The genetic basis of human height : the role of estrogen

Height is a complex physical trait that displays strong heritability. Adult height is related to length of the long bones, which is determined by growth at the epiphyseal growth plate. Longitudinal bone growth occurs via the process of endochondral ossification, where bone forms over the differentiating cartilage template at the growth plate. Estrogen plays a major role in regulating longitudinal bone growth and is responsible for inducing the pubertal growth spurt and fusion of the epiphyseal growth plate. However, the mechanism by which estrogen promotes epiphyseal fusion is poorly understood. It has been hypothesised that estrogen functions to regulate growth plate fusion by stimulating chondrocyte apoptosis, angiogenesis and bone cell invasion in the growth plate. Another theory has suggested that estrogen exposure exhausts the proliferative capacity of growth plate chondrocytes, which accelerates the process of chondrocyte senescence, leading to growth plate fusion. The overall objective of this study was to gain a greater understanding of the molecular mechanisms behind estrogen-mediated growth and height attainment by examining gene regulation in chondrocytes and the role of some of these genes in normal height inheritance. With the heritability of height so well established, the initial hypothesis was that genetic variation in candidate genes associated with longitudinal bone growth would be involved in normal adult height variation. The height-related genes FGFR3, CBFA1, ER and CBFA1 were screened for novel polymorphisms using denaturing HPLC and RFLP analysis. In total, 24 polymorphisms were identified. Two SNPs in ER (rs3757323 C>T and rs1801132 G>C) were strongly associated with adult male height and displayed an 8 cm and 9 cm height difference between homozygous genotypes, respectively. The TC haplotype of these SNPs was associated with a 6 cm decrease in height and remarkably, no homozygous carriers of the TC haplotype were identified in tall subjects. No significant associations with height were found for polymorphisms in the FGFR3, CBFA1 or VDR genes. In the epiphyseal growth plate, chondrocyte proliferation, matrix synthesis and chondrocyte hypertrophy are all major contributors to long bone growth. As estrogen plays such a significant role in both growth and final height attainment, another hypothesis of this study was that estrogen exerted its effects in the growth plate by influencing chondrocyte proliferation and mediating the expression of chondrocyte marker genes. The examination of genes regulated by estrogen in chondrocyte-like cells aimed to identify potential regulators of growth plate fusion, which may further elucidate mechanisms involved in the cessation of linear growth. While estrogen did not dramatically alter the proliferation of the SW1353 cell line, gene expression experiments identified several estrogen regulated genes. Sixteen chondrocyte marker genes were examined in response to estrogen concentrations ranging from 10-12 M to 10-8 M over varying time points. Of the genes analysed, IHH, FGFR3, collagen II and collagen X were not readily detectable and PTHrP, GHR, ER, BMP6, SOX9 and TGF1 mRNAs showed no significant response to estrogen treatments. However, the expression of MMP13, CBFA1, BCL-2 and BAX genes were significantly decreased. Interestingly, the majority of estrogen regulated genes in SW1353 cells are expressed in the hypertrophic zone of the growth plate. Estrogen is also known to regulate systemic GH secretion and local GH action. At the molecular level, estrogen functions to inhibit GH action by negatively regulating GH signalling. GH treated SW1353 cells displayed increases in MMP9 mRNA expression (4.4-fold) and MMP13 mRNA expression (64-fold) in SW1353 cells. Increases were also detected in their respective proteins. Treatment with AG490, an established JAK2 inhibitor, blocked the GH mediated stimulation of both MMP9 and MMP13 mRNA expression. The application of estrogen and GH to SW1353 cells attenuated GH-stimulated MMP13 levels, but did not affect MMP9 levels. Investigation of GH signalling revealed that SW1353 cells have high levels of activated JAK2 and exposure to GH, estrogen, AG490 and other signalling inhibitors did not affect JAK2 phosphorylation. Interestingly, AG490 treatment dramatically decreased ERK2 signalling, although GH did stimulate ERK2 phosphorylation above control levels. AG490 also decreased CBFA1 expression, a transcription factor known to activate MMP9 and MMP13. Finally, GH and estrogen treatment increased expression of SOCS3 mRNA, suggesting that SOCS3 may regulate JAK/STAT signalling in SW1353 cells. The modulation of GH-mediated MMP expression by estrogen in SW1353 cells represents a potentially novel mechanism by which estrogen may regulate longitudinal bone growth. However, further investigation is required in order to elucidate the precise mechanisms behind estrogen and GH regulation of MMP13 expression in SW1353 cells. This study has provided additional evidence that estrogen and the ER gene are major factors in the regulation of growth and the determination of adult height. Newly identified polymorphisms in the ER gene not only contribute to our understanding of the genetic basis of human height, but may also be useful in association studies examining other complex traits. This study also identified several estrogen regulated genes and indicated that estrogen modifies the expression of genes which are primarily expressed in the hypertrophic region of the epiphyseal growth plate. Furthermore, synergistic studies incorporating GH and estrogen have revealed the ability of estrogen to attenuate the effects of GH on MMP13 expression, revealing potential pathways by which estrogen may modulate growth plate fusion, longitudinal bone growth and even arthritis.

Current rural valuation practice : a survey of valuers and agribusiness managers on farm management and sustainable rural land use

Over the past 20 years the nature of rural valuation practice has required most rural valuers to undertake studies in both agriculture (farm management) and valuation, especially if carrying out valuation work for financial institutions. The additional farm financial and management information obtained by rural valuers exceeds that level of information required to value commercial, retail and industrial by the capitalisation of net rent/profit valuation method and is very similar to the level of information required for the valuation of commercial and retail property by the Discounted Cash Flow valuation method. On this basis the valuers specialising in rural valuation practice have the necessary skills and information to value rural properties by an income valuation method, which can focus on the long term environmental and economic sustainability of the property being valued. This paper will review the results of an extensive survey carried out by rural property valuers in Australia, in relation to the impact of farm management on rural property values and sustainable rural land use. A particular focus of the research relates to the increased awareness of the problems of rural land degradation in Australia and the subsequent impact such problems have on the productivity of rural land. These problems of sustainable land use have resulted in the need to develop an approach to rural valuation practice that allows the valuer to factor the past management practices on the subject rural property into the actual valuation figure. An analysis of the past farm management and the inclusion of this data into the valuation methodology provides a much more reliable indication of farm sustainable economic value than the existing direct comparison valuation methodology.

Developing a best practice framework for implementing public private partnerships (PPP) in Hong Kong

Public Private Partnership (PPP) is a well established methodology for procuring public works projects. By incorporating the private sector’s expertise, efficiency, innovation, business sense, risk sharing, financing etc. into public works projects, the quality of public services and facilities can be uplifted. Like many jurisdictions, Hong Kong is also keen to take aboard this methodology which is so familiar but yet so distant. Although they have been one of the first jurisdictions to utilise the private sector in public works projects, their comfortable financial reserves has meant that there has been no urge to push the movement until recently. PPP has become increasingly popular amongst governments. The Hong Kong Special Administrative Region (HKSAR) government is no exception. Some of the more active works departments have commissioned studies to investigate the best ways to deliver these projects, others have even trialed the method themselves. The efficiency Unit of the HKSAR government has also become an active arm in conducting research in this area. Although so, the information that is currently available is still very broad. Building from their works there is a need to develop a best practice framework for implementing PPP projects in Hong Kong by incorporating international experiences. To develop a best practice framework will require thorough investigation into the benefits, difficulties and critical success factor of PPP. PPP should also be compared with other procurement methods. In order to do so it is important to clearly understand the local situation by an analysis of projects conducted to date. Lessons learnt can further be derived from other countries and incorporated to those derived locally. Finally the best conditions in terms of project nature, complexity, types, and scales for adopting PPP should be derived. The aim and objectives of this study were achieved via a comprehensive literature review, in-depth case analyses, interview survey with experts from both Hong Kong and overseas, and finally a large scale data collection was conducted via a questionnaire survey with PPP practitioners. These findings were further triangulated before they were used as the basis to form the best practice framework presented in this thesis. The framework was then further validated by PPP experts to ensure it is comprehensive, objective, reliable and practical. This study has presented a methodology that can be adopted for future studies. It has also updated our knowledge on the development trends of PPP as well as opened up the experiences of other jurisdictions. The findings have shown that the local industry is familiar with “what” should be done in PPP projects but they are unsure of “how” these goals can be achieved. This framework has allowed this further knowledge to be delivered to PPP practitioners. As a result, the development of this framework can help to resolve the current economic crisis by encouraging more developments and business opportunities for the private sector. In addition, the correct projects can be delivered by PPP, the advantages of PPP can be maximised, and the general public can benefit from the private sector’s participation.

Assessing the energy efficiency of gear oils via the FZG test machine

Energy efficient lubricants are becoming increasingly popular. This is due to a global increase in environmental awareness combined with the potential of reducing operating costs. A new test method of evaluating the energy efficiency of gear oils has been described in this report. The method involves measuring the power required by an FZG test rig to run while using a particular test lubricant. For each oil that was being evaluated, the rig was run for 10 minutes at a load stage of 10. Six extreme pressure (EP) industrial gear oils of mineral base were tested. The difference in power requirements between the best and the worst performing oils was 2.77 and 3.24 kW, respectively. This equates to a 14.6% reduction in power, a significant amount if considered in relation to a high powered industrial machine. The oils of superior performance were noticed to run at reduced temperatures. They were also more expensive than the other products of lesser performance.

A method of lines approach for modelling saltwater intrusion in coastal aquifiers

The equations governing saltwater intrusion in coastal aquifers are complex. Backward Euler time stepping approaches are often used to advance the solution to these equations in time, which typically requires that small time steps be taken in order to ensure that an accurate solution is obtained. We show that a method of lines approach incorporating variable order backward differentiation formulas can greatly improve the efficiency of the time stepping process.

Toward a fuzzy domain ontology extraction method for adaptive e-learning

With the widespread applications of electronic learning (e-Learning) technologies to education at all levels, increasing number of online educational resources and messages are generated from the corresponding e-Learning environments. Nevertheless, it is quite difficult, if not totally impossible, for instructors to read through and analyze the online messages to predict the progress of their students on the fly. The main contribution of this paper is the illustration of a novel concept map generation mechanism which is underpinned by a fuzzy domain ontology extraction algorithm. The proposed mechanism can automatically construct concept maps based on the messages posted to online discussion forums. By browsing the concept maps, instructors can quickly identify the progress of their students and adjust the pedagogical sequence on the fly. Our initial experimental results reveal that the accuracy and the quality of the automatically generated concept maps are promising. Our research work opens the door to the development and application of intelligent software tools to enhance e-Learning.

Current rural valuation practice : a survey of NSW valuers and agribusiness managers

Despite the advances that have been made in relation to the valuation of Commercial, Industrial and retail property, there has not been the same progress in relation to the valuation of rural property. Although number of rural property valuations also require the valuer to carry out a full analysis of the economic performance of the farming operations, as well as the long term environmental viability of the farm, this information is rarely used to assess the value of the property, nor is it even used for a secondary valuation method. Over the past 20 years the nature of rural valuation practice has required most rural valuers to undertake studies in both agriculture (farm management) and valuation, especially if carrying out valuation work for financial institutions. The additional farm financial and management information obtained by rural valuers exceeds that level of information required to value commercial, retail and industrial by the capitalisation of net rent/profit valuation method and is very similar to the level of information required for the valuation of commercial and retail property by the Discounted Cash Flow valuation method. On this basis the valuers specialising in rural valuation practice have the necessary skills and information to value rural properties by an income valuation method. Although the direct comparison method of valuation has been sufficient in the past to value rural properties the future use of the method as the main valuation method is limited and valuers need to adopt an income valuation method as at least a secondary valuation method to overcome the problems associated with the use of direct comparison as the only rural property valuation method, especially in view of the impact that farm technical, financial and environmental .management can have on rural property values. This paper will review the results of an extensive survey carried out by rural property valuers and agribusiness managers in NSW, in relation to the impact of farm management on rural property values and rural property valuation practice.

The use of income valuation methods to value rural property

Despite the advances that have been made in relation to the valuation of commercial, industrial and retail property, there has not been the same progress in relation to the valuation of rural property. Although the majority of rural property valuations also require the valuer to carry out a full analysis of the economic performance of the farming operations, this information is rarely used to assess the value of the property, nor is it even used for a secondary valuation method. Over the past 20 years the nature of rural valuation practice has required rural valuers to undertake studies in both agriculture (farm management) and valuation, especially if carrying out valuation work for financial institutions. The additional farm financial information obtained by rural valuers exceeds that level of information required to value commercial, retail and industrial by the capitalisation of net rent/profit valuation method and is very similar to the level of information required for the valuation of commercial and retail property by the Discounted Cash Flow valuation method. On this basis the valuers specialising in rural valuation practice should have the necessary skills and information to value rural properties by an income valuation method. Although the direct comparison method of valuation has been sufficient in the past to value rural properties the future use of the method as the main valuation method is limited and valuers need to adopt an income valuation method as at least a secondary valuation method to overcome the problems associated with the use of direct comparison as the only rural property valuation method. This paper will review the results of an extensive survey carried out by rural property valuers in New South Wales (NSW), Australia, in relation to the impact of farm management on rural property values and rural property income potential.

Calculation of habitable dwelling surfaces : an empirical analysis for the agglomerations of Munich and Sydney

In many countries the calculation of habitable dwelling surface is characterised by a chaotic variety of calculation variants hardly comprehensible for the end user - sometimes not even reproducible for the expert. Therefore dossiers were analysed on the basis of a random choice in order to determine the method according to which the habitable dwelling surface was measured and to find out wether customers can scrutinize the calculations. The paper compares Sydney and Munich, where in both cases property prices are situated at the high end of the market

Moderating drinking by correspondence : an evaluation of a new method of intervention

Recognizing the need to offer alternative methods of brief interventions, this study developed correspondence treatments for low-dependent problem drinkers and evaluated their impact. One hundred and twenty-one problem drinkers were recruited by media advertisements and were randomly allocated to a full cognitive behavioural treatment programme (CBT) or to a minimal intervention condition (MI) that gave information regarding alcohol misuse and instructions to record drinking. As predicted, CBT was more effective than MI in reducing alcohol consumption over the 4-month controlled trial period. CBT produced a 50% fall in consumption, bringing the average intake of subjects within recommended maximum levels. Treatment gains at 6 months were well maintained to 12 months. High levels of consumer satisfaction, a high representation of women and a substantial participation from isolated rural areas attested to the feasibility of the correspondence programme as an alternative treatment. However, some drinking occasions still involved high intake for a significant subgroup of subjects, and this issue will be addressed in future programmes. The results supported the use of correspondence delivery as a means of promoting early engagement and equity of access between city and country areas.

Patterns of fitting cosmetically tinted contact lenses

Cosmetically tinted soft contact lenses are an attractive option for contact lens wearers. Data that we have gathered from annual contact lens fitting surveys demonstrate that those wearing tinted lenses are more likely to be female (4.6% of all soft lenses fitted vs. 1.6% for males; p < 0.0001) and younger (27 11 years vs. 33 13 years for those wearing non-tinted lenses; p < 0.0001). Tinted lenses tend to be worn more on a part-time basis and are replaced less frequently than non-tinted lenses. The decline in fitting tinted lenses over the past 12 years may be due to (a) the current limited availability of tinted lenses in silicone hydrogel materials and daily disposable replacement frequencies, which together represent a significant majority (78%) of new soft lenses fits today, (b) growing concerns among lens wearers and practitioners relating to the risks of complications associated with the wearing of tinted lenses, and (c) reduced promotion of such lenses by the contact lens industry.

Does chemometrics enhance the performance of electroanalysis?

This review explores the question whether chemometrics methods enhance the performance of electroanalytical methods. Electroanalysis has long benefited from the well-established techniques such as potentiometric titrations, polarography and voltammetry, and the more novel ones such as electronic tongues and noses, which have enlarged the scope of applications. The electroanalytical methods have been improved with the application of chemometrics for simultaneous quantitative prediction of analytes or qualitative resolution of complex overlapping responses. Typical methods include partial least squares (PLS), artificial neural networks (ANNs), and multiple curve resolution methods (MCR-ALS, N-PLS and PARAFAC). This review aims to provide the practising analyst with a broad guide to electroanalytical applications supported by chemometrics. In this context, after a general consideration of the use of a number of electroanalytical techniques with the aid of chemometrics methods, several overviews follow with each one focusing on an important field of application such as food, pharmaceuticals, pesticides and the environment. The growth of chemometrics in conjunction with electronic tongue and nose sensors is highlighted, and this is followed by an overview of the use of chemometrics for the resolution of complicated profiles for qualitative identification of analytes, especially with the use of the MCR-ALS methodology. Finally, the performance of electroanalytical methods is compared with that of some spectrophotometric procedures on the basis of figures-of-merit. This showed that electroanalytical methods can perform as well as the spectrophotometric ones. PLS-1 appears to be the method of practical choice if the %relative prediction error of not, vert, similar±10% is acceptable.

Fingerprinting of complex mixtures with the use of high performance liquid chromatography, inductively coupled plasma atomic emission spectroscopy and chemometrics

The molecular and metal profile fingerprints were obtained from a complex substance, Atractylis chinensis DC—a traditional Chinese medicine (TCM), with the use of the high performance liquid chromatography (HPLC) and inductively coupled plasma atomic emission spectroscopy (ICP-AES) techniques. This substance was used in this work as an example of a complex biological material, which has found application as a TCM. Such TCM samples are traditionally processed by the Bran, Cut, Fried and Swill methods, and were collected from five provinces in China. The data matrices obtained from the two types of analysis produced two principal component biplots, which showed that the HPLC fingerprint data were discriminated on the basis of the methods for processing the raw TCM, while the metal analysis grouped according to the geographical origin. When the two data matrices were combined into a one two-way matrix, the resulting biplot showed a clear separation on the basis of the HPLC fingerprints. Importantly, within each different grouping the objects separated according to their geographical origin, and they ranked approximately in the same order in each group. This result suggested that by using such an approach, it is possible to derive improved characterisation of the complex TCM materials on the basis of the two kinds of analytical data. In addition, two supervised pattern recognition methods, K-nearest neighbors (KNNs) method, and linear discriminant analysis (LDA), were successfully applied to the individual data matrices—thus, supporting the PCA approach.

Simultaneous determination of three synthetic glucocorticoids by differential pulse stripping voltammetry with the aid of chemometrics

A novel voltammetric method for simultaneous determination of the glucocorticoid residues prednisone, prednisolone, and dexamethasone was developed. All three compounds were reduced at a mercury electrode in a Britton-Robinson buffer (pH 3.78), and well-defined voltammetric waves were observed. However, the voltammograms of these three compounds overlapped seriously and showed nonlinear character, and thus, it was difficult to analyze the compounds individually in their mixtures. In this work, two chemometrics methods, principal component regression (PCR) and partial least squares (PLS), were applied to resolve the overlapped voltammograms, and the calibration models were established for simultaneous determination of these compounds. Under the optimum experimental conditions, the limits of detection (LOD) were 5.6, 8.3, and 16.8 µg l-1 for prednisone, prednisolone, and dexamethasone, respectively. The proposed method was also applied for the determination of these glucocorticoid residues in the rabbit plasma and human urine samples with satisfactory results.