Molecular Genetic Background of Tumours in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a hereditary tumour predisposition syndrome. Its phenotype includes benign cutaneous and uterine leiomyomas (CLM, ULM) with high penetrance and rarer renal cell cancer (RCC), most commonly of papillary type 2 subtype. Over 130 HLRCC families have been identified world-wide but the RCC phenotype seems to concentrate in families from Finland and North America for unknown reasons. HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. FH encodes the enzyme fumarase from mitochondrial citric acid cycle. Fumarase enzyme activity or type or site of the FH mutation are unassociated with disease phenotype. The strongest evidence for tumourigenesis mechanism in HLRCC supports a hypoxia inducible factor driven process called pseudohypoxia resulting from accumulation of the fumarase substrate fumarate. In this study, to assess the importance of gene- or exon-level deletions or amplifications of FH in patients with HLRCC-associated phenotypes, multiplex ligation-dependent probe amplification (MLPA) method was used. One novel FH mutation, deletion of exon 1, was found in a Swedish male patient with an evident HLRCC phenotype with CLM, RCC, and a family history of ULM and RCC. Six other patients with CLM and 12 patients with only RCC or uterine leiomyosarcoma (ULMS) remained FH mutation-negative. These results suggest that copy number aberrations of FH or its exons are an infrequent cause of HLRCC and that only co-occurrence of benign tumour types justifies FH-mutation screening in RCC or ULMS patients. Determination of the genomic profile of 11 HLRCC-associated RCCs from Finnish patients was performed by array comparative genomic hybridization. The most common copy number aberrations were gains of 2, 7, and 17 and losses of 13q12.3-q21.1, 14, 18, and X. When compared to aberrations of sporadic papillary RCCs, HLRCC-associated RCCs harboured a distinct DNA copy number profile and lacked many of the changes characterizing the sporadic RCCs. The findings suggest a divergent molecular pathway for tumourigenesis of papillary RCCs in HLRCC. In order to find a genetic modifier of RCC risk in HLRCC, genome-wide linkage and identical by descent (IBD) analysis studies were performed in Finnish HLRCC families with microsatellite marker mapping and SNP-array platforms. The linkage analysis identified only one locus of interest, the FH gene locus in 1q43, but no mutations were found in the genes of the region. IBD analysis yielded no convincing haplotypes shared by RCC patients. Although these results do not exclude the existence of a genetic modifier for RCC risk in HLRCC, they emphasize the role of FH mutations in the malignant tumourigenesis of HLRCC. To study the benign tumours in HLRCC, genome-wide DNA copy number and gene expression profiles of sporadic and HLRCC ULMs were defined with modern SNP- and gene-expression array platforms. The gene expression array suggests novel genes involved in FH-deficient ULM tumourigenesis and novel genes with putative roles in propagation of sporadic ULM. Both the gene expression and copy number profiles of HLRCC ULMs differed from those of sporadic ULMs indicating distinct molecular basis of the FH-deficient HLRCC tumours.

Persistence of bellyache bush (Jatropha gossypifolia L.) soil seed banks

Bellyache bush (Jatropha gossypifolia L.) is an invasive shrub that adversely impacts agricultural and natural systems of northern Australia. While several techniques are available to control bellyache bush, depletion of soil seed banks is central to its management. A 10-year study determined the persistence of intact and ant-discarded bellyache bush seeds buried in shade cloth packets at six depths (ranging from 0 to 40 cm) under both natural rainfall and rainfall-excluded conditions. A second study monitored changes in seedling emergence over time, to provide an indication of the natural rate of seed bank depletion at two sites (rocky and heavy clay) following the physical removal of all bellyache bush plants. Persistence of seed in the burial trial varied depending on seed type, rainfall conditions and burial depth. No viable seeds of bellyache bush remained after 72 months irrespective of seed type under natural rainfall conditions. When rainfall was excluded seeds persisted for much longer, with a small portion (0.4%) of ant-discarded seeds still viable after 120 months. Seed persistence was prolonged (> 96 months to decline to < 1% viability) at all burial depths under rainfall-excluded conditions. In contrast, under natural rainfall, surface located seeds took twice as long (70 months) to decline to 1% viability compared with buried seeds (35 months). No seedling emergence was observed after 58 months and 36 months at the rocky and heavy clay soil sites, respectively. These results suggest that the required duration of control programs on bellyache bush may vary due to the effect of biotic and abiotic factors on persistence of soil seed banks.

Evaluation of rumen fatty acid hydrogenation intermediates and differences in bacterial communities after feeding wheat- or corn-based dried distillers grains to feedlot cattle

The effect of partially replacing rolled barley (86.6% of control diet) with 20% wheat dried distillers grains plus solubles (DDGS), 40% wheat DDGS, 20% corn DDGS, or 40% corn DDGS (dietary DM basis) on rumen fluid fatty acid (FA) composition and some rumen bacterial communities was evaluated using 100 steers (20 per treatment). Wheat DDGS increased the 11t-to 10t-18:1 ratio (P < 0.05) in rumen fluid and there was evidence that the conversion of trans-18:1 to 18:0 was reduced in the control and wheat DDGS diets but not in the corn DDGS diet. Bacterial community profiles obtained using denaturing gradient gel electrophoresis and evaluated by Pearson correlation similarity matrices were not consistent for diet and, therefore, these could not be linked to different specific rumen FA. This inconsistency may be related to the nature of diets fed (dominant effect of barley), limited change in dietary composition as the result of DDGS inclusion, large animal-to-animal variation, and possibly additional stress as a result of transport just before slaughter. Ruminal densities of a key fiber-digesting bacteria specie that produces 11t-18:1 from linoleic and linolenic acids (Butyrivibrio fibrisolvens), and a lactate producer originally thought responsible for production of 10t, 12c-18:2 (Megasphaera elsdenii) were not influenced by diet (P > 0.05).

Efficacy of nano-silver in alleviating bacteria-related blockage in cut rose cv. Movie Star stems

Postharvest treatments with nano-silver (NS) significantly improve water relations and therefore prolong the vase life of several cut flowers, including rose (Rosa hybrida cv. Movie Star). The efficacy of NS in alleviating bacterial related blockage in the stem-ends of cut cv. Movie Star was further investigated. Four dominant bacteria strains Pseudomonas fluorescens, Aeromonas sp., Comamonas acidovorans and Chryseomonas luteola were isolated from the stem-ends of cut roses. High numbers of the isolated bacteria at 10 8colony forming unitsmL -1 vase solution led to a sharp reduction in vase life, flower fresh weight, and water uptake. In vitro assessments of the antibacterial activity of NS against the four bacterial strains was >80% at 5mgL -1 and nearly 100% at 50mgL -1. Bacterial blockage in the stem-ends of cut cv. Movie Star roses with and without NS pulse treatments was assessed during the vase period using scanning electron microscopy. Following a 50mgL -1 NS pulse treatment, there were few bacterial cells on the cut surface of the stems even on day 7. Moreover, no obvious bacterial blockage was observed inside the xylem vessels. In contrast, the cut surface of control stems was covered with bacteria and associated amorphous substances, and numerous bacteria were found in the xylem vessels. © 2012 Elsevier B.V.

Biocontrol of Chromolaena odorata in Timor Leste

Chromolaena odorata (L.) King and Robinson (Asteraceae) is a major weed in Timor Leste, affecting grazing lands and subsistence farms, reducing productivity and food security. It was the focus of a biocontrol project funded by the Australian Government from 2005-2009. During this period, the gall fly Cecidochares connexa (Macquart) (Diptera: Tephritidae) was introduced from Papua New Guinea and Indonesia, where it is widespread. From these initial releases, the gall fly established at seven sites and was subsequently re-distributed to most areas in Timor Leste where chromolaena was a problem. It established at most of the release sites that were revisited and caused a visible reduction in plant density and height. Overall, control of chromolaena by the gall fly in Timor Leste is limited by the severe dry season and the widespread use of fire in clearing lands for agriculture, both of which reduce the ability of gall fly populations to persist at damaging levels. Thus additional agents that can tolerate prolonged dry periods are required to increase the level of control of chromolaena.

Identification of a class of non-linear systems

This paper considers the on-line identification of a non-linear system in terms of a Hammerstein model, with a zero-memory non-linear gain followed by a linear system. The linear part is represented by a Laguerre expansion of its impulse response and the non-linear part by a polynomial. The identification procedure involves determination of the coefficients of the Laguerre expansion of correlation functions and an iterative adjustment of the parameters of the non-linear gain by gradient methods. The method is applicable to situations involving a wide class of input signals. Even in the presence of additive correlated noise, satisfactory performance is achieved with the variance of the error converging to a value close to the variance of the noise. Digital computer simulation establishes the practicability of the scheme in different situations.

Genetic diversity of subgroup 1 ilarviruses from eastern Australia

This is the first report of the genetic diversity within ilarvirus subgroup 1 from eastern Australia. It supports the separation of tobacco streak virus (TSV) strains from parthenium (Parthenium hysterophorus) and crownbeard (Verbescina encelioides) based on serology and host specificity. It has confirmed one previously described strain of TSV as a member of the species Strawberry necrotic shock virus and another as a new subgroup 1 ilarvirus, ageratum latent virus (AgLV), from Ageratum houstonianum. A multiplex RT-PCR showed that the genetically distinct strains of TSV and AgLV were commonly found in symptomless infections in virus-specific alternative weed hosts growing over a wide geographical range in eastern Australia. TSV has been one of the most damaging viruses in Australian oilseed and pulse crops in recent years, and this study has provided the taxonomic knowledge essential for the development of control programs for these viruses. © 2013 Springer-Verlag Wien.

Applications of a sugar-based surveillance system to track arboviruses in wild mosquito populations

Effective arbovirus surveillance is essential to ensure the implementation of control strategies, such as mosquito suppression, vaccination, or dissemination of public warnings. Traditional strategies employed for arbovirus surveillance, such as detection of virus or virus-specific antibodies in sentinel animals, or detection of virus in hematophagous arthropods, have limitations as an early-warning system. A system was recently developed that involves collecting mosquitoes in CO2-baited traps, where the insects expectorate virus on sugar-baited nucleic acid preservation cards. The cards are then submitted for virus detection using molecular assays. We report the application of this system for detecting flaviviruses and alphaviruses in wild mosquito populations in northern Australia. This study was the first to employ nonpowered passive box traps (PBTs) that were designed to house cards baited with honey as the sugar source. Overall, 20/144 (13.9%) of PBTs from different weeks contained at least one virus-positive card. West Nile virus Kunjin subtype (WNVKUN), Ross River virus (RRV), and Barmah Forest virus (BFV) were detected, being identified in 13/20, 5/20, and 2/20 of positive PBTs, respectively. Importantly, sentinel chickens deployed to detect flavivirus activity did not seroconvert at two Northern Territory sites where four PBTs yielded WNVKUN. Sufficient WNVKUN and RRV RNA was expectorated onto some of the honey-soaked cards to provide a template for gene sequencing, enhancing the utility of the sugar-bait surveillance system for investigating the ecology, emergence, and movement of arboviruses. © 2014, Mary Ann Liebert, Inc.

On various types of decoupling for time-varying system

This paper deals with the problem of decoupling a class of linear time-varying multi-variable systems, based on the defining property that the impulse response matrix of a decoupled system is diagonal. Depending on the properties of the coefficient matrices of the vector differential equation of the open-loop system, the system may be uniformly or totally decoupled. The necessary and sufficient conditions that permit a system to be uniformly or totally decoupled by state variable feedback are given. The main contribution of this paper is the precise definition of these two classes of decoupling and a rigorous derivation of the necessary and sufficient conditions which show the necessity of requiring that the system be of constant ordered rank with respect to observability. A simple example illustrates the importance of having several definitions of decoupling. Finally, the results are specialized to the case of time invariant systems.

Solution of a class of vibration problems by flowgraph methods

A 4-degree-of-freedom single-input system and a 3-degree-of-freedom multi-input system are solved by the Coates', modified Coates' and Chan-Mai flowgraph methods. It is concluded that the Chan-Mai flowgraph method is superior to other flowgraph methods in such cases.

Editorial of "International Journal of Critical Indigenous Studies Volume 3, Number 2, 2010"

In this of the International Journal of Critical Indigenous Studies, the articles reveal how competing economies of knowledge, capital and values are operationalised through colonising power within inter-subjective relations. Writing in the Australian context, Greg Blyton demonstrates how tobacco was used by colonists as a means of control and exchange in their relations with Indigenous people. He focuses on the Hunter region of New South Wales, Australia, in the early to mid-nineteenth century to reveal how colonists exchanged tobacco for food, safe passage and Indigenous services. Blyton suggests that these colonial practices enabled tobacco addiction to spread throughout the region, passing from one generation of Indigenous people to another. He asks us to consider the link between the colonial generation of Indigenous tobacco consumption and addiction, and Indigenous mortality rates today whereby twenty percent of deaths are attributed to smoking.

Constrained linear filter and its relation to singular optimal control

This paper presents an analysis of an optimal linear filter in the presence of constraints on the moan squared values of the estimates from the viewpoint of singular optimal control. The singular arc has been shown to satisfy the generalized Legcndrc-Clebseh condition and Jacobson's condition. Both the cases of white measurement noise and coloured measurement noise are considered. The constrained estimate is shown to be a linear transformation of the unconstrained Kalman estimate.

Nonlinear Control Design for an Air-breathing Engine with State Estimation

A nonlinear control design approach is presented in this paper for a challenging application problem of ensuring robust performance of an air-breathing engine operating at supersonic speed. The primary objective of control design is to ensure that the engine produces the required thrust that tracks the commanded thrust as closely as possible by appropriate regulation of the fuel flow rate. However, since the engine operates in the supersonic range, an important secondary objective is to ensure an optimal location of the shock in the intake for maximum pressure recovery with a sufficient margin. This is manipulated by varying the throat area of the nozzle. The nonlinear dynamic inversion technique has been successfully used to achieve both of the above objectives. In this problem, since the process is faster than the actuators, independent control designs have also been carried out for the actuators as well to assure the satisfactory performance of the system. Moreover, an extended Kalman Filter based state estimation design has been carried out both to filter out the process and sensor noises as well as to make the control design operate based on output feedback. Promising simulation results indicate that the proposed control design approach is quite successful in obtaining robust performance of the air-breathing system.

Participation or further exclusion? : Contestations over forest conservation and control in the East Usambara Mountains, Tanzania

This Ph.D. thesis Participation or Further Exclusion? Contestations over Forest Conservation and Control in the East Usambara Mountains, Tanzania describes and analyses the shift in the prevailing discourse of forest and biodiversity conservation policies and strategies towards more participatory approaches in Tanzania, and the changes in the practises of resource control. I explore the scope for and limits to the different actors and groups who are considered to form the community, to participate in resource control, in a specific historical and socio-economic context. I analyse whether, how and to which extent the targets of such participatory conservation interventions have been able to affect the formal rules and practices of resource control, and explore their different responses and discursive and other strategies in relation to conservation efforts. I approach the problematic through exploring certain participatory conservation interventions and related negotiations between the local farmers, government officials and the external actors in the case of two protected forest reserves in the southern part of the East Usambaras, Tanzania. The study area belongs to the Eastern Arc Mountains that are valued globally and nationally for their high level of biodiversity and number of endemic and near endemic species. The theoretical approach draws from theorising on power, participation and conservation in anthropology of development and post-structuralist political ecology. The material was collected in three stages between 2003 and 2008 by using an ethnographic approach. I interviewed and observed the actors and their resource use and control practices at the local level, including the representatives of the villagers living close to the protected forests and the conservation agency, but also followed the selected processes and engaged with the non-local agencies involved in the conservation efforts in the East Usambaras. In addition, the more recent processes of change and the actors strategies in resource control were contextualised against the social and environmental history of the study area and the evolvement of institutions of natural resource control. My findings indicate that the discourse of participation that has emerged in global conservation policy debate within the past three decades, and is being institutionalised in the national policies in many countries, including Tanzania, has shaped the practices of forest conservation in the East Usambaras, although in a fragmented and uneven way. Instrumental interpretation of participation, in which it is to serve the goals of improving the control of the forest and making it more acceptable and efficient, has prevailed among the governmental actors and conservation organisations. Yet, there is variation between the different projects and actors promoting participatory conservation regarding the goals and means of participation, e.g. to which extent the local people are to be involved in decision-making. The actors representing communities also have their diverse agendas, understandings and experiences regarding the rationality, outcomes and benefits of being involved in forest control, making the practices of control fluid. The elements of the exclusive conservation thinking and practices co-exist with the more recent participatory processes, and continue to shape the understandings and strategies of the actors involved in resource control. The ideas and narratives of the different discourses are reproduced and selectively used by the parties involved. The idea of forest conservation is not resisted as such by most of the actors at local level, quite the opposite. However, the strict regulations and rules governing access to resources, such as valuable timber species, continue to be disputed by many. Furthermore, the history of control, such as past injustices related to conservation and unfulfilled promises, undermines the participation of certain social groups in resource control and benefit sharing. This also creates controversies in the practices of conservation, and fuels conflicts regarding the establishment of new protected areas. In spite of this, the fact that the representatives of the communities have been invited to the arenas where information is shared, and principles and conditions of forest control and benefit sharing are discussed and partly decided upon, has created expectations among the participants, and opened up opportunities for some of the local actors to enhance their own, and sometimes wider interests in relation to resource control and the related benefits. The local actors experiences of the previous government and other interventions strongly affect how they position themselves in relation to conservation interventions, and their responses and strategies. However, my findings also suggest, in a similar way to research conducted in some other protected areas, that the benefits of participation in conservation and resource control tend to accrue unevenly between different groups of local people, e.g. due to unequal access to information and differences in their initial resources and social position.

On the stabilization of uniformly decoupled systems by state variable feedback

Conditions under which the asymptotic stabilization of uniformly decoupled time-varying multivariate systems is possible are explored. This is accomplished by developing a canonical form for integrator uniformly decoupled system in which the coefficient matrices have a simple structure. The procedures developed rely on certain conditions on the given system and yield explicit expressions for the stabilization compensators.