The translation of cell-based therapies:clinical landscape and manufacturing challenges

Cell-based therapies have the potential to make a large contribution toward currently unmet patient need and thus effective manufacture of these products is essential. Many challenges must be overcome before this can become a reality and a better definition of the manufacturing requirements for cell-based products must be obtained. The aim of this study is to inform industry and academia of current cell-based therapy clinical development and to identify gaps in their manufacturing requirements. A total of 1342 active cell-based therapy clinical trials have been identified and characterized based on cell type, target indication and trial phase. Multiple technologies have been assessed for the manufacture of these cell types in order to facilitate product translation and future process development.

Clogging in subsurface-flow treatment wetlands:measurement, modeling and management

This paper reviews the state of the art in measuring, modeling, and managing clogging in subsurface-flow treatment wetlands. Methods for measuring in situ hydraulic conductivity in treatment wetlands are now available, which provide valuable insight into assessing and evaluating the extent of clogging. These results, paired with the information from more traditional approaches (e.g., tracer testing and composition of the clog matter) are being incorporated into the latest treatment wetland models. Recent finite element analysis models can now simulate clogging development in subsurface-flow treatment wetlands with reasonable accuracy. Various management strategies have been developed to extend the life of clogged treatment wetlands, including gravel excavation and/or washing, chemical treatment, and application of earthworms. These strategies are compared and available cost information is reported. © 2012 Elsevier Ltd.

The East-Central European new donors:mapping capacity building and remaining challenges

In the past decade, the East-Central European countries were provided significant external capacity building assistance to help their emergence as donors of foreign aid. This paper aims to map these capacity development programmes and identify where they have helped and what challenges remain for the new donors. The main conclusion is that although capacity building has been instrumental in building organisational structures, working procedures and training staff, deeper underlying problems such as low levels of financing, lacking political will, the need for visibility and low staff numbers continue to hinder the new international development policies. Copyright © 2013 John Wiley & Sons, Ltd.

On modeling and satisfaction of non-functional requirements using cloud computing

Specification of the non-functional requirements of applications and determining the required resources for their execution are activities that demand a great deal of technical knowledge, frequently resulting in an inefficient use of resources. Cloud computing is an alternative for provisioning of resources, which can be done using either the provider's own infrastructure or the infrastructure of one or more public clouds, or even a combination of both. It enables more flexibly/elastic use of resources, but does not solve the specification problem. In this paper we present an approach that uses models at runtime to facilitate the specification of non-functional requirements and resources, aiming to facilitate dynamic support for application execution in cloud computing environments with shared resources. © 2013 IEEE.

Human brain slices for epilepsy research:pitfalls, solutions and future challenges

Increasingly, neuroscientists are taking the opportunity to use live human tissue obtained from elective neurosurgical procedures for electrophysiological studies in vitro. Access to this valuable resource permits unique studies into the network dynamics that contribute to the generation of pathological electrical activity in the human epileptic brain. Whilst this approach has provided insights into the mechanistic features of electrophysiological patterns associated with human epilepsy, it is not without technical and methodological challenges. This review outlines the main difficulties associated with working with epileptic human brain slices from the point of collection, through the stages of preparation, storage and recording. Moreover, it outlines the limitations, in terms of the nature of epileptic activity that can be observed in such tissue, in particular, the rarity of spontaneous ictal discharges, we discuss manipulations that can be utilised to induce such activity. In addition to discussing conventional electrophysiological techniques that are routinely employed in epileptic human brain slices, we review how imaging and multielectrode array recordings could provide novel insights into the network dynamics of human epileptogenesis. Acute studies in human brain slices are ultimately limited by the lifetime of the tissue so overcoming this issue provides increased opportunity for information gain. We review the literature with respect to organotypic culture techniques that may hold the key to prolonging the viability of this material. A combination of long-term culture techniques, viral transduction approaches and electrophysiology in human brain slices promotes the possibility of large scale monitoring and manipulation of neuronal activity in epileptic microcircuits.

Guest editors’ introduction: is the HRM process important? Past, current, and future challenges

Ten years ago, Bowen and Ostroff (2004) criticized the one-sided focus on the content-based approach, where researchers take into account the inherent virtues (or vices) associated with the content of HR practices to explain performance. They explicitly highlight the role of the psychological processes through which employees attach meaning to HRM. In this first article of the special section entitled “Is the HRM Process Important?” we present an overview of past, current, and future challenges. For past challenges, we attempt to categorize the various research streams that originated from the seminal piece. To outline current challenges, we present the results of a content analysis of the original 15 articles put forward for the special section. In addition, we provide the overview of a caucus focused on this theme that was held at the Academy of Management annual meeting in Boston in 2012. In conclusion, we discuss future challenges relating to the HRM process approach and review the contributions that have been selected—against a competitive field—for this special issue

Theoretical modeling and experimental validation of fluid-loaded micro rectangular plates

This paper presents a theoretical model on the vibration analysis of micro scale fluid-loaded rectangular isotropic plates, based on the Lamb's assumption of fluid-structure interaction and the Rayleigh-Ritz energy method. An analytical solution for this model is proposed, which can be applied to most cases of boundary conditions. The dynamical experimental data of a series of microfabricated silicon plates are obtained using a base-excitation dynamic testing facility. The natural frequencies and mode shapes in the experimental results are in good agreement with the theoretical simulations for the lower order modes. The presented theoretical and experimental investigations on the vibration characteristics of the micro scale plates are of particular interest in the design of microplate based biosensing devices. Copyright © 2009 by ASME.

Planar solid oxide fuel cell modeling and optimization targeting the stack's temperature gradient minimization

Minimization of undesirable temperature gradients in all dimensions of a planar solid oxide fuel cell (SOFC) is central to the thermal management and commercialization of this electrochemical reactor. This article explores the effective operating variables on the temperature gradient in a multilayer SOFC stack and presents a trade-off optimization. Three promising approaches are numerically tested via a model-based sensitivity analysis. The numerically efficient thermo-chemical model that had already been developed by the authors for the cell scale investigations (Tang et al. Chem. Eng. J. 2016, 290, 252-262) is integrated and extended in this work to allow further thermal studies at commercial scales. Initially, the most common approach for the minimization of stack's thermal inhomogeneity, i.e., usage of the excess air, is critically assessed. Subsequently, the adjustment of inlet gas temperatures is introduced as a complementary methodology to reduce the efficiency loss due to application of excess air. As another practical approach, regulation of the oxygen fraction in the cathode coolant stream is examined from both technical and economic viewpoints. Finally, a multiobjective optimization calculation is conducted to find an operating condition in which stack's efficiency and temperature gradient are maximum and minimum, respectively.

Acumen : an open-source testbed for cyber-physical systems research

Developing Cyber-Physical Systems requires methods and tools to support simulation and verification of hybrid (both continuous and discrete) models. The Acumen modeling and simulation language is an open source testbed for exploring the design space of what rigorousbut- practical next-generation tools can deliver to developers of Cyber- Physical Systems. Like verification tools, a design goal for Acumen is to provide rigorous results. Like simulation tools, it aims to be intuitive, practical, and scalable. However, it is far from evident whether these two goals can be achieved simultaneously. This paper explains the primary design goals for Acumen, the core challenges that must be addressed in order to achieve these goals, the “agile research method” taken by the project, the steps taken to realize these goals, the key lessons learned, and the emerging language design.

Optimizing rate algorithms in wireless networks

Since wireless network optimisations can be typically designed and evaluated independently of one another under the assumption that they can be applied jointly or independently. In this paper, we have analysis some rate algorithms in wireless networks. Since wireless networks have different standards in IEEE with peculiar features, data rate is one of those important parameters that wireless networks depend on for performances. The optimisation of this network is dependent on the behaviour of a particular rate algorithm in a network scenario. We have considered some first and second generation's rate algorithm, and it is all about selecting an appropriate data rate that any available wireless network can utilise for transmission in order to achieve a good performance. We have designed and analysis a wireless network and results obtained for some rate algorithms, like ONOE and AARF.

Pattern competition in volumetricaly heated fluids

Finite element simulations have been performed along side Galerkin-type calculations that examined the development of volumetrically heated flow patterns in a horizontal layer controlled by the Prandtl number, Pr, and the Grashof number, Gr. The fluid was bounded by an isothermal plane above an adiabatic plane. In the simulations performed here, a number of convective polygonal planforms occurred, as Gr increased above the critical Grashof number, Grc at Pr = 7, while roll structures were observed for Pr < 1 at 2Grc.

Multiscale modelling:approaches and challenges

Multiscale systems that are characterized by a great range of spatial–temporal scales arise widely in many scientific domains. These range from the study of protein conformational dynamics to multiphase processes in, for example, granular media or haemodynamics, and from nuclear reactor physics to astrophysics. Despite the diversity in subject areas and terminology, there are many common challenges in multiscale modelling, including validation and design of tools for programming and executing multiscale simulations. This Theme Issue seeks to establish common frameworks for theoretical modelling, computing and validation, and to help practical applications to benefit from the modelling results. This Theme Issue has been inspired by discussions held during two recent workshops in 2013: ‘Multiscale modelling and simulation’ at the Lorentz Center, Leiden (http://www.lorentzcenter.nl/lc/web/2013/569/info.php3?wsid=569&venue=Snellius), and ‘Multiscale systems: linking quantum chemistry, molecular dynamics and microfluidic hydrodynamics’ at the Royal Society Kavli Centre. The objective of both meetings was to identify common approaches for dealing with multiscale problems across different applications in fluid and soft matter systems. This was achieved by bringing together experts from several diverse communities.