Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens

The biological impact of Rho depends critically on the precise subcellular localization of its active, GTP-loaded form. This can potentially be determined by the balance between molecules that promote nucleotide exchange or GTP hydrolysis. However, how these activities may be coordinated is poorly understood. We now report a molecular pathway that achieves exactly this coordination at the epithelial zonula adherens. We identify an extramitotic activity of the centralspindlin complex, better understood as a cytokinetic regulator, which localizes to the interphase zonula adherens by interacting with the cadherin-associated protein, α-catenin. Centralspindlin recruits the RhoGEF, ECT2, to activate Rho and support junctional integrity through myosin IIA. Centralspindlin also inhibits the junctional localization of p190 B RhoGAP, which can inactivate Rho. Thus, a conserved molecular ensemble that governs Rho activation during cytokinesis is used in interphase cells to control the Rho GTPase cycle at the zonula adherens

Government grants - an abrogation or management of risks?

New public management (NPFM), with its hands-on, private sector-style performance measurement, output control, parsimonious use of resources, disaggreation of public sector units and greater competition in the public sector, has significantly affected charitable and nonprofit organisations delivering community services (Hood, 1991; Dunleavy, 1994; George & Wilding, 2002). The literature indicates that nonprofit organisations under NPM believe they are doing more for less: while administration is increasing, core costs are not being met; their dependence on government funding comes at the expense of other funding strategies; and there are concerns about proportionality and power asymmetries in the relationship (Kerr & Savelsberg, 2001; Powell & Dalton, 2011; Smith, 2002, p. 175; Morris, 1999, 2000a). Government agencies are under increased pressure to do more with less, demonstrate value for money, measure social outcomes, not merely outputs and minimise political risk (Grant, 2008; McGreogor-Lowndes, 2008). Government-community service organisation relationships are often viewed as 'uneasy alliances' characterised by the pressures that come with the parties' differing roles and expectations and the pressures that come with the parties' differing roles and expectations and the pressurs of funding and security (Productivity Commission, 2010, p. 308; McGregor-Lowndes, 2008, p. 45; Morris, 200a). Significant community services are now delivered to citizens through such relationships, often to the most disadvantaged in the community, and it is important for this to be achieved with equity, efficiently and effectively. On one level, the welfare state was seen as a 'risk management system' for the poor, with the state mitigating the risks of sickness, job loss and old age (Giddens, 1999) with the subsequent neoliberalist outlook shifting this risk back to households (Hacker, 2006). At the core of this risk shift are written contracts. Vincent-Jones (1999,2006) has mapped how NPM is characterised by the use of written contracts for all manner of relations; e.g., relgulation of dealings between government agencies, between individual citizens and the state, and the creation of quais-markets of service providers and infrastructure partners. We take this lens of contracts to examine where risk falls in relation to the outsourcing of community services. First we examine the concept of risk. We consider how risk might be managed and apportioned between governments and community serivce organisations (CSOs) in grant agreements, which are quasiy-market transactions at best. This is informed by insights from the law and economics literature. Then, standard grant agreements covering several years in two jurisdictions - Australia and the United Kingdom - are analysed, to establish the risk allocation between government and CSOs. This is placed in the context of the reform agenda in both jurisdictions. In Australia this context is th enonprofit reforms built around the creation of a national charities regulator, and red tape reduction. In the United Kingdom, the backdrop is the THird Way agenda with its compacts, succeed by Big Society in a climate of austerity. These 'case studies' inform a discussion about who is best placed to bear and manage the risks of community service provision on behalf of government. We conclude by identifying the lessons to be learned from our analysis and possible pathways for further scholarship.

A novel tuning method for advanced line drop compensator and its application to response coordination of distributed generation with voltage regulating devices

Nowadays, integration of small-scale electricity generators, known as Distributed Generation (DG), into distribution networks has become increasingly popular. This tendency together with the falling price of DG units has a great potential in giving the DG a better chance to participate in voltage regulation process, in parallel with other regulating devices already available in the distribution systems. The voltage control issue turns out to be a very challenging problem for distribution engineers, since existing control coordination schemes need to be reconsidered to take into account the DG operation. In this paper, a control coordination approach is proposed, which is able to utilize the ability of the DG as a voltage regulator, and at the same time minimize the interaction of DG with another DG or other active devices, such as On-load Tap Changing Transformer (OLTC). The proposed technique has been developed based on the concepts of protection principles (magnitude grading and time grading) for response coordination of DG and other regulating devices and uses Advanced Line Drop Compensators (ALDCs) for implementation. A distribution feeder with tap changing transformer and DG units has been extracted from a practical system to test the proposed control technique. The results show that the proposed method provides an effective solution for coordination of DG with another DG or voltage regulating devices and the integration of protection principles has considerably reduced the control interaction to achieve the desired voltage correction.

Go your own way : reporting of fundraising in Australian charity financial statements

Australian charities are facing increased public scrutiny of their financial reports, which must now be submitted to the national regulator, the Australian Charities and Not-for-profits Commission. Some may wish to use reports to create so-called 'fundraising efficiency league tables'. This article seeks to provide a description of current best practice in fundraising financial reporting by examining annual reports that have been recognised with industry awards. We find a wide variation in how terms have been used, with no patterns discernible. Moreoever, reporting is influenced by regulatory requirements in the relevant jurisdiction, which differ substantially. It is unlikely that league tables will be meaningful if constructed from charities' current annual financial statements.

Power quality improvements in low voltage distribution networks containing distributed energy resources

In this thesis various schemes using custom power devices for power quality improvement in low voltage distribution network are studied. Customer operated distributed generators makes a typical network non-radial and affect the power quality. A scheme considering different algorithm of DSTATCOM is proposed for power circulation and islanded operation of the system. To compensate reactive power overflow and facilitate unity power factor, a UPQC is introduced. Stochastic analysis is carried out for different scenarios to get a comprehensive idea about a real life distribution network. Combined operation of static compensator and voltage regulator is tested for the optimum quality and stability of the system.

Using law to identify, manage and prevent child maltreatment

This chapter identifies ways in which laws are capable of responding to child maltreatment, both as an immediate regulator of conduct, and as an influence on a society’s cultural development and approach to children’s welfare. Informed by practices and experiences in selected common law systems, the chapter provides examples of legal mechanisms that can inform discussion of optimal strategies to identify and manage child maltreatment in many different societies. Both positive and negative aspects of these mechanisms are noted. While controversies arise as to what kinds of laws are best in preventing and responding to child maltreatment, and even, more fundamentally, whether there is a role for law in protecting children, this chapter offers evidence that a variety of legal tools can be employed to address child abuse and neglect, for any cultural setting in which there is willingness to act to prevent and treat its various forms.

Lipid-modified azurin of Neisseria meningitidis is a copper protein localized on the outer membrane surface and not regulated by FNR

The laz gene of Neisseria meningitidis is predicted to encode a lipid-modified azurin (Laz). Laz is very similar to azurin, a periplasmic protein, which belongs to the copper-containing proteins in the cupredoxin superfamily. In other bacteria, azurin is an electron donor to nitrite reductase, an important enzyme in the denitrifying process. It is not known whether Laz could function as an electron transfer protein in this important pathogen. Laz protein was heterologously expressed in Escherichia coli and purified. Electrospray mass spectrometry indicated that the Laz protein contains one copper ion. Laz was shown to be redox-active in the presence of its redox center copper ion. When oxidized, Laz exhibits an intense blue colour and absorbs visible light around 626 nm. The absorption is lost when exposed to diethyldithiocarbamate, a copper chelating agent. Polyclonal antibodies were raised against purified Laz for detecting expression of Laz under different growth conditions and to determine the orientation of Laz on the outer membrane. The expression of Laz under microaerobic and microaerobic denitrifying conditions was slightly higher than that under aerobic conditions. However, the expression of Laz was similar between the wild type strain and an fnr mutant, suggesting that Fumarate/Nitrate reduction regulator (FNR) does not regulate the expression of Laz despite the presence of a partial FNR box upstream of the laz gene. We propose that some Laz protein is exposed on the outer membrane surface of N. meningitidis as the αLaz antibodies can increase killing by complement in a capsule deficient N. meningitidis strain, in a dose-dependent fashion.

WT1 interacts with MAD2 and regulates mitotic checkpoint function

Tumour suppressors safeguard the fidelity of the mitotic checkpoint by transcriptional regulation of genes that encode components of the mitotic checkpoint complex (MCC). Here we report a new role for the tumour suppressor and transcription factor, WT1, in the mitotic checkpoint. We show that WT1 regulates the MCC by directly interacting with the spindle assembly checkpoint protein, MAD2. WT1 colocalizes with MAD2 during mitosis and preferentially binds to the functionally active, closed-conformer, C-MAD2. Furthermore, WT1 associates with the MCC containing MAD2, BUBR1 and CDC20, resulting in prolonged inhibition of the anaphase-promoting complex/cyclosome (APC/C) and delayed degradation of its substrates SECURIN and CYCLIN B1. Strikingly, RNA interference-mediated depletion of WT1 leads to enhanced turnover of SECURIN, decreased lag time to anaphase and defects in chromosome segregation. Our findings identify WT1 as a regulator of the mitotic checkpoint and chromosomal stability.

Multi-rotor with suspended load: System dynamics and control toolbox

There is an increasing demand for Unmanned Aerial Systems (UAS) to carry suspended loads as this can provide significant benefits to several applications in agriculture, law enforcement and construction. The load impact on the underlying system dynamics should not be neglected as significant feedback forces may be induced on the vehicle during certain flight manoeuvres. The constant variation in operating point induced by the slung load also causes conventional controllers to demand increased control effort. Much research has focused on standard multi-rotor position and attitude control with and without a slung load. However, predictive control schemes, such as Nonlinear Model Predictive Control (NMPC), have not yet been fully explored. To this end, we present a novel controller for safe and precise operation of multi-rotors with heavy slung load in three dimensions. The paper describes a System Dynamics and Control Simulation Toolbox for use with MATLAB/SIMULINK which includes a detailed simulation of the multi-rotor and slung load as well as a predictive controller to manage the nonlinear dynamics whilst accounting for system constraints. It is demonstrated that the controller simultaneously tracks specified waypoints and actively damps large slung load oscillations. A linear-quadratic regulator (LQR) is derived and control performance is compared. Results show the improved performance of the predictive controller for a larger flight envelope, including aggressive manoeuvres and large slung load displacements. The computational cost remains relatively small, amenable to practical implementations.

Just label it: Consumer rights, GM food labelling, and international trade

In the United States, there has been fierce debate over state, federal and international efforts to engage in genetically modified food labelling (GM food labelling). A grassroots coalition of consumers, environmentalists, organic farmers, and the food movement has pushed for law reform in respect of GM food labelling. The Just Label It campaign has encouraged United States consumers to send comments to the United States Food and Drug Administration to label genetically modified foods. This Chapter explores the various justifications made in respect of genetically modified food labelling. There has been a considerable effort to portray the issue of GM food labelling as one of consumer rights as part of ‘the right to know’. There has been a significant battle amongst farmers over GM food labelling – with organic farmers and biotechnology companies, fighting for precedence. There has also been a significant discussion about the use of GM food labelling as a form of environmental legislation. The prescriptions in GM food labelling regulations may serve to promote eco-labelling, and deter greenwashing. There has been a significant debate over whether GM food labelling may serve to regulate corporations – particularly from the food, agriculture, and biotechnology industries. There are significant issues about the interaction between intellectual property laws – particularly in respect of trade mark law and consumer protection – and regulatory proposals focused upon biotechnology. There has been a lack of international harmonization in respect of GM food labelling. As such, there has been a major use of comparative arguments about regulator models in respect of food labelling. There has also been a discussion about international law, particularly with the emergence of sweeping regional trade proposals, such as the Trans-Pacific Partnership, and the Trans-Atlantic Trade and Investment Partnership. This Chapter considers the United States debates over genetically modified food labelling – at state, federal, and international levels. The battles often involved the use of citizen-initiated referenda. The policy conflicts have been policy-centric disputes – pitting organic farmers, consumers, and environmentalists against the food industry and biotechnology industry. Such battles have raised questions about consumer rights, public health, freedom of speech, and corporate rights. The disputes highlighted larger issues about lobbying, fund-raising, and political influence. The role of money in United States has been a prominent concern of Lawrence Lessig in his recent academic and policy work with the group, Rootstrikers. Part 1 considers the debate in California over Proposition 37. Part 2 explores other key state initiatives in respect of GM food labelling. Part 3 examines the Federal debate in the United States over GM food labelling. Part 4 explores whether regional trade agreements – such as the Trans-Pacific Partnership (TPP) and the Trans-Atlantic Trade and Investment Partnership (TTIP) – will impact upon

Submission to the Productivity Commission draft report business set-up, transfer and closure

The Commission has released a Draft Report on Business Set-Up, Transfer and Closure for public consultation and input. It is pleasing to note that three chapters of the Draft Report address aspects of personal and corporate insolvency. Nevertheless, we continue to make the submission to national policy inquiries and discussions that a comprehensive review should be undertaken of the regulation of insolvency and restructuring in Australia. The last comprehensive review of the insolvency system was by the Australian Law Reform Commission (the Harmer Report) and was handed down in 1988. Whilst there have been aspects of our insolvency laws that have been reviewed since that time, none has been able to provide the clear and comprehensive analysis that is able to come from a more considered review. Such a review ought to be conducted by the Australian Law Reform Commission or similar independent panel set up for the task. We also suggest that there is a lack of data available to assist with addressing questions raised by the Draft Report. There is a need to invest in finding out, in a rigorous and informed way, how the current law operates. Until there is a willingness to make a public investment in such research with less reliance upon the anecdotal (often from well-meaning but ultimately inadequately informed participants and others) the government cannot be sure that the insolvency regime we have provides the most effective regime to underpin Australia’s commercial and financial dealings, nor that any change is justified. We also make the submission that there are benefits in a serious investigation into a merged regulatory architecture of personal and corporate insolvency and a combined personal and corporate insolvency regulator.

Provisioning a 3.3 MW PhotoVoltaic generation system onto a distribution authority’s 11 kV rural feeder

This paper describes part of an engineering study that was undertaken to demonstrate that a multi-megawatt Photovoltaic (PV) generation system could be connected to a rural 11 kV feeder without creating power quality issues for other consumers. The paper concentrates solely on the voltage regulation aspect of the study as this was the most innovative part of the study. The study was carried out using the time-domain software package, PSCAD/EMTDC. The software model included real time data input of actual measured load and scaled PV generation data, along with real-time substation voltage regulator and PV inverter reactive power control. The outputs from the model plot real-time voltage, current and power variations throughout the daily load and PV generation variations. Other aspects of the study not described in the paper include the analysis of harmonics, voltage flicker, power factor, voltage unbalance and system losses.

Failure to launch: The self-regulating Md -MYB10R6 gene from apple is active in flowers but not leaves of Petunia

Coloured foliage due to anthocyanin pigments (bronze/red/black) is an attractive trait that is often lacking in many bedding, ornamental and horticultural plants. Apples (Malus × domestica) containing an allelic variant of the anthocyanin regulator, Md-MYB10R6, are highly pigmented throughout the plant, due to autoregulation by MYB10 upon its own promoter. We investigated whether Md-MYB10R6 from apple is capable of functioning within the heterologous host Petunia hybrida to generate plants with novel pigmentation patterns. The Md-MYB10R6 transgene (MYB10–R6pro:MYB10:MYB10term) activated anthocyanin synthesis when transiently expressed in Antirrhinumroseadorsea petals and petunia leaf discs. Stable transgenic petunias containing Md-MYB10R6 lacked foliar pigmentation but had coloured flowers, complementing the an2 phenotype of ‘Mitchell’ petunia. The absence of foliar pigmentation was due to the failure of the Md-MYB10R6 gene to self-activate in vegetative tissues, suggesting that additional protein partners are required for Md-MYB10 to activate target genes in this heterologous system. In petunia flowers, where endogenous components including MYB-bHLH-WDR (MBW) proteins were present, expression of the Md-MYB10R6 promoter was initiated, allowing auto-regulation to occur and activating anthocyanin production. Md-MYB10 is capable of operating within the petunia MBW gene regulation network that controls the expression of the anthocyanin biosynthesis genes, AN1 (bHLH) and MYBx (R3-MYB repressor) in petals.

Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human

Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR.

Conserved gene structure and function of interleukin-10 in teleost fish

Interleukin-10 (IL-10) is an important immunoregulatory cytokine produced by various types of cells. Researchers describe here the isolation and characterization of olive flounder IL-10 (ofIL-10) cDNA and genomic organization. The ofIL-10 gene encodes a 187 amino acid protein and is composed of a five exon/four intron structure, similar to other known IL-10 genes. The ofIL-10 promoter sequence analysis shows a high level of homology in putative binding sites for transcription factors which are sufficient for transcriptional regulation ofIL-10. Important structural residues are maintained in the ofIL-10 protein including the four cysteines responsible for the two intra-chain disulfide bridges reported for human IL-10 and two extra cysteine residues that exist only in fish species. The phylogenetic analysis clustered ofIL-10 with other fish IL-10s and apart from mammalian IL-10 molecules. Quantitative real-time Polymerase Chain Reaction (PCR) analysis demonstrated ubiquitous ofIL-10 gene expression in the 13 tissues examined. Additionally, the induction of ofIL-10 gene expression was observed in the kidney tissue from olive flounder infected with bacteria (Edawardsiella tarda) or virus (Viral Hemorrhagic Septicemia Virus; VHSV). These data indicate that IL-10 is an important immune regulator that is conserved strictly genomic organization and function during the evolution of vertebrate immunity.