Control of action potential duration alternans in canine cardiac ventricular tissue

Cardiac electrical alternans, characterized by a beat-to-beat alternation in action potential waveform, is a naturally occurring phenomenon, which can occur at sufficiently fast pacing rates. Its presence has been putatively linked to the onset of cardiac reentry, which is a precursor to ventricular fibrillation. Previous studies have shown that closed-loop alternans control techniques that apply a succession of externally administered cycle perturbations at a single site provide limited spatially-extended alternans elimination in sufficiently large cardiac substrates. However, detailed experimental investigations into the spatial dynamics of alternans control have been restricted to Purkinje fiber studies. A complete understanding of alternans control in the more clinically relevant ventricular tissue is needed. In this paper, we study the spatial dynamics of alternans and alternans control in arterially perfused canine right ventricular preparations using an optical mapping system capable of high-resolution fluorescence imaging. Specifically, we quantify the spatial efficacy of alternans control along 2.5 cm of tissue, focusing on differences in spatial control between different subregions of tissue. We demonstrate effective control of spatially-extended alternans up to 2.0 cm, with control efficacy attenuating as a function of distance. Our results provide a basis for future investigations into electrode-based control interventions of alternans in cardiac tissue.     

Conjugate heat transfer of laminar mixed convection of a nanofluid through an inclined tube with circumferentially non-uniform heating

Laminar mixed convection of a nanofluid consisting of water and Al₂O₃ in an inclined tube with heating at the top half surface of a copper tube has been studied numerically. The bottom half of the tube wall is assumed to be adiabatic (presenting a tube of a solar collector). Heat conduction mechanism through the tube wall is considered. Three-dimensional governing equations with using two-phase mixture model have been solved to investigate hydrodynamic and thermal behaviours of the nanofluid over wide range of nanoparticle volume fractions. For a given nanoparticle mean diameter the effects of nanoparticle volume fractions on the hydrodynamics and thermal parameters are presented and discussed at different Richardson numbers and different tube inclinations. Significant augmentation on the heat transfer coefficient as well as on the wall shear stress is seen.     

Synthetic single-framework antibody library integrated with rapid affinity maturation by VL shuffling

Affinity maturation is often applied to improve the properties of antibodies isolated from universal antibody libraries in vitro. A synthetic human scFv antibody library was constructed in single immunoglobulin framework to enable rapid affinity maturation by updated Kunkel's mutagenesis. The initial diversity was generated predominantly in the V(H) domain combined with only 36 V(L) domain variants yielding 3 × 10(10) unique members in the phage-displayed library. After three rounds of panning the enriched V(H) genes from the primary library selections against lysozyme were incorporated into a ready-made circular single-stranded affinity maturation library containing 7 × 10(8) V(L) gene variants. Several unique antibodies with 0.8-10 nM (K(d), dissociation constant) affinities against lysozyme were found after panning from the affinity maturation library, contrasted by only one anti-lysozyme scFv clone with K(d) <20 nM among the clones panned from the primary universal library. The presented single-framework strategy provides a way to convey significant amount of functional V(H) domain diversity to affinity maturation without bimolecular ligation leading to a diverse set of antibodies with binding affinities in the low nanomolar range.     

An ultra-low-voltage ultra-low-power CMOS active mixer

The scaling of CMOS technology has greatly influenced the design of analog and radio-frequency circuits. In particular, as technology advances, due to the use of lower supply voltage the available voltage headroom is decreased. In this paper, after a brief overview of conventional low-power CMOS active mixer structures, we introduce an active mixer structure with sub-mW-level power consumption that is capable of operating from a supply voltage comparable or lower than the threshold voltage of the transistor. In addition, the proposed architecture provides a performance and conversion gain (CG) that compares favorably or exceeds those of the state-of-the-art designs. As a proof-of-concept, a wide-band DC to 8.5 GHz down-conversion mixer is designed and fabricated in a 90-nm CMOS process. Measurement results show that the mixer achieves a CG as high as 18 dB while consuming 98 μW from a 0.3-V supply.     

Transition from open-pit to underground as a new optimization challenge in mining engineering

There are many deposits that have the potential to be mined by a combined method of open-pit and underground. In this manner, the most sensitive problem is the determination of the optimal transition depth from open-pit to underground or vice versa. To calculate this depth, a model based on block economic values of open-pit and underground methods together with the Net Present Value (NPV) attained through mining is first presented. During the model, NPV of open-pit is compared to the value of underground for the similar levels. A hypothetical example is used in order to analyze the model in detail. Based on the assumptions made such as: a discount rate of 15 %, each pair of contiguous level-cuts have to mine during one year, and one level as the height of crown pillar, the optimal transition depth was determined to be equal to 62.5 m. Then, level 6 was considered as the suitable crown pillar. Finally, maximum total NPV of the combined mining was calculated to be 25.54 units of currency.     

Concurrent engineering: A compromising approach to develop a feasible and customer-pleasing product

To develop a customer-pleasing and economically and technically feasible product, it is necessary to utilize the best possible knowledge of the market, the customers, the core product technology, and the cost implications of design alternatives. It requires the concurrent involvement of team members from merchandizing, product development, and purchasing and production-engineering departments of the enterprise. The merchandizing department identifies customer needs however, considering only customers’ requirements, without technical information it is not possible to develop a feasible product. Conversely, the function-oriented designers in the product development department determine the subsystems’ weight, which are technically feasible but may ignore the qualitative issues desired by the customers. To identify the economic feasibility of the product, the purchasing and production-engineering departments calculate the estimated cost by evaluating the cost implications of the design alternatives. Therefore, to produce an economically and technically feasible product with customer pleasing quality, a trade-off among these three sets of weights is essential. Here, we propose an optimization model that assimilates three sets of weights of the subsystems to a final one. The resultant set of weights will represent the effects of concurrent cooperation among merchandizing, product development, purchasing and production-engineering departments of the enterprise.     

An assessment of the ability of computational fluid dynamic models to predict reactive gas–solid flows in a fluidized bed

Fine grid, two dimensional simulations of reactive gas–solid flows occurring in a fluidized bed reactor were carried out using the Eulerian multi-fluid kinetic theory of granular flow (KTGF) approach in the commercial flow solver, ANSYS FLUENT 12.1. The fuel reactor of a pilot scale Chemical Looping Combustion rig, operated in the bubbling fluidization regime at the Vienna University of Technology, was simulated. Grid dependence studies were carried out as well as sensitivity studies to the fuel inlet condition and the inclusion of gas phase turbulence. Simulations could not accurately reproduce the experimental trend for the case when highly reactive nickel oxide was used as the oxygen carrier material, but in general satisfactory quantitative agreement was observed. The failure to correctly capture the experimental trend was primarily attributed to the fine length-scales at the feed gas inlets not being adequately resolved even at the finest grid investigated. The trend quickly worsened when coarser grids were used, indicating that the generality of the model is lost when grid dependence effects are present. A number of possible dimensional effects were also discussed. Subsequently, the model was used to successfully capture another experimental trend obtained with a much less reactive ilmenite oxygen carrier material. The model captured this trend correctly because the reaction was now limited by the reaction rate and not by species transfer to the large scale gas-emulsion interfaces. Results were therefore not as sensitive to the correct hydrodynamic modelling of the interface, especially near the gas inlets, and the model retained its generality over a wide range of operating conditions.     

Modelling quality dynamics,business value and firm performance in a big data analytics environment

Big data analytics have become an increasingly important component for firms across advanced economies. This paper examines the quality dynamics in big data environment that are linked with enhancing business value and firm performance (FPER). The study identifies that system quality (i.e. system reliability, accessibility, adaptability, integration, response time and privacy) and information quality (i.e. completeness, accuracy, format and currency) are key to enhance business value and FPER in a big data environment. The study also proposes that the relationship between quality and FPER is mediated by business value of big data. Drawing on the resource-based theory and the information systems success literature, this study extends knowledge in this domain by linking system quality, information quality, business value and FPER.     

Biological Functions and Current Advances in Isolation and Detection Strategies for Exosome Nanovesicles

Exosomes are nanoscale (≈30–150 nm) extracellular vesicles of endocytic origin that are shed by most types of cells and circulate in bodily fluids. Exosomes carry a specific composition of proteins, lipids, RNA, and DNA and can work as cargo to transfer this information to recipient cells. Recent studies on exosomes have shown that they play an important role in various biological processes, such as intercellular signaling, coagulation, inflammation, and cellular homeostasis. These functional roles are attributed to their ability to transfer RNA, proteins, enzymes, and lipids, thereby affecting the physiological and pathological conditions in various diseases, including cancer and neurodegenerative, infectious, and autoimmune diseases (e.g., cancer initiation, progression, and metastasis). Due to these unique characteristics, exosomes are considered promising biomarkers for the diagnosis and prognosis of various diseases via noninvasive or minimally invasive procedures. Over the last decade, a plethora of methodologies have been developed for analyzing disease‐specific exosomes using optical and nonoptical tools. Here, the major biological functions, significance, and potential role of exosomes as biomarkers and therapeutics are discussed. Furthermore, an overview of the most commonly used techniques for exosome analysis, highlighting the major technical challenges and limitations of existing techniques, is presented.