Interactions and turnover of the muscular dystrophy protein myotilin

The striated muscle sarcomere is a force generating and transducing unit as well as an important sensor of extracellular cues and a coordinator of cellular signals. The borders of individual sarcomeres are formed by the Z-disks. The Z-disk component myotilin interacts with Z-disk core structural proteins and with regulators of signaling cascades. Missense mutations in the gene encoding myotilin cause dominantly inherited muscle disorders, myotilinopathies, by an unknown mechanism. In this thesis the functions of myotilin were further characterized to clarify the molecular biological basis and the pathogenetic mechanisms of inherited muscle disorders, mainly caused by mutated myotilin. Myotilin has an important function in the assembly and maintenance of the Z-disks probably through its actin-organizing properties. Our results show that the Ig-domains of myotilin are needed for both binding and bundling actin and define the Ig domains as actin-binding modules. The disease-causing mutations appear not to change the interplay between actin and myotilin. Interactions between Z-disk proteins regulate muscle functions and disruption of these interactions results in muscle disorders. Mutations in Z-disk components myotilin, ZASP/Cypher and FATZ-2 (calsarcin-1/myozenin-2) are associated with myopathies. We showed that proteins from the myotilin and FATZ families interact via a novel and unique type of class III PDZ binding motif with the PDZ domains of ZASP and other Enigma family members and that the interactions can be modulated by phosphorylation. The morphological findings typical of myotilinopathies include Z-disk alterations and aggregation of dense filamentous material. The causes and mechanisms of protein aggregation in myotilinopathy patients are unknown, but impaired degradation might explain in part the abnormal protein accumulation. We showed that myotilin is degraded by the calcium-dependent, non-lysosomal cysteine protease calpain and by the proteasome pathway, and that wild type and mutant myotilin differ in their sensitivity to degradation. These studies identify the first functional difference between mutated and wild type myotilin. Furthermore, if degradation of myotilin is disturbed, it accumulates in cells in a manner resembling that seen in myotilinopathy patients. Based on the results, we propose a model where mutant myotilin escapes proteolytic breakdown and forms protein aggregates, leading to disruption of myofibrils and muscular dystrophy. In conclusion, the main results of this study demonstrate that myotilin is a Z-disk structural protein interacting with several Z-disk components. The turnover of myotilin is regulated by calpain and the ubiquitin proteasome system and mutations in myotilin seem to affect the degradation of myotilin, leading to protein accumulations in cells. These findings are important for understanding myotilin-linked muscle diseases and designing treatments for these disorders.

High-temperature heat capacity and heat content of CaCu3Ti4O12 (CCTO)

The isobaric heat capacity of CaCu3Ti4O12 (CCTO) was measured from 300 to 1100 K using differential scanning calorimetry (DSC). The results were verified using drop calorimetric measurement of enthalpy increment (H-T - H-298.15) at T= 973 and 1073 K. The samples were dropped from room temperature into a calorimeter maintained at high temperature. The results show small negative deviation from Neumann-Kopp rule. The enthalpy and entropy increments are computed as a function of temperature and compared with values available in the literature. The results obtained in this study are consistent with available information on enthalpy and Gibbs energy of formation of CCTO.

Bismuth sulfide: A high-capacity anode for sodium-ion batteries

Exploring high-performance anode materials is currently one of the most urgent issues towards practical sodium-ion batteries (SIBs). In this work, Bi2S3 is demonstrated to be a high-capacity anode for SIBs for the first time. The specific capacity of Bi2S3 nanorods achieves up to 658 and 264 mAh g-1 at a current density of 100 and 2000 mA g-1, respectively. A full cell with Na3V2(PO4)3-based cathode is also assembled as a proof of concept and delivers 340 mAh g-1 at 100 mA g-1. The sodium storage mechanism of Bi2S3 is investigated by ex-situ XRD coupled with high-resolution TEM (HRTEM), and it is found that sodium storage is achieved by a combined conversion-intercalation mechanism.

3D Fe2(MoO4)3 microspheres with nanosheet constituents as high-capacity anode materials for lithium-ion batteries

Three-dimensional (3D) Fe2(MoO4)3 microspheres with ultrathin nanosheet constituents are first synthesized as anode materials for the lithium-ion battery. It is interesting that the single-crystalline nanosheets allow rapid electron/ion transport on the inside, and the high porosity ensures fast diffusion of liquid electrolyte in energy storage applications. The electrochemical properties of Fe2(MoO4)3 as anode demonstrates that 3D Fe2(MoO4)3 microspheres deliver an initial capacity of 1855 mAh/g at a current density of 100 mA/g. Particularly, when the current density is increased to 800 mA/g, the reversible capacity of Fe2(MoO4)3 anode still arrived at 456 mAh/g over 50 cycles. The large and reversible capacities and stable charge–discharge cycling performance indicate that Fe2(MoO4)3 is a promising anode material for lithium battery applications. Graphical abstract The electrochemical properties of Fe2(MoO4)3 as anode demonstrates that 3D Fe2(MoO4)3 microspheres delivered an initial capacity of 1855 mAh/g at a current density of 100 mA/g. When the current density was increased to 800 mA/g, the Fe2(MoO4)3 still behaved high reversible capacity and good cycle performance.

Enhanced adsorption capacity of activated alumina by impregnation with alum for removal of As(V) from water

Alum-impregnated activated alumina (AIAA) was investigated in the present work as an adsorbent for the removal of As(V) from water by batch mode. Adsorption study at different pH values shows that the efficiency of AIAA is much higher than as such activated alumina and is suitable for treatment of drinking water. The adsorption isotherm experiments indicated that the uptake of As(V) increased with increasing As(V) concentration from 1 to 25 mg/l and followed Langmuir-type adsorption isotherm. Speciation diagram shows that in the pH range of 2.8–11.5, arsenate predominantly exists as H2AsO4− and HAsO42− species and hence it is presumed that these are the major species being adsorbed on the surface of AIAA. Intraparticle diffusion and kinetic studies revealed that adsorption of As(V) was due to physical adsorption as well as through intraparticle diffusion. Effect of interfering ions revealed that As(V) sorption is strongly influenced by the presence of phosphate ion. The presence of arsenic on AIAA is depicted from zeta potential measurement, scanning electron microscopy (SEM) and energy-dispersive analysis of X-ray (EDAX) mapping study. Alum-impregnated activated alumina successfully removed As(V) to below 40 ppb (within the permissible limit set by WHO) from water, when the initial concentration of As(V) is 10 mg/l.

Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells

Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.

Analytical models for capacity estimation of IEEE 802.11 WLANs using DCF for internet applications

We provide analytical models for capacity evaluation of an infrastructure IEEE 802.11 based network carrying TCP controlled file downloads or full-duplex packet telephone calls. In each case the analytical models utilize the attempt probabilities from a well known fixed-point based saturation analysis. For TCP controlled file downloads, following Bruno et al. (In Networking '04, LNCS 2042, pp. 626-637), we model the number of wireless stations (STAs) with ACKs as a Markov renewal process embedded at packet success instants. In our work, analysis of the evolution between the embedded instants is done by using saturation analysis to provide state dependent attempt probabilities. We show that in spite of its simplicity, our model works well, by comparing various simulated quantities, such as collision probability, with values predicted from our model. Next we consider N constant bit rate VoIP calls terminating at N STAs. We model the number of STAs that have an up-link voice packet as a Markov renewal process embedded at so called channel slot boundaries. Analysis of the evolution over a channel slot is done using saturation analysis as before. We find that again the AP is the bottleneck, and the system can support (in the sense of a bound on the probability of delay exceeding a given value) a number of calls less than that at which the arrival rate into the AP exceeds the average service rate applied to the AP. Finally, we extend the analytical model for VoIP calls to determine the call capacity of an 802.11b WLAN in a situation where VoIP calls originate from two different types of coders. We consider N-1 calls originating from Type 1 codecs and N-2 calls originating from Type 2 codecs. For G711 and G729 voice coders, we show that the analytical model again provides accurate results in comparison with simulations.

Water management capacity building to support rapidly developing mining economies

Many developing countries are experiencing rapid expansion in mining with associated water impacts. In most cases mining expansion is outpacing the building of national capacity to ensure that sustainable water management practices are implemented. Since 2011, Australia's International Mining for Development Centre (IM4DC) has funded capacity building in such countries including a program of water projects. Five projects in particular (principally covering experiences from Peru, Colombia, Ghana, Zambia, Indonesia, Philippines and Mongolia) have provided insight into water capacity building priorities and opportunities. This paper reviews the challenges faced by water stakeholders, and proposes the associated capacity needs. The paper uses the evidence derived from the IM4DC projects to develop a set of specific capacity-building recommendations. Recommendations include: the incorporation of mine water management in engineering and environmental undergraduate courses; secondments of staff to suitable partner organisations; training to allow site staff to effectively monitor water including community impacts; leadership training to support a water stewardship culture; training of officials to support implementation of catchment management approaches; and the empowerment of communities to recognise and negotiate solutions to mine-related risks. New initiatives to fund the transfer of multi-disciplinary knowledge from nations with well-developed water management practices are called for.

Correlation of structural disorder with the reversible discharge capacity of nickel hydroxide electrode

Hydrothermal treatment of a slurry of badly crystalline (beta(bc)) nickel hydroxide at different temperatures (65-170 degrees C) results in the progressive ordering of the structure by the step-wise elimination of disorders. Interstratification is eliminated at 140 degrees C, while cation vacancies are eliminated at 170 degrees C. A small percentage of stacking faults continue to persist even in `crystalline' samples. Electrochemical investigations show that the crystalline nickel hydroxide has a very low (0.4 e/Ni) reversible charge storage capacity. An incidence of at least 15% stacking faults combined with cation vacancies is essential for nickel hydroxide to perform close to its theoretical (1 e/ Ni) discharge capacity. (c) 2005 The Electrochemical Society.

Global and EU governance for sustainable forest management with special reference to capacity building in Ethiopia and Southern Sudan

The purpose of this study was to produce information on and practical recommendations for informed decision-making on and capacity building for sustainable forest management (SFM) and good forest governance. This was done within the overall global framework for sustainable development with special emphasis on the EU and African frameworks and on Southern Sudan and Ethiopia in particular. The case studies on Southern Sudan and Ethiopia focused on local, national and regional issues. Moreover, this study attempted to provide both theoretical and practical new insight. The aim was to build an overall theoretical framework and to study its key contents and main implications for SFM and good forest governance at all administration levels, for providing new tools for capacity building in natural resources management. The theoretical framework and research approach were based on the original research problem and the general and specific aims of the study. The key elements of the framework encompass sustainable development, global and EU governance, sustainable forest management (SFM), good forest governance, as well as international and EU law. The selected research approach comprised matrix-based assessment of international, regional (EU and Africa) and national (Southern Sudan and Ethiopia) policy and legal documents. The specific case study on Southern Sudan also involved interviews and group discussions with local community members and government officials. As a whole, this study attempted to link the global, regional, national and local levels in forest-sector development and especially to analyse how the international policy development in environmental and forestry issues is reflected in field-level progress towards SFM and good forest governance, for the specific cases of Southern Sudan and Ethiopia. The results on Southern Sudan focused on the existing situation and perceived needs in capacity building for SFM and good forest governance at all administration levels. Specifically, the results of the case study on Southern Sudan presented the current situation in selected villages in the northern parts of Renk County in Upper Nile State, and the implications of Multilateral Environmental Agreements (MEAs) and of the new forest policy framework for capacity building actions. The results on Ethiopia focused on training, extension, research, education and new curriculum development within higher education institutions and particularly at the Wondo Genet College of Forestry and Natural Resources (WGCF-NR), which administratively lies under Hawassa University. The results suggest that, for both cases studies, informed decision-making on and capacity building for SFM and good forest governance require comprehensive, long-term, cross-sectoral, coherent and consistent approaches within the dynamic and evolving overall global framework, including its multiple inter-linked levels. The specific priority development and focus areas comprised the establishment of SFM and good forest governance in accordance with the overall sustainable development priorities and with more focus on the international trade in forest products that are derived from sustainable and legal sources with an emphasis on effective forest law enforcement and governance at all levels. In Upper Nile State in Southern Sudan there were positive development signals such as the will of the local people to plant more multipurpose trees on farmlands and range lands as well as the recognition of the importance of forests and trees for sustainable rural development where food security is a key element. In addition, it was evident that the local communities studied in Southern Sudan also wanted to establish good governance systems through partnerships with all actors and through increased local responsibilities. The results also suggest that the implementation of MEAs at the local level in Southern Sudan requires mutually supportive and coherent approaches within the agreements as well as significantly more resources and financial and technical assistance for capacity building, training and extension. Finally, the findings confirm the importance of full utilization of the existing local governance and management systems and their traditional and customary knowledge and practices, and of new development partnerships with full participation of all stakeholders. The planned new forest law for Southern Sudan, based on an already existing new forest policy, is expected to recognize the roles of local-level actors, and it would thus obviously facilitate the achieving of sustainable forest management.

Cultural differences and capability transfer in cross-border acquisitions: the mediating roles of capability complementarity, absorptive capacity, and social integration

This paper presents an integrative model of the impact of cultural differences on capability transfer in cross-border acquisitions. We propose that cultural differences affect the post-acquisition capability transfer through their impact on social integration, potential absorptive capacity, and capability complementarity. Two dynamic variables – the use of social integration mechanisms, and the degree of operational integration of the acquired unit – are proposed to moderate the effects of cultural differences on social integration and potential absorptive capacity. The implications for acquisition research and practice are discussed.

An analytical model for capacity evaluation of VoIP on HCCA and TCP file transfers over EDCA in an IEEE 802.11e WLAN

In the context of the IEEE 802.11e standard for WLANs, we provide an analytical model for obtaining the maximum number of VoIP calls that can be supported on HCCA, such that the delay QoS constraint of the accepted calls is met, when TCP downloads are coexistent on EDCA. In this scenario, we derive the TCP download throughput by using an analytical model for the case where only TCP sessions are present in the WLAN. We show that the analytical model for combined voice and TCP transfers provides accurate results in comparison with simulations (using ns-2).

An analytical model for the capacity estimation of combined VoIP and TCP file transfers over EDCA in an IEEE 802.11e WLAN

In this paper we develop and numerically explore the modeling heuristic of using saturation attempt probabilities as state dependent attempt probabilities in an IEEE 802.11e infrastructure network carrying packet telephone calls and TCP controlled file downloads, using Enhanced Distributed Channel Access (EDCA). We build upon the fixed point analysis and performance insights in [1]. When there are a certain number of nodes of each class contending for the channel (i.e., have nonempty queues), then their attempt probabilities are taken to be those obtained from saturation analysis for that number of nodes. Then we model the system queue dynamics at the network nodes. With the proposed heuristic, the system evolution at channel slot boundaries becomes a Markov renewal process, and regenerative analysis yields the desired performance measures.The results obtained from this approach match well with ns2 simulations. We find that, with the default IEEE 802.11e EDCA parameters for AC 1 and AC 3, the voice call capacity decreases if even one file download is initiated by some station. Subsequently, reducing the voice calls increases the file download capacity almost linearly (by 1/3 Mbps per voice call for the 11 Mbps PHY).

Bearing capacity of interfering multiple strip footings by using lower bound finite elements limit analysis

The ultimate bearing capacity of a number of multiple strip footings, identically spaced and equally loaded to failure at the same time,is computed by using the lower bound limit analysis in combination with finite elements. The efficiency factor due to the component of soil unit weight, is computed with respect to changes in the clear spacing (xi(gamma)) between the footings. It is noted that the failure load for a footing in the group becomes always greater than that of a single isolated footing. The values of xi(gamma) for the smooth footings are found to be always lower than the rough footings. The values ofxi(gamma) are found to increase continuously with a decrease in the spacing between footings. As compared to the available theoretical and experimental results reported in literature, the present analysis provides generally a little lower values of xi(gamma). (C) 2010 Elsevier Ltd. All rights reserved.