High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-Hodgkin's Lymphoma

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

The pathobiology of mammographic density

High mammographic density confers a significantly increased risk of breast cancer. As it is relatively common in the normal population the risk of cancer attributable to increased mammographic density could potentially account for an important percentage of total BCa cases. The underlying cause for high mammographic density and its association with increased BCa risk and progression is unknown. In this review we describe the work that has been done to define the histopathological characteristics of mammographic density. Mammograms define breast tissues with areas of high density due to an increased amount of radio-opaque tissue (stromal and epithelial cells) and also less areas of radiolucent fat. Histological work however can define the roles played by each cell type. We review the work that has been performed assessing changes in epithelial cells, stromal cells, the extracellular matrix, and immune infiltrate. To determine how these changes may be increasing breast cancer risk we also discuss the roles of each of the cell types in breast cancer initiation and progression.

Control of density of self-organized carbon nanotube arrays by catalyst pretreatment through plasma immersion ion implantation

A simple and effective method of controlling the growth of vertically aligned carbon nanotube arrays in a lowerature plasma is presented. Ni catalyst was pretreated by plasma immersion ion implantation prior to the nanotube growth by plasma-enhanced chemical vapor deposition. Both the size distribution and the areal density of the catalyst nanoparticles decrease due to the ion-surface interactions. Consequently, the resulting size distribution of the vertically aligned carbon nanotubes is reduced to 50 ∼ 100 nm and the areal density is lowered (by a factor of ten) to 10 8 cm -2, which is significantly different from the very-high-density carbon nanotube forests commonly produced by thermal chemical vapor deposition. The efficiency of this pretreatment is compared with the existing techniques such as neutral gas annealing and plasma etching. These results are highly relevant to the development of the next-generation nanoelectronic and optoelectronic devices that require effective control of the density of nanotube arrays.

High-resolution SNP microarray investigation of copy number variations on chromosome 18 in a control cohort

Copy number variations (CNVs) as described in the healthy population are purported to contribute significantly to genetic heterogeneity. Recent studies have described CNVs using lymphoblastoid cell lines or by application of specifically developed algorithms to interrogate previously described data. However, the full extent of CNVs remains unclear. Using high-density SNP array, we have undertaken a comprehensive investigation of chromosome 18 for CNV discovery and characterisation of distribution and association with chromosome architecture. We identified 399 CNVs, of which loss represents 98%, 58% are less than 2.5 kb in size and 71% are intergenic. Intronic deletions account for the majority of copy number changes with gene involvement. Furthermore, one-third of CNVs do not have putative breakpoints within repetitive sequences. We conclude that replicative processes, mediated either by repetitive elements or microhomology, account for the majority of CNVs in the healthy population. Genomic instability involving the formation of a non-B structure is demonstrated in one region.

How can land and urban development make houses healthier?

Traditionally, the main focus of the professional community involved with indoor air quality has been indoor pollution sources, preventing or reducing their emissions, as well as lowering the impact of the sources by replacing the polluted indoor air with "fresh" outdoor air. However, urban outdoor air cannot often be considered "fresh", as it contains high concentrations of pollutants emitted from motor vehicles - the main outdoor pollution sources in cities. Evidence from epidemiological studies conducted worldwide demonstrates that outdoor air quality has considerable effects on human health, despite the fact that people spend the majority of their time indoors. This is because pollution from outdoors penetrates indoors and becomes a major constituent of indoor pollution. Urban land and transport development has significant impact on the overall air quality of the urban airshed as well as the pollution concentration in the vicinity of high-density traffic areas. Therefore, an overall improvement in indoor air quality would be achieved by lowering urban airshed pollution, as well as by lowering the impact of the hot spots on indoor air. This paper explores the elements of urban land and vehicle transport developments, their impact on global and local air quality, and how the science of outdoor pollution generation and transport in the air could be utilized in urban development towards lowering indoor air pollution.

Airborne particulate matter at a bus station : concentration levels and governing parameters

Traffic emissions are an important contributor to ambient air pollution, especially in large cities featuring extensive and high density traffic networks. Bus fleets represent a significant part of inner city traffic causing an increase in exposure to general public, passengers and drivers along bus routes and at bus stations. Limited information is available on quantification of the levels, and governing parameters affecting the air pollution exposure at bus stations. The presented study investigated the bus emissions-dominated ambient air in a large, inner city bus station, with a specific focus on submicrometer particles. The study’s objectives were (i) quantification of the concentration levels; (ii) characterisation of the spatio-temporal variation; (iii) identification of the parameters governing the emissions levels at the bus station and (iv) assessment of the relationship between particle concentrations measured at the street level (background) and within the bus station. The results show that up to 90% of the emissions at the station are ultrafine particles (smaller than 100 nm), with the concentration levels up to 10 times the value of urban ambient air background (annual) and up to 4 times the local ambient air background. The governing parameters affecting particle concentration at the station were bus flow rate and meteorological conditions (wind velocity). Particle concentration followed a diurnal trend, with an increase in the morning and evening, associated with traffic rush hours. Passengers’ exposure could be significant compared to the average outdoor and indoor exposure levels.

Non-alcoholic fatty liver disease : can ultrasound assist in early diagnosis of prediabetes and delay progression to type2 diabetes mellitus

Non Alcoholic Fatty Liver Disease (NAFLD) is a condition that is frequently seen but seldom investigated. Until recently, NAFLD was considered benign, self-limiting and unworthy of further investigation. This opinion is based on retrospective studies with relatively small numbers and scant follow-up of histology data. (1) The prevalence for adults, in the USA is, 30%, and NAFLD is recognized as a common and increasing form of liver disease in the paediatric population (1). Australian data, from New South Wales, suggests the prevalence of NAFLD in “healthy” 15 year olds as being 10%.(2) Non-alcoholic fatty liver disease is a condition where fat progressively invades the liver parenchyma. The degree of infiltration ranges from simple steatosis (fat only) to steatohepatitis (fat and inflammation) steatohepatitis plus fibrosis (fat, inflammation and fibrosis) to cirrhosis (replacement of liver texture by scarred, fibrotic and non functioning tissue).Non-alcoholic fatty liver is diagnosed by exclusion rather than inclusion. None of the currently available diagnostic techniques -liver biopsy, liver function tests (LFT) or Imaging; ultrasound, Computerised tomography (CT) or Magnetic Resonance Imaging (MRI) are specific for non-alcoholic fatty liver. An association exists between NAFLD, Non Alcoholic Steatosis Hepatitis (NASH) and irreversible liver damage, cirrhosis and hepatoma. However, a more pervasive aspect of NAFLD is the association with Metabolic Syndrome. This Syndrome is categorised by increased insulin resistance (IR) and NAFLD is thought to be the hepatic representation. Those with NAFLD have an increased risk of death (3) and it is an independent predictor of atherosclerosis and cardiovascular disease (1). Liver biopsy is considered the gold standard for diagnosis, (4), and grading and staging, of non-alcoholic fatty liver disease. Fatty-liver is diagnosed when there is macrovesicular steatosis with displacement of the nucleus to the edge of the cell and at least 5% of the hepatocytes are seen to contain fat (4).Steatosis represents fat accumulation in liver tissue without inflammation. However, it is only called non-alcoholic fatty liver disease when alcohol - >20gms-30gms per day (5), has been excluded from the diet. Both non-alcoholic and alcoholic fatty liver are identical on histology. (4).LFT’s are indicative, not diagnostic. They indicate that a condition may be present but they are unable to diagnosis what the condition is. When a patient presents with raised fasting blood glucose, low HDL (high density lipoprotein), and elevated fasting triacylglycerols they are likely to have NAFLD. (6) Of the imaging techniques MRI is the least variable and the most reproducible. With CT scanning liver fat content can be semi quantitatively estimated. With increasing hepatic steatosis, liver attenuation values decrease by 1.6 Hounsfield units for every milligram of triglyceride deposited per gram of liver tissue (7). Ultrasound permits early detection of fatty liver, often in the preclinical stages before symptoms are present and serum alterations occur. Earlier, accurate reporting of this condition will allow appropriate intervention resulting in better patient health outcomes. References 1. Chalasami N. Does fat alone cause significant liver disease: It remains unclear whether simple steatosis is truly benign. American Gastroenterological Association Perspectives, February/March 2008 www.gastro.org/wmspage.cfm?parm1=5097 Viewed 20th October, 2008 2. Booth, M. George, J.Denney-Wilson, E: The population prevalence of adverse concentrations with adiposity of liver tests among Australian adolescents. Journal of Paediatrics and Child Health.2008 November 3. Catalano, D, Trovato, GM, Martines, GF, Randazzo, M, Tonzuso, A. Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study .Liver Int.2008; February 1280-9 4. Choudhury, J, Sanysl, A. Clinical aspects of Fatty Liver Disease. Semin in Liver Dis. 2004:24 (4):349-62 5. Dionysus Study Group. Drinking factors as cofactors of risk for alcohol induced liver change. Gut. 1997; 41 845-50 6. Preiss, D, Sattar, N. Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci.2008; 115 141-50 7. American Gastroenterological Association. Technical review on nonalcoholic fatty liver disease. Gastroenterology.2002; 123: 1705-25

Energy efficient multi storey residential developments

Worldwide, the current pattern of urban development is unsustainable and metropolitan planning and development strategies deliver poor environmental outcomes in relation to energy production. As a result, an increasing number of governments and private sector development companies are initiating projects that aim to deliver enhanced environmental outcomes rather than a ‘business as usual’ approach. This paper will summarise the findings from a study that explored the link between building orientation and energy efficiencies in sub-tropical and tropical climates. The study used a new thermal modelling software tool developed by CSIRO that responds more accurately to residential heating and cooling energy performance in those climate zones. This software tool responds to industry criticisms regarding cold climate modelling systems that do not make sufficient allowance for natural ventilation. The study examined a range of low, medium and high-density dwelling types and investigated the impact of orientation, insulation, ventilation and shading devices on energy efficiencies. This paper will examine the findings from the medium and high-density case study developments as these are relevant to residential developments in many South East Asian countries, such as Singapore, Hong Kong and Malaysia. Finally, the paper will explore the potential benefits that medium and high-density residential developments have in the development of ‘solar cities’ and ‘solar suburbs’.

The passionate critic

It's hard to be dispassionate about Reyner Banham. For me, and for the plethora of other people with strong opinions about Banham, his writing is compelling, and one’s connection to him as a figure quite personal. For me, frankly, he rocks. As a landscape architect, I gleaned most of my knowledge about Modern architecture from Banham. His Theory and Design in the First Machine Age, along with Rowe and Koetter’s Collage City and Venturi’s Complexity and Contradiction in Architecture were the most influential books in my library, by far. Later, as a budding “real scholar”, I was disappointed to find that, while these authors had serious credibility, the writings themselves were regarded as “polemical” – when in fact what I admired about them most was their ability and willingness to make rough groupings and gross generalizations, and to offer fickle opinions. It spoke to me of a real personal engagement and an active, participatory reading of the architectural culture they discussed. They were at their best in their witty, cutting, but generally pithy, creative prose, such as in Rowe’s extrapolation of the modern citizen as the latest “noble savage”, or Banham railing against conservative social advocates and their response to high density housing: “those who had just re-discovered ‘community’ in the slums would fear megastructure as much as any other kind of large-scale renewal program, and would see to it that the people were never ready.” Any reader of Banham will be able to find a gem that will relate, somehow, personally, to what they are doing right now. For Banham, it was all personal, and the gaps in his scholarship, rather, were the dispassionate places: “Such bias is essential – an unbiased historian is a pointless historian – because history is an essentially critical activity, a constant re-scrutiny and rearrangement of the profession.” Reyner Banham: Historian of the Immediate Future, Nigel Whiteley’s recent “intellectual biography” (the MIT Press, 2002), allowed me to revisit Banham’s passionate mode of criticism and to consider what his legacy might be. The book examines Banham’s body of work, grouped according to his various primary fascinations, as well as his relationship to contemporaneous theoretical movements, such as postmodernism. His mode of practice, as a kind of creative critic, is also considered in some depth. While there are points where the book delves into Banham’s personal life, on the whole Whiteley is very rigorous in considering and theorizing the work itself: more than 750 articles and twelve books. In academic terms, this is good practice. However, considering the entirely personal nature of Banham’s writing itself, this separation seems artificial. Banham, as he himself noted, “didn’t mind a gossip”, and often when reading the book I was curious about what was happening to him at the time. Banham’s was an amazing type of intellectual practice, and one that academics (a term he hated) could do well to learn from. While Whiteley spends a lot of time arguing for his practice to be regarded as such, and makes strong points about both the role of the critic, and the importance of journalism, rather than scholarly publishing, I found myself wondering what his study looked like. What books he had in his library. Did he smoke when he wrote? What sort of teaching load did he have? He is an inspiration to design writers and thinkers, and I, personally, wanted to know how he did it.

Accidental amenity

Landscape in Australian multi-unit residential developments has passed through a number of phases. Can we make the successes more intentional than serendipitous? When did the block of flats become renamed "multi-unit residential"? Perhaps it coincided with a realization by Australians that medium - and high-density urban housing was neither an attack on the quarter-acre block nor a synonym for public housing. Higher densities allow people to participate in the city, and the expansion of unit-based housing represents Australians' growing love of cities for their urban and cosmopolitan values. As our attitude to the city has changed, so have the types of multi-unit residential stock changed - in their spatial qualities as well as their role in the landscape.

Multilineage differentiation potential of bone and cartilage cells derived from explant culture

To date, mesenchymal stem cells (MSCs) from various tissues have been reported, but the yield and differentiation potential of different tissue-derived MSCs is still not clear. This study was undertaken in an attempt to investigate the multilineage stem cell potential of bone and cartilage explant cultures in comparison with bone marrow derived mesenchymal stem cells (BMSCs). The results showed that the surface antigen expression of tissue-derived cells was consistent with that of mesenchymal stem cells, such as lacking the haematopoietic and common leukocyte markers (CD34, CD45) while expressing markers related to adhesion (CD29, CD166) and stem cells (CD90, CD105). The tissue-derived cells were able to differentiate into osteoblast, chondrocyte and adipocyte lineage pathways when stimulated in the appropriate differentiating conditions. However, compared with BMSCs, tissue-derived cells showed less capacity for multilineage differentiation when the level of differentiation was assessed in monolayer culture by analysing the expression of tissue-specific genes by reverse transcription polymerase chain reaction (RT-PCR) and histology. In high density pellet cultures, tissue-derived cells were able to differentiate into chondrocytes, expressing chondrocyte markers such as proteoglycans, type II collagen and aggrecan. Taken together, these results indicate that cells derived from tissue explant cultures reserved certain degree of differentiation properties of MSCs in vitro.

Green a city grow a wall

As Brisbane grows, it is rapidly becoming akin to any other city in the world with its typical stark grey concrete buildings rather than being characterized by its subtropical element of abundant green vegetation. Living Walls can play a vital role in restoring the loss of this distinct local element of a subtropical city. This paper will start by giving an overview of the traditional methods of greening subtropical cities with the use of urban parks and street trees. Then, by examining a recent heat imaging map of Brisbane, the effect of green cover with the built environment will be shown. With this information from a macro level, this paper will proceed to examine a typical urban block within the Central Business District (CBD) to demonstrate urban densification in relation to greenery in the city. Then, this paper will introduce the new technology where Living Walls have the untapped potential of effectively greening a city where land is scarce and given over to high density development. Living Walls incorporated into building design does not only enhance the subtropical lifestyle that is being lost in modern cities but is also an effective means for addressing climate change. This paper will serve as a preliminary investigation into the effects of incorporating Living Walls into cities. By growing a Living Wall onto buildings, we can be part of an effective design solution for countering global warming and at the same time, Living Walls can return local character to subtropical cities, thereby greening the city as well.

A comparative study : regulatory requirements on subdivisions for increasing passive cooling

A major project in the Sustainable Built Assets core area is the Sustainable Sub-divisions – Ventilation Project that is the second stage of a planned series of research projects focusing on sustainable sub-divisions. The initial project, Sustainable Sub-divisions: Energy focused on energy efficiency and examined the link between dwelling energy efficiency and sub-divisional layout. In addition, the potential for on site electricity generation, especially in medium and high-density developments, was also examined. That project recommended that an existing lot-rating methodology be adapted for use in SEQ through the inclusion of sub divisional appropriate ventilation data. Acquiring that data is the object of this project. The Sustainable Sub-divisions; Ventilation Project will produce a series of reports. The first report (Report 2002-077-B-01) summarised the results from an industry workshop and interviews that were conducted to ascertain the current attitudes and methodologies used in contemporary sub-division design in South East Queensland. The second report (Report 2002-077-B-02) described how the project is being delivered as outlined in the Project Agreement. It included the selection of the case study dwellings and monitoring equipment and data management process. This third report (Report 2002-077-B-03) provides an analysis and review of the approaches recommended by leading experts, government bodies and professional organizations throughout Australia that aim to increase the potential for passive cooling and heating at the subdivision stage. This data will inform issues discussed on the development of the enhanced lot-rating methodology in other reports of this series. The final report, due in June 2007, will detail the analysis of data for winter 2006 and summer 2007, leading to the development and delivery of the enhanced lot-rating methodology.

The impact of property title type on residential property returns

Residential property in New Zealand comprises both freestanding residential properties and medium to high density residential properties. Medium to high density residential property comprises the typical units, townhouses and semi-detached houses common in most residential property markets. However, in many of the larger cities of New Zealand the free standing residential property market has evolved into two separate markets being freehold residential property and cross lease residential property. Cross leases have developed as a form of infill housing to reduce the urban sprawl in major canters, while reducing the time and cost for residential property developers. A cross lease is created when an existing freestanding residential property subdivides a portion of the existing land for the erection of another house on the original title, basically dividing one larger residential section into two smaller residential blocks. This paper will analyse house prices in Christchurch over the period 1992 to 2006 to determine if the various housing markets have shown similar capital returns or if there is a specific preference for a particular residential property title.

Increased cardio-metabolic risk is associated with increased TV viewing time

Purpose: Television viewing time, independent of leisure-time physical activity, has cross-sectional relationships with the metabolic syndrome and its individual components. We examined whether baseline and five-year changes in self-reported television viewing time are associated with changes in continuous biomarkers of cardio-metabolic risk (waist circumference, triglycerides, high density lipoprotein cholesterol, systolic and diastolic blood pressure, fasting plasma glucose; and a clustered cardio-metabolic risk score) in Australian adults. Methods: AusDiab is a prospective, population-based cohort study with biological, behavioral, and demographic measures collected in 1999–2000 and 2004–2005. Non-institutionalized adults aged ≥ 25 years were measured at baseline (11,247; 55% of those completing an initial household interview); 6,400 took part in the five-year follow-up biomedical examination, and 3,846 met the inclusion criteria for this analysis. Multiple linear regression analysis was used and unstandardized B coefficients (95% CI) are provided. Results: Baseline television viewing time (10 hours/week unit) was not significantly associated with change in any of the biomarkers of cardio-metabolic risk. Increases in television viewing time over five years (10 hours/week unit) were associated with increases in: waist circumference (cm) (men: 0.43 (0.08, 0.78), P = 0.02; women: 0.68 (0.30, 1.05), P <0.001), diastolic blood pressure (mmHg) (women: 0.47 (0.02, 0.92), P = 0.04), and the clustered cardio-metabolic risk score (women: 0.03 (0.01, 0.05), P = 0.007). These associations were independent of baseline television viewing time and baseline and change in physical activity and other potential confounders. Conclusion: These findings indicate that an increase in television viewing time is associated with adverse cardio-metabolic biomarker changes. Further prospective studies using objective measures of several sedentary behaviors are required to confirm causality of the associations found.