- and heavy-duty vehicles, reduction in rolling and aerodynamic resistance. Projections for the Program Success case indicate that by 2035, the average fuel economy of on-road, light-duty vehicle stock could be 47% to 76
Controlling fungal biofilms with functional drug delivery denture biomaterials.
Wen, Jianchuan; Jiang, Fuguang; Yeh, Chih-Ko; Sun, Yuyu
2016-04-01
Candida-associated denture stomatitis (CADS), caused by colonization and biofilm-formation of Candida species on denture surfaces, is a significant clinical concern. We show here that modification of conventional denture materials with functional groups can significantly increase drug binding capacity and control drug release rate of the resulting denture materials for potentially managing CADS. In our approach, poly(methyl methacrylate) (PMMA)-based denture resins were surface grafted with three kinds of polymers, poly(1-vinyl-2-pyrrolidinone) (PNVP), poly(methacrylic acid) (PMAA), and poly(2-hydroxyethyl methacrylate) (PHEMA), through plasma-initiated grafting polymerization. With a grafting yield as low as 2 wt%, the three classes of new functionalized denture materials showed significantly higher drug binding capacities toward miconazole, a widely used antifungal drug, than the original PMMA denture resin control, leading to sustained drug release and potent biofilm-controlling effects against Candida. Among the three classes of functionalized denture materials, PNVP-grafted resin provided the highest miconazole binding capability and the most powerful antifungal and biofilm-controlling activities. Drug binding mechanisms were studied. These results demonstrated the importance of specific interactions between drug molecules and functional groups on biomaterials, shedding lights on future design of CADS-managing denture materials and other related devices for controlled drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.
Heard, Charles M; Johnson, Sarah; Moss, Gary; Thomas, Chris P
2006-07-06
Extracts of guarana (Paullinia cupana) feature as putatively stimulating ingredients in a number of foods, drinks and dietary/herbal supplements. The objective of this work was to investigate in vitro the transdermal delivery of the major pharmacologically active compounds contained in guarana extract. Saturated solutions of guarana were prepared in polyethylene glycol 400 (PEG400), propylene glycol (PG) and H(2)O at 32 degrees C. Guarana extract was also formulated in Duro-tak 2287 transdermal adhesive in a range of concentrations and the diffusional release was determined in addition to adhesive properties. Transdermal delivery across full thickness pig ear skin was investigated in vitro using Franz-type diffusion cells, with reverse-phase HPLC being used for the quantification of the permeation of theobromine (TB), theophylline (TP), (+)-catechin (C) and caffeine (CF). Based upon a combination of release and adhesive property data a patch containing 5.55 mg guarana extract cm(-2) was deemed optimal. The general trend for the delivery of the 4 analytes was: water >5.55 mg cm(-2) patch approximately PG>PEG400. For CF the greatest steady state flux was obtained from the water vehicle: 19 microg cm(-2)h(-1), with approximately 420 microg cm(-2) permeating after 24h. This was some 6x times more than from the drug-in-adhesive patch and 10x greater than PG, a well-known penetration enhancer, and 50x that of the 'regular' excipient PEG400. A water vehicle also provided the greatest delivery of TB (0.45 microg cm(-2) h(-1)), TP (0.022 microg cm(-2) h(-1)), and C (0.10 microg cm(-2) h(-1)). An inverse relationship was noted between lipophilicity and k(p) in each vehicle. The simultaneous transdermal delivery of the major actives of guarana was established, with permeation rates being highly concentration and vehicle dependent.
Investigating the In-Vehicle Crowding Cost Functions for Public Transit Modes
Qin, Feifei
2014-01-01
In the densely populated metropolitan area, empirical studies have found that overcrowding inside transit vehicles has become substantially worse and worse over recent years. Chronic in-vehicle crowding is not only caused by a lack of physical infrastructure, but also triggered by inadequate service provisions. Given the prevalence of overcrowded transit vehicles, this paper conducts both quantitative and qualitative studies, especially focusing on remodeling the in-vehicle crowding cost func...
Development of A Hydraulic Drive for a novel Diesel-Hydraulic system for Large commercial Vehicles
DEFF Research Database (Denmark)
Stecki, J. S.; Conrad, Finn; Matheson, P.
2002-01-01
The objectives and results of the research project Hybrid Diesel-Hydraulic System for Large commercial vehicles, e.g. urban freight delivery, buses or garbage trucks. The paper presents and discusses the research and development of the system, modelling approach and results from preliminary...... performance tests on a 10 ton vehicle....
Simanullang, Herlin
2013-01-01
Vehicle Routing Problem (VRP) is a problem of combinatorial optimization complexeses that has essential role in management distribution system which is aimed to minimize the needed cost, the cost is determined in relationship with the distance of route which is taken by the distribution vehicle. The characteristic from VRP is the use of vehicle in certain capacity and its activity is centralized in one depot to serve the customer on certain locations with certain known demand. ...
Fuel cells for vehicle applications in cars - bringing the future closer
Panik, Ferdinand
Among all alternative drive systems, the fuel cell electric propulsion system has the highest potential to compete with the internal combustion engine. For this reason, Daimler-Benz AG has entered into a co-operative alliance with Ballard Power Systems, with the objectives of bringing fuel cell vehicles to the market. Apart from the fuel cell itself, fuel cell vehicles require comprehensive system technology to provide fuel and air supply, cooling, energy management, electric and electronic functions. The system technology determines to a large extent the cost, weight, efficiency, performance and overall customer benefit of fuel cell vehicles. Hence, Daimler-Benz and Ballard are pooling their expertise in fuel cell system technology in a joint company, with the aim of bringing their fuel cell vehicular systems to the stage of maturity required for market entry as early as possible. Hydrogen-fuelled zero-emission fuel cell transit `buses' will be the first market segment addressed, with an emphasis on the North American and European markets. The first buses are already scheduled for delivery to customers in late 1997. Since a liquid fuel like methanol is easier to handle in passenger cars, fuel reforming technologies are developed and will shortly be demonstrated in a prototype, as well. The presentation will cover concepts of fuel cell vehicles with an emphasis on system technology, the related testing procedures and results as well as an outline of market entry strategies.
Analysis of an Automated Vehicle Routing Problem in Logistics considering Path Interruption
Directory of Open Access Journals (Sweden)
Yong Zhang
2017-01-01
Full Text Available The application of automated vehicles in logistics can efficiently reduce the cost of logistics and reduce the potential risks in the last mile. Considering the path restriction in the initial stage of the application of automated vehicles in logistics, the conventional model for a vehicle routing problem (VRP is modified. Thus, the automated vehicle routing problem with time windows (AVRPTW model considering path interruption is established. Additionally, an improved particle swarm optimisation (PSO algorithm is designed to solve this problem. Finally, a case study is undertaken to test the validity of the model and the algorithm. Four automated vehicles are designated to execute all delivery tasks required by 25 stores. Capacities of all of the automated vehicles are almost fully utilised. It is of considerable significance for the promotion of automated vehicles in last-mile situations to develop such research into real problems arising in the initial period.
Kieler-Ferguson, Heidi M.
2013-01-17
For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting. Although a number of macromolecular-drug conjugates have progressed to clinical trials, tuning drug release to maintain efficacy in conjunction with controlling drug toxicity has prevented the clinical adoption of many vehicles. In this article, we review the motivations for and approaches to polymer and liposomal delivery with regard to camptothecin and cisplatin delivery. WIREs Nanomed Nanobiotechnol 2013, 5:130-138. doi: 10.1002/wnan.1209 For further resources related to this article, please visit the WIREs website. Conflict of interest: Drs Kieler-Ferguson and Fréchet declare no conflicts of interest. Dr Szoka is the founder of a liposome drug delivery company that is not working on any of the compounds mentioned in this article. © 2013 Wiley Periodicals, Inc.
Update on the Vancouver Fuel Cell Vehicle Program
International Nuclear Information System (INIS)
Rothwell, B.
2004-01-01
'Full text:' The Vancouver Fuel Cell Vehicle Program (VFCVP) is a $5.8 million initiative designed to test four Ford Focus Fuel Cell Vehicles for three years in the Lower Mainland of British Columbia. The project is the first of its kind in Canada and is led by Fuel Cells Canada (FCC), the Ford Motor Company (Ford), and the Governments of Canada and British Columbia. This presentation will provide program details and an update on activities leading up to currently planned delivery to Vancouver in November 2004. The VFCVP will test the performance, durability and reliability of the Ford fuel cell vehicle cars in real-world conditions and will examine fuelling issues and solutions, the reduction of greenhouse gas emissions and public acceptance of hydrogen fuel cell vehicles. The program will generate data to help evolve the technology and develop international codes and standards E cents Epnd the implementation and adoption of fuel cell technology. (author)
Ba, Wenqiang; Li, Zhou; Wang, Lisheng; Wang, Ding; Liao, Weiguo; Fan, Wentao; Wu, Yinai; Liao, Fengyun; Yu, Jianye
2016-08-01
The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box-Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (Jss) of SIN from PLO was 146.55 ± 2.93 μg/cm(2)/h, significantly higher than that of gel (120.39 μg/cm(2)/h) and the amount of SIN deposited in skin from the PLO was 10.08 ± 0.86 μg/cm(2), significantly larger than that from gel (6.01 ± 0.04 μg/cm(2)). In vivo skin microdialysis studies showed that the maximum concentration (Cmax) of SIN from PLO in "permeation study" and "drug-deposition study" were 150.27 ± 20.85 μg/ml and 67.95 μg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73 μg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.
Byk, G; Soto, J; Mattler, C; Frederic, M; Scherman, D
1998-01-01
The development of new gene delivery technologies is a prerequisite towards gene therapy clinical trials. Because gene delivery mediated by viral vectors remains of limited scope due to immunological and propagation risks, the development of new non-viral gene delivery systems is of crucial importance. We have synthesized a secondary library of mono-functionalized poly-(guanidinium)amines generated from a library of mono-functionalized polyamines applying the concept of "libraries from libraries." The method allows a quick and easy access to mono-functionalized geometrically varied poly-(guanidinium)amines. The new building blocks were introduced into cationic lipids to obtain novel poly-(guanidinium)amine lipids, which are potential DNA vectors for gene delivery. Copyright 1998 John Wiley & Sons, Inc.
Zhang, Li; Zhou, Qing; Song, Wen; Wu, Kaimin; Zhang, Yumei; Zhao, Yimin
2017-10-11
Surface functionalization by small interfering RNA (siRNA) is a novel strategy for improved implant osseointegration. A gene delivery system with safety and high transfection activity is a crucial factor for an siRNA-functionalized implant to exert its biological function. To this end, polyethylene glycol (PEG) and polyethylenimine (PEI) dual-functionalized graphene oxide (GO; nGO-PEG-PEI) may present a promising siRNA vector. In this study, nanosized nGO-PEG-PEI was prepared and optimized for siRNA delivery. Titania nanotubes (NTs) fabricated by anodic oxidation were biomodified with nGO-PEG-PEI/siRNA by cathodic electrodeposition, designated as NT-GPP/siRNA. NT-GPP/siRNA possessed benign cytocompatibility, as evaluated by cell adhesion and proliferation. Cellular uptake and knockdown efficiency of the NT-GPP/siRNA were assessed by MC3T3-E1 cells, which exhibited high siRNA delivery efficiency and sustained target gene silencing. Casein kinase-2 interacting protein-1 (Ckip-1) is a negative regulator of bone formation. siRNA-targeting Ckip-1 (siCkip-1) was introduced to the implant, and a series of in vitro and in vivo experiments were carried out to evaluate the osteogenic capacity of NT-GPP/siCkip-1. NT-GPP/siCkip-1 dramatically improved the in vitro osteogenic differentiation of MC3T3-E1 cells in terms of improved osteogenesis-related gene expression, and increased alkaline phosphatase (ALP) production, collagen secretion, and extracellular matrix (ECM) mineralization. Moreover, NT-GPP/siCkip-1 led to apparently enhanced in vivo osseointegration, as indicated by histological staining and EDX line scanning. Collectively, these findings suggest that NT-GPP/siRNA represents a practicable and promising approach for implant functionalization, showing clinical potential for dental and orthopedic applications.
Variability in syringe components and its impact on functionality of delivery systems.
Rathore, Nitin; Pranay, Pratik; Eu, Bruce; Ji, Wenchang; Walls, Ed
2011-01-01
drug out of the syringe and into the site of administration. Complete understanding of the spring force, syringe barrel dimensions, needle size, and drug product properties is essential for robust device design. It is equally important to estimate the extent of variability that exists in these components and the resulting impact it could have on the performance of the device. In this work, we studied the impact of variability in syringe and device components on the delivery forces associated with syringe injection. More specifically, the effect of barrel size, needle size, autoinjector spring force, and frictional forces has been evaluated. An analytical model based on underlying physics is developed that can be used to predict the functionality of the autoinjector.
Challenges in the Tracking and Prediction of Scheduled-Vehicle Journeys
DEFF Research Database (Denmark)
Jensen, Christian Søndergaard; Tiesyte, Dalia
2007-01-01
this type of knowledge with minimal cost. This paper characterizes the problem of real-time vehicle tracking using wireless communication, and of predicting the future status of the vehicles when their movements are restricted to given routes and when they follow schedules with a best effort. The paper...... discusses challenges related to tracking, to the prediction of future travel times, and to historical data analysis. It also suggests approaches to addressing the challenges.......A number of applications in areas such as logistics, cargo delivery, and collective transport involve the management of fleets of vehicles that are expected to travel along known routes according to fixed schedules. Due to road construction, accidents, and other unanticipated conditions...
Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei
2014-01-01
To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells. PMID:24591829
Energy Technology Data Exchange (ETDEWEB)
Wilde, Andreas
2009-10-27
Due to the relatively low energy density of electrical energy storage devices, the control strategy of hybrid electric vehicles has to fulfil a variety of requirements in order to provide both, the availability of hybrid functions, and their efficient execution. Energy consuming functions such as electric drive or electric boost need a high amount of energy stored in the battery. On the other hand for the optimum use of the energy regeneration function a lower state of charge is preferable in order to enable storage of the kinetic energy of the vehicle in all situations, including upon deceleration from high speeds or downhill driving. These diverging requirements yield a conflict of objectives for the charging strategy of hybrid electric vehicles. This work proposes a way to overcome the restrictions on efficiency in hybrid electric vehicles without deteriorating overall driving performance by charging or discharging the traction battery, and by setting the energy management parametres according to the current and forthcoming driving situation. Specific charging and electric drive strategies are presented for various driving situations which are identified by sensors such as navigation systems, cameras or radar. Necessary sensor data fusion methods for driving situation identification are described and a modular function architecture for predictive energy management is derived that is plug-and-play compatible with a broad fleet of vehicles. In order to evaluate its potential, this work also focuses on the simulation of the energy functions and their implementation into an experimental vehicle. This allows measurements under real traffic conditions and a sensivity analysis of the main module interactions within the architecture. (orig.)
Optimization of a truck-drone in tandem delivery network using k-means and genetic algorithm
Energy Technology Data Exchange (ETDEWEB)
Ferrandez, S. M.; Harbison, T.; Weber, T.; Sturges, R.; Rich, R.
2016-07-01
The purpose of this paper is to investigate the effectiveness of implementing unmanned aerial delivery vehicles in delivery networks. We investigate the notion of the reduced overall delivery time, energy, and costs for a truck-drone network by comparing the in-tandem system with a stand-alone delivery effort. The objectives are (1) to investigate the time, energy, and costs associated to a truck-drone delivery network compared to standalone truck or drone, (2) to propose an optimization algorithm that determines the optimal number of launch sites and locations given delivery requirements, and drones per truck, (3) to develop mathematical formulations for closed form estimations for the optimal number of launch locations, optimal total time, as well as the associated cost for the system. The design of the algorithm herein computes the minimal time of delivery utilizing K-means clustering to find launch locations, as well as a genetic algorithm to solve the truck route as a traveling salesmen problem (TSP). The optimal solution is determined by finding the minimum cost associated to the parabolic convex cost function. The optimal min-cost is determined by finding the most efficient launch locations using K-means algorithms to determine launch locations and a genetic algorithm to determine truck route between those launch locations. Results show improvements with in-tandem delivery efforts as opposed to standalone systems. Further, multiple drones per truck are more optimal and contribute to savings in both energy and time. For this, we sampled various initialization variables to derive closed form mathematical solutions for the problem. Ultimately, this provides the necessary analysis of an integrated truck-drone delivery system which could be implemented by a company in order to maximize deliveries while minimizing time and energy. Closed-form mathematical solutions can be used as close estimators for final costs and time. (Author)
Silica-Coated Liposomes for Insulin Delivery
Neelam Dwivedi; M. A. Arunagirinathan; Somesh Sharma; Jayesh Bellare
2010-01-01
Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evid...
Directory of Open Access Journals (Sweden)
HU Qi-guo
2017-01-01
Full Text Available For reducing the vehicle compartment low frequency noise, the Optimal Latin hypercube sampling method was applied to perform experimental design for sampling in the factorial design space. The thickness parameters of the panels with larger acoustic contribution was considered as factors, as well as the vehicle mass, seventh rank modal frequency of body, peak sound pressure of test point and sound pressure root-mean-square value as responses. By using the RBF(radial basis function neuro-network method, an approximation model of four responses about six factors was established. Further more, error analysis of established approximation model was performed in this paper. To optimize the panel’s thickness parameter, the adaptive simulated annealing algorithm was im-plemented. Optimization results show that the peak sound pressure of driver’s head was reduced by 4.45dB and 5.47dB at frequency 158HZ and 134Hz respec-tively. The test point pressure were significantly reduced at other frequency as well. The results indicate that through the optimization the vehicle interior cavity noise was reduced effectively, and the acoustical comfort of the vehicle was im-proved significantly.
Alendronate functionalized mesoporous hydroxyapatite nanoparticles for drug delivery
Energy Technology Data Exchange (ETDEWEB)
Li, Dongdong, E-mail: lidongchem@sina.cn [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Zhu, Yuntao; Liang, Zhiqiang [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)
2013-06-01
Highlights: ► The synthesized mesoporous hydroxyapatite has nanostructure and bioactivity. ► The materials have high surface area and amino group. ► The materials show higher drug loading and slower release rate than pure HAP. - Abstract: Mesoporous nanosized hydroxyapatite (HAP) functionalized by alendronate (ALN) was synthesized using cationic surfactant CTAB as template. The structural, morphological and textural properties were fully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and N{sub 2} adsorption/desorption. Then the obtained materials were performed as drug delivery carriers using ibuprofen (IBU) as a model drug to investigate their drug storage/release properties in simulated body fluid (SBF). The materials showed relatively slower release rate compared with HAP due to the ionic interaction between -NH{sub 3}{sup +} on the matrix and -COO{sup −}belongs to IBU. The system provides a new concept for improving the drug loading or slowing down the release rate.
Alendronate functionalized mesoporous hydroxyapatite nanoparticles for drug delivery
International Nuclear Information System (INIS)
Li, Dongdong; Zhu, Yuntao; Liang, Zhiqiang
2013-01-01
Highlights: ► The synthesized mesoporous hydroxyapatite has nanostructure and bioactivity. ► The materials have high surface area and amino group. ► The materials show higher drug loading and slower release rate than pure HAP. - Abstract: Mesoporous nanosized hydroxyapatite (HAP) functionalized by alendronate (ALN) was synthesized using cationic surfactant CTAB as template. The structural, morphological and textural properties were fully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and N 2 adsorption/desorption. Then the obtained materials were performed as drug delivery carriers using ibuprofen (IBU) as a model drug to investigate their drug storage/release properties in simulated body fluid (SBF). The materials showed relatively slower release rate compared with HAP due to the ionic interaction between -NH 3 + on the matrix and -COO − belongs to IBU. The system provides a new concept for improving the drug loading or slowing down the release rate
DEFF Research Database (Denmark)
Helsgaun, Keld
This report describes the implementation of an extension of the Lin-Kernighan-Helsgaun TSP solver for solving constrained traveling salesman and vehicle routing problems. The extension, which is called LKH-3, is able to solve a variety of well-known problems, including the sequential ordering...... problem (SOP), the traveling repairman problem (TRP), variants of the multiple travel-ing salesman problem (mTSP), as well as vehicle routing problems (VRPs) with capacity, time windows, pickup-and-delivery and distance constraints. The implementation of LKH-3 builds on the idea of transforming...... the problems into standard symmetric traveling salesman problems and handling constraints by means of penalty functions. Extensive testing on benchmark instances from the literature has shown that LKH-3 is effective. Best known solutions are often obtained, and in some cases, new best solutions are found...
Discrete Optimization Model for Vehicle Routing Problem with Scheduling Side Cosntraints
Juliandri, Dedy; Mawengkang, Herman; Bu'ulolo, F.
2018-01-01
Vehicle Routing Problem (VRP) is an important element of many logistic systems which involve routing and scheduling of vehicles from a depot to a set of customers node. This is a hard combinatorial optimization problem with the objective to find an optimal set of routes used by a fleet of vehicles to serve the demands a set of customers It is required that these vehicles return to the depot after serving customers’ demand. The problem incorporates time windows, fleet and driver scheduling, pick-up and delivery in the planning horizon. The goal is to determine the scheduling of fleet and driver and routing policies of the vehicles. The objective is to minimize the overall costs of all routes over the planning horizon. We model the problem as a linear mixed integer program. We develop a combination of heuristics and exact method for solving the model.
Rumiana Koynova
2008-01-01
Efficient delivery of genetic material to cells is needed for tasks of utmost importance in laboratory and clinic, such as gene transfection and gene silencing. Synthetic cationic lipids can be used as delivery vehicles for nucleic acids and are now considered the most promising non-viral gene carriers. They form complexes (lipoplexes) with the polyanionic nucleic acids. A critical obstacle for clinical application of the lipid-mediated DNA delivery (lipofection) is its unsatisfactory efficie...
Multicriteria vehicle routing problem solved by artificial immune system
Directory of Open Access Journals (Sweden)
Bogna MRÓWCZYŃSKA
2015-09-01
Full Text Available Vehicles route planning in large transportation companies, where drivers are workers, usually takes place on the basis of experience or intuition of the employees. Because of the cost and environmental protection, it is important to save fuel, thus planning routes in an optimal way. In this article an example of the problem is presented solving delivery vans route planning taking into account the distance and travel time within the constraints of vehicle capacities, restrictions on working time of drivers and having varying degrees of movement. An artificial immune system was used for the calculations.
Wendel, Sebastian O; Menon, Sailesh; Alshetaiwi, Hamad; Shrestha, Tej B; Chlebanowski, Lauren; Hsu, Wei-Wen; Bossmann, Stefan H; Narayanan, Sanjeev; Troyer, Deryl L
2015-01-01
The recent WHO report on antibiotic resistances shows a dramatic increase of microbial resistance against antibiotics. With only a few new antibiotics in the pipeline, a different drug delivery approach is urgently needed. We have obtained evidence demonstrating the effectiveness of a cell based drug delivery system that utilizes the innate immune system as targeting carrier for antibacterial drugs. In this study we show the efficient loading of neutrophil granulocytes with chlorhexidine and the complete killing of E. coli as well as Fusobacterium necrophorum in in-vitro studies. Fusobacterium necrophorum causes hepatic abscesses in cattle fed high grain diets. We also show in a mouse model that this delivery system targets infections of F. necrophorum in the liver and reduces the bacterial burden by an order of magnitude from approximately 2•106 to 1•105.
Measured Noise from Small Unmanned Aerial Vehicles
Cabell, Randolph; McSwain, Robert; Grosveld, Ferdinand
2016-01-01
Proposed uses of small unmanned aerial vehicles (UAVs), including home package delivery, have the potential to expose large portions of communities to a new noise source. This paper discusses results of flyover noise measurements of four small UAVs, including an internal combustion-powered model airplane and three battery-powered multicopters. Basic noise characteristics of these vehicles are discussed, including spectral properties and sound level metrics such as sound pressure level, effective perceived noise level, and sound exposure level. The size and aerodynamic characteristics of the multicopters in particular make their flight path susceptible to atmospheric disturbances such as wind gusts. These gusts, coupled with a flight control system that varies rotor speed to maintain vehicle stability, create an unsteady acoustic signature. The spectral variations resulting from this unsteadiness are explored, in both hover and flyover conditions for the multicopters. The time varying noise, which differs from the relatively steady noise generated by large transport aircraft, may complicate the prediction of human annoyance using conventional sound level metrics.
Transportable Emissions Testing Laboratory for Alternative Vehicles Emissions Testing
Energy Technology Data Exchange (ETDEWEB)
Clark, Nigel
2012-01-31
The overall objective of this project was to perform research to quantify and improve the energy efficiency and the exhaust emissions reduction from advanced technology vehicles using clean, renewable and alternative fuels. Advanced vehicle and alternative fuel fleets were to be identified, and selected vehicles characterized for emissions and efficiency. Target vehicles were to include transit buses, school buses, vocational trucks, delivery trucks, and tractor-trailers. Gaseous species measured were to include carbon monoxide, carbon dioxide, oxides of nitrogen, hydrocarbons, and particulate matter. An objective was to characterize particulate matter more deeply than by mass. Accurate characterization of efficiency and emissions was to be accomplished using a state-of-the-art portable emissions measurement system and an accompanying chassis dynamometer available at West Virginia University. These two units, combined, are termed the Transportable Laboratory. An objective was to load the vehicles in a real-world fashion, using coast down data to establish rolling resistance and wind drag, and to apply the coast down data to the dynamometer control. Test schedules created from actual vehicle operation were to be employed, and a specific objective of the research was to assess the effect of choosing a test schedule which the subject vehicle either cannot follow or can substantially outperform. In addition the vehicle loading objective was to be met better with an improved flywheel system.
Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang
2016-07-01
Functionalization of therapeutic carrier biomaterials can potentially provide additional benefits in drug delivery for disease treatment. Given that this modification determines final therapeutic efficacy of drug carriers, here, we investigate systematically the role of grafting amount of antioxidant gallic acid (GA) onto GN in situ gelling copolymers made of biodegradable gelatin and thermo-responsive poly(N-isopropylacrylamide) for intracameral delivery of pilocarpine in antiglaucoma treatment. As expected, increasing redox reaction time increased total antioxidant activities and free radical scavenging abilities of synthesized carrier biomaterials. The hydrophilic nature of antioxidant molecules strongly affected physicochemical properties of carrier materials with varying GA grafting amounts, thereby dictating in vitro release behaviors and mechanisms of pilocarpine. In vitro oxidative stress challenges revealed that biocompatible carriers with high GA content alleviated lens epithelial cell damage and reduced reactive oxygen species. Intraocular pressure and pupil diameter in glaucomatous rabbits showed correlations with GA-mediated release of pilocarpine. Additionally, enhanced pharmacological treatment effects prevented corneal endothelial cell loss during disease progression. Increasing GA content increased total antioxidant level and decreased nitrite level in the aqueous humor, suggesting a much improved antioxidant status in glaucomatous eyes. This work significantly highlights the dependence of physicochemical properties, drug release behaviors, and bioactivities on intrinsic antioxidant capacities of therapeutic carrier biomaterials for glaucoma treatment. Development of injectable biodegradable polymer depots and functionalization of carrier biomaterials with antioxidant can potentially provide benefits such as improved bioavailability, controlled release pattern, and increased therapeutic effect in intracameral pilocarpine administration for glaucoma
Czech Academy of Sciences Publication Activity Database
Al Samad, A.; Bethry, A.; Janoušková, Olga; Ciccione, J.; Wenk, C.; Coll, J.-L.; Subra, G.; Etrych, Tomáš; El Omar, F.; Bakkour, Y.; Coudane, J.; Nottelet, B.
2018-01-01
Roč. 39, č. 3 (2018), s. 1-5, č. článku 1700502. ISSN 1022-1336 R&D Projects: GA MŠk(CZ) LO1507; GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 Keywords : drug delivery systems * functionalization of polymers * photochemistry Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 4.265, year: 2016
Directory of Open Access Journals (Sweden)
Sanela Čajlaković Kurtalić
2014-09-01
Full Text Available In this paper we presented a research that estimates general psychological and functional characteristics of motor vehicle drivers, with the goal of determining the adverse effects of noise and vibration on the drivers. The study was conducted on a sample of 56 participants, professional drivers of motor vehicles, randomly chosen from companies of various types operating in transport of passengers and goods. For the evaluation of the results,we used descriptive and correlational analysis. The results showed that there were significant negative side effects caused by the nature of work of drivers, especially those under the influence of noise and vibration, which are even more significant in older participants and those with more years of service and those who spend more time driving during the interval of 24 hours , as well as those who drive heavier vehicles.
Walker, Guy, H.; Stanton, Neville, A.; Salmon, Paul
2016-01-01
Driver trust has potentially important implications for how vehicle technology is used and interacted with. In this paper it will be seen how driver trust functions and how it can be understood and manipulated by insightful vehicle design. It will review the theoretical literature to define steps that can be taken establish trust in vehicle technology in the first place, maintain trust in the long term, and even re-establish trust that has been lost along the way. The implication throughout i...
Kamel, Maedeh; Raissi, Heidar; Morsali, Ali; Shahabi, Mahnaz
2018-03-01
In the present work, we have studied the drug delivery performance of the functionalized (5, 5) single-walled carbon nanotube with a carboxylic acid group for Flutamide anticancer drug in the gas phase as well as water solution by means of density functional theory calculations. The obtained results confirmed the energetic stability of the optimized geometries and revealed that the nature of drug adsorption on the functionalized carbon nanotube is physical. Our computations showed that the hydrogen bonding between active sites of Flutamide molecule and the carboxyl functional group of the nanotube plays a vital role in the stabilization of the considered configurations. The natural bond orbital analysis suggested that the functionalized nanotube plays the role of an electron donor and Flutamide molecule acts as an electron acceptor at the investigated complexes. In addition, molecular dynamics simulation is also utilized to investigate the effect of functionalized carbon nanotube chirality on the dynamic process of drug molecule adsorption on the nanotube surface. Simulation results demonstrated that drug molecules are strongly adsorbed on the functionalized nanotube surface with (10,5) chirality, as reflected by the most negative van der Waals interaction energy and a high number of hydrogen bonds between the functionalized nanotube and drug molecules.
Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells.
Directory of Open Access Journals (Sweden)
Sanne Hindriksen
Full Text Available The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools. We demonstrate transduction of a panel of cell lines with Cas9 and an sgRNA sequence, which results in efficient knockout of all four targeted subunits of the chromosomal passenger complex (CPC. We further show that introduction of a homology directed repair template into the same CRISPR/Cas9 baculovirus facilitates introduction of specific point mutations and endogenous gene tags. Tagging of the CPC recruitment factor Haspin with the fluorescent reporter YFP allowed us to study its native localization as well as recruitment to the cohesin subunit Pds5B.
Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells.
Hindriksen, Sanne; Bramer, Arne J; Truong, My Anh; Vromans, Martijn J M; Post, Jasmin B; Verlaan-Klink, Ingrid; Snippert, Hugo J; Lens, Susanne M A; Hadders, Michael A
2017-01-01
The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools. We demonstrate transduction of a panel of cell lines with Cas9 and an sgRNA sequence, which results in efficient knockout of all four targeted subunits of the chromosomal passenger complex (CPC). We further show that introduction of a homology directed repair template into the same CRISPR/Cas9 baculovirus facilitates introduction of specific point mutations and endogenous gene tags. Tagging of the CPC recruitment factor Haspin with the fluorescent reporter YFP allowed us to study its native localization as well as recruitment to the cohesin subunit Pds5B.
Opportunity costs calculation in agent-based vehicle routing and scheduling
Mes, Martijn R.K.; van der Heijden, Matthijs C.; Schuur, Peter
2006-01-01
In this paper we consider a real-time, dynamic pickup and delivery problem with timewindows where orders should be assigned to one of a set of competing transportation companies. Our approach decomposes the problem into a multi-agent structure where vehicle agents are responsible for the routing and
Recombinant Amphiphilic Protein Micelles for Drug Delivery
Kim, Wookhyun; Xiao, Jiantao; Chaikof, Elliot L.
2011-01-01
Amphiphilic block polypeptides can self-assemble into a range of nanostructures in solution, including micelles and vesicles. Our group has recently described the capacity of recombinant amphiphilic diblock copolypeptides to form highly stable micelles. In this report, we demonstrate the utility of protein nanoparticles to serve as a vehicle for controlled drug delivery. Drug-loaded micelles were produced by encapsulating dipyridamole as a model hydrophobic drug with anti-inflammatory activit...
Watkinson, R M; Guy, R H; Oliveira, G; Hadgraft, J; Lane, M E
2011-01-01
Previously, we have reported the effects of water, ethanol, propylene glycol and various binary and ternary mixtures of these solvents on the permeation of ibuprofen in model membranes and in skin. The present study investigates the influence of lipophilic vehicles on the transport of ibuprofen in silicone membrane and in human skin. The permeation of ibuprofen was measured from mineral oil (MO), Miglyol® 812 (MG) and binary mixtures of MO and MG. The solubility of ibuprofen was 5-fold higher in MG than in MO, however, the permeation of ibuprofen from the pure vehicles and combinations of both was comparable in silicone membrane. Additionally, there were no significant differences in skin permeation for MO and MG vehicles. When the permeation of various hydrophilic and lipophilic vehicles is considered, a trend between flux values for the model membrane and skin is evident (r(2) = 0.71). The findings suggest that silicone membrane may provide information on qualitative trends in skin permeation for vehicles of diverse solubility and partition characteristics. Copyright © 2010 S. Karger AG, Basel.
DEFF Research Database (Denmark)
Olesen, Uffe Høgh; Mogensen, Mette; Haedersdal, Merete
2017-01-01
Ablative fractional laser (AFXL) is an emerging method that enhances topical drug delivery. Penetrating the skin in microscopic, vertical channels, termed microscopic treatment zones (MTZs), the fractional technique circumvents the skin barrier and allows increased uptake of topically applied dru...... was overall greater for more superficial MTZs. In conclusion, vehicle type affects filling of MTZs, which may be of importance for AFXL-assisted drug delivery....
Home Delivery and the Impacts on Urban Freight Transport : A Review
Visser, J.G.S.N.; Nemoto, T.; Browne, M.
2014-01-01
This review paper discusses the latest developments in internet shopping, home delivery and the potential impacts on city logistics and alternative vehicle use. The review has illustrated the rapid changes during the past few years and the potentially important impacts on patterns of transport
A review on electrospun nanofibers for oral drug delivery
Directory of Open Access Journals (Sweden)
Abbas Akhgari
2017-10-01
Full Text Available Nowadays, polymer nanofibers have gained attention due to remarkable characteristics such as high porosity and large surface area to volume ratio. Among their fabrication methods, electrospinning technique has been attracted as a simple and reproducible approach. It is a versatile, simple and cost-effective technique for the production of continuous nanofibers with acceptable characteristics such as high porosity, high surface area to volume ratio, high loading capacity and encapsulation efficiency, delivery of multiple drugs, and enhancement of drug solubility. Due to these properties electrospun nanofibers have been extensively used for different biomedical applications including wound dressing, tissue engineering, enzyme immobilization, artificial organs, and drug delivery. Different synthetic and natural polymers have been successfully electrospun into ultrafine fibers. Using electrospun nanofibers as vehicles for oral drug delivery has been investigated in different release manners- fast, biphasic or sustained release. This article presents a review on application of electrospinning technique in oral drug delivery.
Broadband vehicle-to-vehicle communication using an extended autonomous cruise control sensor
Heddebaut, M.; Rioult, J.; Ghys, J. P.; Gransart, Ch; Ambellouis, S.
2005-06-01
For several years road vehicle autonomous cruise control (ACC) systems as well as anti-collision radar have been developed. Several manufacturers currently sell this equipment. The current generation of ACC sensors only track the first preceding vehicle to deduce its speed and position. These data are then used to compute, manage and optimize a safety distance between vehicles, thus providing some assistance to car drivers. However, in real conditions, to elaborate and update a real time driving solution, car drivers use information about speed and position of preceding and following vehicles. This information is essentially perceived using the driver's eyes, binocular stereoscopic vision performed through the windscreens and rear-view mirrors. Furthermore, within a line of vehicles, the frontal road perception of the first vehicle is very particular and highly significant. Currently, all these available data remain strictly on-board the vehicle that has captured the perception information and performed these measurements. To get the maximum effectiveness of all these approaches, we propose that this information be shared in real time with the following vehicles, within the convoy. On the basis of these considerations, this paper technically explores a cost-effective solution to extend the basic ACC sensor function in order to simultaneously provide a vehicle-to-vehicle radio link. This millimetre wave radio link transmits relevant broadband perception data (video, localization...) to following vehicles, along the line of vehicles. The propagation path between the vehicles uses essentially grazing angles of incidence of signals over the road surface including millimetre wave paths beneath the cars.
IVHM Framework for Intelligent Integration for Vehicle Health Management
Paris, Deidre; Trevino, Luis C.; Watson, Michael D.
2005-01-01
Integrated Vehicle Health Management (IVHM) systems for aerospace vehicles, is the process of assessing, preserving, and restoring system functionality across flight and techniques with sensor and communication technologies for spacecraft that can generate responses through detection, diagnosis, reasoning, and adapt to system faults in support of Integrated Intelligent Vehicle Management (IIVM). These real-time responses allow the IIVM to modify the affected vehicle subsystem(s) prior to a catastrophic event. Furthermore, this framework integrates technologies which can provide a continuous, intelligent, and adaptive health state of a vehicle and use this information to improve safety and reduce costs of operations. Recent investments in avionics, health management, and controls have been directed towards IIVM. As this concept has matured, it has become clear that IIVM requires the same sensors and processing capabilities as the real-time avionics functions to support diagnosis of subsystem problems. New sensors have been proposed, in addition to augment the avionics sensors to support better system monitoring and diagnostics. As the designs have been considered, a synergy has been realized where the real-time avionics can utilize sensors proposed for diagnostics and prognostics to make better real-time decisions in response to detected failures. IIVM provides for a single system allowing modularity of functions and hardware across the vehicle. The framework that supports IIVM consists of 11 major on-board functions necessary to fully manage a space vehicle maintaining crew safety and mission objectives. These systems include the following: Guidance and Navigation; Communications and Tracking; Vehicle Monitoring; Information Transport and Integration; Vehicle Diagnostics; Vehicle Prognostics; Vehicle Mission Planning, Automated Repair and Replacement; Vehicle Control; Human Computer Interface; and Onboard Verification and Validation. Furthermore, the presented
Imani, Rana; Prakash, Satya; Vali, Hojatollah; Faghihi, Shahab
2018-05-29
The successful application of nucleic acid-based therapy for the treatment of various cancers is largely dependent on a safe and efficient delivery system. A dual-functionalized graphene oxide (GO)-based nanocarrier with the conjugation of aminated-polyethylene glycol (PEG-diamine) and octa-arginine (R8) for the intracellular delivery of nucleic acids is proposed. The functionalized sites are covalently co-conjugated and the PEG : R8 molar ratio is optimized at 10 : 1 to achieve a hydrocolloidally stable size of 252 ± 2.0 nm with an effective charge of +40.97 ± 1.05 and an amine-rich content of 10.87 ± 0.4 μmol g-1. The uptake of the nanocarrier in breast cancer cell lines, MCF-7 and MDA-MB 231, is investigated. The siRNA and pDNA condensation ability in the presence and absence of enzymes and the endosomal buffering capacity, as well as the intracellular localization of the gene/nanocarrier complex are also evaluated. Furthermore, the delivery of functional genes associated with the nanocarrier is assessed using c-Myc protein knockdown and EGFP gene expression. The effective uptake of the nanocarrier by the cells shows superior cytocompatibility, and protects the siRNA and pDNA against enzyme degradation while inhibiting their migration with N : P ratios of 10 and 5, respectively. The co-conjugation of PEG-diamine and the cationic cell-penetrating peptide (CPP) into the GO nanocarrier also provides a superior internalization efficacy of 85% in comparison with a commercially available transfection reagent. The c-Myc protein knockdown and EGFP expression, which are induced by the nanocarrier, confirm that the optimized PEG-diamine/R8-functionalized GO could effectively deliver pDNA and siRNA into the cells and interfere with gene expression.
AVIATR—Aerial Vehicle for In-situ and Airborne Titan Reconnaissance
DEFF Research Database (Denmark)
Barnes, Jason W.; Lemke, Lawrence; Foch, Rick
2012-01-01
We describe a mission concept for a stand-alone Titan airplane mission: Aerial Vehicle for In-situ and Airborne Titan Reconnaissance (AVIATR). With independent delivery and direct-to-Earth communications, AVIATR could contribute to Titan science either alone or as part of a sustained Titan...... Exploration Program. As a focused mission, AVIATR as we have envisioned it would concentrate on the science that an airplane can do best: exploration of Titan's global diversity. We focus on surface geology/hydrology and lower-atmospheric structure and dynamics. With a carefully chosen set of seven...... of a Space Vehicle (SV) for cruise, an Entry Vehicle (EV) for entry and descent, and the Air Vehicle (AV) to fly in Titan's atmosphere. Using an Earth-Jupiter gravity assist trajectory delivers the spacecraft to Titan in 7.5 years, after which the AVIATR AV would operate for a 1-Earth-year nominal mission...
Drug delivery approaches for breast cancer
Directory of Open Access Journals (Sweden)
Singh SK
2017-08-01
Full Text Available Santosh Kumar Singh,1 Shriti Singh,2 James W Lillard Jr,1 Rajesh Singh1 1Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, USA; 2Department of Kriya Sharir, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India Abstract: Breast cancer is one of the most common cancers affecting women worldwide. The controlled release of drugs to the precise site of the disease using a nanocarrier vehicle increases the therapeutic efficiency of the drugs. Nanotechnology-based approaches used to endorse clinical improvement from a disease also help to understand the interaction of malignant cells with their microenvironment. Receptor-based targeting is another approach for drug delivery which is undergoing clinical trials. Nanoparticles (NPs delivery has been proven to promise high loading capacity, less toxicity, and stability of the drugs or biomolecules compared to traditional chemotherapeutic drugs. The goal of this review is to present the current problems of breast cancer therapy and discuss the NP-based targeting to overcome the hurdles of conventional drug therapy approach. Keywords: breast cancer, nanoparticles, drug delivery systems
Directory of Open Access Journals (Sweden)
Noel T. Mueller
2017-12-01
Full Text Available Cesarean (C-section delivery, recently shown to cause excess weight gain in mice, perturbs human neonatal gut microbiota development due to the lack of natural mother-to-newborn transfer of microbes. Neonates excrete first the in-utero intestinal content (referred to as meconium hours after birth, followed by intestinal contents reflective of extra-uterine exposure (referred to as transition stool 2 to 3 days after birth. It is not clear when the effect of C-section on the neonatal gut microbiota emerges. We examined bacterial DNA in carefully-collected meconium, and the subsequent transitional stool, from 59 neonates [13 born by scheduled C-section and 46 born by vaginal delivery] in a private hospital in Brazil. Bacterial DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced using the Illumina MiSeq (San Diego, CA, USA platform. We found evidence of bacterial DNA in the majority of meconium samples in our study. The bacterial DNA structure (i.e., beta diversity of meconium differed significantly from that of the transitional stool microbiota. There was a significant reduction in bacterial alpha diversity (e.g., number of observed bacterial species and change in bacterial composition (e.g., reduced Proteobacteria in the transition from meconium to stool. However, changes in predicted microbiota metabolic function from meconium to transitional stool were only observed in vaginally-delivered neonates. Within sample comparisons showed that delivery mode was significantly associated with bacterial structure, composition and predicted microbiota metabolic function in transitional-stool samples, but not in meconium samples. Specifically, compared to vaginally delivered neonates, the transitional stool of C-section delivered neonates had lower proportions of the genera Bacteroides, Parabacteroides and Clostridium. These differences led to C-section neonates having lower predicted abundance of microbial genes related to metabolism of
Hu, Caibiao; Gu, Chengyu; Fang, Qiao; Wang, Qiang; Xia, Qiang
2016-02-01
The present study investigated a self-double-emulsifying drug delivery system loaded with epigallocatechin-3-gallate to improve epigallocatechin-3-gallate skin retention. The long chain solid lipids (cetostearyl alcohol) and macadamia oil were utilized as a carrier to deliver the bioactive ingredient. Response surface methodology was used to optimize the formulation, and the solid lipid to total lipid weight ratio, concentration of epigallocatechin-3-gallate and hydrophilic surfactant on skin retention were found to be the principal factors. The optimum formulation with high encapsulation efficiency (95.75%), self-double-emulsification performance (99.58%) and skin retention (87.24%) were derived from the fitted models and experimentally examined, demonstrating a reasonable agreement between experimental and predicted values. Epigallocatechin-3-gallate-self-double-emulsifying drug delivery system was found to be stable for 3 months. Transdermal studies could explain a higher skin diffusion of epigallocatechin-3-gallate from the self-double-emulsifying drug delivery system compared with EGCG aqueous solution. In vitro cytotoxicity showed that epigallocatechin-3-gallate-self-double-emulsifying drug delivery system did not exert hazardous effect on L929 cells up to 1:10. © The Author(s) 2015.
Optimal Path Determination for Flying Vehicle to Search an Object
Heru Tjahjana, R.; Heri Soelistyo U, R.; Ratnasari, L.; Irawanto, B.
2018-01-01
In this paper, a method to determine optimal path for flying vehicle to search an object is proposed. Background of the paper is controlling air vehicle to search an object. Optimal path determination is one of the most popular problem in optimization. This paper describe model of control design for a flying vehicle to search an object, and focus on the optimal path that used to search an object. In this paper, optimal control model is used to control flying vehicle to make the vehicle move in optimal path. If the vehicle move in optimal path, then the path to reach the searched object also optimal. The cost Functional is one of the most important things in optimal control design, in this paper the cost functional make the air vehicle can move as soon as possible to reach the object. The axis reference of flying vehicle uses N-E-D (North-East-Down) coordinate system. The result of this paper are the theorems which say that the cost functional make the control optimal and make the vehicle move in optimal path are proved analytically. The other result of this paper also shows the cost functional which used is convex. The convexity of the cost functional is use for guarantee the existence of optimal control. This paper also expose some simulations to show an optimal path for flying vehicle to search an object. The optimization method which used to find the optimal control and optimal path vehicle in this paper is Pontryagin Minimum Principle.
Energy Technology Data Exchange (ETDEWEB)
Giessler, Martin; Paul, Jens; Gauterin, Frank [Karlsruher Institut fuer Technologie (KIT), Karlsruhe (Germany). Inst. fuer Fahrzeugsystemtechnik (FAST); Fritz, Alexander; Sander, Oliver; Mueller-Glaser, Klaus D. [Karlsruher Institut fuer Technologie (KIT), Karlsruhe (Germany). Inst. fuer Technik der Informationsverarbeitung (ITIV)
2012-11-01
At the Karlsruher Institute of Technology (KIT) a vehicle was converted for full battery electric drive within a cooperation of several faculties under the direction of the chair of vehicle technology. Within this paper the developed software to control the main functions of the vehicle will be presented and potentials to increase the energy efficiency will be discussed. The software based vehicle control unit is the central control unit to realize drivers command with respect to the system parameters, which are important for safety, dynamics, range and comfort of the vehicle. The structure of the software architecture, the interaction with the main electric vehicle specific control units and components and the main implemented functions will be described within this paper. The converted vehicle consists mainly of one electric motor with water cooled power electronics that drives the front axle, 21 battery modules controlled and managed by the battery management system, one on board charging device and an universal control unit. Not only strategies for power recovery while braking, but also strategies for driving and operation can help increase the energy efficiency. Select measures to recover and safe energy are also shown. (orig.)
Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery.
Hu, Jingjing; Su, Yunzhang; Zhang, Hongfeng; Xu, Tongwen; Cheng, Yiyun
2011-12-01
In this study, dendrimers was synthesized by introducing functional groups into the interior pockets of fully acetylated dendrimers. NMR techniques including COSY and 2D-NOESY revealed the molecular structures of the synthesized dendrimers and the encapsulation of guest molecule such as methotrexate within their interior pockets. The synthesized polymeric nanocarriers showed much lower cytotoxicity on two cell lines than cationic dendrimers, and exhibited better performance than fully acetylated dendrimers in the sustained release of methotrexate. The results provided a new strategy in the design of non-toxic dendrimers with high performance in the delivery of anti-cancer drugs for clinical applications. Copyright © 2011 Elsevier Ltd. All rights reserved.
Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E
2017-04-01
Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.
Patching, Simon G
2017-03-01
Glucose transporters (GLUTs) at the blood-brain barrier maintain the continuous high glucose and energy demands of the brain. They also act as therapeutic targets and provide routes of entry for drug delivery to the brain and central nervous system for treatment of neurological and neurovascular conditions and brain tumours. This article first describes the distribution, function and regulation of glucose transporters at the blood-brain barrier, the major ones being the sodium-independent facilitative transporters GLUT1 and GLUT3. Other GLUTs and sodium-dependent transporters (SGLTs) have also been identified at lower levels and under various physiological conditions. It then considers the effects on glucose transporter expression and distribution of hypoglycemia and hyperglycemia associated with diabetes and oxygen/glucose deprivation associated with cerebral ischemia. A reduction in glucose transporters at the blood-brain barrier that occurs before the onset of the main pathophysiological changes and symptoms of Alzheimer's disease is a potential causative effect in the vascular hypothesis of the disease. Mutations in glucose transporters, notably those identified in GLUT1 deficiency syndrome, and some recreational drug compounds also alter the expression and/or activity of glucose transporters at the blood-brain barrier. Approaches for drug delivery across the blood-brain barrier include the pro-drug strategy whereby drug molecules are conjugated to glucose transporter substrates or encapsulated in nano-enabled delivery systems (e.g. liposomes, micelles, nanoparticles) that are functionalised to target glucose transporters. Finally, the continuous development of blood-brain barrier in vitro models is important for studying glucose transporter function, effects of disease conditions and interactions with drugs and xenobiotics.
The Time-Dependent Multiple-Vehicle Prize-Collecting Arc Routing Problem
DEFF Research Database (Denmark)
Black, Daniel; Eglese, Richard; Wøhlk, Sanne
2015-01-01
-life traffic situations where the travel times change with the time of day are taken into account. Two metaheuristic algorithms, one based on Variable Neighborhood Search and one based on Tabu Search, are proposed and tested for a set of benchmark problems, generated from real road networks and travel time......In this paper, we introduce a multi vehicle version of the Time-Dependent Prize-Collecting Arc Routing Problem (TD-MPARP). It is inspired by a situation where a transport manager has to choose between a number of full truck load pick-ups and deliveries to be performed by a fleet of vehicles. Real...
This report identifies the security approach associated with a communications data delivery system that supports vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) communications. The report describes the risks associated with communication...
Nonlinear H∞ Optimal Control Scheme for an Underwater Vehicle with Regional Function Formulation
Directory of Open Access Journals (Sweden)
Zool H. Ismail
2013-01-01
Full Text Available A conventional region control technique cannot meet the demands for an accurate tracking performance in view of its inability to accommodate highly nonlinear system dynamics, imprecise hydrodynamic coefficients, and external disturbances. In this paper, a robust technique is presented for an Autonomous Underwater Vehicle (AUV with region tracking function. Within this control scheme, nonlinear H∞ and region based control schemes are used. A Lyapunov-like function is presented for stability analysis of the proposed control law. Numerical simulations are presented to demonstrate the performance of the proposed tracking control of the AUV. It is shown that the proposed control law is robust against parameter uncertainties, external disturbances, and nonlinearities and it leads to uniform ultimate boundedness of the region tracking error.
Sami, Haider; Maparu, Auhin K.; Kumar, Ashok; Sivakumar, Sri
2012-01-01
Towards the goal of development of a generic nanomaterial delivery system and delivery of the ‘as prepared’ nanoparticles without ‘further surface modification’ in a generic way, we have fabricated a hybrid polymer capsule as a delivery vehicle in which nanoparticles are loaded within their cavity. To this end, a generic approach to prepare nanomaterials-loaded polyelectrolyte multilayered (PEM) capsules has been reported, where polystyrene sulfonate (PSS)/polyallylamine hydrochloride (PAH) polymer capsules were employed as nano/microreactors to synthesize variety of nanomaterials (metal nanoparticles; lanthanide doped inorganic nanoparticles; gadolinium based nanoparticles, cadmium based nanoparticles; different shapes of nanoparticles; co-loading of two types of nanoparticles) in their hollow cavity. These nanoparticles-loaded capsules were employed to demonstrate generic delivery of payload of nanoparticles intracellularly (HeLa cells), without the need of individual nanoparticle surface modification. Validation of intracellular internalization of nanoparticles-loaded capsules by HeLa cells was ascertained by confocal laser scanning microscopy. The green emission from Tb3+ was observed after internalization of LaF3:Tb3+(5%) nanoparticles-loaded capsules by HeLa cells, which suggests that nanoparticles in hybrid capsules retain their functionality within the cells. In vitro cytotoxicity studies of these nanoparticles-loaded capsules showed less/no cytotoxicity in comparison to blank capsules or untreated cells, thus offering a way of evading direct contact of nanoparticles with cells because of the presence of biocompatible polymeric shell of capsules. The proposed hybrid delivery system can be potentially developed to avoid a series of biological barriers and deliver multiple cargoes (both simultaneous and individual delivery) without the need of individual cargo design/modification. PMID:22649489
Directory of Open Access Journals (Sweden)
Haider Sami
Full Text Available Towards the goal of development of a generic nanomaterial delivery system and delivery of the 'as prepared' nanoparticles without 'further surface modification' in a generic way, we have fabricated a hybrid polymer capsule as a delivery vehicle in which nanoparticles are loaded within their cavity. To this end, a generic approach to prepare nanomaterials-loaded polyelectrolyte multilayered (PEM capsules has been reported, where polystyrene sulfonate (PSS/polyallylamine hydrochloride (PAH polymer capsules were employed as nano/microreactors to synthesize variety of nanomaterials (metal nanoparticles; lanthanide doped inorganic nanoparticles; gadolinium based nanoparticles, cadmium based nanoparticles; different shapes of nanoparticles; co-loading of two types of nanoparticles in their hollow cavity. These nanoparticles-loaded capsules were employed to demonstrate generic delivery of payload of nanoparticles intracellularly (HeLa cells, without the need of individual nanoparticle surface modification. Validation of intracellular internalization of nanoparticles-loaded capsules by HeLa cells was ascertained by confocal laser scanning microscopy. The green emission from Tb(3+ was observed after internalization of LaF(3:Tb(3+(5% nanoparticles-loaded capsules by HeLa cells, which suggests that nanoparticles in hybrid capsules retain their functionality within the cells. In vitro cytotoxicity studies of these nanoparticles-loaded capsules showed less/no cytotoxicity in comparison to blank capsules or untreated cells, thus offering a way of evading direct contact of nanoparticles with cells because of the presence of biocompatible polymeric shell of capsules. The proposed hybrid delivery system can be potentially developed to avoid a series of biological barriers and deliver multiple cargoes (both simultaneous and individual delivery without the need of individual cargo design/modification.
Lee, Sang Gon; Kim, Sung Rae; Cho, Hye In; Kang, Mean Hyung; Yeom, Dong Woo; Lee, Seo Hyun; Lee, Sangkil; Choi, Young Wook
2014-01-01
To develop an external vehicle for skin hydration and enhanced dermal drug delivery, a hydrogel-based ultra-moisturizing cream (HUMC) was successfully formulated with carbopol 934P, urea, Tinocare GL, grape seed oil, and other excipients. The HUMC showed plastic flow behavior due to a gel structure with a cream base. Different types of drug-free vehicles such as a hydrogel, conventional cream (CC), and three HUMCs were prepared and subjected to an in vivo skin hydration test on a hairless mouse using a corneometer. Hydration effect (∆AU) was in the order of HUMC2>HUMC1 ≥ CC>HUMC3>hydrogel. Using nile red (NR) and 5-carboxyfluorescein (5-CF) as lipophilic and hydrophilic fluorescent probes, respectively, in vitro skin permeation and accumulation studies were conducted using Franz diffusion cells. The values of steady-state flux (Jss, ng/h/cm(2)) were obtained: 74.8 (CC), 145.6 (HUMC1), and 161.9 (HUMC2) for NR delivery; 6.8 (CC), 8.3 (HUMC1), and 10.9 (HUMC2) for 5-CF delivery. The amounts retained in the skin at 12 h (Qr, ng/cm(2)) were determined: 86.4 (CC) and 102.0 (HUMC2) for NR; and 70.1 (CC) and 195.6 (HUMC2) for 5-CF. Confocal microscopy was used to visualize the distribution of the fluorescent probes. NR tended to be localized into the deeper part of the skin with adipose tissue whereas 5-CF localized in the upper layer of the skin. Thus we propose that HUMC2 is an efficacious vehicle for skin hydration and enhances dermal delivery of lipophilic and hydrophilic drugs.
Discovery of Cationic Polymers for Non-viral Gene Delivery using Combinatorial Approaches
Barua, Sutapa; Ramos, James; Potta, Thrimoorthy; Taylor, David; Huang, Huang-Chiao; Montanez, Gabriela; Rege, Kaushal
2015-01-01
Gene therapy is an attractive treatment option for diseases of genetic origin, including several cancers and cardiovascular diseases. While viruses are effective vectors for delivering exogenous genes to cells, concerns related to insertional mutagenesis, immunogenicity, lack of tropism, decay and high production costs necessitate the discovery of non-viral methods. Significant efforts have been focused on cationic polymers as non-viral alternatives for gene delivery. Recent studies have employed combinatorial syntheses and parallel screening methods for enhancing the efficacy of gene delivery, biocompatibility of the delivery vehicle, and overcoming cellular level barriers as they relate to polymer-mediated transgene uptake, transport, transcription, and expression. This review summarizes and discusses recent advances in combinatorial syntheses and parallel screening of cationic polymer libraries for the discovery of efficient and safe gene delivery systems. PMID:21843141
Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel
2016-01-01
Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo. PMID:27278929
Aerodynamic resistance reduction of electric and hybrid vehicles
1979-01-01
The generation of an EHV aerodynamic data base was initiated by conducting full-scale wind tunnel tests on 16 vehicles. Zero-yaw drag coefficients ranged from a high of 0.58 for a boxey delivery van and an open roadster to a low of about 0.34 for a current 4-passenger prototype automobile which was designed with aerodynamics as an integrated parameter. Characteristic effects of aspect ratio or fineness ratio which might appear if electric vehicle shape proportions were to vary significantly from current automobiles were identified. Some preliminary results indicate a 5 to 10% variation in drag over the range of interest. Effective drag coefficient wind-weighting factors over J227a driving cycles in the presence of annual mean wind fields were identified. Such coefficients, when properly weighted, were found to be from 5 to 65% greater than the zero-yaw drag coefficient in the cases presented. A vehicle aerodynamics bibliography of over 160 entries, in six general categories is included.
Géral, Claire; Angelova, Angelina; Lesieur, Sylviane
2013-01-01
Neurodegenerative diseases represent a major public health problem, but beneficial clinical treatment with neurotrophic factors has not been established yet. The therapeutic use of neurotrophins has been restrained by their instability and rapid degradation in biological medium. A variety of strategies has been proposed for the administration of these leading therapeutic candidates, which are essential for the development, survival and function of human neurons. In this review, we describe the existing approaches for delivery of brain-derived neurotrophic factor (BDNF), which is the most abundant neurotrophin in the mammalian central nervous system (CNS). Biomimetic peptides of BDNF have emerged as a promising therapy against neurodegenerative disorders. Polymer-based carriers have provided sustained neurotrophin delivery, whereas lipid-based particles have contributed also to potentiation of the BDNF action. Nanotechnology offers new possibilities for the design of vehicles for neuroprotection and neuroregeneration. Recent developments in nanoscale carriers for encapsulation and transport of BDNF are highlighted. PMID:24300402
Yoshida, Mikako; Murayama, Ryoko; Haruna, Megumi; Matsuzaki, Masayo; Yoshimura, Kenichi; Murashima, Sachiyo; Kozuma, Shiro
2013-04-01
To compare the pelvic floor function between women with and without stress urinary incontinence after vaginal delivery. Seventeen women (age 35.5 ± 3.5) were prospectively studied at about 6 weeks, 3 months, and 6 months after vaginal delivery. Urinary incontinence was assessed by the International Consultation on Incontinence Questionnaire - Short Form. Pelvic floor function was assessed by antero-posterior diameter of the levator hiatus using transperineal ultrasound. Five of 17 women experienced postpartum stress urinary incontinence. The antero-posterior diameter of the levator hiatus at rest was significantly longer in stress urinary incontinent women than in continent women until 3 months after delivery (p continent women and stress urinary incontinent women. Regardless of urinary incontinence, the antero-posterior diameter of the levator hiatus at rest shortened at 6 months postpartum, compared to 6 weeks postpartum (p continent women by 6 months postpartum (p = 0.02). The extended pelvic floor may be a cause of stress urinary incontinence in the postpartum period. Therefore, treatment to improve the extended pelvic floor should be developed for the prevention of stress urinary incontinence.
MODELING OF TARGETED DRUG DELIVERY PART II. MULTIPLE DRUG ADMINISTRATION
Directory of Open Access Journals (Sweden)
A. V. Zaborovskiy
2017-01-01
Full Text Available In oncology practice, despite significant advances in early cancer detection, surgery, radiotherapy, laser therapy, targeted therapy, etc., chemotherapy is unlikely to lose its relevance in the near future. In this context, the development of new antitumor agents is one of the most important problems of cancer research. In spite of the importance of searching for new compounds with antitumor activity, the possibilities of the “old” agents have not been fully exhausted. Targeted delivery of antitumor agents can give them a “second life”. When developing new targeted drugs and their further introduction into clinical practice, the change in their pharmacodynamics and pharmacokinetics plays a special role. The paper describes a pharmacokinetic model of the targeted drug delivery. The conditions under which it is meaningful to search for a delivery vehicle for the active substance were described. Primary screening of antitumor agents was undertaken to modify them for the targeted delivery based on underlying assumptions of the model.
Dual-functionalized graphene oxide for enhanced siRNA delivery to breast cancer cells.
Imani, Rana; Shao, Wei; Taherkhani, Samira; Emami, Shahriar Hojjati; Prakash, Satya; Faghihi, Shahab
2016-11-01
The aim of this study is to improve hydrocolloid stability and siRNA transfection ability of a reduced graphene oxide (rGO) based nano-carrier using a phospholipid-based amphiphilic polymer (PL-PEG) and cell penetrating peptide (CPPs). The dual functionalized nano-carrier is comprehensively characterized for its chemical structure, size, surface charge and morphology as well as thermal stability. The nano-carrier cytocompatibility, siRNA condensation ability both in the presence and absence of enzyme, endosomal buffering capacity, cellular uptake and intracellular localization are also assessed. The siRNA loaded nano-carrier is used for internalization to MCF-7 cells and its gene silencing ability is compared with AllStars Hs Cell Death siRNA as a model gene. The nano-carrier remains stable in biological solution, exhibits excellent cytocompatibility, retards the siRNA migration and protects it against enzyme degradation. The buffering capacity analysis shows that incorporation of the peptide in nano-carrier structure would increase the resistance to endo/lysosomal like acidic condition (pH 6-4) The functionalized nano-carrier which is loaded with siRNA in an optimal N:P ratio presents superior internalization efficiency (82±5.1% compared to HiPerFect(®)), endosomal escape quality and capable of inducing cell death in MCF-7 cancer cells (51±3.1% compared to non-treated cells). The success of siRNA-based therapy is largely dependent on the safe and efficient delivery system, therefore; the dual functionalized rGO introduced here could have a great potential to be used as a carrier for siRNA delivery with relevancy in therapeutics and clinical applications. Copyright © 2016 Elsevier B.V. All rights reserved.
Advancing the vesosome, a multifunctional drug delivery platform, toward applied in vivo testing
Wong, Benjamin J.
An optimal drug delivery vehicle should circulate long enough to reach the site of illness or disease, possess a large drug loading capacity, retain its contents over the course of treatment, and be able deliver its contents at a rate appropriate for maximum therapeutic benefit at the site of interest. The vesosome, a large lipid bilayer enclosing multiple, smaller liposomes, is our solution to addressing these needs. The external lipid bilayer offers a second barrier of protection for interior components and can also serve as the anchor for active targeting components. Furthermore, internal compartmentalization permits customization of separate environments for multiple therapeutics and release triggers. Previous work established the ability of the vesosome to retain its contents in vitro an order of magnitude longer than liposomes. To be viable in vivo, the vesosome must be functionalized for biocompatibility and tracking, and its synthetic procedure must be repeatable, reliable and result in a purified product. The vesosome was functionalized by introducing biocompatible polymers, such as poly(ethylene glycol) (PEG), and fluorescent dyes in their lipid-bound forms into the external membrane of the vesosome. The external vesosomal membrane is formed from large, flat lipid sheets in the interdigitated (L betaI) phase which, when heated, are used to encapsulate smaller drug-containing vesicles. Through X-Ray diffraction (XRD) and freeze-fracture transmission electron microscopy (FF-TEM), we established that the molar amounts of functionalized lipid required to label the vesosome for tracking and biocompatibility (˜5--7mol% total) did not prevent the formation of the interdigitated phase. Thus, functionalization of the external vesosome membrane can be achieved through functionalization of interdigitated sheets. For in vivo testing, functionalized vesosomes must be separated from unencapsulated vesicles and purification was performed using size exclusion
Eighteen-Month Final Evaluation of UPS Second Generation Diesel Hybrid-Electric Delivery Vans
Energy Technology Data Exchange (ETDEWEB)
Lammert, M.; Walkowicz, K.
2012-09-01
A parallel hybrid-electric diesel delivery van propulsion system was evaluated at a UPS facility in Minneapolis using on-vehicle data logging, fueling, and maintenance records. Route and drive cycle analysis showed different duty cycles for hybrid vs. conventional delivery vans; routes were switched between the study groups to provide a valid comparison. The hybrids demonstrated greater advantage on the more urban routes; the initial conventional vans' routes had less dense delivery zones. The fuel economy of the hybrids on the original conventional group?s routes was 10.4 mpg vs. 9.2 mpg for the conventional group on those routes a year earlier. The hybrid group's fuel economy on the original hybrid route assignments was 9.4 mpg vs. 7.9 mpg for the conventional group on those routes a year later. There was no statistically significant difference in total maintenance cost per mile or for the vehicle total cost of operation per mile. Propulsion-related maintenance cost per mile was 77% higher for the hybrids, but only 52% more on a cost-per-delivery-day basis. Laboratory dynamometer testing demonstrated 13%-36% hybrid fuel economy improvement, depending on duty cycle, and up to a 45% improvement in ton-mi/gal. NOx emissions increased 21%-49% for the hybrids in laboratory testing.
Duffy, James B.
1993-01-01
The purpose of the Advanced Transportation System Study (ATSS) task area 1 study effort is to examine manned launch vehicle booster concepts and two-way cargo transfer and return vehicle concepts to determine which of the many proposed concepts best meets NASA's needs for two-way transportation to low earth orbit. The study identified specific configurations of the normally unmanned, expendable launch vehicles (such as the National Launch System family) necessary to fly manned payloads. These launch vehicle configurations were then analyzed to determine the integrated booster/spacecraft performance, operations, reliability, and cost characteristics for the payload delivery and return mission. Design impacts to the expendable launch vehicles which would be required to perform the manned payload delivery mission were also identified. These impacts included the implications of applying NASA's man-rating requirements, as well as any mission or payload unique impacts. The booster concepts evaluated included the National Launch System (NLS) family of expendable vehicles and several variations of the NLS reference configurations to deliver larger manned payload concepts (such as the crew logistics vehicle (CLV) proposed by NASA JSC). Advanced, clean sheet concepts such as an F-1A engine derived liquid rocket booster (LRB), the single stage to orbit rocket, and a NASP-derived aerospace plane were also included in the study effort. Existing expendable launch vehicles such as the Titan 4, Ariane 5, Energia, and Proton were also examined. Although several manned payload concepts were considered in the analyses, the reference manned payload was the NASA Langley Research Center's HL-20 version of the personnel launch system (PLS). A scaled up version of the PLS for combined crew/cargo delivery capability, the HL-42 configuration, was also included in the analyses of cargo transfer and return vehicle (CTRV) booster concepts. In addition to strictly manned payloads, two-way cargo
Biophysical aspects of using liposomes as delivery vehicles.
Ulrich, Anne S
2002-04-01
Liposomes are used as biocompatible carriers of drugs, peptides, proteins, plasmic DNA, antisense oligonucleotides or ribozymes, for pharmaceutical, cosmetic, and biochemical purposes. The enormous versatility in particle size and in the physical parameters of the lipids affords an attractive potential for constructing tailor-made vehicles for a wide range of applications. Some of the recent literature will be reviewed here and presented from a biophysical point of view, thus providing a background for the more specialized articles in this special issue on liposome technology. Different properties (size, colloidal behavior, phase transitions, and polymorphism) of diverse lipid formulations (liposomes, lipoplexes, cubic phases, emulsions, and solid lipid nanoparticles) for distinct applications (parenteral, transdermal, pulmonary, and oral administration) will be rationalized in terms of common structural, thermodynamic and kinetic parameters of the lipids. This general biophysical basis helps to understand pharmaceutically relevant aspects such as liposome stability during storage and towards serum, the biodistribution and specific targeting of cargo, and how to trigger drug release and membrane fusion. Methods for the preparation and characterization of liposomal formulations in vitro will be outlined, too.
Targeted drug delivery using temperature-sensitive liposomes
International Nuclear Information System (INIS)
Magin, R.L.; Niesman, M.R.
1984-01-01
Liposomes are receiving considerable attention as vehicles for selective drug delivery. One method of targeting liposomal contents involves the combination of local hyperthermia with temperature-sensitive liposomes. Such liposomes have been used to increase the uptake of methotrexate and cis-platinum into locally heated mouse tumors. However, additional information is needed on the mechanism of liposome drug release and the physiologic deposition of liposomes in vivo before clinical trails are begun. Current research is directed at studying the encapsulation and release of water soluble drugs from temperature-sensitive liposomes. The influence of liposome size, structure, and composition on the rapid release in plasma of cytosine arabinoside, cis-platinum, and the radiation sensitizer SR-2508 are described. These results demonstrate potential applications for temperature-sensitive liposomes in selective drug delivery
Foraida, Zahraa I.; Sharikova, Anna; Peerzada, Lubna N.; Khmaladze, Alexander; Larsen, Melinda; Castracane, James
2017-08-01
Sustained delivery of growth factors, proteins, drugs and other biologically active molecules is necessary for tissue engineering applications. Electrospun fibers are attractive tissue engineering scaffolds as they partially mimic the topography of the extracellular matrix (ECM). However, they do not provide continuous nourishment to the tissue. In search of a biomimetic scaffold for salivary gland tissue regeneration, we previously developed a blend nanofiber scaffold composed of the protein elastin and the synthetic polymer polylactic-co-glycolic acid (PLGA). The nanofiber scaffold promoted in vivo-like salivary epithelial cell tissue organization and apicobasal polarization. However, in order to enhance the salivary cell proliferation and biomimetic character of the scaffold, sustained growth factor delivery is needed. The composite nanofiber scaffold was optimized to act as a growth factor delivery system using epidermal growth factor (EGF) as a model protein. The nanofiber/EGF hybrid nanofibers were synthesized by double emulsion electrospinning where EGF is emulsified within a water/oil/water (w/o/w) double emulsion system. Successful incorporation of EGF was confirmed using Raman spectroscopy. EGF release profile was characterized using enzyme-linked immunosorbent assay (ELIZA) of the EGF content. Double emulsion electrospinning resulted in slower release of EGF. We demonstrated the potential of the proposed double emulsion electrospun nanofiber scaffold for the delivery of growth factors and/or drugs for tissue engineering and pharmaceutical applications.
Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles.
Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi
2015-04-01
Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.
Optimization of a truck-drone in tandem delivery network using k-means and genetic algorithm
Directory of Open Access Journals (Sweden)
Sergio Mourelo Ferrandez
2016-04-01
Full Text Available Purpose: The purpose of this paper is to investigate the effectiveness of implementing unmanned aerial delivery vehicles in delivery networks. We investigate the notion of the reduced overall delivery time, energy, and costs for a truck-drone network by comparing the in-tandem system with a stand-alone delivery effort. The objectives are (1 to investigate the time, energy, and costs associated to a truck-drone delivery network compared to standalone truck or drone, (2 to propose an optimization algorithm that determines the optimal number of launch sites and locations given delivery requirements, and drones per truck, (3 to develop mathematical formulations for closed form estimations for the optimal number of launch locations, optimal total time, as well as the associated cost for the system. Design/methodology/approach: The design of the algorithm herein computes the minimal time of delivery utilizing K-means clustering to find launch locations, as well as a genetic algorithm to solve the truck route as a traveling salesmen problem (TSP. The optimal solution is determined by finding the minimum cost associated to the parabolic convex cost function. The optimal min-cost is determined by finding the most efficient launch locations using K-means algorithms to determine launch locations and a genetic algorithm to determine truck route between those launch locations. Findings: Results show improvements with in-tandem delivery efforts as opposed to standalone systems. Further, multiple drones per truck are more optimal and contribute to savings in both energy and time. For this, we sampled various initialization variables to derive closed form mathematical solutions for the problem. Originality/value: Ultimately, this provides the necessary analysis of an integrated truck-drone delivery system which could be implemented by a company in order to maximize deliveries while minimizing time and energy. Closed-form mathematical solutions can be used as
An optimization approach for communal home meal delivery service : A case study
Bräysy, Olli; Nakari, Pentti; Dullaert, Wout; Neittaanmäki, Pekka
2009-01-01
This paper is the first to discuss the communal home meal delivery problem. The problem can be modelled as a multiple travelling salesman problem with time windows, that is closely related to the well-studied vehicle routing problem with time windows. Experimental results are reported for a
International Nuclear Information System (INIS)
Sawant, V.J.; Bamane, S.R.; Shejwal, R.V.; Patil, S.B.
2016-01-01
The functionalization and surface engineering of CoFe 2 O 4 and ZnFe 2 O 4 nanoparticles were performed by coating with PEG and Chitosan respectively using simple wet co-precipitation. Then multiactive therapeutic drug curcumin was loaded to form drug delivery nanohybrids by precipitation. These nanohybrids were characterized separately using UV–vis, FTIR, PL spectroscopy, XRD, VSM, SEM and TEM analysis. The moderate antibacterial activities of the nanohybrids were elaborated by in vitro antibacterial screening on Escherichia coli and Staphylococcus aureus. The anticancer potentials, apoptotic effects and enhanced drug delivery properties of these nanohybrids were confirmed and compared on MCF-7 cells by in vitro MTT assay. The drug delivery activities for hydrophobic drug and anticancer effects of chitosan coated zinc ferrite functionalized nanoparticles were higher than PEG coated cobalt ferrite nanohybrids. - Highlights: • CoFe 2 O 4 and ZnFe 2 O 4 nanoparticles were surface functionalized with PEG and Chitosan respectively. • Hydrophobic multi therapeutic anticancer drug curcumin was loaded into these nanohybrids and their structure, morphologies were confirmed. • The effects of PEG and Chitosan coating over ferrites for curcumin release have been elaborated, and the Chitosan coated curcumin loaded Zinc ferrite nanohybrid exhibited higher drug delivery and anticancer effects.
Energy Technology Data Exchange (ETDEWEB)
Sawant, V.J., E-mail: v11131@rediffmail.com [Department of Chemistry, Smt.K.W.College, Sangli, MS 416416 (India); Bamane, S.R. [Department of Chemistry, Raja Shripatrao Bhagwantrao College, Aundh, Satara, MS (India); Shejwal, R.V. [L.B.S. College, Satara, MS (India); Patil, S.B. [A.Birnale College of Pharmacy, Sangli, MS (India)
2016-11-01
The functionalization and surface engineering of CoFe{sub 2}O{sub 4} and ZnFe{sub 2}O{sub 4} nanoparticles were performed by coating with PEG and Chitosan respectively using simple wet co-precipitation. Then multiactive therapeutic drug curcumin was loaded to form drug delivery nanohybrids by precipitation. These nanohybrids were characterized separately using UV–vis, FTIR, PL spectroscopy, XRD, VSM, SEM and TEM analysis. The moderate antibacterial activities of the nanohybrids were elaborated by in vitro antibacterial screening on Escherichia coli and Staphylococcus aureus. The anticancer potentials, apoptotic effects and enhanced drug delivery properties of these nanohybrids were confirmed and compared on MCF-7 cells by in vitro MTT assay. The drug delivery activities for hydrophobic drug and anticancer effects of chitosan coated zinc ferrite functionalized nanoparticles were higher than PEG coated cobalt ferrite nanohybrids. - Highlights: • CoFe{sub 2}O{sub 4} and ZnFe{sub 2}O{sub 4} nanoparticles were surface functionalized with PEG and Chitosan respectively. • Hydrophobic multi therapeutic anticancer drug curcumin was loaded into these nanohybrids and their structure, morphologies were confirmed. • The effects of PEG and Chitosan coating over ferrites for curcumin release have been elaborated, and the Chitosan coated curcumin loaded Zinc ferrite nanohybrid exhibited higher drug delivery and anticancer effects.
Mobile robot vehicles for physical security
International Nuclear Information System (INIS)
McGovern, D.E.
1987-07-01
A fleet of vehicles is being developed and maintained by Sandia National Labs for studies in remote control and autonomous operation. These vehicles range from modified commercial vehicles to specially constructed mobile platforms and are utilized as test beds for developing concepts in the application of robotics to interior and exterior physical security. Actuators control the vehicle speed, brakes, and steering through manual input from a remote driving station or through some level of digital computer control. On-board processing may include simple vehicle control functions or may allow for unmanned, autonomous operation. communication links are provided for digital communication between control computers, television transmission for vehicle vision, and voice for local control. With these vehicles, SNL can develop, test, and evaluate sensors, processing requirements, various methods of actuator implementation, operator controlled feedback requirements, and vehicle operations. A description of the major features and uses for each of the vehicles in the fleet is provided
Mobile robot vehicles for physical security
International Nuclear Information System (INIS)
Mc Govern, D.E.
1987-01-01
A fleet of vehicles is being developed and maintained by Sandia National Labs for studies in remote control and autonomous operation. These vehicles range from modified commercial vehicles to specially constructed mobile platforms and are utilized as test beds for developing concepts in the application of robotics to interior and exterior physical security. Actuators control the vehicle speed, brakes, and steering through manual input from a remote driving station or through some level of digital computer control. On-board processing may include simple vehicle control functions or may allow for unmanned, autonomous operation. Communication links are provided for digital communication between control computers, television transmission for vehicle vision, and voice for local control. With these vehicles, SNL can develop, test, and evaluate sensors, processing requirements, various methods of actuator implementation, operator controlled feedback requirements, and vehicle operations. A description of the major features and uses for each of the vehicles in the fleet is provided
Mobile robot vehicles for physical security
International Nuclear Information System (INIS)
McGovern, D.E.
1987-06-01
A fleet of vehicles is being developed and maintained by Sandia National Labs for studies in remote control and autonomous operation. These vehicles range from modified commercial vehicles to specially constructed mobile platforms and are utilized as test beds for developing concepts in the application of robotics to interior and exterior physical security. Actuators control the vehicle speed, brakes, and steering through manual input from a remote driving station or through some level of digital computer control. On-board processing may include simple vehicle control functions or may allow for unmanned, autonomous operation. Communication links are provided for digital communication between control computers, television transmission for vehicle vision, and voice for local control. With these vehicles, SNL can develop, test, and evaluate sensors, processing requirements, various methods of actuator implementation, operator controlled feedback requirements, and vehicle operations. A description of the major features and uses for each of the vehicles in the fleet is provided. 4 refs., 1 fig., 1 tab
Biocompatibility of Chitosan Carriers with Application in Drug Delivery
Directory of Open Access Journals (Sweden)
Ana Grenha
2012-09-01
Full Text Available Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures.
Wang, Junjuan; Wang, Jiaqiu; Lu, Ping; Cai, Youzhi; Wang, Yafei; Hong, Lan; Ren, Hao; Heng, Boon Chin; Liu, Hua; Zhou, Jing; Ouyang, Hongwei
2015-09-01
FTY720 has recently been approved as an oral drug for treating relapsing forms of multiple sclerosis, and exerts its therapeutic effect by acting as an immunological inhibitor targeting the sphingosine-1-phosphate (S1P) receptor subtype (S1P1) of T cells. Recently studies demonstrated positive efficacy of this drug on spinal cord injury (SCI) in animal models after systemic administration, albeit with significant adverse side effects. We hereby hypothesize that localized delivery of FTY720 can promote SCI recovery by reducing pathological astrogliosis. The mechanistic functions of FTY720 were investigated in vitro and in vivo utilizing immunofluorescence, histology, MRI and behavioral analysis. The in vitro study showed that FTY720 can reduce astrocyte migration and proliferation activated by S1P. FTY720 can prolong internalization of S1P1 and exert antagonistic effects on S1P1. In vivo study of SCI animal models demonstrated that local delivery of FTY720 with polycaprolactone (PCL) membrane significantly decreased S1P1 expression and glial scarring compared with the control group. Furthermore, FTY720-treated groups exhibited less cavitation volume and neuron loss, which significantly improved recovery of motor function. These findings demonstrated that localized delivery of FTY720 can promote SCI recovery by targeting the S1P1 receptor of astrocytes, provide a new therapeutic strategy for SCI treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.
Spray-on transdermal drug delivery systems.
Ibrahim, Sarah A
2015-02-01
Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.
Advanced technology mobile robotics vehicle fleet
International Nuclear Information System (INIS)
McGovern, D.E.
1987-03-01
A fleet of vehicles is being developed and maintained by Sandia National Laboratories for studies in remote control and autonomous operation. The vehicles range from modified commercial vehicles to specially constructed mobile platforms and are utilized as testbeds for developing concepts in the areas of remote control (teleoperation) and computer control (autonomy). Actuators control the vehicle speed, brakes, and steering via manual input from a remote driving station or through some level of digital computer control. On-board processing may include simple vehicle control functions or may allow for unmanned, autonomous operation. Communication links are provided for digital communication between control computers, television transmission for vehicle vision, and voice for local control. SNL can develop, test, and evaluate sensors, processing requirements, various methods of actuator implementation, operator controlled feedback requirements, and vehicle operations. A description of the major features and uses for each of the vehicles in the fleet is provided
Shah, D K; Khandavilli, S; Panchagnula, R
2008-09-01
Vehicles and permeation enhancers (PEs) used in transdermal drug delivery (TDD) of a drug can affect skin hydration, integrity and permeation of the solute administered. This investigation was designed to study the effect of the most commonly used vehicles and PEs on rat skin hydration, barrier function and permeation of an amphiphilic drug, imipramine hydrochloride (IMH). An array of well-established techniques were used to confirm the findings of the study. Thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy were used to determine changes in skin hydration. Alteration of the stratum corneum (SC) structure was investigated using FTIR studies. To monitor the barrier function alteration, transepidermal water loss (TEWL) measurement and permeation studies were performed. Our findings indicate that with hydration, there was an increase in the bound water content of the skin, and pseudoequilibrium of hydration (a drastic decrease in hydration rate) was achieved at around 12 h. Hydration increased the ratio between amide-I and amide-II peaks in FTIR and reduced the C-H stretching peak area. Both propylene glycol (PG) and ethanol (EtOH) dehydrated skin, with the latter showing a predominant effect. Furthermore, it was confirmed that PG and EtOH decreased the bound water content due to alteration in the protein domains and extraction of SC lipids, respectively. The effect of hydration on the SC was found to be similar to that reported for temperature. Permeation studies revealed that the dehydration caused by vehicles decreased IMH flux, whereas the flux was enhanced by PEs. The role of partition was predominant for the permeation of IMH through dehydrated skin. A synergistic effect was observed for PG and menthol in the enhancement of IMH. Further findings provided strong evidence that PG affects protein domains and EtOH extracts lipids from the bilayer. Both PG and EtOH, with or without PEs, increased TEWL. Initial TEWL was well
Predicting Light-Duty Vehicle Fuel Economy as a Function of Highway Speed
Energy Technology Data Exchange (ETDEWEB)
Thomas, John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hwang, Ho-Ling [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); West, Brian [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Huff, Shean [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
2013-04-08
The www.fueleconomy.gov website offers information such as window label fuel economy for city, highway, and combined driving for all U.S.-legal light-duty vehicles from 1984 to the present. The site is jointly maintained by the U.S. Department of Energy and the U.S. Environmental Protection Agency (EPA), and also offers a considerable amount of consumer information and advice pertaining to vehicle fuel economy and energy related issues. Included with advice pertaining to driving styles and habits is information concerning the trend that as highway cruising speed is increased, fuel economy will degrade. An effort was undertaken to quantify this conventional wisdom through analysis of dynamometer testing results for 74 vehicles at steady state speeds from 50 to 80 mph. Using this experimental data, several simple models were developed to predict individual vehicle fuel economy and its rate of change over the 50-80 mph speed range interval. The models presented require a minimal number of vehicle attributes. The simplest model requires only the EPA window label highway mpg value (based on the EPA specified estimation method for 2008 and beyond). The most complex of these simple model uses vehicle coast-down test coefficients (from testing prescribed by SAE Standard J2263) known as the vehicle Target Coefficients, and the raw fuel economy result from the federal highway test. Statistical comparisons of these models and discussions of their expected usefulness and limitations are offered.
A branch-and-cut algorithm for the Time Window Assignment Vehicle Routing Problem
K. Dalmeijer (Kevin); R. Spliet (Remy)
2016-01-01
textabstractThis paper presents a branch-and-cut algorithm for the Time Window Assignment Vehicle Routing Problem (TWAVRP), the problem of assigning time windows for delivery before demand volume becomes known. A novel set of valid inequalities, the precedence inequalities, is introduced and
Functionalization of 3D scaffolds with protein-releasing biomaterials for intracellular delivery.
Seras-Franzoso, Joaquin; Steurer, Christoph; Roldán, Mònica; Vendrell, Meritxell; Vidaurre-Agut, Carla; Tarruella, Anna; Saldaña, Laura; Vilaboa, Nuria; Parera, Marc; Elizondo, Elisa; Ratera, Imma; Ventosa, Nora; Veciana, Jaume; Campillo-Fernández, Alberto J; García-Fruitós, Elena; Vázquez, Esther; Villaverde, Antonio
2013-10-10
Appropriate combinations of mechanical and biological stimuli are required to promote proper colonization of substrate materials in regenerative medicine. In this context, 3D scaffolds formed by compatible and biodegradable materials are under continuous development in an attempt to mimic the extracellular environment of mammalian cells. We have here explored how novel 3D porous scaffolds constructed by polylactic acid, polycaprolactone or chitosan can be decorated with bacterial inclusion bodies, submicron protein particles formed by releasable functional proteins. A simple dipping-based decoration method tested here specifically favors the penetration of the functional particles deeper than 300μm from the materials' surface. The functionalized surfaces support the intracellular delivery of biologically active proteins to up to more than 80% of the colonizing cells, a process that is slightly influenced by the chemical nature of the scaffold. The combination of 3D soft scaffolds and protein-based sustained release systems (Bioscaffolds) offers promise in the fabrication of bio-inspired hybrid matrices for multifactorial control of cell proliferation in tissue engineering under complex architectonic setting-ups. © 2013.
Chitosan-based delivery systems for diclofenac delivery: preparation and characterization
Energy Technology Data Exchange (ETDEWEB)
Dreve, Simina; Kacso, Irina; Bratu, Ioan; Indrea, Emil, E-mail: simina.dreve@itim-cj.r [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath, 400293 Cluj-Napoca (Romania)
2009-08-01
The preparation and characterization of novel materials for drug delivery has rapidly gained importance in development of innovative medicine. The paper concerns the uses of chitosan as an excipient in oral formulations and as a drug delivery vehicle for burnt painful injuries. The use of chitosan (CTS) as base in polyelectrolyte complex systems, to prepare liquid release systems as hydrogels and solid release systems as sponges is presented. In this paper the preparation of CTS hydrogels and sponges carrying diclofenac (DCF), as anti-inflammatory drug is reported. The immobilization of DCF in CTS is done by mixing the CTS hydrogel with the anti-inflammatory drug solutions. The concentration of anti-inflammatory drug in the CTS hydrogel generating the sponges was of 57 mg/l, 72 mg/l and 114 mg/l. The CTS sponges with anti-inflammatory drugs were prepared by freeze-drying at -610{sup 0}C and 0,09 atm. The characterization of the hydrogels and sponges was done by infrared spectra (FTIR) and ultraviolet-visible spectroscopy (UV-VIS). The results indicated the formation of CTS-DCF intermediates. The DCF molecules are forming temporary chelates in CTS hydrogels and sponges and they are compatible with skin or some of biological fluids with satisfactory results.
Chitosan-based delivery systems for diclofenac delivery: preparation and characterization
International Nuclear Information System (INIS)
Dreve, Simina; Kacso, Irina; Bratu, Ioan; Indrea, Emil
2009-01-01
The preparation and characterization of novel materials for drug delivery has rapidly gained importance in development of innovative medicine. The paper concerns the uses of chitosan as an excipient in oral formulations and as a drug delivery vehicle for burnt painful injuries. The use of chitosan (CTS) as base in polyelectrolyte complex systems, to prepare liquid release systems as hydrogels and solid release systems as sponges is presented. In this paper the preparation of CTS hydrogels and sponges carrying diclofenac (DCF), as anti-inflammatory drug is reported. The immobilization of DCF in CTS is done by mixing the CTS hydrogel with the anti-inflammatory drug solutions. The concentration of anti-inflammatory drug in the CTS hydrogel generating the sponges was of 57 mg/l, 72 mg/l and 114 mg/l. The CTS sponges with anti-inflammatory drugs were prepared by freeze-drying at -610 0 C and 0,09 atm. The characterization of the hydrogels and sponges was done by infrared spectra (FTIR) and ultraviolet-visible spectroscopy (UV-VIS). The results indicated the formation of CTS-DCF intermediates. The DCF molecules are forming temporary chelates in CTS hydrogels and sponges and they are compatible with skin or some of biological fluids with satisfactory results.
Preparation and Characterization of a Lecithin Nanoemulsion as a Topical Delivery System
Zhou, Huafeng; Yue, Yang; Liu, Guanlan; Li, Yan; Zhang, Jing; Gong, Qiu; Yan, Zemin; Duan, Mingxing
2010-01-01
Purpose of this study was to establish a lecithin nanoemulsion (LNE) without any synthetic surfactant as a topical delivery vehicle and to evaluate its topical delivery potential by the following factors: particle size, morphology, viscosity, stability, skin hydration and skin penetration. Experimental results demonstrated that an increasing concentration of soybean lecithin and glycerol resulted in a smaller size LNE droplet and increasing viscosity, respectively. The droplet size of optimized LNE, with the glycerol concentration above 75% (w/w), changed from 92 (F10) to 58 nm (F14). Additionally, LNE, incorporated into o/w cream, improved the skin hydration capacity of the cream significantly with about 2.5-fold increase when the concentration of LNE reached 10%. LNE was also demonstrated to improve the penetrability of Nile red (NR) dye into the dermis layer, when an o/w cream, incorporated with NR-loaded LNE, applied on the abdominal skin of rat in vivo. Specifically, the arbitrary unit (ABU) of fluorescence in the dermis layer that had received the cream with a NR-loaded LNE was about 9.9-fold higher than the cream with a NR-loaded general emulsion (GE). These observations suggest that LNE could be used as a promising topical delivery vehicle for lipophilic compounds.
Cardiopulmonary function and oxygen delivery during total liquid ventilation.
Tsagogiorgas, Charalambos; Alb, Markus; Herrmann, Peter; Quintel, Michael; Meinhardt, Juergen P
2011-10-01
Total liquid ventilation (TLV) with perfluorocarbons has shown to improve cardiopulmonary function in the injured and immature lung; however there remains controversy over the normal lung. Hemodynamic effects of TLV in the normal lung currently remain undetermined. This study compared changes in cardiopulmonary and circulatory function caused by either liquid or gas tidal volume ventilation. In a prospective, controlled study, 12 non-injured anesthetized, adult New Zealand rabbits were primarily conventionally gas-ventilated (CGV). After instrumentation for continuous recording of arterial (AP), central venous (CVP), left artrial (LAP), pulmonary arterial pressures (PAP), and cardiac output (CO) animals were randomized into (1) CGV group and (2) TLV group. In the TLV group partial liquid ventilation was initiated with instillation of perfluoroctylbromide (12 ml/kg). After 15 min, TLV was established for 3 hr applying a volume-controlled, pressure-limited, time-cycled ventilation mode using a double-piston configured TLV. Controls (CGV) remained gas-ventilated throughout the experiment. During TLV, heart rate, CO, PAP, MAP, CVP, and LAP as well as derived hemodynamic variables, arterial and mixed venous blood gases, oxygen delivery, PVR, and SVR did not differ significantly compared to CGV. Liquid tidal volumes suitable for long-term TLV in non-injured rabbits do not significantly impair CO, blood pressure, and oxygen dynamics when compared to CGV. Copyright © 2011 Wiley-Liss, Inc.
Vargas-Melendez, Leandro; Boada, Beatriz L; Boada, Maria Jesus L; Gauchia, Antonio; Diaz, Vicente
2017-04-29
Vehicles with a high center of gravity (COG), such as light trucks and heavy vehicles, are prone to rollover. This kind of accident causes nearly 33 % of all deaths from passenger vehicle crashes. Nowadays, these vehicles are incorporating roll stability control (RSC) systems to improve their safety. Most of the RSC systems require the vehicle roll angle as a known input variable to predict the lateral load transfer. The vehicle roll angle can be directly measured by a dual antenna global positioning system (GPS), but it is expensive. For this reason, it is important to estimate the vehicle roll angle from sensors installed onboard in current vehicles. On the other hand, the knowledge of the vehicle's parameters values is essential to obtain an accurate vehicle response. Some of vehicle parameters cannot be easily obtained and they can vary over time. In this paper, an algorithm for the simultaneous on-line estimation of vehicle's roll angle and parameters is proposed. This algorithm uses a probability density function (PDF)-based truncation method in combination with a dual Kalman filter (DKF), to guarantee that both vehicle's states and parameters are within bounds that have a physical meaning, using the information obtained from sensors mounted on vehicles. Experimental results show the effectiveness of the proposed algorithm.
Nanostructured Surfaces for Drug Delivery and Anti-Fibrosis
Kam, Kimberly Renee
Effective and cost-efficient healthcare is at the forefront of public discussion; on both personal and policy levels, technologies that improve therapeutic efficacy without the use of painful hypodermic needle injections or the use of harsh chemicals would prove beneficial to patients. Nanostructured surfaces as structure-mediated permeability enhancers introduce a potentially revolutionary approach to the field of drug delivery. Parental administration routes have been the mainstay technologies for delivering biologics because these therapeutics are too large to permeate epithelial barriers. However, there is a significant patient dislike for hypodermic needles resulting in reduced patient compliance and poor therapeutic results. We present an alternative strategy to harness the body's naturally occurring biological processes and transport mechanisms to enhance the drug transport of biologics across the epithelium. Our strategy offers a paradigm shift from traditional biochemical drug delivery vehicles by using nanotopography to loosen the epithelial barrier. Herein, we demonstrate that nanotopographical cues can be used to enable biologics > 66 kDa to be transported across epithelial monolayers by increasing paracellular transport. When placed in contact with epithelial cells, nanostructured films significantly increase the transport of albumin, IgG, and a model therapeutic, etanercept. Our work highlights the potential to use drug delivery systems which incorporate nanotopographical cues to increase the transport of biologics across epithelial tissue. Furthermore, we describe current advancements in nano- and microfabrication for applications in anti-fibrosis and wound healing. Influencing cellular responses to biomaterials is crucial in the field of tissue engineering and regenerative medicine. Since cells are surrounded by extracellular matrix features that are on the nanoscale, identifying nanostructures for imparting desirable cellular function could greatly
Highly water-soluble, porous, and biocompatible boron nitrides for anticancer drug delivery.
Weng, Qunhong; Wang, Binju; Wang, Xuebin; Hanagata, Nobutaka; Li, Xia; Liu, Dequan; Wang, Xi; Jiang, Xiangfen; Bando, Yoshio; Golberg, Dmitri
2014-06-24
Developing materials for "Nano-vehicles" with clinically approved drugs encapsulated is envisaged to enhance drug therapeutic effects and reduce the adverse effects. However, design and preparation of the biomaterials that are porous, nontoxic, soluble, and stable in physiological solutions and could be easily functionalized for effective drug deliveries are still challenging. Here, we report an original and simple thermal substitution method to fabricate perfectly water-soluble and porous boron nitride (BN) materials featuring unprecedentedly high hydroxylation degrees. These hydroxylated BNs are biocompatible and can effectively load anticancer drugs (e.g., doxorubicin, DOX) up to contents three times exceeding their own weight. The same or even fewer drugs that are loaded on such BN carriers exhibit much higher potency for reducing the viability of LNCaP cancer cells than free drugs.
Albumin-mediated delivery of siRNA
DEFF Research Database (Denmark)
Bienk, Konrad
2015-01-01
. The human body, however, possesses several natural transport mechanisms for active transport of molecules. Amongst these is albumin, which is the most abundant plasma protein and has a circulatory half-life of ~21 days, partially due to engagement and recycling by the neonatal Fc receptor (FcRn). Albumin...... vehicle. This proof of concept silencing showed that siRNA can be used for therapeutic purposes without the use of non-biocompatible polymer or lipid materials. This work, therefore, provides a novel technology platform for the safe delivery of siRNA therapeutics....
Energy Technology Data Exchange (ETDEWEB)
Wallner, Stefan; Lamke, Martin; Sedlacek, Martin [ZF Friedrichshafen AG (Germany)
2009-07-01
Hybrid technology offers solutions to the intensely increasing delivery traffic requirements, such as a significant reduction in fuel consumption and noticeably reduced emissions. Diverse requirements result from the multitude of possible applications in delivery traffic. In response, ZF has developed a parallel hybrid system based on a modular and standardized transmission family. Composed of the automatic AS Tronic lite transmission, an electric machine, inverter, a highvoltage battery, wiring and a hybrid control unit, this system can be integrated into present vehicle concepts. Including start-stop operation, recuperation, boosting, purely electric driving and emission-free auxiliary drive, it offers the functionality of a full hybrid. (orig.)
Directory of Open Access Journals (Sweden)
Leilei Wang
2017-11-01
Full Text Available Vehicular ad hoc networks (VANETs have emerged as a new powerful technology for data transmission between vehicles. Efficient data transmission accompanied with low data delay plays an important role in selecting the ideal data forwarding path in VANETs. This paper proposes a new opportunity routing protocol for data forwarding based on vehicle mobility association (OVMA. With assistance from the vehicle mobility association, data can be forwarded without passing through many extra intermediate nodes. Besides, each vehicle carries the only replica information to record its associated vehicle information, so the routing decision can adapt to the vehicle densities. Simulation results show that the OVMA protocol can extend the network lifetime, improve the performance of data delivery ratio, and reduce the data delay and routing overhead when compared to the other well-known routing protocols.
Directory of Open Access Journals (Sweden)
Hua-Ping Huang
2015-04-01
Full Text Available Chewing gum has been reported to enhance bowel function. However, the efficacy remains unclear for women undergoing cesarean delivery. The aim of this meta-analysis is to evaluate the efficacy of chewing gum for recovering intestinal function following cesarean delivery in the early postoperative period. Electronic databases including MEDLINE, EMBASE, Cochrane Library were searched to identify English language randomized controlled trials comparing chewing gum with other procedures for promoting the recovery of intestinal function after cesarean delivery. Two of the authors independently extracted data from the eligibility studies, and Review Manager Version 5.2 was used to pool the data. Finally, five randomized controlled trials involving 882 patients were included and all the trials were considered as at high risk of bias. The pooled findings showed that chewing gum after cesarean delivery can significantly shorten the time to first flatus [standardized mean difference (SMD = −0.73; 95% confidence interval (CI = −1.01 to −0.14; p < 0.001]; time to first hearing of normal intestinal sounds (SMD = −0.69; 95% CI = −1.20 to −0.17; p = 0.009; I² = 92%. Time to the first defecation (SMD = −0.53; 95% CI = −1.61 to −0.07; p = 0.07; I² = 92% and length of hospital stay (SMD = −0.59; 95% CI = −1.18 to 0.00; p = 0.05; I² = 93% were also reduced in the chewing gum group; however, these results were not statistically significant. The current evidence suggests that chewing gum has a positive effect on intestinal function recovery following cesarean delivery in the early postoperative period. However, more large-scale and high-quality randomized controlled trials are needed to confirm these results.
Macrophages with cellular backpacks for targeted drug delivery to the brain.
Klyachko, Natalia L; Polak, Roberta; Haney, Matthew J; Zhao, Yuling; Gomes Neto, Reginaldo J; Hill, Michael C; Kabanov, Alexander V; Cohen, Robert E; Rubner, Michael F; Batrakova, Elena V
2017-09-01
Most potent therapeutics are unable to cross the blood-brain barrier following systemic administration, which necessitates the development of unconventional, clinically applicable drug delivery systems. With the given challenges, biologically active vehicles are crucial to accomplishing this task. We now report a new method for drug delivery that utilizes living cells as vehicles for drug carriage across the blood brain barrier. Cellular backpacks, 7-10 μm diameter polymer patches of a few hundred nanometers in thickness, are a potentially interesting approach, because they can act as drug depots that travel with the cell-carrier, without being phagocytized. Backpacks loaded with a potent antioxidant, catalase, were attached to autologous macrophages and systemically administered into mice with brain inflammation. Using inflammatory response cells enabled targeted drug transport to the inflamed brain. Furthermore, catalase-loaded backpacks demonstrated potent therapeutic effects deactivating free radicals released by activated microglia in vitro. This approach for drug carriage and release can accelerate the development of new drug formulations for all the neurodegenerative disorders. Copyright © 2017. Published by Elsevier Ltd.
Functional nutrients in infants born by vaginal delivery or Cesarean section
Directory of Open Access Journals (Sweden)
Gianluca Lista
2017-12-01
Full Text Available The development of a proper neonatal microbiota is of great importance, especially for the effects that dysbiosis has in acute and chronic diseases’ onset. The microbiota, particularly the intestinal one, plays a crucial role in maintaining the health of the host, preventing colonization by pathogenic bacteria and significantly influencing the development and maturation of a normal gastrointestinal mucosal immunity. Several factors may interfere with the physiological development of microbiota, such as diseases during pregnancy, type of delivery, maternal nutrition, type of neonatal feeding, use of antibiotics, exposition to hospital environment (e.g., neonatal intensive care unit and genetic factors. Thanks to a proper maternal and neonatal supplementation with specific functional nutrients, it is now possible to correct dysbiosis, thus reducing the risks for the newborn’s health. In this review of the literature, we give an overview of the studies highlighting the composition of the maternal, fetal and neonatal microbiota, the factors potentially responsible for dysbiosis and the use of functional nutrients to prevent diseases’ onset.
Review on Automotive Power Generation System on Plug-in Hybrid Electric Vehicles & Electric Vehicles
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Leong Yap Wee
2016-01-01
Full Text Available Regenerative braking is a function to recharge power bank on the Plug-in electric vehicles (PHEV and electric vehicles (EV. The weakness of this system is, it can only perform its function when the vehicle is slowing down or by stepping the brake foot pedal. In other words, the electricity recharging system is inconsistent, non-continuous and geography dependent. To overcome the weakness of the regenerative braking system, it is suggested that to apply another generator which is going to be parallel with the regenerative braking system so that continuous charging can be achieved. Since the ironless electricity generator has a less counter electromotive force (CEMF comparing to an ironcored electricity generator and no cogging torque. Applying the ironless electricity generator parallel to the regenerative braking system is seen one of the options which creates sustainable charging system compared to cored electricity generator.
Directory of Open Access Journals (Sweden)
Li L
2014-02-01
Full Text Available Lei Li,1,* Dongxi Xiang,2,* Sarah Shigdar,2 Wenrong Yang,3 Qiong Li,2 Jia Lin,4 Kexin Liu,1 Wei Duan2 1College of Pharmacy, Dalian Medical University, Dalian, People's Republic of China; 2School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia; 3School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, Waurn Ponds, VIC, Australia; 4Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, People's Republic of China *These authors contributed equally to this work Abstract: To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles were synthesized and functionalized with ribonucleic acid (RNA Aptamers (Apts against epithelial cell adhesion molecule (EpCAM for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01. Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug
Nanodiamonds act as Trojan horse for intracellular delivery of metal ions to trigger cytotoxicity.
Zhu, Ying; Zhang, Yu; Shi, Guosheng; Yang, Jinrong; Zhang, Jichao; Li, Wenxin; Li, Aiguo; Tai, Renzhong; Fang, Haiping; Fan, Chunhai; Huang, Qing
2015-02-05
Nanomaterials hold great promise for applications in the delivery of various molecules with poor cell penetration, yet its potential for delivery of metal ions is rarely considered. Particularly, there is limited insight about the cytotoxicity triggered by nanoparticle-ion interactions. Oxidative stress is one of the major toxicological mechanisms for nanomaterials, and we propose that it may also contribute to nanoparticle-ion complexes induced cytotoxicity. To explore the potential of nanodiamonds (NDs) as vehicles for metal ion delivery, we used a broad range of experimental techniques that aimed at getting a comprehensive assessment of cell responses after exposure of NDs, metal ions, or ND-ion mixture: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Trypan blue exclusion text, optical microscope observation, synchrotron-based scanning transmission X-ray microscopy (STXM) and micro X-ray fluorescence (μXRF) microscopy, inductively coupled plasma-mass spectrometry (ICP-MS), reactive oxygen species (ROS) assay and transmission electron microscopy (TEM) observation. In addition, theoretical calculation and molecular dynamics (MD) computation were used to illustrate the adsorption properties of different metal ion on NDs as well as release profile of ion from ND-ion complexes at different pH values. The adsorption capacity of NDs for different metal ions was different, and the adsorption for Cu2+ was the most strong among divalent metal ions. These different ND-ion complexes then had different cytotoxicity by influencing the subsequent cellular responses. Detailed investigation of ND-Cu2+ interaction showed that the amount of released Cu2+ from ND-Cu2+ complexes at acidic lysosomal conditions was much higher than that at neutral conditions, leading to the elevation of intracellular ROS level, which triggered cytotoxicity. By theoretical approaches, we demonstrated that the functional carbon surface and cluster structures of NDs made them
Evaluating the use of an urban consolidation centre and electric vehicles in central London
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Michael Browne
2011-07-01
Full Text Available The paper focuses on the role that can be played by urban consolidation centres (UCCs in reducing freight traffic and its environmental impacts in towns and cities. It is based on the before and after evaluation of a trial led by a major stationery and office supplies company in which urban freight deliveries in central London made from a depot in the suburbs using diesel vehicles were replaced with the use of an urban micro-consolidation centre located in the delivery area together with the use of electrically-assisted cargo tricycles and electric vans. The results show that the total distance travelled and the CO2eq emissions per parcel delivered fell by 20% and 54% respectively as a result of this delivery system. However, the evaluation has also indicated that the distance travelled per parcel rose substantially in the City of London delivery area as a result of the electric vehicles having far smaller load limits in both weight and volume compared with diesel vans. But, at the same time, the trial system was able to virtually eliminate CO2eq emissions per parcel delivered in the City of London. The trial proved successful from the company's perspective in transport, environmental and financial terms. The company therefore decided to continue the operation beyond the end of the trial with it being officially launched during 2010.
Kieler-Ferguson, Heidi M.; Frechet, Jean; Szoka, Francis C.
2013-01-01
For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting
The GREET Model Expansion for Well-to-Wheels Analysis of Heavy-Duty Vehicles
Energy Technology Data Exchange (ETDEWEB)
Cai, Hao [Argonne National Lab. (ANL), Argonne, IL (United States); Burnham, Andrew [Argonne National Lab. (ANL), Argonne, IL (United States); Wang, Michael [Argonne National Lab. (ANL), Argonne, IL (United States); Hang, Wen [Argonne National Lab. (ANL), Argonne, IL (United States); Vyas, Anant [Argonne National Lab. (ANL), Argonne, IL (United States)
2015-05-01
Heavy-duty vehicles (HDVs) account for a significant portion of the U.S. transportation sector’s fuel consumption, greenhouse gas (GHG) emissions, and air pollutant emissions. In our most recent efforts, we expanded the Greenhouse gases, Regulated Emissions, and Energy use in Transportation (GREETTM) model to include life-cycle analysis of HDVs. In particular, the GREET expansion includes the fuel consumption, GHG emissions, and air pollutant emissions of a variety of conventional (i.e., diesel and/or gasoline) HDV types, including Class 8b combination long-haul freight trucks, Class 8b combination short-haul freight trucks, Class 8b dump trucks, Class 8a refuse trucks, Class 8a transit buses, Class 8a intercity buses, Class 6 school buses, Class 6 single-unit delivery trucks, Class 4 single-unit delivery trucks, and Class 2b heavy-duty pickup trucks and vans. These vehicle types were selected to represent the diversity in the U.S. HDV market, and specific weight classes and body types were chosen on the basis of their fuel consumption using the 2002 Vehicle Inventory and Use Survey (VIUS) database. VIUS was also used to estimate the fuel consumption and payload carried for most of the HDV types. In addition, fuel economy projections from the U.S. Energy Information Administration, transit databases, and the literature were examined. The U.S. Environmental Protection Agency’s latest Motor Vehicle Emission Simulator was employed to generate tailpipe air pollutant emissions of diesel and gasoline HDV types.
Bacteria-mediated in vivo delivery of quantum dots into solid tumor
International Nuclear Information System (INIS)
Liu, Ying; Zhou, Mei; Luo, Dan; Wang, Lijun; Hong, Yuankai; Yang, Yepeng; Sha, Yinlin
2012-01-01
Highlights: ► New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. ► Bifidobacterium bifidum delivery system has intrinsic biocompatibility. ► The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.
Ballistic delivery capability is essential to delivering vaccines and other therapeutics effectively to both livestock and wildlife in many global scenarios. Here, lyophilized poly(ethylene glycol) (PEG)-glycolide dimethacrylate crosslinked but degradable hydrogels were assessed as payload vehicles ...
Duan, Xiaoping; Guan, Hui; Cao, Ying; Kleinerman, Eugenie S
2009-01-01
This study evaluated the therapeutic efficacy of interleukin 12 (IL-12) gene therapy in Ewing sarcoma and whether murine mesenchymal stem cells (MSCs) could serve as vehicles for IL-12 gene delivery. MSCs were isolated from murine bone marrow cells. Cells were phenotyped using flow cytometry. Cultured MSCs differentiated into osteocytes and adipocytes using the appropriate media. Freshly isolated MSCs were transfected with adenoviral vectors containing either the beta-galactosidase (Ad:beta-gal) or the IL-12 (Ad:IL-12) gene. Expression of IL-12 was confirmed using reverse transcription polymerase chain reaction. Mice with TC71 Ewing sarcoma tumors were then treated intravenously with MSCs transfected with Ad:beta-gal or Ad:IL-12. Tumors were measured and analyzed by immunohistochemical analysis for expression of IL-12 protein. Expression of both p35 and p40 IL-12 subunits was demonstrated in MSCs transfected in vitro with Ad:IL-12. IL-12 expression was seen in tumors from mice treated with MSCs transfected with Ad:IL-12. Tumor growth was also significantly inhibited compared with that in mice treated with MSCs transfected with Ad:beta-gal. MSCs can be transfected with the IL-12 gene. These transfected cells localize to tumors after intravenous injection and induce local IL-12 protein production and the regression of established tumors. Copyright (c) 2008 American Cancer Society.
Relkin, Perla
2016-10-01
The 6th international symposium in the series "Delivery of Functionality in Complex Food Systems: Physically inspired approaches from nanoscale to microscal" was held in the heart of Paris from 14 to 17 July, 2015. It brought together PhD students, academic food researchers and industrials from diversified food sectors. The scientific sessions of this meeting were constructed around important topics dealing with 1) Engineering of tailored-made structures in bio-based systems; 2) Complexity and emergent phenomena in the integrative food science; 3) Investigation of nano and microstructures in the bulk and at interfaces; 4) Modeling approaches from bio-molecules and matrix structures to functionality; 5) Tuning binding & release of bioactive compounds by matrix modulation, and finally; 6) Tuning the delivery of functionality to the body. These topics were selected to cover different scientific fields and to show the contribution of food physical structures to development of health- and plaisure-supporting food functions. The oral communications were all introduced by key note speakers and they were all illustrated by outstanding high quality short communications. One of the most original features of this symposium was the increasing number of presentations using multiscale and modeling approaches illustrating the concept of complexity and emergent phenomena integrative food science. These highlighted the importance of studies on interactions between structure properties of engineered delivery systems and human body (sensory properties, digestion, release, bioavailability and bioaccessibility). Copyright © 2016 Elsevier Ltd. All rights reserved.
Probiotic Delivery through Fermentation: Dairy vs. Non-Dairy Beverages
Chaminda Senaka Ranadheera; Janak K. Vidanarachchi; Ramon Silva Rocha; Adriano G. Cruz; Said Ajlouni
2017-01-01
Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, mainly through the process of replacing or including beneficial bacteria in the gastrointestinal tract. Fermented dairy foods such as yogurt, fermented milk and cheese are the major vehicle in delivering probiotics, and probiotic delivery have been traditionally associated with these fermented dairy foods. Additionally, many other non-dairy probiotic products and non-food form ...
Reversible Masking Using Low-Molecular-Weight Neutral Lipids to Achieve Optimal-Targeted Delivery
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Nancy Smyth Templeton
2012-01-01
Full Text Available Intravenous injection of therapeutics is required to effectively treat or cure metastatic cancer, certain cardiovascular diseases, and other acquired or inherited diseases. Using this route of delivery allows potential uptake in all disease targets that are accessed by the bloodstream. However, normal tissues and organs also have the potential for uptake of therapeutic agents. Therefore, investigators have used targeted delivery to attempt delivery solely to the target cells; however, use of ligands on the surface of delivery vehicles to target specific cell surface receptors is not sufficient to avoid nonspecific uptake. PEGylation has been used for decades to try to avoid nonspecific uptake but suffers from many problems known as “The PEGylation Dilemma.” We have solved this dilemma by replacing PEGylation with reversible masking using low-molecular-weight neutral lipids in order to achieve optimal-targeted delivery solely to target cells. Our paper will focus on this topic.
Mesoporous persistent nanophosphors for in vivo optical bioimaging and drug-delivery
Maldiney, Thomas; Ballet, Benoit; Bessodes, Michel; Scherman, Daniel; Richard, Cyrille
2014-10-01
Based upon the ambitious idea that one single particle could serve multiple purposes at the same time, the combination and simultaneous use of imaging and therapeutics has lately arisen as one of the most promising prospects among nanotechnologies directed toward biomedical applications. Intended for both therapeutics and diagnostics in vivo, highly complex nanostructures were specifically designed to simultaneously act as optical imaging probes and delivery vehicles. Yet, such multifunctional photonic nanoplatforms usually exploit fluorescence phenomena which require constant excitation light through biological tissues and thus significantly reduce the detection sensitivity due to the autofluorescence from living animals. In order to overcome this critical issue, the present article introduces a novel multifunctional agent based on persistent luminescence mesoporous nanoparticles. Being composed of a hybrid chromium-doped zinc gallate core/mesoporous silica shell architecture, we show that this nanotechnology can be used as an efficient doxorubicin-delivery vehicle presenting a higher cytotoxicity toward U87MG cells than its unloaded counterpart in vitro. In addition, we demonstrate that a persistent luminescence signal from these doxorubicin-loaded mesoporous nanophosphors opens a new way to highly sensitive detection in vivo, giving access to the real-time biodistribution of the carrier without any autofluorescence from the animal tissues. This new persistent luminescence-based hybrid nanotechnology can be easily applied to the delivery of any therapeutic agent, thus constituting a versatile and sensitive optical nanotool dedicated to both therapeutic and diagnostic applications in vivo.Based upon the ambitious idea that one single particle could serve multiple purposes at the same time, the combination and simultaneous use of imaging and therapeutics has lately arisen as one of the most promising prospects among nanotechnologies directed toward biomedical
The next step in gene delivery: molecular engineering of adeno-associated virus serotypes.
Wang, Jinhui; Faust, Susan M; Rabinowitz, Joseph E
2011-05-01
Delivery is at the heart of gene therapy. Viral DNA delivery systems are asked to avoid the immune system, transduce specific target cell types while avoiding other cell types, infect dividing and non-dividing cells, insert their cargo within the host genome without mutagenesis or to remain episomal, and efficiently express transgenes for a substantial portion of a lifespan. These sought-after features cannot be associated with a single delivery system, or can they? The Adeno-associated virus family of gene delivery vehicles has proven to be highly malleable. Pseudotyping, using AAV serotype 2 terminal repeats to generate designer shells capable of transducing selected cell types, enables the packaging of common genomes into multiple serotypes virions to directly compare gene expression and tropism. In this review the ability to manipulate this virus will be examined from the inside out. The influence of host cell factors and organism biology including the immune response on the molecular fate of the viral genome will be discussed as well as differences in cellular trafficking patterns and uncoating properties that influence serotype transduction. Re-engineering the prototype vector AAV2 using epitope insertion, chemical modification, and molecular evolution not only demonstrated the flexibility of the best-studied serotype, but now also expanded the tool kit for molecular modification of all AAV serotypes. Current AAV research has changed its focus from examination of wild-type AAV biology to the feedback of host cell/organism on the design and development of a new generation of recombinant AAV delivery vehicles. This article is part of a Special Section entitled "Special Section: Cardiovascular Gene Therapy". Copyright © 2010 Elsevier Ltd. All rights reserved.
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Hiroyuki Sakai
Full Text Available Although low executive functioning is a risk factor for vehicle crashes among elderly drivers, the neural basis of individual differences in this cognitive ability remains largely unknown. Here we aimed to examine regional frontal gray matter volume associated with executive functioning in normal aging individuals, using voxel-based morphometry (VBM. To this end, 39 community-dwelling elderly volunteers who drove a car on a daily basis participated in structural magnetic resonance imaging, and completed two questionnaires concerning executive functioning and risky driving tendencies in daily living. Consequently, we found that participants with low executive function capacity were prone to risky driving. Furthermore, VBM analysis revealed that lower executive function capacity was associated with smaller gray matter volume in the supplementary motor area (SMA. Thus, the current data suggest that SMA volume is a reliable predictor of individual differences in executive function capacity as a risk factor for vehicle crashes among elderly persons. The implication of our results is that regional frontal gray matter volume might underlie the variation in driving tendencies among elderly drivers. Therefore, detailed driving behavior assessments might be able to detect early neurodegenerative changes in the frontal lobe in normal aging adults.
Intelligent behaviors through vehicle-to-vehicle and vehicle-to-infrastructure communication
Garcia, Richard D.; Sturgeon, Purser; Brown, Mike
2012-06-01
The last decade has seen a significant increase in intelligent safety devices on private automobiles. These devices have both increased and augmented the situational awareness of the driver and in some cases provided automated vehicle responses. To date almost all intelligent safety devices have relied on data directly perceived by the vehicle. This constraint has a direct impact on the types of solutions available to the vehicle. In an effort to improve the safety options available to a vehicle, numerous research laboratories and government agencies are investing time and resources into connecting vehicles to each other and to infrastructure-based devices. This work details several efforts in both the commercial vehicle and the private auto industries to increase vehicle safety and driver situational awareness through vehicle-to-vehicle and vehicle-to-infrastructure communication. It will specifically discuss intelligent behaviors being designed to automatically disable non-compliant vehicles, warn tractor trailer vehicles of unsafe lane maneuvers such as lane changes, passing, and merging, and alert drivers to non-line-of-sight emergencies.
Svejkosky, Joseph
The spectral signatures of vehicles in hyperspectral imagery exhibit temporal variations due to the preponderance of surfaces with material properties that display non-Lambertian bi-directional reflectance distribution functions (BRDFs). These temporal variations are caused by changing illumination conditions, changing sun-target-sensor geometry, changing road surface properties, and changing vehicle orientations. To quantify these variations and determine their relative importance in a sub-pixel vehicle reacquisition and tracking scenario, a hyperspectral vehicle BRDF sampling experiment was conducted in which four vehicles were rotated at different orientations and imaged over a six-hour period. The hyperspectral imagery was calibrated using novel in-scene methods and converted to reflectance imagery. The resulting BRDF sampled time-series imagery showed a strong vehicle level BRDF dependence on vehicle shape in off-nadir imaging scenarios and a strong dependence on vehicle color in simulated nadir imaging scenarios. The imagery also exhibited spectral features characteristic of sampling the BRDF of non-Lambertian targets, which were subsequently verified with simulations. In addition, the imagery demonstrated that the illumination contribution from vehicle adjacent horizontal surfaces significantly altered the shape and magnitude of the vehicle reflectance spectrum. The results of the BRDF sampling experiment illustrate the need for a target vehicle BRDF model and detection scheme that incorporates non-Lambertian BRDFs. A new detection algorithm called Eigenvector Loading Regression (ELR) is proposed that learns a hyperspectral vehicle BRDF from a series of BRDF measurements using regression in a lower dimensional space and then applies the learned BRDF to make test spectrum predictions. In cases of non-Lambertian vehicle BRDF, this detection methodology performs favorably when compared to subspace detections algorithms and graph-based detection algorithms that
DEFF Research Database (Denmark)
Wen, Min; Krapper, Emil; Larsen, Jesper
2011-01-01
in their fresh meat supply logistics system. The problem consists of a 1‐week planning horizon, heterogeneous vehicles, and drivers with predefined work regulations. These regulations include, among other things, predefined workdays, fixed starting time, maximum weekly working duration, and a break rule......The world's second largest producer of pork, Danish Crown, also provides a fresh meat supply logistics system within Denmark. This is used by the majority of supermarkets in Denmark. This article addresses an integrated vehicle routing and driver scheduling problem arising at Danish Crown....... The objective is to minimize the total delivery cost that is a weighted sum of two kinds of delivery costs. A multilevel variable neighborhood search heuristic is proposed for the problem. In a preprocessing step, the problem size is reduced through an aggregation procedure. Thereafter, the aggregated weekly...
Energy Technology Data Exchange (ETDEWEB)
Mandal, Subhra [Department of Tumor Immunology, Radboud University Nijmegen Medical Centre (Netherlands); Bakeine, Gerald J., E-mail: Jamesbakeine1@yahoo.com [Department of Internal Medicine and Therapeutics-Section of Clinical Toxicology, University of Pavia, Piazza Botta 10, 27100 Pavia (Italy); Krol, Silke [Institute of Neurology, Fondazione IRCCS Carlo Besta, Milan (Italy); Ferrari, Cinzia; Clerici, Anna M.; Zonta, Cecilia; Cansolino, Laura [Department of Surgery, Laboratory of Experimental Surgery, University of Pavia (Italy); Ballarini, Francesca [Department of Nuclear and Theoretical Physics, University of Pavia (Italy); Bortolussi, Silva [Department of Nuclear and Theoretical Physics, University of Pavia (Italy)] [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy); Stella, Subrina; Protti, Nicoletta [Department of Nuclear and Theoretical Physics, University of Pavia (Italy); Bruschi, Piero [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy); Altieri, Saverio [Department of Nuclear and Theoretical Physics, University of Pavia (Italy)] [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy)
2011-12-15
The aim of this study is to optimize targeted boron delivery to cancer cells and its tracking down to the cellular level. To this end, we describe the design and synthesis of novel nanovectors that double as targeted boron delivery agents and fluorescent imaging probes. Gold nanoparticles were coated with multilayers of polyelectrolytes functionalized with the fluorescent dye (FITC), boronophenylalanine and folic acid. In vitro confocal fluorescence microscopy demonstrated significant uptake of the nanoparticles in cancer cells that are known to overexpress folate receptors. - Highlights: Black-Right-Pointing-Pointer Synthesis of multi-labeled gold nanoparticles for selective boron delivery to tumor cells. Black-Right-Pointing-Pointer Tumor selectivity is achieved through folic acid receptor targeting. Black-Right-Pointing-Pointer Optical fluorescent microscopy allows tracking of cellular uptake of the gold nanoparticle. Black-Right-Pointing-Pointer In vitro tests demonstrate selective nanoparticle up in folate receptor positive tumor cells.
A COOPERATIVE ASSISTANCE SYSTEM BETWEEN VEHICLES FOR ELDERLY DRIVERS
Directory of Open Access Journals (Sweden)
Naohisa HASHIMOTO
2009-01-01
Full Text Available This paper proposes a new concept of elderly driver assistance systems, which performs the assistance by cooperative driving between two vehicles, and describes some experiments with elderly drivers. The assistance consists of one vehicle driven by an elderly driver called a guest vehicle and the other driven by a assisting driver called a host vehicle, and the host vehicle assists or escorts the guest vehicle through the inter-vehicle communications. The functions of the systems installed on a single-seat electric vehicle are highly evaluated by subjects of elderly drivers in virtual streets on a test track.
Liposomal Tumor Targeting in Drug Delivery Utilizing MMP-2- and MMP-9-Binding Ligands
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Oula Penate Medina
2011-01-01
Full Text Available Nanotechnology offers an alternative to conventional treatment options by enabling different drug delivery and controlled-release delivery strategies. Liposomes being especially biodegradable and in most cases essentially nontoxic offer a versatile platform for several different delivery approaches that can potentially enhance the delivery and targeting of therapies to tumors. Liposomes penetrate tumors spontaneously as a result of fenestrated blood vessels within tumors, leading to known enhanced permeability and subsequent drug retention effects. In addition, liposomes can be used to carry radioactive moieties, such as radiotracers, which can be bound at multiple locations within liposomes, making them attractive carriers for molecular imaging applications. Phage display is a technique that can deliver various high-affinity and selectivity peptides to different targets. In this study, gelatinase-binding peptides, found by phage display, were attached to liposomes by covalent peptide-PEG-PE anchor creating a targeted drug delivery vehicle. Gelatinases as extracellular targets for tumor targeting offer a viable alternative for tumor targeting. Our findings show that targeted drug delivery is more efficient than non-targeted drug delivery.
Hola, Katerina; Markova, Zdenka; Zoppellaro, Giorgio; Tucek, Jiri; Zboril, Radek
2015-11-01
In this critical review, we outline various covalent and non-covalent approaches for the functionalization of iron oxide nanoparticles (IONPs). Tuning the surface chemistry and design of magnetic nanoparticles are described in relation to their applicability in advanced medical technologies and biotechnologies including magnetic resonance imaging (MRI) contrast agents, targeted drug delivery, magnetic separations and immobilizations of proteins, enzymes, antibodies, targeting agents and other biosubstances. We review synthetic strategies for the controlled preparation of IONPs modified with frequently used functional groups including amine, carboxyl and hydroxyl groups as well as the preparation of IONPs functionalized with other species, e.g., epoxy, thiol, alkane, azide, and alkyne groups. Three main coupling strategies for linking IONPs with active agents are presented: (i) chemical modification of amine groups on the surface of IONPs, (ii) chemical modification of bioactive substances (e.g. with fluorescent dyes), and (iii) the activation of carboxyl groups mainly for enzyme immobilization. Applications for drug delivery using click chemistry linking or biodegradable bonds are compared to non-covalent methods based on polymer modified condensed magnetic nanoclusters. Among many challenges, we highlight the specific surface engineering allowing both therapeutic and diagnostic applications (theranostics) of IONPs and magnetic/metallic hybrid nanostructures possessing a huge potential in biocatalysis, green chemistry, magnetic bioseparations and bioimaging. Copyright © 2015 Elsevier Inc. All rights reserved.
Elastic liposomes as novel carriers: recent advances in drug delivery
Hussain, Afzal; Singh, Sima; Sharma, Dinesh; Webster, Thomas J; Shafaat, Kausar; Faruk, Abdul
2017-01-01
Elastic liposomes (EL) are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. PMID:28761343
Directory of Open Access Journals (Sweden)
Jennifer K Sabo
Full Text Available Repair in multiple sclerosis involves remyelination, a process in which axons are provided with a new myelin sheath by new oligodendrocytes. Bone morphogenic proteins (BMPs are a family of growth factors that have been shown to influence the response of oligodendrocyte progenitor cells (OPCs in vivo during demyelination and remyelination in the adult brain. We have previously shown that BMP4 infusion increases numbers of OPCs during cuprizone-induced demyelination, while infusion of Noggin, an endogenous antagonist of BMP4 increases numbers of mature oligodendrocytes and remyelinated axons following recovery. Additional studies have shown that insulin-like growth factor-1 (IGF-1 promotes the survival of OPCs during cuprizone-induced demyelination. Based on these data, we investigated whether myelin repair could be further enhanced by sequential infusion of these agents firstly, BMP4 to increase OPC numbers, followed by either Noggin or IGF-1 to increase the differentiation and survival of the newly generated OPCs. We identified that sequential delivery of BMP4 and IGF-1 during cuprizone challenge increased the number of mature oligodendrocytes and decreased astrocyte numbers following recovery compared with vehicle infused mice, but did not alter remyelination. However, sequential delivery of BMP4 and Noggin during cuprizone challenge did not alter numbers of oligodendrocytes or astrocytes in the corpus callosum compared with vehicle infused mice. Furthermore, electron microscopy analysis revealed no change in average myelin thickness in the corpus callosum between vehicle infused and BMP4-Noggin infused mice. Our results suggest that while single delivery of Noggin or IGF-1 increased the production of mature oligodendrocytes in vivo in the context of demyelination, only Noggin infusion promoted remyelination. Thus, sequential delivery of BMP4 and Noggin or IGF-1 does not further enhance myelin repair above what occurs with delivery of Noggin
Experimental investigation of a quad-rotor biplane micro air vehicle
Bogdanowicz, Christopher Michael
Micro air vehicles are expected to perform demanding missions requiring efficient operation in both hover and forward flight. This thesis discusses the development of a hybrid air vehicle which seamlessly combines both flight capabilities: hover and high-speed forward flight. It is the quad-rotor biplane, which weighs 240 grams and consists of four propellers with wings arranged in a biplane configuration. The performance of the vehicle system was investigated in conditions representative of flight through a series of wind tunnel experiments. These studies provided an understanding of propeller-wing interaction effects and system trim analysis. This showed that the maximum speed of 11 m/s and a cruise speed of 4 m/s were achievable and that the cruise power is approximately one-third of the hover power. Free flight testing of the vehicle successfully highlighted its ability to achieve equilibrium transition flight. Key design parameters were experimentally investigated to understand their effect on overall performance. It was found that a trade-off between efficiency and compactness affects the final choice of the design. Design improvements have allowed for decreases in vehicle weight and ground footprint, while increasing structural soundness. Numerous vehicle designs, models, and flight tests have proven system scalability as well as versatility, including an upscaled model to be utilized in an extensive commercial package delivery system. Overall, the quad-rotor biplane is proven to be an efficient and effective multi-role vehicle.
Energy Technology Data Exchange (ETDEWEB)
Wang, Lijuan; Duran, Adam; Kelly, Kenneth; Konan, Arnaud; Lammert, Michael; Prohaska, Robert
2016-10-06
In this paper, researchers at the National Renewable Energy Laboratory present the results of simulation studies to evaluate potential fuel savings as a result of improvements to vehicle rolling resistance, coefficient of drag, and vehicle weight as well as hybridization for four power trains for medium-duty parcel delivery vehicles. The vehicles will be modeled and simulated over 1,290 real-world driving trips to determine the fuel savings potential based on improvements to each technology and to identify best use cases for each platform. The results of impacts of new technologies on fuel saving will be presented, and the most favorable driving routes on which to adopt them will be explored.
Directory of Open Access Journals (Sweden)
Liu LY
2016-02-01
Full Text Available Liyao Liu, Cuiping Zhou, Xuejun Xia, Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China Purpose: Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs loaded with insulin following insulin–phospholipid complex preparation, with the aim of developing a method for oral insulin delivery.Methods: Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin–phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats.Results: Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant
Cooperative Path-Planning for Multi-Vehicle Systems
Directory of Open Access Journals (Sweden)
Qichen Wang
2014-11-01
Full Text Available In this paper, we propose a collision avoidance algorithm for multi-vehicle systems, which is a common problem in many areas, including navigation and robotics. In dynamic environments, vehicles may become involved in potential collisions with each other, particularly when the vehicle density is high and the direction of travel is unrestricted. Cooperatively planning vehicle movement can effectively reduce and fairly distribute the detour inconvenience before subsequently returning vehicles to their intended paths. We present a novel method of cooperative path planning for multi-vehicle systems based on reinforcement learning to address this problem as a decision process. A dynamic system is described as a multi-dimensional space formed by vectors as states to represent all participating vehicles’ position and orientation, whilst considering the kinematic constraints of the vehicles. Actions are defined for the system to transit from one state to another. In order to select appropriate actions whilst satisfying the constraints of path smoothness, constant speed and complying with a minimum distance between vehicles, an approximate value function is iteratively developed to indicate the desirability of every state-action pair from the continuous state space and action space. The proposed scheme comprises two phases. The convergence of the value function takes place in the former learning phase, and it is then used as a path planning guideline in the subsequent action phase. This paper summarizes the concept and methodologies used to implement this online cooperative collision avoidance algorithm and presents results and analysis regarding how this cooperative scheme improves upon two baseline schemes where vehicles make movement decisions independently.
Protein-Based Drug-Delivery Materials
Directory of Open Access Journals (Sweden)
Dave Jao
2017-05-01
Full Text Available There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function—including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments—are summarized at the end of this review.
Handbook of Intelligent Vehicles
2012-01-01
The Handbook of Intelligent Vehicles provides a complete coverage of the fundamentals, new technologies, and sub-areas essential to the development of intelligent vehicles; it also includes advances made to date, challenges, and future trends. Significant strides in the field have been made to date; however, so far there has been no single book or volume which captures these advances in a comprehensive format, addressing all essential components and subspecialties of intelligent vehicles, as this book does. Since the intended users are engineering practitioners, as well as researchers and graduate students, the book chapters do not only cover fundamentals, methods, and algorithms but also include how software/hardware are implemented, and demonstrate the advances along with their present challenges. Research at both component and systems levels are required to advance the functionality of intelligent vehicles. This volume covers both of these aspects in addition to the fundamentals listed above.
A33 antibody-functionalized exosomes for targeted delivery of doxorubicin against colorectal Cancer.
Li, Yan; Gao, Yuan; Gong, Chunai; Wang, Zhuo; Xia, Qingming; Gu, Fenfen; Hu, Chuling; Zhang, Lijuan; Guo, Huiling; Gao, Shen
2018-06-20
Exosomes have emerged as a promising drug carrier with low immunogenicity, high biocompatibility and delivery efficiency. Here in, we isolated exosomes from A33-positive LIM1215 cells (A33-Exo) and loaded them with doxorubicin (Dox). Furthermore, we coated surface-carboxyl superparamagnetic iron oxide nanoparticles (US) with A33 antibodies (A33Ab-US), expecting that these A33 antibodies on the surface of the nanoparticles could bind to A33-positive exosomes and form a complex (A33Ab-US-Exo/Dox) to target A33-positive colon cancer cells. The results showed that A33Ab-US-Exo/Dox had good binding affinity and antiproliferative effect in LIM1215 cells, as shown by increased uptake of the complex. In vivo study showed that A33Ab-US-Exo/Dox had an excellent tumor targeting ability, and was able to inhibit tumor growth and prolong the survival of the mice with reduced cardiotoxicity. In summary, exosomes functionalized by targeting ligands through coating with high-density antibodies may prove to be a novel delivery system for targeted drugs against human cancers. Copyright © 2018 Elsevier Inc. All rights reserved.
An analysis of costs of vehicle repairs in a transportation company. Part II
Directory of Open Access Journals (Sweden)
Paweł DROŹDZIEL
2012-01-01
Full Text Available This paper presents the next results of the statistical analysis of the operating parameters of numbers of vehicle, which was operated by the Poczta Polska (Polish Mail delivery office in Lublin. The calculations were based on data from service in the years 2008–2010.
Affordable Flight Demonstration of the GTX Air-Breathing SSTO Vehicle Concept
Krivanek, Thomas M.; Roche, Joseph M.; Riehl, John P.; Kosareo, Daniel N.
2003-01-01
The rocket based combined cycle (RBCC) powered single-stage-to-orbit (SSTO) reusable launch vehicle has the potential to significantly reduce the total cost per pound for orbital payload missions. To validate overall system performance, a flight demonstration must be performed. This paper presents an overview of the first phase of a flight demonstration program for the GTX SSTO vehicle concept. Phase 1 will validate the propulsion performance of the vehicle configuration over the supersonic and hypersonic air- breathing portions of the trajectory. The focus and goal of Phase 1 is to demonstrate the integration and performance of the propulsion system flowpath with the vehicle aerodynamics over the air-breathing trajectory. This demonstrator vehicle will have dual mode ramjetkcramjets, which include the inlet, combustor, and nozzle with geometrically scaled aerodynamic surface outer mold lines (OML) defining the forebody, boundary layer diverter, wings, and tail. The primary objective of this study is to demon- strate propulsion system performance and operability including the ram to scram transition, as well as to validate vehicle aerodynamics and propulsion airframe integration. To minimize overall risk and develop ment cost the effort will incorporate proven materials, use existing turbomachinery in the propellant delivery systems, launch from an existing unmanned remote launch facility, and use basic vehicle recovery techniques to minimize control and landing requirements. A second phase would demonstrate propulsion performance across all critical portions of a space launch trajectory (lift off through transition to all-rocket) integrated with flight-like vehicle systems.
DEFF Research Database (Denmark)
Simonsen, Lene; Høy, Gert; Didriksen, Erik
2004-01-01
was to develop a formulation which combines calcipotriol and betamethasone dipropionate in a single vehicle hereby achieving optimal delivery of both substances into the skin. As the two substances are incompatible in aqueous and alcoholic medias, different non-aqueous formulations were prepared. Skin permeation...
Multi-protein delivery by nanodiamonds promotes bone formation.
Moore, L; Gatica, M; Kim, H; Osawa, E; Ho, D
2013-11-01
Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE(®) for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation.
Wang, Hao; Liu, Kan; Chen, Kuan-Ju; Lu, Yujie; Wang, Shutao; Lin, Wei-Yu; Guo, Feng; Kamei, Ken-ichiro; Chen, Yi-Chun; Ohashi, Minori; Wang, Mingwei; Garcia, Mitch André; Zhao, Xing-Zhong; Shen, Clifton K-F; Tseng, Hsian-Rong
2010-10-26
Nanoparticles are regarded as promising transfection reagents for effective and safe delivery of nucleic acids into a specific type of cells or tissues providing an alternative manipulation/therapy strategy to viral gene delivery. However, the current process of searching novel delivery materials is limited due to conventional low-throughput and time-consuming multistep synthetic approaches. Additionally, conventional approaches are frequently accompanied with unpredictability and continual optimization refinements, impeding flexible generation of material diversity creating a major obstacle to achieving high transfection performance. Here we have demonstrated a rapid developmental pathway toward highly efficient gene delivery systems by leveraging the powers of a supramolecular synthetic approach and a custom-designed digital microreactor. Using the digital microreactor, broad structural/functional diversity can be programmed into a library of DNA-encapsulated supramolecular nanoparticles (DNA⊂SNPs) by systematically altering the mixing ratios of molecular building blocks and a DNA plasmid. In vitro transfection studies with DNA⊂SNPs library identified the DNA⊂SNPs with the highest gene transfection efficiency, which can be attributed to cooperative effects of structures and surface chemistry of DNA⊂SNPs. We envision such a rapid developmental pathway can be adopted for generating nanoparticle-based vectors for delivery of a variety of loads.
McClements, David Julian
2013-12-01
The oral bioavailability of many lipophilic bioactives, such as pharmaceuticals and nutraceuticals, is relatively low due to their poor solubility, permeability and/or chemical stability within the human gastrointestinal tract (GIT). The oral bioavailability of lipophilic bioactives can be improved by designing food matrices that control their release, solubilization, transport and absorption within the GIT. This article discusses the challenges associated with delivering lipophilic bioactive components, the impact of food composition and structure on oral bioavailability and the design of functional and medical foods for improving the oral bioavailability of lipophilic bioactives. Food-based delivery systems can be used to improve the oral bioavailability of lipophilic bioactives. There are a number of potential advantages to delivering lipophilic bioactives using functional or medical foods: greater compliance than conventional delivery forms; increased bioavailability and efficacy; and reduced variability in biological effects. However, food matrices are structurally complex multicomponent materials and research is still needed to identify optimum structures and compositions for particular bioactives.
Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying
2015-09-01
Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary
Ďuriniková, E; Kučerová, L; Matúšková, M
2014-01-01
Mesenchymal stem/stromal cells (MSC) possess a set of several fairly unique properties which make them ideally suitable both for cellular therapies and regenerative medicine. These include: relative ease of isolation, the ability to differentiate along mesenchymal and non-mesenchymal lineages in vitro and the ability to be extensively expanded in culture without a loss of differentiative capacity. MSC are not only hypoimmunogenic, but they mediate immunosuppression upon transplantation, and possess pronounced anti-inflammatory properties. They are able to home to damaged tissues, tumors, and metastases following systemic administration. The ability of homing holds big promise for tumor-targeted delivery of therapeutic agents. Viruses are naturally evolved vehicles efficiently transferring their genes into host cells. This ability made them suitable for engineering vector systems for the delivery of genes of interest. MSC can be retrovirally transduced with genes encoding prodrug-converting genes (suicide genes), which are not toxic per se, but catalyze the formation of highly toxic metabolites following the application of a nontoxic prodrug. The homing ability of MSC holds advantages compared to virus vehicles which display many shortcomings in effective delivery of the therapeutic agents. Gene therapies mediated by viruses are limited by their restricted ability to track cancer cells infiltrating into the surrounding tissue, and by their low migratory capacity towards tumor. Thus combination of cellular therapy and gene delivery is an attractive option - it protects the vector from immune surveillance, and supports targeted delivery of a therapeutic gene/protein to the tumor site.
Linden, van der E.; Ubbink, J.; Duchateau, G.
2010-01-01
The Wageningen Delivery of Functionality symposium covered all aspects involved with food structural design to arrive at high-quality foods which meet demanding customer expectations and regulatory requirements. The symposium integrated aspects from the structural organization of foods at molecular
Directory of Open Access Journals (Sweden)
Ante Galić
2013-12-01
Full Text Available Using new optimization methods and information-communications technology has become the key issue in the competition among the distributers of fast-moving consumer goods. Introducing a delivery optimization system instead of manual routing enables significant cost savings. The prerequisites for optimization are stable information system and efficient company management. The rich vehicle routing problem model is discussed and the effects of implementing the delivery optimization system are presented. For four years of continuous utilisation, the system has helped the distributer to reduce the overall distribution costs. It also made possible to close down several depots and handle more customer requests without investing in the vehicle fleet. The developed optimization system enabled the distributer to adapt to the new distribution schedule and react to first indicators of recession very fast. Normal 0 21 false false false HR X-NONE X-NONE
Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing.
Tan, Yang Fei; Mundargi, Raghavendra C; Chen, Min Hui Averil; Lessig, Jacqueline; Neu, Björn; Venkatraman, Subbu S; Wong, Tina T
2014-05-14
Efficient and safe delivery systems for siRNA therapeutics remain a challenge. Elevated secreted protein, acidic, and rich in cysteine (SPARC) protein expression is associated with tissue scarring and fibrosis. Here we investigate the feasibility of encapsulating SPARC-siRNA in the bilayers of layer-by-layer (LbL) nanoparticles (NPs) with poly(L-arginine) (ARG) and dextran (DXS) as polyelectrolytes. Cellular binding and uptake of LbL NPs as well as siRNA delivery were studied in FibroGRO cells. siGLO-siRNA and SPARC-siRNA were efficiently coated onto hydroxyapatite nanoparticles. The multilayered NPs were characterized with regard to particle size, zeta potential and surface morphology using dynamic light scattering and transmission electron microscopy. The SPARC-gene silencing and mRNA levels were analyzed using ChemiDOC western blot technique and RT-PCR. The multilayer SPARC-siRNA incorporated nanoparticles are about 200 nm in diameter and are efficiently internalized into FibroGRO cells. Their intracellular fate was also followed by tagging with suitable reporter siRNA as well as with lysotracker dye; confocal microscopy clearly indicates endosomal escape of the particles. Significant (60%) SPARC-gene knock down was achieved by using 0.4 pmole siRNA/μg of LbL NPs in FibroGRO cells and the relative expression of SPARC mRNA reduced significantly (60%) against untreated cells. The cytotoxicity as evaluated by xCelligence real-time cell proliferation and MTT cell assay, indicated that the SPARC-siRNA-loaded LbL NPs are non-toxic. In conclusion, the LbL NP system described provides a promising, safe and efficient delivery platform as a non-viral vector for siRNA delivery that uses biopolymers to enhance the gene knock down efficiency for the development of siRNA therapeutics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Model for determining and optimizing delivery performance in industrial systems
Directory of Open Access Journals (Sweden)
Fechete Flavia
2017-01-01
Full Text Available Performance means achieving organizational objectives regardless of their nature and variety, and even overcoming them. Improving performance is one of the major goals of any company. Achieving the global performance means not only obtaining the economic performance, it is a must to take into account other functions like: function of quality, delivery, costs and even the employees satisfaction. This paper aims to improve the delivery performance of an industrial system due to their very low results. The delivery performance took into account all categories of performance indicators, such as on time delivery, backlog efficiency or transport efficiency. The research was focused on optimizing the delivery performance of the industrial system, using linear programming. Modeling the delivery function using linear programming led to obtaining precise quantities to be produced and delivered each month by the industrial system in order to minimize their transport cost, satisfying their customers orders and to control their stock. The optimization led to a substantial improvement in all four performance indicators that concern deliveries.
Modeling and predicting low-speed vehicle emissions as a function of driving kinematics.
Hao, Lijun; Chen, Wei; Li, Lei; Tan, Jianwei; Wang, Xin; Yin, Hang; Ding, Yan; Ge, Yunshan
2017-05-01
An instantaneous emission model was developed to model and predict the real driving emissions of the low-speed vehicles. The emission database used in the model was measured by using portable emission measurement system (PEMS) under actual traffic conditions in the rural area, and the characteristics of the emission data were determined in relation to the driving kinematics (speed and acceleration) of the low-speed vehicle. The input of the emission model is driving cycle, and the model requires instantaneous vehicle speed and acceleration levels as input variables and uses them to interpolate the pollutant emission rate maps to calculate the transient pollutant emission rates, which will be accumulated to calculate the total emissions released during the whole driving cycle. And the vehicle fuel consumption was determined through the carbon balance method. The model predicted the emissions and fuel consumption of an in-use low-speed vehicle type model, which agreed well with the measured data. Copyright © 2016. Published by Elsevier B.V.
Fritsch, Gudrun
The booklet discusses and reports on a study of elicited imitation as a vehicle for assessing the language-functioning level of echolalic autistic children. An historical overview is presented of the diagnosis of early infantile autism. The question of whether or not early infantile autism is a distinct syndrome is addressed. The theoretical and…
Energy use and life cycle greenhouse gas emissions of drones for commercial package delivery.
Stolaroff, Joshuah K; Samaras, Constantine; O'Neill, Emma R; Lubers, Alia; Mitchell, Alexandra S; Ceperley, Daniel
2018-02-13
The use of automated, unmanned aerial vehicles (drones) to deliver commercial packages is poised to become a new industry, significantly shifting energy use in the freight sector. Here we find the current practical range of multi-copters to be about 4 km with current battery technology, requiring a new network of urban warehouses or waystations as support. We show that, although drones consume less energy per package-km than delivery trucks, the additional warehouse energy required and the longer distances traveled by drones per package greatly increase the life-cycle impacts. Still, in most cases examined, the impacts of package delivery by small drone are lower than ground-based delivery. Results suggest that, if carefully deployed, drone-based delivery could reduce greenhouse gas emissions and energy use in the freight sector. To realize the environmental benefits of drone delivery, regulators and firms should focus on minimizing extra warehousing and limiting the size of drones.
Poly(ester amide-Poly(ethylene oxide Graft Copolymers: Towards Micellar Drug Delivery Vehicles
Directory of Open Access Journals (Sweden)
Gregory J. Zilinskas
2012-01-01
Full Text Available Micelles formed from amphiphilic copolymers are promising materials for the delivery of drug molecules, potentially leading to enhanced biological properties and efficacy. In this work, new poly(ester amide-poly(ethylene oxide (PEA-PEO graft copolymers were synthesized and their assembly into micelles in aqueous solution was investigated. It was possible to tune the sizes of the micelles by varying the PEO content of the polymers and the method of micelle preparation. Under optimized conditions, it was possible to obtain micelles with diameters less than 100 nm as measured by dynamic light scattering and transmission electron microscopy. These micelles were demonstrated to encapsulate and release a model drug, Nile Red, and were nontoxic to HeLa cells as measured by an MTT assay. Overall, the properties of these micelles suggest that they are promising new materials for drug delivery systems.
Copper-free click-chemistry platform to functionalize cisplatin prodrugs.
Pathak, Rakesh K; McNitt, Christopher D; Popik, Vladimir V; Dhar, Shanta
2014-06-02
The ability to rationally design and construct a platform technology to develop new platinum(IV) [Pt(IV)] prodrugs with functionalities for installation of targeting moieties, delivery systems, fluorescent reporters from a single precursor with the ability to release biologically active cisplatin by using well-defined chemistry is critical for discovering new platinum-based therapeutics. With limited numbers of possibilities considering the sensitivity of Pt(IV) centers, we used a strain-promoted azide-alkyne cycloaddition approach to provide a platform, in which new functionalities can easily be installed on cisplatin prodrugs from a single Pt(IV) precursor. The ability of this platform to be incorporated in nanodelivery vehicle and conjugation to fluorescent reporters were also investigated. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Calcipotriol delivery into the skin with PEGylated liposomes
DEFF Research Database (Denmark)
Knudsen, Nina Østergaard; Rønholt, Stine; Salte, Ragnhild Djønne
2012-01-01
The d-vitamin analogue calcipotriol is commonly used for topical treatment of psoriasis, but skin penetration is required for calcipotriol to reach its pharmacological target: the keratinocytes in the lower epidermis. Liposomes can enhance the delivery of drugs into the skin, but a major challenge...... of the liposomes and the ability to deliver membrane-intercalated calcipotriol into the skin. Inclusion of 0.5, l and 5mol% PEG-DSPE in the membrane enhanced the colloidal stability of the liposomes without compromising the delivery of calcipotriol from the vehicle into excised pig skin. Calcipotriol...... to large multilamellar vesicles, indicating that the liposomes to some extent migrate as intact vesicles into the stratum corneum. However, calcipotriol penetrated the skin better than the lipid component of the liposomes, suggesting that at least a fraction of the drug is released from the liposomes...
Branch-and-Cut-and-Price for the Pickup and Delivery Problem with Time Windows
DEFF Research Database (Denmark)
Røpke, Stefan; Cordeau, Jean-Francois
2009-01-01
In the pickup and delivery problem with time windows (PDPTW), vehicle routes must be designed to satisfy a set of transportation requests, each involving a pickup and a delivery location, under capacity, time window, and precedence constraints. This paper introduces a new branch......-and-cut-and-price algorithm in which lower bounds are computed by solving through column generation the linear programming relaxation of a set partitioning formulation. Two pricing subproblems are considered in the column generation algorithm: an elementary and a non-elementary shortest path problem. Valid inequalities...
Consumer Vehicle Choice Model Documentation
Energy Technology Data Exchange (ETDEWEB)
Liu, Changzheng [ORNL; Greene, David L [ORNL
2012-08-01
In response to the Fuel Economy and Greenhouse Gas (GHG) emissions standards, automobile manufacturers will need to adopt new technologies to improve the fuel economy of their vehicles and to reduce the overall GHG emissions of their fleets. The U.S. Environmental Protection Agency (EPA) has developed the Optimization Model for reducing GHGs from Automobiles (OMEGA) to estimate the costs and benefits of meeting GHG emission standards through different technology packages. However, the model does not simulate the impact that increased technology costs will have on vehicle sales or on consumer surplus. As the model documentation states, “While OMEGA incorporates functions which generally minimize the cost of meeting a specified carbon dioxide (CO2) target, it is not an economic simulation model which adjusts vehicle sales in response to the cost of the technology added to each vehicle.” Changes in the mix of vehicles sold, caused by the costs and benefits of added fuel economy technologies, could make it easier or more difficult for manufacturers to meet fuel economy and emissions standards, and impacts on consumer surplus could raise the costs or augment the benefits of the standards. Because the OMEGA model does not presently estimate such impacts, the EPA is investigating the feasibility of developing an adjunct to the OMEGA model to make such estimates. This project is an effort to develop and test a candidate model. The project statement of work spells out the key functional requirements for the new model.
Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery
Badeau, Barry A.; Comerford, Michael P.; Arakawa, Christopher K.; Shadish, Jared A.; Deforest, Cole A.
2018-03-01
The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.
Microneedle Patches as Drug and Vaccine Delivery Platform.
Li, Junwei; Zeng, Mingtao; Shan, Hu; Tong, Chunyi
2017-01-01
Transcutaneous delivery is the ideal method for delivering therapeutic reagents or vaccines into skin. With their promise of self-administration, cost-effective and high efficiency, microneedle patches have been studied intensively as therapeutic and vaccination delivery platform that replaces injection by syringe. This review aims to summarize the recent advancements of microneedle patches in application for drugs and vaccine delivery. We reviewed the most of recently published papers on microneedle patches, summarized their evolution, classification, state-of the-art capabilities and discussed promising application in drugs and vaccine delivery. With the rapid development of nanotechnology, microneedle patches have been improved by switching from undissolving to dissolving microneedles, and their safety has also improved dramatically. As a drug delivery tool, microneedle patches can deliver bioactive molecular of different physical size. Additionally, microneedle patches can be coated or encapsulate with DNA vaccine, subunit antigen, inactivated or live virus vaccine. Combining clinical results with the results of patient interview, microneedle patches are found to be feasible and are predicated to soon be acceptable for the medical service. In this review, we summarized the evolution, current and future application of microneedle patches as delivery vehicle for drugs and vaccines. Compared with traditional delivery tools, microneedle patches have many advantages, such as providing pain-free, non-invasive, convenient route for reagent administration and delivery, with no cold chain required for storage and transportation as well as decreasing sharp medical waste, needle-caused injury and transmission of blood-borne infectious disease in rural area. However, even though there are dramatic progress in preclinical investigation of microneedle patches, further testing will be required for clinical application. Further research should be implemented in multiple fields
Raichel, Daniel R.
2005-09-01
The criteria for NVH design are to a large degree determined by the types of vehicles and the perceived desires of the purchasers of vehicles, as well as the cost of incorporating NVH measures. Vehicles may be classified into specific types, e.g., economy car, midsize passenger, near-luxury and luxury passenger cars, sports cars, vans, minivans, and sports utility vehicles of varying sizes. The owner of a luxury sedan would expect a quiet ride with minimal vibration and harshness-however, if that sedan is to display sporting characteristics, some aspects of NVH may actually have to be increased in order to enhance a feeling of driver exhilaration. A discussion of the requirements for specific types of vehicles is provided, with due regard for effects on the usability of installed sound/video systems, driver and passenger fatigue, feel of steering mechanisms and other mechanical components, consumer market research, etc. A number of examples of vehicles on the market are cited.
An overview of Ball Aerospace cryogen storage and delivery systems
International Nuclear Information System (INIS)
Marquardt, J; Keller, J; Mills, G; Schmidt, J
2015-01-01
Starting on the Gemini program in the 1960s, Beech Aircraft (now Ball Aerospace) has been designing and manufacturing dewars for a variety of cryogens including liquid hydrogen and oxygen. These dewars flew on the Apollo, Skylab and Space Shuttle spacecraft providing fuel cell reactants resulting in over 150 manned spaceflights. Since Space Shuttle, Ball has also built the liquid hydrogen fuel tanks for the Boeing Phantom Eye unmanned aerial vehicle. Returning back to its fuel cell days, Ball has designed, built and tested a volume-constrained liquid hydrogen and oxygen tank system for reactant delivery to fuel cells on unmanned undersea vehicles (UUVs). Herein past history of Ball technology is described. Testing has been completed on the UUV specific design, which will be described. (paper)
Optimal Routing for Heterogeneous Fixed Fleets of Multicompartment Vehicles
Directory of Open Access Journals (Sweden)
Qian Wang
2014-01-01
Full Text Available We present a metaheuristic called the reactive guided tabu search (RGTS to solve the heterogeneous fleet multicompartment vehicle routing problem (MCVRP, where a single vehicle is required for cotransporting multiple customer orders. MCVRP is commonly found in delivery of fashion apparel, petroleum distribution, food distribution, and waste collection. In searching the optimum solution of MCVRP, we need to handle a large amount of local optima in the solution spaces. To overcome this problem, we design three guiding mechanisms in which the search history is used to guide the search. The three mechanisms are experimentally demonstrated to be more efficient than the ones which only apply the known distance information. Armed with the guiding mechanisms and the well-known reactive mechanism, the RGTS can produce remarkable solutions in a reasonable computation time.
Directory of Open Access Journals (Sweden)
Lyndon Jones
2012-01-01
Full Text Available Contact lenses, as an alternative drug delivery vehicle for the eye compared to eye drops, are desirable due to potential advantages in dosing regimen, bioavailability and patient tolerance/compliance. The challenge has been to engineer and develop these materials to sustain drug delivery to the eye for a long period of time. In this study, model silicone hydrogel materials were created using a molecular imprinting strategy to deliver the antibiotic ciprofloxacin. Acetic and acrylic acid were used as the functional monomers, to interact with the ciprofloxacin template to efficiently create recognition cavities within the final polymerized material. Synthesized materials were loaded with 9.06 mM, 0.10 mM and 0.025 mM solutions of ciprofloxacin, and the release of ciprofloxacin into an artificial tear solution was monitored over time. The materials were shown to release for periods varying from 3 to 14 days, dependent on the loading solution, functional monomer concentration and functional monomer:template ratio, with materials with greater monomer:template ratio (8:1 and 16:1 imprinted tending to release for longer periods of time. Materials with a lower monomer:template ratio (4:1 imprinted tended to release comparatively greater amounts of ciprofloxacin into solution, but the release was somewhat shorter. The total amount of drug released from the imprinted materials was sufficient to reach levels relevant to inhibit the growth of common ocular isolates of bacteria. This work is one of the first to demonstrate the feasibility of molecular imprinting in model silicone hydrogel-type materials.
Oral delivery of anticancer drugs
DEFF Research Database (Denmark)
Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T
2013-01-01
The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...
Benefits of a parallel hybrid electric architecture on medium commercial vehicles
Energy Technology Data Exchange (ETDEWEB)
Boot, Marco Aimo; Consano, Ludovico [Iveco S.p.A, Turin (Italy)
2009-07-01
different end users (Iveco key customers) have been an important opportunity to reach the project goals in a short time and to collect many operational and functional impressions directly from customers. The results achieved during the performance testing are in line with the project expectations, especially in term of fuel consumption and driveability feeling. The vehicle measurements show an improvement of 20% less (average) in fuel consumption in different delivery mission and context of use in comparison with a baseline Eurocargo truck. (orig.)
77 FR 34149 - Heavy-Duty Highway Program: Revisions for Emergency Vehicles and SCR Maintenance
2012-06-08
... selective catalytic reduction technologies. Third, EPA is proposing to offer short-term relief for nonroad..., Attention Docket No. EPA-HQ-OAR-2011-1032. Such deliveries are only accepted during the Docket's normal..., especially given some emergency vehicles' extreme duty cycles. By this action, EPA intends to help our nation...
Advances in polyelectrolyte multilayer nanofilms as tunable drug delivery systems
Jiang, Bingbing; Barnett, John B; Li, Bingyun
2009-01-01
There has been considerable interest in polyelectrolyte multilayer nanofilms, which have a variety of applications ranging from optical and electrochemical materials to biomedical devices. Polyelectrolyte multilayer nanofilms are constructed from aqueous solutions using electrostatic layer-by-layer self-assembly of oppositely-charged polyelectrolytes on a solid substrate. Multifunctional polyelectrolyte multilayer nanofilms have been studied using charged dyes, metal and inorganic nanoparticles, DNA, proteins, and viruses. In the past few years, there has been increasing attention to developing polyelectrolyte multilayer nanofilms as drug delivery vehicles. In this mini-review, we present recent developments in polyelectrolyte multilayer nanofilms with tunable drug delivery properties, with particular emphasis on the strategies in tuning the loading and release of drugs in polyelectrolyte multilayer nanofilms as well as their applications. PMID:24198464
Nanochemistry of protein-based delivery agents
Rajendran, Subin; Udenigwe, Chibuike; Yada, Rickey
2016-07-01
The past decade has seen an increased interest in the conversion of food proteins into functional biomaterials, including their use for loading and delivery of physiologically active compounds such as nutraceuticals and pharmaceuticals. Proteins possess a competitive advantage over other platforms for the development of nanodelivery systems since they are biocompatible, amphipathic, and widely available. Proteins also have unique molecular structures and diverse functional groups that can be selectively modified to alter encapsulation and release properties. A number of physical and chemical methods have been used for preparing protein nanoformulations, each based on different underlying protein chemistry. This review focuses on the chemistry of the reorganization and/or modification of proteins into functional nanostructures for delivery, from the perspective of their preparation, functionality, stability and physiological behavior.
Liu, Hanqing; Tu, Zhigang; Feng, Fan; Shi, Haifeng; Chen, Keping; Xu, Ximing
2015-06-01
A virosome is an innovative hybrid drug delivery system with advantages of both viral and non-viral vectors. Studies have shown that a virosome can carry various biologically active molecules, such as nucleic acids, peptides, proteins and small organic molecules. Targeted drug delivery using virosome-based systems can be achieved through surface modifications of virosomes. A number of virosome-based prophylactic and therapeutic products with high safety profiles are currently available in the market. Cancer treatment is a big battlefield for virosome-based drug delivery systems. This review provides an overview of the general concept, preparation procedures, working mechanisms, preclinical studies and clinical applications of virosomes in cancer treatment.
ELECTROMAGNETIC BIOSPHERE POLLUTION BY MOTOR TRANSPORT (VEHICLES, ELECTRIC VEHICLES, HYBRID VEHICLES
Directory of Open Access Journals (Sweden)
S. Selivanov
2009-01-01
Full Text Available The physics of the electromagnetic field is considered. The analysis of electromagnetic radiation on the human-being, the origin of which is the vehicle the electric vehicle, the hybrid vehicle is being considered. The monitoring of electromagnetic radiation of vehicles is carried out.
Bacteria-mediated in vivo delivery of quantum dots into solid tumor
Energy Technology Data Exchange (ETDEWEB)
Liu, Ying [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Zhou, Mei [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Luo, Dan; Wang, Lijun; Hong, Yuankai [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Yang, Yepeng, E-mail: yangyepeng@bjmu.edu.cn [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Sha, Yinlin, E-mail: shyl@hsc.pku.edu.cn [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Biomed-X Center, Peking University, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China)
2012-09-07
Highlights: Black-Right-Pointing-Pointer New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. Black-Right-Pointing-Pointer Bifidobacterium bifidum delivery system has intrinsic biocompatibility. Black-Right-Pointing-Pointer The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.
How to electrify more of the public to lease electric vehicles
Energy Technology Data Exchange (ETDEWEB)
Huestis, E.P. [City of Vacaville, CA (United States)
2000-07-01
The City of Vacaville, in Northern California, aims to become the city which boast the highest number of electric vehicles per capita (residential) in both California and the United States. To that effect, it secured a $300,000 grant from the Congestion Mitigation and Air Quality Improvement Program in order to provide an incentive of $6,000 to 35 customers over the life of the three-year lease of a qualifying electric vehicle. Additional electric charging infrastructure throughout the Vacaville and the replacement of some aging City fleet vehicles with electric vehicles will be possible using the remainder of the grant money. The incentive program proved so popular, through word of mouth and positive press coverage, that 75 customers expressed an interest in the program. Several of the customers had just taken delivery of an electric vehicle from General Motors or Ford. Unable to provide the same incentive to all customers from the original grant, the City of Vacaville applied for a $600,000 additional grant from the Congestion Mitigation and Air Quality to serve 50 more customers, as well as for the provision of additional charging stations at strategic locations. The expansion of the program has received preliminary approval for its second grant application.
Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle
International Nuclear Information System (INIS)
Chandra, Sudeshna; Noronha, Glen; Dietrich, Sascha; Lang, Heinrich; Bahadur, Dhirendra
2015-01-01
Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH 2 CH 2 C(O)O(CH 2 CH 2 O) 9 CH 3 and CH 2 CH 2 C(O)O(CH 2 CH 2 O) 2 C 2 H 5 , respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe 3 O 4 ) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells
Functionalization of Carbon Nanomaterial Surface by Doxorubicin and Antibodies to Tumor Markers
Perepelytsina, Olena M.; Yakymchuk, Olena M.; Sydorenko, Mychailo V.; Bakalinska, Olga N.; Bloisi, Francesco; Vicari, Luciano Rosario Maria
2016-06-01
The actual task of oncology is effective treatment of cancer while causing a minimum harm to the patient. The appearance of polymer nanomaterials and technologies launched new applications and approaches of delivery and release of anticancer drugs. The goal of work was to test ultra dispersed diamonds (UDDs) and onion-like carbon (OLCs) as new vehicles for delivery of antitumor drug (doxorubicin (DOX)) and specific antibodies to tumor receptors. Stable compounds of UDDs and OLCs with DOX were obtained. As results of work, an effectiveness of functionalization was 2.94 % w/ w for OLC-DOX and 2.98 % w/ w for UDD-DOX. Also, there was demonstrated that UDD-DOX and OLC-DOX constructs had dose-dependent cytotoxic effect on tumor cells in the presence of trypsin. The survival of adenocarcinoma cells reduced from 52 to 28 % in case of incubation with the UDD-DOX in concentrations from 8.4-2.5 to 670-20 μg/ml and from 72 to 30 % after incubation with OLC-DOX. Simultaneously, antibodies to epidermal growth factor maintained 75 % of the functional activity and specificity after matrix-assisted pulsed laser evaporation deposition. Thus, the conclusion has been made about the prospects of selected new methods and approaches for creating an antitumor agent with capabilities targeted delivery of drugs.
Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment
Directory of Open Access Journals (Sweden)
Chendi Ding
2016-12-01
Full Text Available Benefiting from the development of nanotechnology, drug delivery systems (DDSs with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs, quantum dots (QDs and carbon nanotubes (CNTs. The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules and extrinsic (temperature, light irradiation, magnetic field and ultrasound ones. Clinical applications of DDS, future challenges and perspectives are also mentioned.
Exploring the role of peptides in polymer-based gene delivery.
Sun, Yanping; Yang, Zhen; Wang, Chunxi; Yang, Tianzhi; Cai, Cuifang; Zhao, Xiaoyun; Yang, Li; Ding, Pingtian
2017-09-15
Polymers are widely studied as non-viral gene vectors because of their strong DNA binding ability, capacity to carry large payload, flexibility of chemical modifications, low immunogenicity, and facile processes for manufacturing. However, high cytotoxicity and low transfection efficiency substantially restrict their application in clinical trials. Incorporating functional peptides is a promising approach to address these issues. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we systematically summarize the role of peptides in polymer-based gene delivery, and elaborate how to rationally design polymer-peptide based gene delivery vectors. Polymers are widely studied as non-viral gene vectors, but suffer from high cytotoxicity and low transfection efficiency. Incorporating short, bioactive peptides into polymer-based gene delivery systems can address this issue. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we highlight the peptides' roles in polymer-based gene delivery, and elaborate how to utilize various functional peptides to enhance the transfection efficiency of polymers. The optimized peptide-polymer vectors should be able to alter their structures and functions according to biological microenvironments and utilize inherent intracellular pathways of cells, and consequently overcome the barriers during gene delivery to enhance transfection efficiency. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Turner, Christopher T; McInnes, Steven J P; Melville, Elizabeth; Cowin, Allison J; Voelcker, Nicolas H
2017-01-01
Flightless I (Flii) is elevated in human chronic wounds and is a negative regulator of wound repair. Decreasing its activity improves healing responses. Flii neutralizing antibodies (FnAbs) decrease Flii activity in vivo and hold significant promise as healing agents. However, to avoid the need for repeated application in a clinical setting and to protect the therapeutic antibody from the hostile environment of the wound, suitable delivery vehicles are required. In this study, the use of porous silicon nanoparticles (pSi NPs) is demonstrated for the controlled release of FnAb to diabetic wounds. We achieve FnAb loading regimens exceeding 250 µg antibody per mg of vehicle. FnAb-loaded pSi NPs increase keratinocyte proliferation and enhance migration in scratch wound assays. Release studies confirm the functionality of the FnAb in terms of Flii binding. Using a streptozotocin-induced model of diabetic wound healing, a significant improvement in healing is observed for mice treated with FnAb-loaded pSi NPs compared to controls, including FnAb alone. FnAb-loaded pSi NPs treated with proteases show intact and functional antibody for up to 7 d post-treatment, suggesting protection of the antibodies from proteolytic degradation in wound fluid. pSi NPs may therefore enable new therapeutic approaches for the treatment of diabetic ulcers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Clement, W. F.; Allen, R. W.; Heffley, R. K.; Jewell, W. F.; Jex, H. R.; Mcruer, D. T.; Schulman, T. M.; Stapleford, R. L.
1980-01-01
The NASA Ames Research Center proposed a man-vehicle systems research facility to support flight simulation studies which are needed for identifying and correcting the sources of human error associated with current and future air carrier operations. The organization of research facility is reviewed and functional requirements and related priorities for the facility are recommended based on a review of potentially critical operational scenarios. Requirements are included for the experimenter's simulation control and data acquisition functions, as well as for the visual field, motion, sound, computation, crew station, and intercommunications subsystems. The related issues of functional fidelity and level of simulation are addressed, and specific criteria for quantitative assessment of various aspects of fidelity are offered. Recommendations for facility integration, checkout, and staffing are included.
Ratzon, Navah Z; Ari Shevil, Eynat Ben; Froom, Paul; Friedman, Sharon; Amit, Yehuda
2013-01-01
Pelvic injuries following motor vehicle accidents (MVA) cause disability and affect work capabilities. This study evaluated functional, self-report, and medical-based factors that could predict work capacity as was reflected in a functional capacity evaluation (FCE) among persons who sustained a pelvic injury. It was hypothesized that self-reported functional status and bio-demographic variables would predict work capacity. Sixty-one community-dwelling adults previously hospitalized following a MVA induced pelvic injury. FCE for work performance was conducted using the Physical Work Performance Evaluation (PWPE). Additional data was collected through a demographics questionnaire and the Functional Status Questionnaire. All participants underwent an orthopedic medical examination of the hip and lower extremities. Most participants self-reported that their work capacity post-injury were lower than their job required. PWPE scores indicated below-range functional performance. Regression models predicted 23% to 51% of PWPE subtests. Participants' self-report of functioning (instrumental activities of daily living and work) and bio-demographic variables (gender and age) were better predictors of PWPE scores than factors originating from the medical examination. Results support the inclusion of FCE, in addition to self-report of functioning and medical examination, to evaluate work capacity among individuals' post-pelvic injury and interventions and discharge planning.
Vibrations of a delivery car excited by railway track crossing
International Nuclear Information System (INIS)
Litak, Grzegorz; Borowiec, Marek; Hunicz, Jacek; Koszalka, Grzegorz; Niewczas, Andrzej
2009-01-01
Vertical vibrations of a delivery car passing through railway tracks have been investigated in this paper. The application of recurrence plots allows to examine short time series of acceleration non-stationary courses. Recurrence quantification analysis and square deviations estimated in small windows have been used to monitor car vibrations and transient behaviour. Measuring acceleration on the 'sprung' and 'unsprung' masses of a vehicle has enabled also to test the quality of a car suspension.
International Nuclear Information System (INIS)
Nie Leng; Gao Lizeng; Yan Xiyun; Wang Taihong
2007-01-01
Functionalized tetrapodal ZnO nanostructures are tested in plasmid DNA experiments (1) as a solid-phase adsorbent for plasmid DNA purification (2) as improving reagents in a polymerase chain reaction (PCR) and (3) as novel carriers for gene delivery. The amino-modification, the tetrapod-like shape of the nanostructure and its high biocompatibility all contribute to measurements showing promise for applications. A sol-gel method is used for silica coating and amino-modification. Plasmid DNA is purified through reversible conjugations of amino-modified ZnO tetrapods with DNA. Also, as additional reagents, functionalized tetrapods are shown to improve the amount of PCR product. For transfection, ZnO tetrapods provide some protection against deoxyribonuclease cleavage of plasmid DNA and deliver plasmid DNA into cells with little cytotoxicity
Aptamer-Gated Nanoparticles for Smart Drug Delivery
Directory of Open Access Journals (Sweden)
Huseyin Avni Oktem
2011-08-01
Full Text Available Aptamers are functional nucleic acid sequences which can bind specific targets. An artificial combinatorial methodology can identify aptamer sequences for any target molecule, from ions to whole cells. Drug delivery systems seek to increase efficacy and reduce side-effects by concentrating the therapeutic agents at specific disease sites in the body. This is generally achieved by specific targeting of inactivated drug molecules. Aptamers which can bind to various cancer cell types selectively and with high affinity have been exploited in a variety of drug delivery systems for therapeutic purposes. Recent progress in selection of cell-specific aptamers has provided new opportunities in targeted drug delivery. Especially functionalization of nanoparticles with such aptamers has drawn major attention in the biosensor and biomedical areas. Moreover, nucleic acids are recognized as an attractive building materials in nanomachines because of their unique molecular recognition properties and structural features. A active controlled delivery of drugs once targeted to a disease site is a major research challenge. Stimuli-responsive gating is one way of achieving controlled release of nanoparticle cargoes. Recent reports incorporate the structural properties of aptamers in controlled release systems of drug delivering nanoparticles. In this review, the strategies for using functional nucleic acids in creating smart drug delivery devices will be explained. The main focus will be on aptamer-incorporated nanoparticle systems for drug delivery purposes in order to assess the future potential of aptamers in the therapeutic area. Special emphasis will be given to the very recent progress in controlled drug release based on molecular gating achieved with aptamers.
Impacts of Vehicle (In)Security
Energy Technology Data Exchange (ETDEWEB)
Chugg, J.; Rohde, K.
2015-05-01
Nuclear and radioactive material is routinely transported worldwide every day. Since 2010, the complexity of the transport vehicle to support such activities has grown exponentially. Many core functions of a vehicle are now handled by small embedded computer modules with more being added each year to enhance the owner’s experience and convenience. With a system as complex as today’s automobile, the potential for cyber security issues is certain. Hackers have begun exploring this new domain with public information increasingly disseminated. Because vehicles are allowed into and around secure nuclear facilities, the potential for using a vehicle as a new cyber entry point or vector into the facility is now plausible and must be mitigated. In addition, compromising such a vehicle could aide in illicit removal of nuclear material, putting sensitive cargo at risk. Because cyber attacks can now be introduced using vehicles, cyber security, needs to be integrated into an organization’s design basis threat document. Essentially, a vehicle now extends the perimeter for which security professionals are responsible.Electronic Control Units (ECU) responsible for handling all core and ancillary vehicle functions are interconnected using the controller area network (CAN) bus. A typical CAN network in a modern automobile contains 50 or more ECUs. The CAN protocol now supports a wide variety of areas, including automotive, road transportation, rail transportation, industrial automation, power generation, maritime, military vehicles, aviation, and medical devices. In many ways, the nuclear industry is employing the CAN bus protocol or other similar broadcast serial networks. This paper will provide an overview of the current state of automobile and CAN Bus security, as well as an overview of what has been publicly disclosed by many research organizations. It will then present several hypotheses of how vehicle security issues may impact nuclear activities. An initial
Stochastic time-dependent vehicle routing problem: Mathematical models and ant colony algorithm
Directory of Open Access Journals (Sweden)
Zhengyu Duan
2015-11-01
Full Text Available This article addresses the stochastic time-dependent vehicle routing problem. Two mathematical models named robust optimal schedule time model and minimum expected schedule time model are proposed for stochastic time-dependent vehicle routing problem, which can guarantee delivery within the time windows of customers. The robust optimal schedule time model only requires the variation range of link travel time, which can be conveniently derived from historical traffic data. In addition, the robust optimal schedule time model based on robust optimization method can be converted into a time-dependent vehicle routing problem. Moreover, an ant colony optimization algorithm is designed to solve stochastic time-dependent vehicle routing problem. As the improvements in initial solution and transition probability, ant colony optimization algorithm has a good performance in convergence. Through computational instances and Monte Carlo simulation tests, robust optimal schedule time model is proved to be better than minimum expected schedule time model in computational efficiency and coping with the travel time fluctuations. Therefore, robust optimal schedule time model is applicable in real road network.
Robotic security vehicle for exterior environments
International Nuclear Information System (INIS)
Klarer, P.R.; Workhoven, R.M.
1988-01-01
This paper describes a current effort at Sandia National Labs to develop an outdoor robotic vehicle capable of performing limited security functions autonomously in a structured environment. The present stage of development entails application of algorithms originally developed for the SIR vehicle to a testbed vehicle more appropriate to an outdoor environment. The current effort will culminate in a full scale demonstration of autonomous navigation capabilities on routine patrol and teleoperation by a human operator for alarm assessment and response. Various schemes for implementation of the robot system are discussed, as are plans for further development of the system
A Universal Aptamer Chimera for the Delivery of Functional microRNA-126.
Rohde, Jan-H; Weigand, Julia E; Suess, Beatrix; Dimmeler, Stefanie
2015-06-01
microRNAs (miRs) regulate vascular diseases such as atherosclerosis and cancer. miR-126 is important for endothelial cell signaling and promotes angiogenesis, protects against atherosclerosis, and reduces breast cancer cell growth and metastasis. The overexpression of miR-126, therefore, may be an attractive therapeutic strategy for the treatment of cardiovascular disease or cancer. Here we report a novel strategy to deliver miR-126 to endothelial and breast cancer cells. We tested three different strategies to deliver miR-126 by linking the miR to an aptamer for the ubiquitously expressed transferrin receptor (transferrin receptor aptamer, TRA). Linking the precursor of miR-126 (pre-miR-126) to the TRA by annealing of a complementary stick led to efficient uptake and processing of miR-126, resulting in the delivery of 1.6×10(6)±0.3×10(6) copies miR-126-3p per ng RNA in human endothelial cells and 7.4×10(5)±2×10(5) copies miR-126-3p per ng in MCF7 breast cancer cells. The functionality of the active TRA-miR-126 chimera was further demonstrated by showing that the chimera represses the known miR-126 target VCAM-1 and improved endothelial cell sprouting in a spheroid assay. Moreover, the TRA-miR-126 chimera reduced proliferation and paracrine endothelial cell recruitment of breast cancer cells to a similar extent as miR-126-3p mimics introduced by conventional liposome-based transfection. Together, this data demonstrates that pre-miR-126 can be delivered by a non-specific aptamer to exert biological functions in two different cell models. The use of the TRA-miR-126 chimera or the combination of the delivery strategy with other endothelial or tumor specific aptamers may provide an interesting therapeutic option to treat vascular disease or cancers.
Trajectory generation for an on-road autonomous vehicle
Horst, John; Barbera, Anthony
2006-05-01
We describe an algorithm that generates a smooth trajectory (position, velocity, and acceleration at uniformly sampled instants of time) for a car-like vehicle autonomously navigating within the constraints of lanes in a road. The technique models both vehicle paths and lane segments as straight line segments and circular arcs for mathematical simplicity and elegance, which we contrast with cubic spline approaches. We develop the path in an idealized space, warp the path into real space and compute path length, generate a one-dimensional trajectory along the path length that achieves target speeds and positions, and finally, warp, translate, and rotate the one-dimensional trajectory points onto the path in real space. The algorithm moves a vehicle in lane safely and efficiently within speed and acceleration maximums. The algorithm functions in the context of other autonomous driving functions within a carefully designed vehicle control hierarchy.
41 CFR 101-26.501-6 - Forms used in connection with delivery of vehicles.
2010-07-01
... repairs pursuant to the warranty. (b) Standard Form 368, Quality Deficiency Report (Category II). GSA is constantly striving to improve customer service and the quality of motor vehicles for which it contracts. To... correction. Procedures for documenting and reporting quality deficiencies are set forth in the GSA...
NOx removal from vehicle emissions by functionality surface of asphalt road
International Nuclear Information System (INIS)
Chen Meng; Liu Yanhua
2010-01-01
This paper reported the potential of heterogeneous photocatalysis as an advanced oxidation technology for NO x removal from vehicle emissions by using TiO 2 as a photocatalyst immobilized on the surface of asphalt road. Based on asphalt road material porous characteristic, we utilized permeability technology to make asphalt nano-TiO 2 to be environmental protection materials. And then using scanning electron microscope, we observed the penetrating effect of TiO 2 . The effect of surface friction, humidity and light intensity on NO x removal had been systematically investigated by the use of TiO 2 immobilized on the surface of asphalt road as photocatalytic environmental protection materials. In addition, the decontaminating effect was tested by contrast test in TiO 2 spraying section with non-spraying section, while the productions were used in road environment. Results of experiment revealed that decontaminating rate of the productions ranged from 6% to 12% this kind of photochemical catalysis environmental protection material has good environment purification function.
Lee, Jun Bae; Lee, Dong Ryeol; Choi, Nak Cho; Jang, Jihui; Park, Chun Ho; Yoon, Moung Seok; Lee, Miyoung; Won, Kyoungae; Hwang, Jae Sung; Kim, B Moon
2015-10-12
Over the past decades, there has been a growing interest in dermal drug delivery. Although various novel delivery devices and methods have been developed, dermal delivery is still challenging because of problems such as poor drug permeation, instability of vesicles and drug leakage from vesicles induced by fusion of vesicles. To solve the vesicle instability problems in current dermal delivery systems, we developed materials comprised of liquid crystals as a new delivery vehicle of retinyl palmitate and report the characterization of the liquid crystals using a Mueller matrix polarimetry. The stability of the liquid-crystal materials was evaluated using the polarimeter as a novel evaluation tool along with other conventional methods. The dermal delivery of retinyl palmitate was investigated through the use of confocal Raman spectroscopy. The results indicate that the permeation of retinyl palmitate was enhanced by up to 106% compared to that using an ordinary emulsion with retinyl palmitate. Copyright © 2015 Elsevier B.V. All rights reserved.
Auditory perception of motor vehicle travel paths.
Ashmead, Daniel H; Grantham, D Wesley; Maloff, Erin S; Hornsby, Benjamin; Nakamura, Takabun; Davis, Timothy J; Pampel, Faith; Rushing, Erin G
2012-06-01
These experiments address concerns that motor vehicles in electric engine mode are so quiet that they pose a risk to pedestrians, especially those with visual impairments. The "quiet car" issue has focused on hybrid and electric vehicles, although it also applies to internal combustion engine vehicles. Previous research has focused on detectability of vehicles, mostly in quiet settings. Instead, we focused on the functional ability to perceive vehicle motion paths. Participants judged whether simulated vehicles were traveling straight or turning, with emphasis on the impact of background traffic sound. In quiet, listeners made the straight-or-turn judgment soon enough in the vehicle's path to be useful for deciding whether to start crossing the street. This judgment is based largely on sound level cues rather than the spatial direction of the vehicle. With even moderate background traffic sound, the ability to tell straight from turn paths is severely compromised. The signal-to-noise ratio needed for the straight-or-turn judgment is much higher than that needed to detect a vehicle. Although a requirement for a minimum vehicle sound level might enhance detection of vehicles in quiet settings, it is unlikely that this requirement would contribute to pedestrian awareness of vehicle movements in typical traffic settings with many vehicles present. The findings are relevant to deliberations by government agencies and automobile manufacturers about standards for minimum automobile sounds and, more generally, for solutions to pedestrians' needs for information about traffic, especially for pedestrians with sensory impairments.
Nanochemistry of protein-based delivery agents
Directory of Open Access Journals (Sweden)
Subin R.C.K. Rajendran
2016-07-01
Full Text Available The past decade has seen an increased interest in the conversion of food proteins into functional biomaterials, including their use for loading and delivery of physiologically active compounds such as nutraceuticals and pharmaceuticals. Proteins possess a competitive advantage over other platforms for the development of nanodelivery systems since they are biocompatible, amphipathic, and widely available. Proteins also have unique molecular structures and diverse functional groups that can be selectively modified to alter encapsulation and release properties. A number of physical and chemical methods have been used for preparing protein nanoformulations, each based on different underlying protein chemistry. This review focuses on the chemistry of the reorganization and/or modification of proteins into functional nanostructures for delivery, from the perspective of their preparation, functionality, stability and physiological behavior.
García-Astrain, Clara; Avérous, Luc
2018-06-15
Environment-sensitive alginate-based hydrogels for drug delivery applications are receiving increasing attention. However, most work in this field involves traditional cross-linking strategies which led to hydrogels with poor long-term stability. Herein, a series of chemically cross-linked alginate hydrogels was synthesized via click chemistry using Diels-Alder reaction by reacting furan-modified alginate and bifunctional cross-linkers. Alginate was successfully functionalized with furfurylamine. Then, 3D architectures were synthesized with water-soluble bismaleimides. Different substitution degrees were achieved in order to study the effect of alginate modification and the cross-linking extent over the behaviour of the hydrogels. The ensuing hydrogels were analysed in terms of microstructure, swelling, structure modification and rheological behaviour. The materials response to external stimuli such as pH was also investigated, revealing a pulsatile behaviour in a large pH range (1-13) and a clear pH-dependent swelling. Finally, vanillin release studies were conducted to demonstrate the potential of these biobased materials for drug delivery applications. Copyright © 2018 Elsevier Ltd. All rights reserved.
Reliable communication stack for flexible probe vehicle data collection in vehicular ad hoc networks
DEFF Research Database (Denmark)
Paulin, Thomas
Traffic congestions caused by high vehicular densities are an ever increasing problem for both personal and professional transportation, resulting in significant losses each year. While expanding the road infrastructure often offers a short term solution, more intelligent approaches are necessary...... the communication resource a single access point can provide for delay tolerant applications. 2) We improve the information exchange between road-side units and vehicles by identifying communication characteristics of the road-side unit and use them to determine the optimal location at which the information...... exchange should occur. 3) We extend the coverage range of the road-side units through vehicle to vehicle communication by modifying an existing routing algorithm, improving both delivery rate and communication overhead. Applying the proposed methodologies on the collection of probe data provides...
A hybrid metaheuristic for the time-dependent vehicle routing problem with hard time windows
Directory of Open Access Journals (Sweden)
N. Rincon-Garcia
2017-01-01
Full Text Available This article paper presents a hybrid metaheuristic algorithm to solve the time-dependent vehicle routing problem with hard time windows. Time-dependent travel times are influenced by different congestion levels experienced throughout the day. Vehicle scheduling without consideration of congestion might lead to underestimation of travel times and consequently missed deliveries. The algorithm presented in this paper makes use of Large Neighbourhood Search approaches and Variable Neighbourhood Search techniques to guide the search. A first stage is specifically designed to reduce the number of vehicles required in a search space by the reduction of penalties generated by time-window violations with Large Neighbourhood Search procedures. A second stage minimises the travel distance and travel time in an ‘always feasible’ search space. Comparison of results with available test instances shows that the proposed algorithm is capable of obtaining a reduction in the number of vehicles (4.15%, travel distance (10.88% and travel time (12.00% compared to previous implementations in reasonable time.
Developments and challenges for autonomous unmanned vehicles
Finn, Anthony
2010-01-01
It is widely anticipated that autonomous vehicles will have a transformational impact on military forces and will play a key role in many future force structures. As a result, many tasks have already been identified that unmanned systems could undertake more readily than humans. However, for this to occur, such systems will need to be agile, versatile, persistent, reliable, survivable and lethal. This will require many of the vehicles 'cognitive' or higher order functions to be more fully developed, whereas to date only the 'component' or physical functions have been successfully automated and
Boyhan, Diane; Daniell, Henry
2011-06-01
Current treatment for type I diabetes includes delivery of insulin via injection or pump, which is highly invasive and expensive. The production of chloroplast-derived proinsulin should reduce cost and facilitate oral delivery. Therefore, tobacco and lettuce chloroplasts were transformed with the cholera toxin B subunit fused with human proinsulin (A, B, C peptides) containing three furin cleavage sites (CTB-PFx3). Transplastomic lines were confirmed for site-specific integration of transgene and homoplasmy. Old tobacco leaves accumulated proinsulin up to 47% of total leaf protein (TLP). Old lettuce leaves accumulated proinsulin up to 53% TLP. Accumulation was so stable that up to ~40% proinsulin in TLP was observed even in senescent and dried lettuce leaves, facilitating their processing and storage in the field. Based on the yield of only monomers and dimers of proinsulin (3 mg/g leaf, a significant underestimation), with a 50% loss of protein during the purification process, one acre of tobacco could yield up to 20 million daily doses of insulin per year. Proinsulin from tobacco leaves was purified up to 98% using metal affinity chromatography without any His-tag. Furin protease cleaved insulin peptides in vitro. Oral delivery of unprocessed proinsulin bioencapsulated in plant cells or injectable delivery into mice showed reduction in blood glucose levels similar to processed commercial insulin. C-peptide should aid in long-term treatment of diabetic complications including stimulation of nerve and renal functions. Hyper-expression of functional proinsulin and exceptional stability in dehydrated leaves offer a low-cost platform for oral and injectable delivery of cleavable proinsulin. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.
Directory of Open Access Journals (Sweden)
Khosravian P
2016-12-01
Full Text Available Pegah Khosravian,1 Mehdi Shafiee Ardestani,2 Mehdi Khoobi,3 Seyed Naser Ostad,4 Farid Abedin Dorkoosh,1 Hamid Akbari Javar,1,* Massoud Amanlou5,6,* 1Department of Pharmaceutics, 2Department of Radiopharmacy, 3Department of Pharmaceutical Biomaterials, 4Department of Pharmacology and Toxicology, 5Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, 6Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Abstract: Mesoporous silica nanoparticles (MSNs are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer. Keywords: targeted delivery, mesoporous silica nanoparticle, folic acid, methionine, docetaxel
FedEx Gasoline Hybrid Electric Delivery Truck Evaluation: 6-Month Interim Report
Energy Technology Data Exchange (ETDEWEB)
Barnitt, R.
2010-05-01
This interim report presents partial (six months) results for a technology evaluation of gasoline hybrid electric parcel delivery trucks operated by FedEx in and around Los Angeles, CA. A 12 month in-use technology evaluation comparing in-use fuel economy and maintenance costs of GHEVs and comparative diesel parcel delivery trucks was started in April 2009. Comparison data was collected and analyzed for in-use fuel economy and fuel costs, maintenance costs, total operating costs, and vehicle uptime. In addition, this interim report presents results of parcel delivery drive cycle collection and analysis activities as well as emissions and fuel economy results of chassis dynamometer testing of a gHEV and a comparative diesel truck at the National Renewable Energy Laboratory's (NREL) ReFUEL laboratory. A final report will be issued when 12 months of in-use data have been collected and analyzed.
Directory of Open Access Journals (Sweden)
Haijian Bai
2017-01-01
Full Text Available Considering the complexity of lane changing using automated vehicles and the frequency of turning lanes in city settings, this paper aims to generate an accelerated lane-changing trajectory using vehicle-to-vehicle collaboration (V2VC. Based on the characteristics of accelerated lane changing, we used a polynomial method and cooperative strategies for trajectory planning to establish a lane-changing model under different degrees of collaboration with the following vehicle in the target lane by considering vehicle kinematics and comfort requirements. Furthermore, considering the shortcomings of the traditional elliptical vehicle and round vehicle models, we established a rectangular vehicle model with collision boundary conditions by analysing the relationships between the possible collision points and the outline of the vehicle. Then, we established a simulation model for the accelerated lane-changing process in different environments under different degrees of collaboration. The results show that, by using V2VC, we can achieve safe accelerated lane-changing trajectories and simultaneously satisfy the requirements of vehicle kinematics and comfort control.
Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle
Energy Technology Data Exchange (ETDEWEB)
Chandra, Sudeshna; Noronha, Glen [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India); Dietrich, Sascha; Lang, Heinrich [Technische Universität Chemnitz, Institute of Chemistry, Straße der Nationen 62, d-09111 Chemnitz (Germany); Bahadur, Dhirendra, E-mail: dhirenb@iitb.ac.in [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India)
2015-04-15
Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 9}CH{sub 3} and CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 2}C{sub 2}H{sub 5}, respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe{sub 3}O{sub 4}) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells.
Platelets as Contractile Nanomachines for Targeting Drug Delivery in Hemostasis and Thrombosis
2015-12-01
capsules were suspended in platelet - rich plasma, which was subsequently exposed to 1 U/mL of thrombin, the capsules successfully targeted target...thrombotic sites via integration into the forming fibrin networks and binding to activated platelets . The delivery vehicles successfully adhere to platelet ...rupture has successfully been achieved in static fibrin gels comprised of a high concentration of platelets (Figure 3). Only capsules incorporated into
Drug delivery system design and development for boron neutron capture therapy on cancer treatment
International Nuclear Information System (INIS)
Sherlock Huang, Lin-Chiang; Hsieh, Wen-Yuan; Chen, Jiun-Yu; Huang, Su-Chin; Chen, Jen-Kun; Hsu, Ming-Hua
2014-01-01
We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,L-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content. - Highlights: • Herein, we have synthesized boron-modified diblock copolymer. • Bpin-PLA-PEOz, which will be served as new boron containing vehicle for transporting the boron drug. • This boron containing Bpin-PLA-PEOz micelle was low toxicity can be applied to drug delivery
Gourash, F.
1984-01-01
The test results for a functional model ac motor controller for electric vehicles and a three-phase induction motor which were dynamically tested on the Lewis Research Center road load simulator are presented. Results show that the controller has the capability to meet the SAE-J227a D cycle test schedule and to accelerate a 1576-kg (3456-lb) simulated vehicle to a cruise speed of 88.5 km/hr (55 mph). Combined motor controller efficiency is 72 percent and the power inverter efficiency alone is 89 percent for the cruise region of the D cycle. Steady state test results for motoring, regeneration, and thermal data obtained by operating the simulator as a conventional dynamometer are in agreement with the contractor's previously reported data. The regeneration test results indicate that a reduction in energy requirements for urban driving cycles is attainable with regenerative braking. Test results and data in this report serve as a data base for further development of ac motor controllers and propulsion systems for electric vehicles. The controller uses state-of-the-art silicon controlled rectifier (SCR) power semiconductors and microprocessor-based logic and control circuitry. The controller was developed by Gould Laboratories under a Lewis contract for the Department of Energy's Electric and Hybrid Vehicle program.
Gourash, F.
1984-02-01
The test results for a functional model ac motor controller for electric vehicles and a three-phase induction motor which were dynamically tested on the Lewis Research Center road load simulator are presented. Results show that the controller has the capability to meet the SAE-J227a D cycle test schedule and to accelerate a 1576-kg (3456-lb) simulated vehicle to a cruise speed of 88.5 km/hr (55 mph). Combined motor controller efficiency is 72 percent and the power inverter efficiency alone is 89 percent for the cruise region of the D cycle. Steady state test results for motoring, regeneration, and thermal data obtained by operating the simulator as a conventional dynamometer are in agreement with the contractor's previously reported data. The regeneration test results indicate that a reduction in energy requirements for urban driving cycles is attainable with regenerative braking. Test results and data in this report serve as a data base for further development of ac motor controllers and propulsion systems for electric vehicles. The controller uses state-of-the-art silicon controlled rectifier (SCR) power semiconductors and microprocessor-based logic and control circuitry. The controller was developed by Gould Laboratories under a Lewis contract for the Department of Energy's Electric and Hybrid Vehicle program.
Targeted therapy of hepatocellular carcinoma with aptamer-functionalized biodegradable nanoparticles
Energy Technology Data Exchange (ETDEWEB)
Weigum, Shannon, E-mail: sweigum@txstate.edu [Texas State University, Department of Biology (United States); McIvor, Elizabeth; Munoz, Christopher; Feng, Richard [Texas State University, Department of Chemistry and Biochemistry (United States); Cantu, Travis [Texas State University, Materials Science, Engineering, and Commercialization Program (United States); Walsh, Kyle [Texas State University, Department of Chemistry and Biochemistry (United States); Betancourt, Tania, E-mail: tania.betancourt@txstate.edu [Texas State University, Materials Science, Engineering, and Commercialization Program (United States)
2016-11-15
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, occurring primarily in regions where viral hepatitis infections are common. Unfortunately, most HCC cases remain undiagnosed until late stages of the disease when patient outcome is poor, typically limiting survival from a few months to a year after initial diagnosis. In order to better care for HCC patients, new target-specific approaches are needed to improve early detection and therapeutic intervention. In this work, polymeric nanoparticles functionalized with a HCC-specific aptamer were examined as potential targeted drug delivery vehicles. Specifically, doxorubicin-loaded nanoparticles were prepared via nanoprecipitation of blends of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol). These particles were further functionalized with the HCC-specific TLS11a aptamer. The in vitro interaction and therapeutic efficacy of the aptamer and aptamer-functionalized nanoparticles were characterized in a hepatoma cell line. Nanoparticles were found to be spherical in shape, roughly 100–125 nm in diameter, with a low polydispersity (≤0.2) and slightly negative surface potential. Doxorubicin was encapsulated within the particles at ~40 % efficiency. Drug release was found to occur through anomalous transport influenced by diffusion and polymer relaxation, releasing ~50 % doxorubicin in the first 10 h and full release occurring within 36 h. Confocal microscopy confirmed binding and attachment of aptamer-targeted nanoparticles to the cell surface of cultured HCC cells. Efficacy studies demonstrated a significant improvement in doxorubicin delivery and cell-killing capacity using the aptamer-functionalized, drug-loaded nanoparticles versus controls further supporting use of aptamer nanoparticles as a targeted drug delivery system for HCC tumors.
He, Mingyu; Potuck, Alicia; Kohn, Julie C; Fung, Katharina; Reinhart-King, Cynthia A; Chu, Chih-Chang
2016-02-08
The objective of this study is to develop a new family of biodegradable and biologically active copolymers and their subsequent self-assembled cationic nanoparticles as better delivery vehicles for anticancer drugs to achieve the synergism between the cytotoxicity effects of the loaded drugs and the macrophage inflammatory response of the delivery vehicle. This family of cationic nanoparticles was formulated from a new family of amphiphilic cationic Arginine-Leucine (Arg-Leu)-based poly(ester urea urethane) (Arg-Leu PEUU) synthesized from four building blocks (amino acids, diols, glycerol α-monoallyl ether, and 1,6 hexamethylene diisocyanate). The chemical, physical, and biological properties of Arg-Leu PEUU biomaterials can be tuned by controlling the feed ratio of the four building blocks. The Arg-Leu PEUU copolymers have weight-average molecular weights from 13.4 to 16.8 kDa and glass-transition temperatures from -3.4 to -4.6 °C. The self-assembled cationic nanoparticles (Arg-Leu PEUU NPs) were prepared using a facile dialysis method. Arg-Leu PEUU NPs have average diameters ranging from 187 to 272 nm, show good biocompatibility with 3T3 fibroblasts, and they support bovine aortic endothelial cell (BAEC) proliferation and adhesion. Arg-Leu PEUU NPs also enhanced the macrophages' production of tumor necrosis factor-α (TNF-α) and nitric oxide (NO), but produced relatively low levels of interleukin-10 (IL-10), and therefore, the antitumor activity of macrophages might be enhanced. Arg-Leu PEUU NPs were taken up by HeLa cells after 4 h of incubation. The in vitro hemolysis assay showed the cationic Arg-Leu PEUU NPs increased their chance of endosomal escape at a more acidic pH. Doxorubicin (DOX) was successfully incorporated into the Arg-Leu PEUU NPs, and the DOX-loaded Arg-Leu PEUU NPs exhibited a pH-dependent drug release profile with accelerated release kinetics in a mild acidic condition. The DOX-loaded 6-Arg-4-Leu-4 A/L-2/1 NPs showed higher HeLa cell
Endogenous vehicle-type choices in a monocentric city
DEFF Research Database (Denmark)
Kim, Jinwon
2012-01-01
inconvenience in the choice of vehicle sizes, and the resulting commuting cost is a function of residential density. This vehicle-type choice problem is embedded in an otherwise standardmonocentric city model. A convenience-related advantage in less-dense areas makes our bid–rent curve flatter than...
Enhancement techniques for improving 5-aminolevulinic acid delivery through the skin
Directory of Open Access Journals (Sweden)
Li-Wen Zhang
2011-03-01
Full Text Available Photodynamic therapy (PDT is a popular technique for skin cancer treatment. Protoporphyrin IX, which is a photosensitizing agent, converted enzymatically from the prodrug 5-aminolevulinic acid (ALA, is used as a photosensitizer in PDT for cancer. However, ALA penetrates with difficulty through intact skin; therefore, improving delivery systems for ALA in the skin will play an important role in ALA-PDT. Enhancement of ALA skin penetration can be achieved by physical methods, such as iontophoresis, laser, microneedles, ultrasound, and by adding chemical penetration enhancers, such as, dimethyl sulfoxide, oleic acid, and others, whereas some researches used lipophilic ALA derivatives and different vehicles to improve the transdermal delivery of ALA. This review introduces several enhancement techniques for increasing ALA permeation through the skin.
SIGMA/B, Doses in Space Vehicle for Multiple Trajectories, Various Radiation Source
International Nuclear Information System (INIS)
Jordan, T.M.
2003-01-01
1 - Description of problem or function: SIGMA/B calculates radiation dose at arbitrary points inside a space vehicle, taking into account vehicle geometry, heterogeneous placement of equipment and stores, vehicle materials, time-weighted astronaut positions and many radiation sources from mission trajectories, e.g. geomagnetically trapped protons and electrons, solar flare particles, galactic cosmic rays and their secondary radiations. The vehicle geometry, equipment and supplies, and man models are described by quadric surfaces. The irradiating flux field may be anisotropic. The code can be used to perform simultaneous dose calculations for multiple vehicle trajectories, each involving several radiation sources. Results are presented either as dose as a function of shield thickness, or the dose received through designated outer sections of the vehicle. 2 - Method of solution: Automatic sectoring of the vehicle is performed by a Simpson's rule integration over angle; the dose is computed by a numerical angular integration of the dose attenuation kernels about the dose points. The kernels are curve-fit functions constructed from input data tables. 3 - Restrictions on the complexity of the problem: The code uses variable dimensioning techniques to store data. The only restriction on problem size is the available core storage
International Nuclear Information System (INIS)
Lewis, Anne Marie; Kelly, Jarod C.; Keoleian, Gregory A.
2014-01-01
Highlights: • We modeled life cycle energy and greenhouse gas (GHG) emissions from diverse powertrain vehicles. • Lightweight versions of the vehicle models were compared against baseline models. • Maximum energy and GHG emissions occur with aluminum vs. advanced high strength steel. • Design harmonization method shows 0.2–0.3 kg of support required per 1 kg powertrain mass increase. - Abstract: This work assesses the potential of electrified vehicles and mass reduction to reduce life cycle energy and greenhouse gas (GHG) emissions. Life cycle assessment (LCA) is used to account for processes upstream and downstream of the vehicle operation, thereby incorporating regional variation of energy and GHG emissions due to electricity production and distinct energy and GHG emissions due to conventional and lightweight materials. Design harmonization methods developed in previous work are applied to create baseline and lightweight vehicle models of an internal combustion vehicle (ICV), hybrid electric vehicle (HEV) and plug-in hybrid electric vehicle (PHEV). Thus, each vehicle is designed to be functionally equivalent and incorporate the structural support required for heavier powertrains. Lightweight vehicles are designed using body-in-white (BIW) mass reduction scenarios with aluminum and advanced/high strength steel (A/HSS). For the mass reduction scenarios considered in this work, results indicate that the greatest life cycle energy and GHG emissions reductions occur when steel is replaced by aluminum. However, since A/HSS requires less energy to produce as compared to aluminum, the energy and GHG reductions per unit mass removed is greatest for A/HSS. Results of the design harmonization modeling method show that 0.2–0.3 kg of structural support is required per unit increase in powertrain mass, thus extending previous methods
Veenstra, Marjolein; Roodbergen, Kees Jan; Coelho, Leandro C.; Zhu, Stuart X.
2018-01-01
This paper introduces a simultaneous facility location and vehicle routing problem that arises in health care logistics in the Netherlands. In this problem, the delivery of medication from a local pharmacy can occur via lockers, from where patients that are within the coverage distance of a locker
Dual recombinant Lactococcus lactis for enhanced delivery of DNA vaccine reporter plasmid pPERDBY.
Yagnik, Bhrugu; Sharma, Drashya; Padh, Harish; Desai, Priti
2017-04-01
Food grade Lactococcus lactis has been widely used as an antigen and DNA delivery vehicle. We have previously reported the use of non-invasive L. lactis to deliver the newly constructed immunostimulatory DNA vaccine reporter plasmid, pPERDBY. In the present report, construction of dual recombinant L. lactis expressing internalin A of Listeria monocytogenes and harboring pPERDBY (LL InlA + pPERDBY) to enhance the efficiency of delivery of DNA by L. lactis is outlined. After confirmation and validation of LL InlA + pPERDBY, its DNA delivery potential was compared with previously developed non-invasive r- L. lactis::pPERDBY. The use of invasive L. lactis resulted in around threefold increases in the number of enhanced green fluorescent protein-expressing Caco-2 cells. These findings reinforce the prospective application of invasive strain of L. lactis for delivery of DNA/RNA and antigens. © 2017 The Societies and John Wiley & Sons Australia, Ltd.
Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery
Directory of Open Access Journals (Sweden)
Priya Bawa
2011-12-01
Full Text Available Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.
Feng, Guo-Hua; Hou, Sheng-You
2015-09-01
This paper presents an ionic polymer metal composite (IPMC)-driven tentacle-like biocompatible flexible actuator with double-section curvature tunability. This actuator, possessing an embedded electrical transmission ability that mimics skeletal muscle nerves in the human body, affords versatile device functions. Novel micromachined copper buckles and grid wires are fabricated and their superiority in electricity delivery and driving the IPMC component with less flexural rigidity is demonstrated. In addition, soft conductive wires realized on a polydimethylsiloxane structure function as electrical signal transmitters. A light-emitting diode integrated with the developed actuator offers directional guiding light ability while the actuator performs a snake-like motion. The electrical conductivity and Young’s modulus of the key actuator components are investigated, and flexural rigidity and dynamic behavior analyses of the actuator under electrical manipulation are elaborated.
International Nuclear Information System (INIS)
Feng, Guo-Hua; Hou, Sheng-You
2015-01-01
This paper presents an ionic polymer metal composite (IPMC)-driven tentacle-like biocompatible flexible actuator with double-section curvature tunability. This actuator, possessing an embedded electrical transmission ability that mimics skeletal muscle nerves in the human body, affords versatile device functions. Novel micromachined copper buckles and grid wires are fabricated and their superiority in electricity delivery and driving the IPMC component with less flexural rigidity is demonstrated. In addition, soft conductive wires realized on a polydimethylsiloxane structure function as electrical signal transmitters. A light-emitting diode integrated with the developed actuator offers directional guiding light ability while the actuator performs a snake-like motion. The electrical conductivity and Young’s modulus of the key actuator components are investigated, and flexural rigidity and dynamic behavior analyses of the actuator under electrical manipulation are elaborated. (paper)
Extensions to the Dynamic Aerospace Vehicle Exchange Markup Language
Brian, Geoffrey J.; Jackson, E. Bruce
2011-01-01
The Dynamic Aerospace Vehicle Exchange Markup Language (DAVE-ML) is a syntactical language for exchanging flight vehicle dynamic model data. It provides a framework for encoding entire flight vehicle dynamic model data packages for exchange and/or long-term archiving. Version 2.0.1 of DAVE-ML provides much of the functionality envisioned for exchanging aerospace vehicle data; however, it is limited in only supporting scalar time-independent data. Additional functionality is required to support vector and matrix data, abstracting sub-system models, detailing dynamics system models (both discrete and continuous), and defining a dynamic data format (such as time sequenced data) for validation of dynamics system models and vehicle simulation packages. Extensions to DAVE-ML have been proposed to manage data as vectors and n-dimensional matrices, and record dynamic data in a compatible form. These capabilities will improve the clarity of data being exchanged, simplify the naming of parameters, and permit static and dynamic data to be stored using a common syntax within a single file; thereby enhancing the framework provided by DAVE-ML for exchanging entire flight vehicle dynamic simulation models.
H-II Transfer Vehicle (HTV) and the Operations Concept for Extravehicular Activity (EVA) Hardware
Chullen, Cinda; Blome, Elizabeth; Tetsuya, Sakashita
2011-01-01
With the retirement of the Space Shuttle fleet imminent in 2011, a new operations concept will become reality to meet the transportation challenges of the International Space Station (ISS). The planning associated with the retirement of the Space Shuttle has been underway since the announcement in 2004. Since then, several companies and government entities have had to look for innovative low-cost commercial orbital transportation systems to continue to achieve the objectives of ISS delivery requirements. Several options have been assessed and appear ready to meet the large and demanding delivery requirements of the ISS. Options that have been identified that can facilitate the challenge include the Russian Federal Space Agency's Soyuz and Progress spacecraft, European Space Agency's Automated Transfer Vehicle (ATV), and the Japan Aerospace Exploration Agency's (JAXA s) H-II Transfer Vehicle (HTV). The newest of these options is the JAXA's HTV. This paper focuses on the HTV, mission architecture and operations concept for Extra-Vehicular Activities (EVA) hardware, the associated launch system, and details of the launch operations approach.
Hybrid FSAE Vehicle Realization
2010-12-01
The goal of this multi-year project is to create a fully functional University of Idaho entry in the hybrid FSAE competition. Vehicle integration is underway as part of a variety of 2010-11 senior design projects. This leverages a variety of analytic...
Parametric modeling of components for selection and specification of hybrid vehicle drivetrains
Hofman, T.; Steinbuch, M.; Druten, van R.M.; Serrarens, A.F.A.
2006-01-01
Drivetrain hybridization implies adding a Secondary power source to a Primary power source in order to improve a multiple of driving functions: Fuel economy, Emissions, Driveability, Comfort and Safety. Designing a hybrid vehicle drivetrain fulfilling the required vehicle driving functions is
Torque vectoring for improving stability of small electric vehicles
Grzegożek, W.; Weigel-Milleret, K.
2016-09-01
The electric vehicles solutions based on the individually controlled electric motors propel a single wheel allow to improve the dynamic properties of the vehicle by varying the distribution of the driving torque. Most of the literature refer to the vehicles with a track typical for passenger cars. This paper examines whether the narrow vehicle (with a very small track) torque vectoring bring a noticeable change of the understeer characteristics and whether torque vectoring is possible to use in securing a narrow vehicle from roll over (roll mitigation). The paper contains road tests of the steering characteristics (steady state understeer characteristic quasi-static acceleration with a fixed steering wheel (SH = const) and on the constant radius track (R = const)) of the narrow vehicle. The vehicle understeer characteristic as a function of a power distribution is presented.
Tailoring stimuli-responsive delivery system driven by metal–ligand coordination bonding
Directory of Open Access Journals (Sweden)
Liang H
2017-04-01
Full Text Available Hongshan Liang,1–3 Bin Zhou,4 Yun He,1–3 Yaqiong Pei,1–3 Bin Li,1–3 Jing Li1–31College of Food Science and Technology, Huazhong Agricultural University, 2Key Laboratory of Environment Correlative Dietology, Huazhong Agricultural University, Ministry of Education, 3Functional Food Engineering & Technology Research Center of Hubei Province, Wuhan, Hubei, 4College of Food Science and Technology, Shanghai Ocean University, LinGang New City, Shanghai, People’s Republic of ChinaAbstract: In this study, a novel coordination bonding system based on metal–tannic acid (TA architecture on zein/carboxymethyl chitosan (CMCS nanoparticles (NPs was investigated for the pH-responsive drug delivery. CMCS has been reported to coat on zein NPs as delivery vehicles for drugs or nutrients in previous studies. The cleavage of either the “metal–TA” or “NH2–metal” coordination bonds resulted in significant release of guest molecules with high stimulus sensitivity, especially in mild acidic conditions. The prepared metal–TA-coated zein/CMCS NPs (zein/CMCS-TA/metal NPs could maintain particle size in cell culture medium at 37°C, demonstrating good stability compared with zein/CMCS NPs. In vitro release behavior of doxorubicin hydrochloride (DOX-loaded metal–TA film-coated zein/CMCS NPs (DOX-zein/CMCS-TA/metal NPs showed fine pH responsiveness tailored by the ratio of zein to CMCS as well as the metal species and feeding concentrations. The blank zein/CMCS-TA/metal NPs (NPs-TA/metal were of low cytotoxicity, while a high cytotoxic activity of DOX-zein/CMCS-TA/metal NPs (DOX-NPs-TA/metal against HepG2 cells was demonstrated by in vitro cell assay. Confocal laser scanning microscopy (CLSM and flow cytometry were combined to study the uptake efficiency of DOX-NPs or DOX-NPs-TA/metal. This system showed significant potential as a highly versatile and potent platform for drug delivery. Keywords: coordination bonding, pH-responsive, high stimulus
Compartmental transport model of microbicide delivery by an intravaginal ring
Geonnotti, Anthony R.; Katz, David F.
2010-01-01
Topical antimicrobials, or microbicides, are being developed to prevent HIV transmission through local, mucosal delivery of antiviral compounds. While hydrogel vehicles deliver the majority of current microbicide products, intravaginal rings (IVRs) are an alternative microbicide modality in preclinical development. IVRs provide a long-term dosing alternative to hydrogel use, and might provide improved user adherence. IVR efficacy requires sustained delivery of antiviral compounds to the entire vaginal compartment. A two-dimensional, compartmental vaginal drug transport model was created to evaluate the delivery of drugs from an intravaginal ring. The model utilized MRI-derived ring geometry and location, experimentally defined ring fluxes and vaginal fluid velocities, and biophysically relevant transport theory. Model outputs indicated the presence of potentially inhibitory concentrations of antiviral compounds along the entire vaginal canal within 24 hours following IVR insertion. Distributions of inhibitory concentrations of antiviral compounds were substantially influenced by vaginal fluid flow and production, while showing little change due to changes in diffusion coefficients or ring fluxes. Additionally, model results were predictive of in vivo concentrations obtained in clinical trials. Overall, this analysis initiates a mechanistic computational framework, heretofore missing, to understand and evaluate the potential of IVRs for effective delivery of antiviral compounds. PMID:20222027
The Study of Intelligent Vehicle Navigation Path Based on Behavior Coordination of Particle Swarm.
Han, Gaining; Fu, Weiping; Wang, Wen
2016-01-01
In the behavior dynamics model, behavior competition leads to the shock problem of the intelligent vehicle navigation path, because of the simultaneous occurrence of the time-variant target behavior and obstacle avoidance behavior. Considering the safety and real-time of intelligent vehicle, the particle swarm optimization (PSO) algorithm is proposed to solve these problems for the optimization of weight coefficients of the heading angle and the path velocity. Firstly, according to the behavior dynamics model, the fitness function is defined concerning the intelligent vehicle driving characteristics, the distance between intelligent vehicle and obstacle, and distance of intelligent vehicle and target. Secondly, behavior coordination parameters that minimize the fitness function are obtained by particle swarm optimization algorithms. Finally, the simulation results show that the optimization method and its fitness function can improve the perturbations of the vehicle planning path and real-time and reliability.
Rao, Shasha; Richter, Katharina; Nguyen, Tri-Hung; Boyd, Ben J; Porter, Christopher J H; Tan, Angel; Prestidge, Clive A
2015-12-07
A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.
Motor vehicle evaluative criteria: Using unmet expectations as signals for dissonance
Directory of Open Access Journals (Sweden)
Sanjana Brijball Parumasur
2015-07-01
Full Text Available This study assesses whether motor vehicle consumers base their purchases on functional or symbolic needs. It also evaluates motor vehicle buyer’s level of importance attached to evaluative criteria and the extent to which they believe the purchased vehicle fulfils the evaluative criteria, in order to assess whether expectations have been met or not and hence, the potential for cognitive dissonance. Biographical correlates (race, marital status, age, education, occupation, income, gender are evaluated and the influence of range of motor vehicle is also analysed. A sample of 200 brand new motor vehicle buyers was drawn using the stratified random sampling technique based on range of motor vehicle purchased, month of purchases, gender and age of the buyer. Only new motor vehicle buyers (within KwaZulu-Natal who concluded their purchases in one major, reputable and leading motor vehicle manufacturing company and who owned the vehicle for a maximum period of seven months were considered, so as to avoid cognitive intrusion. The results indicate that consumer’ expectations were not met in terms of price, economy and performance yet these were buyers’ most highly rated evaluative criteria, thereby reflecting the potential for dissonance. Significant biographical correlates were noted in terms of race, age, occupation, income, gender and motor vehicle evaluative criteria. Whilst bottom and middle of the range motor vehicle consumers favour functional or utilitarian value, top of the range motor vehicle consumers aim to fulfil symbolic needs
Kheyfets, Vitaly O; Kieweg, Sarah L
2013-06-01
HIV/AIDS is a growing global pandemic. A microbicide is a formulation of a pharmaceutical agent suspended in a delivery vehicle, and can be used by women to protect themselves against HIV infection during intercourse. We have developed a three-dimensional (3D) computational model of a shear-thinning power-law fluid spreading under the influence of gravity to represent the distribution of a microbicide gel over the vaginal epithelium. This model, accompanied by a new experimental methodology, is a step in developing a tool for optimizing a delivery vehicle's structure/function relationship for clinical application. We compare our model with experiments in order to identify critical considerations for simulating 3D free-surface flows of shear-thinning fluids. Here we found that neglecting lateral spreading, when modeling gravity-induced flow, resulted in up to 47% overestimation of the experimental axial spreading after 90 s. In contrast, the inclusion of lateral spreading in 3D computational models resulted in rms errors in axial spreading under 7%. In addition, the choice of the initial condition for shape in the numerical simulation influences the model's ability to describe early time spreading behavior. Finally, we present a parametric study and sensitivity analysis of the power-law parameters' influence on axial spreading, and to examine the impact of changing rheological properties as a result of dilution or formulation conditions. Both the shear-thinning index (n) and consistency (m) impacted the spreading length and deceleration of the moving front. The sensitivity analysis showed that gels with midrange m and n values (for the ranges in this study) would be most sensitive (over 8% changes in spreading length) to 10% changes (e.g., from dilution) in both rheological properties. This work is applicable to many industrial and geophysical thin-film flow applications of non-Newtonian fluids; in addition to biological applications in microbicide drug delivery.
Effects of vehicle power on passenger vehicle speeds.
McCartt, Anne T; Hu, Wen
2017-07-04
During the past 2 decades, there have been large increases in mean horsepower and the mean horsepower-to-vehicle weight ratio for all types of new passenger vehicles in the United States. This study examined the relationship between travel speeds and vehicle power, defined as horsepower per 100 pounds of vehicle weight. Speed cameras measured travel speeds and photographed license plates and drivers of passenger vehicles traveling on roadways in Northern Virginia during daytime off-peak hours in spring 2013. The driver licensing agencies in the District of Columbia, Maryland, and Virginia provided vehicle information numbers (VINs) by matching license plate numbers with vehicle registration records and provided the age, gender, and ZIP code of the registered owner(s). VINs were decoded to obtain the curb weight and horsepower of vehicles. The study focused on 26,659 observed vehicles for which information on horsepower was available and the observed age and gender of drivers matched vehicle registration records. Log-linear regression estimated the effects of vehicle power on mean travel speeds, and logistic regression estimated the effects of vehicle power on the likelihood of a vehicle traveling over the speed limit and more than 10 mph over the limit. After controlling for driver characteristics, speed limit, vehicle type, and traffic volume, a 1-unit increase in vehicle power was associated with a 0.7% increase in mean speed, a 2.7% increase in the likelihood of a vehicle exceeding the speed limit by any amount, and an 11.6% increase in the likelihood of a vehicle exceeding the limit by 10 mph. All of these increases were highly significant. Speeding persists as a major factor in crashes in the United States. There are indications that travel speeds have increased in recent years. The current findings suggest the trend toward substantially more powerful vehicles may be contributing to higher speeds. Given the strong association between travel speed and crash
Yan, Saisai; Hu, Fan; Hong, Xia; Shuai, Qi
2018-09-01
Silica-encapsulated nanospheres of water-soluble ferrocene complexes WFCs@SiO 2 and WFCs@SiO 2 @glutaraldehyde (GA) were first synthesized by a facile inverse-microemulsion method. The surface functional groups, particle size, and morphologies of nanospheres were characterized by IR spectra, UV-vis absorption spectra, dynamic light scattering (DLS) and SEM images. Single-crystal X-ray diffraction was used to confirm the molecular structure of free ferrocenyl-pyrazol ligand (L) and three WFCs, namely, [Ni(C 22 H 14 F 6 FeN 4 O 4 )(H 2 O) 4 ] (5a), [Mg(C 22 H 14 F 6 FeN 4 O 4 )(H 2 O) 4 ]·3H 2 O (5b), and [Ba(C 22 H 14 F 6 FeN 4 O 4 )(H 2 O) 3 ] (5c). The electrochemical properties of 5a-5c were explored by cyclic voltammetry. The WFCs-loading capacities of 5a-5c in WFCs@SiO 2 were found to be 38.4, 38.2, and 38.1 μg/mg, respectively. Cell studies under two drug delivery modes (free diffusion and endocytosis) were carried out by MTT cell-survival assays and morphological observation of HepG2 cells. It's interesting that the cytotoxicity of WFCs against HepG2 was increased by applying silica nanocarriers. Compared to WFCs@SiO 2 , the modification of GA on the spherical surface provided not only the better water-dispersity but also additional functional groups for further modification of other pharmacophores. The novel nanocarrier system for WFC delivery present a novel concept-of-proof method to protect varieties of affordable metal-based anticancer agents in physiological conditions and provided experimental basis for future studies focusing on drug delivery of other WFCs. Copyright © 2018 Elsevier B.V. All rights reserved.
Deformable microparticles with multiple functions for drug delivery and device testing
Thula, Taili T.
Since the HIV epidemic of the 1990s, researchers have attempted to develop a red blood cell analog. Even though some of these substitutes are now in Phase III of clinical trials, their use is limited by side effects and short half-life in the human body. As a result, there is still a need for an effective erythrocyte analog with minimum immunogenic and side effects, so that it can be used for multiple applications. Finding new approaches to develop more efficient blood substitutes will not only bring valuable advances in the clinical approach, but also in the area of in vitro testing of medical devices. We examined the feasibility of creating a deformable multi-functional, biodegradable, biocompatible particle for applications in drug delivery and device testing. As a preliminary evaluation, we synthesized different types of microcapsules using natural and synthetic polymers, various cross-linking agents, and diverse manufacturing techniques. After fully characterizing of each system, we determined the most promising red blood cell analog in terms of deformability, stability and toxicity. We also examined the encapsulation and release of bovine serum albumin (BSA) within these deformable particles. After removal of cross-linkers, zinc- and copper-alginate microparticles surrounded by multiple polyelectrolyte layers of chitosan oligosaccharide and alginate were deformable and remained stable under physiological pressures applied by the micropipette technique. In addition, multiple coatings decreased toxicity of heavy-metal crosslinked particles. BSA encapsulation and release from chitosan-alginate microspheres were contingent on the crosslinker and number of polyelectrolyte coatings, respectively. Further rheological studies are needed to determine how closely these particles simulate the behavior of erythrocytes. Also, studies on the encapsulation and release of different proteins, including hemoglobin, are needed to establish the desired controlled release of
Multifunctional quantum dots and liposome complexes in drug delivery.
Wang, Qi; Chao, Yi-Min
2017-09-03
Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches.
Multifunctional quantum dots and liposome complexes in drug delivery
Wang, Qi; Chao, Yimin
2018-01-01
Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches. PMID:28866655
DEFF Research Database (Denmark)
Bruun, Jonas; Larsen, Trine Bjørnbo; Jølck, Rasmus Irming
2015-01-01
Clinical applications of siRNA for treating disorders in the central nervous system require development of systemic stable, safe, and effective delivery vehicles that are able to cross the impermeable blood–brain barrier (BBB). Engineering nanocarriers with low cellular interaction during systemi...
Alcohol Advertising and Motor Vehicle Fatalities
Henry Saffer
1994-01-01
The purpose of this paper is to empirically estimate the effect of alcohol advertising on motor vehicle fatalities. The concept of an industry level advertising response function is developed and other empirical issues in estimating the effects of advertising are reviewed. The data set consists of quarterly observations, from 1986 to 1989, for 75 advertising markets in the United States and includes 1200 observations. Since motor vehicle fatalities and alcohol advertising are jointly determin...
Electric vehicle equipment for grid-integrated vehicles
Kempton, Willett
2013-08-13
Methods, systems, and apparatus for interfacing an electric vehicle with an electric power grid are disclosed. An exemplary apparatus may include a station communication port for interfacing with electric vehicle station equipment (EVSE), a vehicle communication port for interfacing with a vehicle management system (VMS), and a processor coupled to the station communication port and the vehicle communication port to establish communication with the EVSE via the station communication port, receive EVSE attributes from the EVSE, and issue commands to the VMS to manage power flow between the electric vehicle and the EVSE based on the EVSE attributes. An electric vehicle may interface with the grid by establishing communication with the EVSE, receiving the EVSE attributes, and managing power flow between the EVE and the grid based on the EVSE attributes.
A Summary of the NASA Design Environment for Novel Vertical Lift Vehicles (DELIVER) Project
Theodore, Colin R.
2018-01-01
The number of new markets and use cases being developed for vertical take-off and landing vehicles continues to explode, including the highly publicized urban air taxi and package deliver applications. There is an equally exploding variety of novel vehicle configurations and sizes that are being proposed to fill these new market applications. The challenge for vehicle designers is that there is currently no easy and consistent way to go from a compelling mission or use case to a vehicle that is best configured and sized for the particular mission. This is because the availability of accurate and validated conceptual design tools for these novel types and sizes of vehicles have not kept pace with the new markets and vehicles themselves. The Design Environment for Novel Vertical Lift Vehicles (DELIVER) project was formulated to address this vehicle design challenge by demonstrating the use of current conceptual design tools, that have been used for decades to design and size conventional rotorcraft, applied to these novel vehicle types, configurations and sizes. In addition to demonstrating the applicability of current design and sizing tools to novel vehicle configurations and sizes, DELIVER also demonstrated the addition of key transformational technologies of noise, autonomy, and hybrid-electric and all-electric propulsion into the vehicle conceptual design process. Noise is key for community acceptance, autonomy and the need to operate autonomously are key for efficient, reliable and safe operations, and electrification of the propulsion system is a key enabler for these new vehicle types and sizes. This paper provides a summary of the DELIVER project and shows the applicability of current conceptual design and sizing tools novel vehicle configurations and sizes that are being proposed for urban air taxi and package delivery type applications.
Ion-Responsive Drug Delivery Systems.
Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro
2018-02-08
Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Peptide and low molecular weight proteins based kidney targeted drug delivery systems.
Xu, Pengfei; Zhang, Hailiang; Dang, Ruili; Jiang, Pei
2018-05-30
Renal disease is a worldwide public health problem, and unfortunately, the therapeutic index of regular drugs is limited. Thus, it is a great need to develop effective treatment strategies. Among the reported strategies, kidney-targeted drug delivery system is a promising method to increase renal efficacy and reduce extra-renal toxicity. In recent years, working as vehicles for targeted drug delivery, low molecular weight proteins (LMWP) and peptide have received immense attention due to their many advantages, such as selective accumulation in kidney, high drug loading capability, control over routes of biodegradation, convenience in modification at the amino terminus, and good biocompatibility. In this review, we describe the current LMWP and peptide carriers for kidney targeted drug delivery systems. In addition, we discuss different linking strategies between carriers and drugs. Furthermore, we briefly outline the current status and attempt to give an outlook on the further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Automated mixed traffic vehicle design AMTV 2
Johnston, A. R.; Marks, R. A.; Cassell, P. L.
1982-01-01
The design of an improved and enclosed Automated Mixed Traffic Transit (AMTT) vehicle is described. AMTT is an innovative concept for low-speed tram-type transit in which suitable vehicles are equipped with sensors and controls to permit them to operate in an automated mode on existing road or walkway surfaces. The vehicle chassis and body design are presented in terms of sketches and photographs. The functional design of the sensing and control system is presented, and modifications which could be made to the baseline design for improved performance, in particular to incorporate a 20-mph capability, are also discussed. The vehicle system is described at the block-diagram-level of detail. Specifications and parameter values are given where available.
Bi-Functionalized Clay Nanotubes for Anti-Cancer Therapy
Directory of Open Access Journals (Sweden)
William R. Grimes
2018-02-01
Full Text Available Systemic toxicity is an undesired consequence of the majority of chemotherapeutic drugs. Multifunctional nanoparticles with combined diagnostic and therapeutic functions show great promise towards personalized nanomedicine. Halloysite clay nanotubes (HNTs have shown potential as a drug delivery vehicle, and its surface can be modified and tailored as a targeted drug delivery system. In this short report, we modified the HNT surface by covalently bonding folic acid (FA and fluorescein isothiocyanate (FITC. The modification of HNTs with folic acid imparts the potential to target tumor cells selectively. The addition of FITC offers a method for quantifying the effectiveness of the FA tagged HNTs ability to target tumor cells. We documented cell uptake of our bi-functionalized HNT (bHNT through phase contrast and epi-fluorescent microscopy. bHNTs showed no signs of cytotoxicity up to a concentration of 150 µg/mL. The increase in cell death with increased bHNT concentration may be due to induced cytotoxicity resulting from intracellular bHNT accumulation that disrupts cellular function leading to cell death. With HNTs recognized as having the ability to serve as both a nanocontainer and nanocarrier, we envision our construct as a potential modular platform for potential use in cancer therapeutics. The HNT interior can be loaded with a variety of anti-cancer drugs (or other chemotherapeutics and serve as a “death cargo” designed to kill cancer cells while providing feedback imaging data on drug efficacy. The surface of the HNT can be modified with gold or silver nanoparticles and used in photothermal therapy by converting light to heat inside tumors. Our HNT-based drug delivery system has the potential to provide localized and targeted therapies that limit or reduce side effects, reduce patient costs and length of hospital stays, and improve quality of life. However, further research is needed to validate the potential of this new
Protamine-based nanoparticles as new antigen delivery systems.
González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia
2015-11-01
The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.
Cell and biomolecule delivery for regenerative medicine
Smith, Ian O; Ma, Peter X
2010-01-01
Regenerative medicine is an exciting field that aims to create regenerative alternatives to harvest tissues for transplantation. In this approach, the delivery of cells and biological molecules plays a central role. The scaffold (synthetic temporary extracellular matrix) delivers cells to the regenerative site and provides three-dimensional environments for the cells. To fulfil these functions, we design biodegradable polymer scaffolds with structural features on multiple size scales. To enhance positive cell–material interactions, we design nano-sized structural features in the scaffolds to mimic the natural extracellular matrix. We also integrate micro-sized pore networks to facilitate mass transport and neo tissue regeneration. We also design novel polymer devices and self-assembled nanospheres for biomolecule delivery to recapitulate key events in developmental and wound healing processes. Herein, we present recent work in biomedical polymer synthesis, novel processing techniques, surface engineering and biologic delivery. Examples of enhanced cellular/tissue function and regenerative outcomes of these approaches are discussed to demonstrate the excitement of the biomimetic scaffold design and biologic delivery in regenerative medicine. PMID:27877317
Nor, M. K. Mohd; Noordin, A.; Ruzali, M. F. S.; Hussen, M. H.; Mustapa@Othman, N.
2017-04-01
Simple Structural Surfaces (SSS) method is offered as a means of organizing the process for rationalizing the basic vehicle body structure load paths. The application of this simplified approach is highly beneficial in the development of modern passenger car structure design. In Malaysia, the SSS topic has been widely adopted and seems compulsory in various automotive programs related to automotive vehicle structures in many higher education institutions. However, there is no real physical model of SSS available to gain considerable insight and understanding into the function of each major subassembly in the whole vehicle structures. Based on this motivation, a real physical SSS of sedan model and the corresponding model vehicle tests of bending is proposed in this work. The proposed approach is relatively easy to understand as compared to Finite Element Method (FEM). The results prove that the proposed vehicle model test is useful to physically demonstrate the importance of providing continuous load path using the necessary structural components within the vehicle structures. It is clearly observed that the global bending stiffness reduce significantly when more panels are removed from the complete SSS model. The analysis shows the front parcel shelf is an important subassembly to sustain bending load.
[A transportation vehicle for laparoscopically obtained follicular specimens].
Fliess, F R; Sudik, R
1984-01-01
Structure, function and first results with a vehicle for transportation were described. This apparatus allows to store laparoscopic harvested follicular fluids for a while in constant temperature and in air condition with 5% CO2 in compressed air. Simultaneously the follicular fluids were transported in this vehicle from operating theatre to the laboratory.
Tang, Xinming; Liu, Xianyong; Yin, Guangwen; Suo, Jingxia; Tao, Geru; Zhang, Sixin; Suo, Xun
2018-01-01
Vaccine delivery is critical in antigen discovery and vaccine efficacy and safety. The diversity of infectious diseases in humans and livestock has required the development of varied delivery vehicles to target different pathogens. In livestock animals, previous strategies for the development of coccidiosis vaccines have encountered several hurdles, limiting the development of multiple species vaccine formulations. Here, we describe a novel vaccine delivery system using transgenic Eimeria tenella expressing immunodominant antigens of Eimeria maxima. In this delivery system, the immune mapped protein 1 of E. maxima (EmIMP1) was delivered by the closely related species of E. tenella to the host immune system during the whole endogenous life cycle. The overexpression of the exogenous antigen did not interfere with the reproduction and immunogenicity of transgenic Eimeria. After immunization with the transgenic parasite, we detected EmIMP1’s and E. maxima oocyst antigens’ specific humoral and cellular immune responses. In particular, we observed partial protection of chickens immunized with transgenic E. tenella against subsequent E. maxima infections. Our results demonstrate that the transgenic Eimeria parasite is an ideal coccidia antigen delivery vehicle and represents a new type of coccidiosis vaccines. In addition, this model could potentially be used in the development of malaria live sporozoite vaccines, in which antigens from different strains can be expressed in the vaccine strain. PMID:29375584
Tang, Xinming; Liu, Xianyong; Yin, Guangwen; Suo, Jingxia; Tao, Geru; Zhang, Sixin; Suo, Xun
2017-01-01
Vaccine delivery is critical in antigen discovery and vaccine efficacy and safety. The diversity of infectious diseases in humans and livestock has required the development of varied delivery vehicles to target different pathogens. In livestock animals, previous strategies for the development of coccidiosis vaccines have encountered several hurdles, limiting the development of multiple species vaccine formulations. Here, we describe a novel vaccine delivery system using transgenic Eimeria tenella expressing immunodominant antigens of Eimeria maxima . In this delivery system, the immune mapped protein 1 of E. maxima (EmIMP1) was delivered by the closely related species of E. tenella to the host immune system during the whole endogenous life cycle. The overexpression of the exogenous antigen did not interfere with the reproduction and immunogenicity of transgenic Eimeria . After immunization with the transgenic parasite, we detected EmIMP1's and E. maxima oocyst antigens' specific humoral and cellular immune responses. In particular, we observed partial protection of chickens immunized with transgenic E. tenella against subsequent E. maxima infections. Our results demonstrate that the transgenic Eimeria parasite is an ideal coccidia antigen delivery vehicle and represents a new type of coccidiosis vaccines. In addition, this model could potentially be used in the development of malaria live sporozoite vaccines, in which antigens from different strains can be expressed in the vaccine strain.
Dual delivery systems based on polyamine analog BENSpm as prodrug and gene delivery vectors
Zhu, Yu
Combination drug and gene therapy shows promise in cancer treatment. However, the success of such strategy requires careful selection of the therapeutic agents, as well as development of efficient delivery vectors. BENSpm (N 1, N11-bisethylnorspermine), a polyamine analogue targeting the intracellular polyamine pathway, draws our special attention because of the following reasons: (1) polyamine pathway is frequently dysregulated in cancer; (2) BENSpm exhibits multiple functions to interfere with the polyamine pathway, such as to up-regulate polyamine metabolism enzymes and down-regulate polyamine biosynthesis enzymes. Therefore BENSpm depletes all natural polyamines and leads to apoptosis and cell growth inhibition in a wide range of cancers; (3) preclinical studies proved that BENSpm can act synergistically with various chemotherapy agents, making it a promising candidate in combination therapy; (4) multiple positive charges in BENSpm enable it as a suitable building block for cationic polymers, which can be further applied to gene delivery. In this dissertation, our goal was to design dual-function delivery vector based on BENSpm that can function as a gene delivery vector and, after intracellular degradation, as an active anticancer agent targeting dysregulated polyamine metabolism. We first demonstrated strong synergism between BENSpm and a potential therapeutic gene product TRAIL. Strong synergism was obtained in both estrogen-dependent MCF-7 breast cancer cells and triple-negative MDA-MB-231 breast cancer cells. Significant dose reduction of TRAIL in combination with BENSpm in MDA-MB-231 cells, together with the fact that BENSpm rendered MCF-7 cells more sensitive to TRAIL treatment verified our rationale of designing BENSpm-based delivery platform. This was expected to be beneficial for overcoming drug resistance in chemotherapy, as well as boosting the therapeutic effect of therapeutic genes. We first designed a lipid-based BENSpm dual vector (Lipo
Energy Technology Data Exchange (ETDEWEB)
Kerschl, Stefan; Hipp, Eberhand; Doebereiner, Rolf [MAN Nutzfahrzeuge AG, Muenchen (Germany)
2009-07-01
In contrast to the passenger car the drive train of commercial vehicles is designed basically in view of a maximum efficiency, because the fuel consumption has a determining portion in the vehicle operating expenses of the operators. The pay load of the vehicle also has a high value, in particular in the small and middle segment from 8 t of total weight. In view of pollutant issues the environmental zones which may be also driven by commercial vehicles only from a certain pollutant class were already furnished by many local authority districts. Additional demands for a purely, emission free electric short distance operation can result from suitable emission editions in bigger towns in future. MAN Nutzfahrzeuge AG meet these topical challenges with the development of a hybriddelivery truck of the 12 t - class. At this the aim is to meet to the demands after low CO{sub 2} issue and purely electric operation by a powerful battery system and the recuperation of brake energy. For the integration of the hybrid components in the vehicle it was respected to preserve the pay load of the vehicle without limiting the functionality. The dimensioning of the hybrid drive train for a delivery truck vehicle, the vehicle integration and the effects on the lifecycle economics are lighted up in the following. (orig.)
Elastic liposomes as novel carriers: recent advances in drug delivery
Directory of Open Access Journals (Sweden)
Hussain A
2017-07-01
Full Text Available Afzal Hussain,1,2 Sima Singh,1 Dinesh Sharma,3 Thomas J Webster,4 Kausar Shafaat,2 Abdul Faruk5 1Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India; 2Faculty of Pharmacy, Sachchidananda Sinha College, Aurangabad, Bihar, India; 3Zifam Pyrex Myanmar Co. Ltd., Yangon, Myanmar; 4Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 5Department of Pharmaceutical Sciences, Hemwati Nandan Bahuguna Garhwal University, Srinagar, Uttarakhand, India Abstract: Elastic liposomes (EL are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. Keywords: elastic liposomes, drug delivery, topical, transdermal, enhanced delivery
International Nuclear Information System (INIS)
Kaplan, E.
1985-01-01
Krypton-81m supplied from a generator by continuous elution with air is used with a gamma-camera computer system to produce a sequence of images from multiple breaths, which reconstructed the time-activity images of the breathing human lung. Functional images are produced by subsequent derivation to show specific variables of the dynamic sequences. The dynamic, quantitative, and regional aspects of the respiratory cycle are thus made available in a single study. The need for the delivery of a constant ratio of /sub 81m/Kr to air is required to accurately produce these various studies