Cytopathological Outcomes of Knocking down Expression of Mitochondrial Complex II Subunits in Dictyostelium discoideum

Mitochondrial Complex II is composed of four core subunits and mutations to any of the subunits result in lowered Complex II activity. Surprisingly, although mutations in any of the subunits can yield similar clinical outcomes, there are distinct differences in the patterns of clinical disease most commonly associated with mutations in different subunits. Thus, mutations to the SdhA subunit most often result in mitochondrial disease phenotypes, whilst mutations to the other subunits SdhB-D more commonly result in tumour formation. The reason the clinical outcomes are so different is unknown. Here, we individually antisense-inhibited three of the Complex II subunits, SdhA, SdhB or SdhC, in the simple model organism Dictyostelium discoideum. Whilst SdhB and SdhC knockdown resulted in growth defects on bacterial lawns, antisense inhibition of SdhA expression resulted in a different pattern of phenotypic defects, including impairments of growth in liquid medium, enhanced intracellular proliferation of the bacterial pathogen Legionella pneumophila and phagocytosis. Knockdown of the individual subunits also produced different abnormalities in mitochondrial function with only SdhA knockdown resulting in broad mitochondrial dysfunction. Furthermore, these defects were shown to be mediated by the chronic activation of the cellular energy sensor AMP-activated protein kinase. Our results are in agreement with a role for loss of function of SdhA but not the other Complex II subunits in impairing mitochondrial oxidative phosphorylation and they suggest a role for AMP-activated protein kinase in mediating the cytopathological outcomes.     

Strategic alignment and value maximization for IT project portfolios

Managing project portfolios has been a challenge to many IT organizations due to the size and complexity of their initiatives that are often cross-functional, fast changing, and transformational in nature. A governance process on project solicitation, evaluation, and monitoring is thus essential to ensure the resulting portfolio creates tangible values, balances across priorities, and supports business objectives. An optimization model to streamline the decision processes for IT portfolios and programs is proposed. We consider project characteristics such as the extent of strategic alignment, expected benefit, development cost, and cross-project synergy to maximize the portfolio value. We also consider team proficiency and resource availability to determine a project portfolio that could be implemented within the overall development time. The multi-objective model identifies the optimal mix among project types and the solution procedure efficiently produces recommendations that are superior to those found with current empirical techniques. We also describe an evolutionary algorithm to find approximate solutions to the optimization model. Possible extensions on how the optimization procedure can go beyond projects to also streamline decisions such as the renewal or replacement of in-flight applications is discussed.     

Book review

Informatics for Development: The New Challenge Khadija Haq (Editor) The North‐South Round Table, PO Box 2006, Islamabad, Pakistan     

Adapting ADtrees for improved performance on large datasets with high-arity features

The ADtree, a data structure useful for caching sufficient statistics, has been successfully adapted to grow lazily when memory is limited and to update sequentially with an incrementally updated dataset. However, even these modified forms of the ADtree still exhibit inefficiencies in terms of both space usage and query time, particularly on datasets with very high dimensionality and with high-arity features. We propose four modifications to the ADtree, each of which can be used to improve size and query time under specific types of datasets and features. These modifications also provide an increased ability to precisely control how an ADtree is built and to tune its size given external memory or speed requirements.     

A low-noise front-end for multiplexed ENG recording using CMOS technology

Multi-electrode cuffs have been proposed as a means for the parallel recording of naturally-occurring neural signals. Compared to a conventional tripole cuff providing a single channel signal, additional information about the velocity and direction of nerve signals can be extracted from the multi-electrode recordings. Moreover, interference suppression is improved and overall power consumption reduced, as the analysis shows. In this paper a new recording system is proposed, each channel of which consists of a low-noise preamplifier employing lateral bipolar transistors to provide an impedance match to the tissue and a path to ground for the switching currents of a single high-gain amplifier, which is multiplexed between the channels. The proposed system provides low-noise, low-power operation and practically identical channel gains and is suitable for integration in a larger CMOS-based system.     

On the reliability of electrostatic NEMS/MEMS devices: Review of present knowledge on the dielectric charging and stiction failure mechanisms and novel characterization methodologies

This paper reviews the state of the art knowledge related to critical failure mechanisms in electrostatic micro- and nano-electromechanical systems (MEMS and NEMS) which are the dielectric charging and stiction. It describes also the recent employed nanoscale characterization techniques for these phenomena based on Kelvin probe force microscopy (KPFM) and force–distance curve measurements. The influence of relative humidity and dielectric deposition conditions on the charging/discharging processes is discussed. Moreover, different stiction mechanisms induced by electrostatic force and/or meniscus formation are analyzed. Finally, novel characterization methods are presented and used to correlate between the results from MEMS devices and metal–insulator–metal (MIM) capacitors. These methods are employed in view of application in electrostatic capacitive MEMS switches and could be easily extended to explore other NEMS/MEMS devices. The study provides an accurate understanding of the charging and stiction related failure mechanisms, presents guidelines for a proper packaging environment, and reveals precise explanations for the literature reported device level measurements of electrostatic MEMS devices.     

Contrast-based evaluation of mar resistance of thermoplastic olefins

The physical aspect of mar behavior is studied by applying a standardized progressive sliding load methodology to smooth and textured automotive-grade thermoplastic olefins. It is shown that surface texture has a strong effect on light scattering and, hence, the propensity for mar visibility. It is also shown that digital imaging via a desktop scanner can be used to quantitatively and objectively assess mar resistance using contrast as a basis. Incorporation of slip agent definitively improves the mar resistance for both types of surfaces. Relationships between contrast, gloss and surface roughness in relation to mar visibility are discussed.     

Exact solutions to the modified 2D Burgers vortex equation: a general result for the unsteady case

Exact solutions to the unsteady modified 2D Burgers vortex equation are obtained for arbitrary forms of the flow parameter γ(t) via Fourier analysis. The result extends the available literature, where only very specific forms of the flow parameter γ(t) have been considered in the unsteady flow cases. One strength of the method is that we need not assume separable solutions.