Reprogramming the cell cycle machinery to treat cardiovascular disease

Coronary artery disease is one of the most common heart pathologies. Restriction of blood flow to the heart by atherosclerotic lesions, leading to angina pectoris and myocardial infarction, damages the heart, resulting in impaired cardiac function. Damaged myocardium is replaced by scar tissue since surviving cardiomyocytes are unable to proliferate to replace lost heart tissue. Although narrowing of the coronary arteries can be treated successfully using coronary revascularisation procedures, re-occlusion of the treated vessels remains a significant clinical problem. Cell cycle control mechanisms are key in both the impaired cardiac repair by surviving cardiomyocytes and re-narrowing of treated vessels by maladaptive proliferation of vascular smooth muscle cells. Strategies targeting the cell cycle machinery in the heart and vasculature offer promise both for the improvement of cardiac repair following MI and the prevention of restenosis and bypass graft failure following revascularisation procedures.

Multivariable cluster analysis for high-speed industrial machinery

The overall operation and internal complexity of a particular production machinery can be depicted in terms of clusters of multidimensional points which describe the process states, the value in each point dimension representing a measured variable from the machinery. The paper describes a new cluster analysis technique for use with manufacturing processes, to illustrate how machine behaviour can be categorised and how regions of good and poor machine behaviour can be identified. The cluster algorithm presented is the novel mean-tracking algorithm, capable of locating N-dimensional clusters in a large data space in which a considerable amount of noise is present. Implementation of the algorithm on a real-world high-speed machinery application is described, with clusters being formed from machinery data to indicate machinery error regions and error-free regions. This analysis is seen to provide a promising step ahead in the field of multivariable control of manufacturing systems.

Trypanosome Prereplication Machinery Contains a Single Functional Orc1/Cdc6 Protein, Which Is Typical of Archaea

In unicellular eukaryotes, such as Saccharomyces cerevisiae, and in multicellular organisms, the replication origin is recognized by the heterohexamer origin recognition complex (ORC) containing six proteins, Orc1 to Orc6, while in members of the domain Archaea, the replication origin is recognized by just one protein, Orc1/Cdc6; the sequence of Orc1/Cdc6 is highly related to those of Orc1 and Cdc6. Similar to Archaea, trypanosomatid genomes contain only one gene encoding a protein named Orc1. Since trypanosome Orc1 is also homologous to Cdc6, in this study we named the Orc1 protein from trypanosomes Orc1/Cdc6. Here we show that the recombinant Orc1/Cdc6 from Trypanosoma cruzi (TcOrc1/Cdc6) and from Trypanosoma brucei (TbOrc1/Cdc6) present ATPase activity, typical of prereplication machinery components. Also, TcOrc1/Cdc6 and TbOrc1/Cdc6 replaced yeast Cdc6 but not Orc1 in a phenotypic complementation assay. The induction of Orc1/Cdc6 silencing by RNA interference in T. brucei resulted in enucleated cells, strongly suggesting the involvement of Orc1/Cdc6 in DNA replication. Orc1/Cdc6 is expressed during the entire cell cycle in the nuclei of trypanosomes, remaining associated with chromatin in all stages of the cell cycle. These results allowed us to conclude that Orc1/Cdc6 is indeed a member of the trypanosome prereplication machinery and point out that trypanosomes carry a prereplication machinery that is less complex than other eukaryotes and closer to archaea.

Changes in the Australian Commonwealth departmental machinery of government 1928-1982

The Commonwealth departmental machinery of government is changed by using Orders in Council to create, abolish or change the name of departments. Since 1906 governments have utilised a particular form of Order in Council, the Administrative Arrangements Order (AAO), as the means to reallocate functions between departments for administration. After 1928 successive governments from Scullin to Fraser gradually streamlined and increasingly used the formal processes for the executive to change departmental arrangements and the practical role of Parliament, in the process of change, virtually disappeared. From 1929 to 1982, 105 separate departments were brought into being, as new departments or through merger, and 91 were abolished, following the merger of their functions in one way or another with other departments. These figures exclude 6 situations where the change was simply that of name alone. Several hundred less substantial transfers of responsibilities were also made between departments. This dissertation describes, documents and analyses all these changes. The above changes can be distilled down to 79 events termed primary decisions. Measures of the magnitude of change arising from the decisions are developed with 157.25 units of change identified as occurring during the period, most being in the Whitlam and Fraser periods. The reasons for the changes were assessed and classified as occurring for reasons of policy, administrative logic or cabinet comfort. 47.2% of the units of change were attributed to policy, 34.9% to administrative logic, 17% to cabinet comfort. Further conclusions are drawn from more detailed analysis of the change and the reasons for the changes.

An effective heuristic for stockyard planning and machinery scheduling at a coal handling facility

Coal handling is a complex process involving different correlated and highly dependent operations such as selecting appropriate product types, planning stockpiles, scheduling stacking and reclaiming activities and managing train loads. Planning these operations manually is time consuming and can result in non-optimized schedules as future impact of decisions may not be appropriately considered. This paper addresses the operational scheduling of the continuous coal handling problem with multiple conflicting objectives. As the problem is NP-hard in nature, an effective heuristic is presented for planning stockpiles and scheduling resources to minimize delays in production and the coal age in the stockyard. A model of stockyard operations within a coal mine is described and the problem is formulated as a Bi- Objective Optimization Problem (BOOP). The algorithm efficacy is demonstrated on different real-life data scenarios. Computational results show that the solution algorithm is effective and the coal throughput is substantially impacted by the conflicting objectives. Together, the model and the proposed heuristic, can act as a decision support system for the stockyard planner to explore the effects of alternative decisions, such as balancing age and volume of stockpiles, and minimizing conflicts due to stacker and reclaimer movements.

eIF5A binds to translational machinery components and affects translation in yeast

The putative translation factor eIF5A is essential for cell viability and is highly conserved from archebacteria to mammals. Although this protein was originally identified as a translation initiation factor, subsequent experiments did not support a role for eIF5A in general translation. In this work, we demonstrate that eIF-5A interacts with structural components of the 80S ribosome, as well as with the translation elongation factor 2 (eEF2). Moreover, eIF5A is further shown to cofractionate with monosomes in a translation-dependent manner. Finally, eIF5A mutants show altered polysome profiles and are sensitive to translation inhibitors. Our results re-establish a function for eIF5A in translation and suggest a role for this factor in translation elongation instead of translation initiation. (c) 2006 Elsevier B.V. All rights reserved.

Different responses in bulk density and saturated hydraulic conductivity to soil deformation by logging machinery on a Ferralsol under native forest

Ferralsols have high structural stability, although structural degradation has been observed to result from forest to tillage or pasture conversion. An experimental series of forest skidder passes in an east Amazonian natural forest was performed for testing the effects of mechanical stress during selective logging operations on a clay-rich Ferralsol under both dry and wet soil conditions. Distinct ruts formed up to 25 cm depth only under wet conditions. After nine passes the initially very low surface bulk density of between 0.69 and 0.80 g cm(-3) increased to 1.05 g cm(-3) in the wet soil and 0.92 g cm(-3) in the dry soil. Saturated hydraulic conductivities, initially > 250 mm h(-1), declined to a minimum of around 10 mm h(-1) in the wet soil after the first pass, and in the dry soil more gradually after nine passes. The contrasting response of bulk density and saturated hydraulic conductivity is explained by exposure of subsoil material at the base of the ruts where macrostructure rapidly deteriorated under wet conditions. We attribute the resultant moderately high hydraulic conductivities to the formation of stable microaggregates with fine sand to coarse silt textures. We conclude that the topsoil macrostructure of Ferralsols is subject to similar deterioration to that of Luvisols in temperate zones. The stable microstructure prevents marked compaction and decrease in hydraulic conductivity under wetter and more plastic soil conditions. However, typical tropical storms may regularly exceed the infiltration capacity of the deformed soils. In the deeper ruts water may concentrate and cause surface run-off, even in gently sloping areas. To avoid soil erosion, logging operations in sloping areas should therefore be restricted to dry soil conditions when rut formation is minimal.

Active control in rotating machinery using magnetic actuators with linear matrix inequalities (LMI) approach

The recent years have seen the appearance of innovative system for acoustic and vibration attenuation, most of them integrating new actuator technologies. In this sense, the study of algorithms for active vibrations control in rotating machinery became an area of enormous interest, mainly due to countless demands of an optimal performance of mechanical systems in aircraft, aerospace and automotive structures. In this way, this paper presents an approach that is numerically verified for active vibration control in a rotor using Active Magnetic Bearings (AMB). The control design in a discrete state-space formulation is carried out through feedback technique and Linear Matrix Inequalities (LMI) approach. LMI is useful for system with uncertainties. The AMB uses electromagnetic forces to support a rotor without mechanical contact. By monitoring the position of the shaft and changing the dynamics of the system accordingly, the AMB keeps the rotor in a desired position. This unique feature has broadened for the applications of AMB and now they can be considered not only as a main support bearing in a machine but also as dampers for vibration control and force actuators. © 2009 Society for Experimental Mechanics Inc.

Development of an instrumentation system embedded on FPGA for real time measurement of mechanical vibrations in rotating machinery

The real-time monitoring of events in an industrial plant is vital, to monitor the actual conditions of operation of the machinery responsible for the manufacturing process. A predictive maintenance program includes condition monitoring of the rotating machinery, to anticipate possible conditions of failure. To increase the operational reliability it is thus necessary an efficient tool to analyze and monitor the equipments, in real-time, and enabling the detection of e.g. incipient faults in bearings. To fulfill these requirements some innovations have become frequent, namely the inclusion of vibration sensors or stator current sensors. These innovations enable the development of new design methodologies that take into account the ease of future modifications, upgrades, and replacement of the monitored machine, as well as expansion of the monitoring system. This paper presents the development, implementation and testing of an instrument for vibration monitoring, as a possible solution to embed in industrial environment. The digital control system is based on an FPGA, and its configuration with an open hardware design tool is described. Special focus is given to the area of fault detection in rolling bearings. © 2012 IEEE.