Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo

Background Huntingtin, the HD gene encoded protein mutated by polyglutamine expansion in Huntington's disease, is required in extraembryonic tissues for proper gastrulation, implicating its activities in nutrition or patterning of the developing embryo. To test these possibilities, we have used whole mount in situ hybridization to examine embryonic patterning and morphogenesis in homozygous Hdhex4/5 huntingtin deficient embryos. Results In the absence of huntingtin, expression of nutritive genes appears normal but E7.0–7.5 embryos exhibit a unique combination of patterning defects. Notable are a shortened primitive streak, absence of a proper node and diminished production of anterior streak derivatives. Reduced Wnt3a, Tbx6 and Dll1 expression signify decreased paraxial mesoderm and reduced Otx2 expression and lack of headfolds denote a failure of head development. In addition, genes initially broadly expressed are not properly restricted to the posterior, as evidenced by the ectopic expression of Nodal, Fgf8 and Gsc in the epiblast and T (Brachyury) and Evx1 in proximal mesoderm derivatives. Despite impaired posterior restriction and anterior streak deficits, overall anterior/posterior polarity is established. A single primitive streak forms and marker expression shows that the anterior epiblast and anterior visceral endoderm (AVE) are specified. Conclusion Huntingtin is essential in the early patterning of the embryo for formation of the anterior region of the primitive streak, and for down-regulation of a subset of dynamic growth and transcription factor genes. These findings provide fundamental starting points for identifying the novel cellular and molecular activities of huntingtin in the extraembryonic tissues that govern normal anterior streak development. This knowledge may prove to be important for understanding the mechanism by which the dominant polyglutamine expansion in huntingtin determines the loss of neurons in Huntington's disease.

Studies of granulosa cell maturation in dominant and subordinate bovine follicles : novel extracellular matrix focimatrix is co-ordinately regulated with cholesterol side-chain cleavage CYP11A1

During growth of antral ovarian follicles granulosa cells first become associated with a novel type of extracellular matrix, focimatrix, and at larger sizes follicles become either subordinate or dominant. To examine this, bovine subordinate (9.0±s.e.m. 0.4 mm; n=16), partially dominant (12.0±0.6 mm; n=18) and fully dominant (15.0±0.4 mm; n=14) follicles were examined by real time RT-PCR analyses of granulosa cells and by immunohistochemistry of focimatrix. Changes in the expression of FSH receptor, LH receptor, cholesterol side-chain cleavage (CYP11A1), 3β-hydroxysteroid dehydrogenase, aromatase (CYP19A1) and inhibin-α and β-B were observed as expected for follicle sizes examined. After adjusting for size differences, only CYP11A1 was significantly different between the groups, and elevated in dominant follicles. Also after adjusting for differences in size there were no significant differences in expression of focimatrix components collagen type IV α-1 (COL4A1), laminin β-2, nidogen 1 (NID1), and perlecan (HSPG2) or the volume density of NID1 and -2 and HSPG2. The volume density of focimatrix components in laminin 111 was significantly elevated in dominant follicles. Adjusting for analysis of more than one follicle per animal and for multiple correlations, CYP11A1 mRNA levels were highly correlated with the focimatrix genes COL4A1, NID1 and -2 and HSPG2. Thus, focimatrix may potentially regulate CYP11A1 expression, and the regulation of both could be important in follicular dominance.

Conceptualisation of articular cartilage as a giant reverse micelle: A hypothetical mechanism for joint biocushioning and lubrication

Phospholipid (PL) molecules form the main structure of the membrane that prevents the direct contact of opposing articular cartilage layers. In this paper we conceptualise articular cartilage as a giant reverse micelle (GRM) in which the highly hydrated three-dimensional network of phospholipids is electrically charged and able to resist compressive forces during joint movement, and hence loading. Using this hypothetical base, we describe a hydrophilic-hydrophilic (HL-HL) biopair model of joint lubrication by contacting cartilages, whose mechanism is reliant on lamellar cushioning. To demonstrate the viability of our concept, the electrokinetic properties of the membranous layer on the articular surface were determined by measuring via microelectrophoresis, the adsorption of ions H, OH, Na and Cl on phospholipid membrane of liposomes, leading to the calculation of the effective surface charge density. The surface charge density was found to be -0.08 ± 0.002 cm-2 (mean ± S.D.) for phospholipid membranes, in 0.155 M NaCl solution and physiological pH. This value was approximately five times less than that measured in 0.01 M NaCl. The addition of synovial fluid (SF) to the 0.155 M NaCl solution reduced the surface charge density by 30% which was attributed to the binding of synovial fluid macromolecules to the phospholipid membrane. Our experiments show that particles charge and interact strongly with the polar core of RM. We demonstrate that particles can have strong electrostatic interactions when ions and macromolecules are solubilized by reverse micelle (RM). Since ions are solubilized by reverse micelle, the surface entropy influences the change in the charge density of the phospholipid membrane on cartilage surfaces. Reverse micelles stabilize ions maintaining equilibrium, their surface charges contribute to the stability of particles, while providing additional screening for electrostatic processes. © 2008 Elsevier Ireland Ltd. All rights reserved.

A voting mechanism for named entity translation in English-Chinese question answering

In this paper, we describe a voting mechanism for accurate named entity (NE) translation in English–Chinese question answering (QA). This mechanism involves translations from three different sources: machine translation,online encyclopaedia, and web documents. The translation with the highest number of votes is selected. We evaluated this approach using test collection, topics and assessment results from the NTCIR-8 evaluation forum. This mechanism achieved 95% accuracy in NEs translation and 0.3756 MAP in English–Chinese cross-lingual information retrieval of QA.

Mechanism of interaction of hydrocalumites (Ca/Al-LDH) with methyl orange and acidic scarlet GR

The development of new materials for water purification is of universal importance. Among these types of materials are layered double hydroxides (LDHs). Non-ionic materials pose a significant problem as pollutants. The interaction of methyl orange (MO) and acidic scarlet GR (GR) adsorption on hydrocalumite (Ca/Al-LDH-Cl) were studied by X-ray diffraction (XRD), infrared spectroscopy (MIR), scanning electron microscope (SEM) and near-infrared spectroscopy (NIR). The XRD results revealed that the basal spacing of Ca/Al-LDH-MO was expanded to 2.45 nm, and the MO molecules were intercalated with a inter-penetrating bilayer model in the gallery of LDH, with 49o tilting angle. Yet Ca/Al-LDH-GR was kept the same d-value as Ca/Al-LDH-Cl. The NIR spectrum for Ca/Al-LDH-MO showed a prominent band around 5994 cm-1, assigned to the combination result of the N-H stretching vibrations, which was considered as a mark to assess MO- ion intercalation into Ca/Al-LDH-Cl interlayers. From SEM images, the particle morphology of Ca/Al-LDH-MO mainly changed to irregular platelets, with a “honey-comb” like structure. Yet the Ca/Al-LDH-GR maintained regular hexagons platelets, which was similar to that of Ca/Al-LDH-Cl. All results indicated that MO- ion was intercalated into Ca/Al-LDH-Cl interlayers, and acidic scarlet GR was only adsorped upon Ca/Al-LDH-Cl surfaces.

Corporate governance mechanisms and earnings management in transitional countries – evidence from Chinese listed firms

The objective of this thesis is to investigate whether the corporate governance practices adopted by Chinese listed firms are associated with the quality of earnings information. Based on a review of agency and institutional theory, this study develops hypotheses that predict the monitoring effectiveness of the board and the audit committee. Using a combination of univariate and multivariate analyses, the association between corporate governance mechanisms and earnings management are tested from 2004 to 2008. Through analysing the empirical results, a number of findings are summarised as below. First, board independence is weakened by the introduction of government officials as independent directors on the boards. Government officials acting as independent directors, claim that they meet the definition of independent director set by the regulation. However, they have some connection with the State, which is the controlling shareholder in listed SOEs affiliated companies. Consequently, the effect of the independent director’s expertise in constraining earnings management is mitigated as demonstrated by an insignificant association between board expertise and earnings management. An alternative explanation for the inefficiency of board independence may point to the pre-selection of independent directors by the powerful CEO. It is argued that a CEO can manipulate the board composition and choose the "desirable" independent directors to monitor themselves. Second, a number of internal mechanisms, such as board size, board activities, and the separation of the roles of the CEO and chair are found to be significantly associated with discretionary accruals. This result suggests that there are advantages in having a large and active board in the Chinese setting. This can offset the disadvantages associated with large boards, such as increased bureaucracy, and hence, increase the constraining effects of a large and resourceful board. Third, factor analysis identifies two factors: CEO power and board power. CEO power is the factor which consists of CEO duality and turnover, and board power is composed of board size and board activity. The results of CEO power show that if a Chinese listed company has CEO duality and turnover at the same time, it is more likely to have a high level of earnings management. The significant and negative relationship between board power and accruals indicate that large boards with frequent meetings can be associated with low level of earnings management. Overall, the factor analysis suggests that certain governance mechanisms complement each other to become more efficient monitors of opportunistic earnings management. A combination of board characteristics can increase the negative association with earnings management. Fourth, the insignificant results between audit committees and earnings management in Chinese listed firms suggests that the Chinese regulator should strengthen the audit committee functions. This thesis calls for listed firms to disclose more information on audit committee composition and activities, which can facilitate future research on the Chinese audit committee’s monitoring role. Fifth, the interactive results between State ownership and board characteristics show that dominant State ownership has a moderating effect on board monitoring power as the State totally controls 42% of the issued shares. The high percentage of State ownership makes it difficult for the non-controlling institutional shareholders to challenge the State’s dominant status. As a result, the association between non-controlling institutional ownership and earnings management is insignificant in most situations. Lastly, firms audited by the international Big4 have lower abnormal accruals than firms audited by domestic Chinese audit firms. In addition, the inverse U-shape relationship between audit tenure and earnings quality demonstrates the changing effects of audit quality after a certain period of appointment. Furthermore, this thesis finds that listing in Hong Kong Stock Exchanges can be an alternative governance mechanism to discipline Chinese firms to follow strict Hong Kong listing requirements. Management of Hong Kong listed companies are exposed to the scrutiny of international investors and Hong Kong regulators. This in turn reduces their chances of conducting self-interested earnings manipulation. This study is designed to fill the gap in governance literature in China that is related to earnings management. Previous research on corporate governance mechanisms and earnings management in China is not conclusive. The current research builds on previous literature and provides some meaningful implications for practitioners, regulators, academic, and international investors who have investment interests in a transitional country. The findings of this study contribute to corporate governance and earnings management literature in the context of the transitional economy of China. The use of alternative measures for earnings management yields similar results compared with the accruals models and produces additional findings.

Deformation behaviours of coarse-grained and nanocrystalline Mg-5wt% Al alloys

Magnesium alloys have been of growing interest to various engineering applications, such as the automobile, aerospace, communication and computer industries due to their low density, high specific strength, good machineability and availability as compared with other structural materials. However, most Mg alloys suffer from poor plasticity due to their Hexagonal Close Packed structure. Grain refinement has been proved to be an effective method to enhance the strength and alter the ductility of the materials. Several methods have been proposed to produce materials with nanocrystalline grain structures. So far, most of the research work on nanocrystalline materials has been carried out on Face-Centered Cubic and Body-Centered Cubic metals. However, there has been little investigation of nanocrystalline Mg alloys. In this study, bulk coarse-grained and nanocrystalline Mg alloys were fabricated by a mechanical alloying method. The mixed powder of Mg chips and Al powder was mechanically milled under argon atmosphere for different durations of 0 hours (MA0), 10 hours (MA10), 20 hours (MA20), 30 hours (MA30) and 40 hours (MA40), followed by compaction and sintering. Then the sintered billets were hot-extruded into metallic rods with a 7 mm diameter. The obtained Mg alloys have a nominal composition of Mg–5wt% Al, with grain sizes ranging from 13 μm down to 50 nm, depending on the milling durations. The microstructure characterization and evolution after deformation were carried out by means of Optical microscopy, X-Ray Diffraction, Scanning Electron Microscopy, Transmission Electron Microscopy, Scanning Probe Microscopy and Neutron Diffraction techniques. Nanoindentaion, compression and micro-compression tests on micro-pillars were used to study the size effects on the mechanical behaviour of the Mg alloys. Two kinds of size effects on the mechanical behaviours and deformation mechanisms were investigated: grain size effect and sample size effect. The nanoindentation tests were composed of constant strain rate, constant loading rate and indentation creep tests. The normally reported indentation size effect in single crystal and coarse-grained crystals was observed in both the coarse-grained and nanocrystalline Mg alloys. Since the indentation size effect is correlated to the Geometrically Necessary Dislocations under the indenter to accommodate the plastic deformation, the good agreement between the experimental results and the Indentation Size Effect model indicated that, in the current nanocrystalline MA20 and MA30, the dislocation plasticity was still the dominant deformation mechanism. Significant hardness enhancement with decreasing grain size, down to 58 nm, was found in the nanocrystalline Mg alloys. Further reduction of grain size would lead to a drop in the hardness values. The failure of grain refinement strengthening with the relatively high strain rate sensitivity of nanocrystalline Mg alloys suggested a change in the deformation mechanism. Indentation creep tests showed that the stress exponent was dependent on the loading rate during the loading section of the indentation, which was related to the dislocation structures before the creep starts. The influence of grain size on the mechanical behaviour and strength of extruded coarse-grained and nanocrystalline Mg alloys were investigated using uniaxial compression tests. The macroscopic response of the Mg alloys transited from strain hardening to strain softening behaviour, with grain size reduced from 13 ìm to 50 nm. The strain hardening was related to the twinning induced hardening and dislocation hardening effect, while the strain softening was attributed to the localized deformation in the nanocrystalline grains. The tension–compression yield asymmetry was noticed in the nanocrystalline region, demonstrating the twinning effect in the ultra-fine-grained and nanocrystalline region. The relationship k tensions < k compression failed in the nanocrystalline Mg alloys; this was attributed to the twofold effect of grain size on twinning. The nanocrystalline Mg alloys were found to exhibit increased strain rate sensitivity with decreasing grain size, with strain rate ranging from 0.0001/s to 0.01/s. Strain rate sensitivity of coarse-grained MA0 was increased by more than 10 times in MA40. The Hall-Petch relationship broke down at a critical grain size in the nanocrystalline region. The breakdown of the Hall-Petch relationship and the increased strain rate sensitivity were due to the localized dislocation activities (generalization and annihilation at grain boundaries) and the more significant contribution from grain boundary mediated mechanisms. In the micro-compression tests, the sample size effects on the mechanical behaviours were studied on MA0, MA20 and MA40 micro-pillars. In contrast to the bulk samples under compression, the stress-strain curves of MA0 and MA20 micro-pillars were characterized with a number of discrete strain burst events separated by nearly elastic strain segments. Unlike MA0 and MA20, the stress-strain curves of MA40 micro-pillars were smooth, without obvious strain bursts. The deformation mechanisms of the MA0 and MA20 micro-pillars under micro-compression tests were considered to be initially dominated by deformation twinning, followed by dislocation mechanisms. For MA40 pillars, the deformation mechanisms were believed to be localized dislocation activities and grain boundary related mechanisms. The strain hardening behaviours of the micro-pillars suggested that the grain boundaries in the nanocrystalline micro-pillars would reduce the source (nucleation sources for twins/dislocations) starvation hardening effect. The power law relationship of the yield strength on pillar dimensions in MA0, MA20 supported the fact that the twinning mechanism was correlated to the pre-existing defects, which can promote the nucleation of the twins. Then, we provided a latitudinal comparison of the results and conclusions derived from the different techniques used for testing the coarse-grained and nanocrystalline Mg alloy; this helps to better understand the deformation mechanisms of the Mg alloys as a whole. At the end, we summarized the thesis and highlighted the conclusions, contributions, innovations and outcomes of the research. Finally, it outlined recommendations for future work.

Modeling of a magneto-rheological (MR) fluid damper using a self tuning fuzzy mechanism

A magneto-rheological (MR) fluid damper is a semi-active control device that has recently begun to receive more attention in the vibration control community. However, the inherent nonlinear nature of the MR fluid damper makes it challenging to use this device to achieve high damping control system performance. Therefore the development of an accurate modeling method for a MR fluid damper is necessary to take advantage of its unique characteristics. Our goal was to develop an alternative method for modeling a MR fluid damper by using a self tuning fuzzy (STF) method based on neural technique. The behavior of the researched damper is directly estimated through a fuzzy mapping system. In order to improve the accuracy of the STF model, a back propagation and a gradient descent method are used to train online the fuzzy parameters to minimize the model error function. A series of simulations had been done to validate the effectiveness of the suggested modeling method when compared with the data measured from experiments on a test rig with a researched MR fluid damper. Finally, modeling results show that the proposed STF interference system trained online by using neural technique could describe well the behavior of the MR fluid damper without need of calculation time for generating the model parameters.

Formation mechanisms of secondary organic aerosols in relation to laser printer emissions

Due to their large surface area, complex chemical composition and high alveolar deposition rate, ultrafine particles (UFPs) (< 0.1 ìm) pose a significant risk to human health and their toxicological effects have been acknowledged by the World Health Organisation. Since people spend most of their time indoors, there is a growing concern about the UFPs present in some indoor environments. Recent studies have shown that office machines, in particular laser printers, are a significant indoor source of UFPs. The majority of printer-generated UFPs are organic carbon and it is unlikely that these particles are emitted directly from the printer or its supplies (such as paper and toner powder). Thus, it was hypothesised that these UFPs are secondary organic aerosols (SOA). Considering the widespread use of printers and human exposure to these particles, understanding the processes involved in particle formation is of critical importance. However, few studies have investigated the nature (e.g. volatility, hygroscopicity, composition, size distribution and mixing state) and formation mechanisms of these particles. In order to address this gap in scientific knowledge, a comprehensive study including state-of-art instrumental methods was conducted to characterise the real-time emissions from modern commercial laser printers, including particles, volatile organic compounds (VOCs) and ozone (O3). The morphology, elemental composition, volatility and hygroscopicity of generated particles were also examined. The large set of experimental results was analysed and interpreted to provide insight into: (1) Emissions profiles of laser printers: The results showed that UFPs dominated the number concentrations of generated particles, with a quasi unimodal size distribution observed for all tests. These particles were volatile, non-hygroscopic and mixed both externally and internally. Particle microanalysis indicated that semi-volatile organic compounds occupied the dominant fraction of these particles, with only trace quantities of particles containing Ca and Fe. Furthermore, almost all laser printers tested in this study emitted measurable concentrations of VOCs and O3. A positive correlation between submicron particles and O3 concentrations, as well as a contrasting negative correlation between submicron particles and total VOC concentrations were observed during printing for all tests. These results proved that UFPs generated from laser printers are mainly SOAs. (2) Sources and precursors of generated particles: In order to identify the possible particle sources, particle formation potentials of both the printer components (e.g. fuser roller and lubricant oil) and supplies (e.g. paper and toner powder) were investigated using furnace tests. The VOCs emitted during the experiments were sampled and identified to provide information about particle precursors. The results suggested that all of the tested materials had the potential to generate particles upon heating. Nine unsaturated VOCs were identified from the emissions produced by paper and toner, which may contribute to the formation of UFPs through oxidation reactions with ozone. (3) Factors influencing the particle emission: The factors influencing particle emissions were also investigated by comparing two popular laser printers, one showing particle emissions three orders of magnitude higher than the other. The effects of toner coverage, printing history, type of paper and toner, and working temperature of the fuser roller on particle number emissions were examined. The results showed that the temperature of the fuser roller was a key factor driving the emission of particles. Based on the results for 30 different types of laser printers, a systematic positive correlation was observed between temperature and particle number emissions for printers that used the same heating technology and had a similar structure and fuser material. It was also found that temperature fluctuations were associated with intense bursts of particles and therefore, they may have impact on the particle emissions. Furthermore, the results indicated that the type of paper and toner powder contributed to particle emissions, while no apparent relationship was observed between toner coverage and levels of submicron particles. (4) Mechanisms of SOA formation, growth and ageing: The overall hypothesis that UFPs are formed by reactions with the VOCs and O3 emitted from laser printers was examined. The results proved this hypothesis and suggested that O3 may also play a role in particle ageing. In addition, knowledge about the mixing state of generated particles was utilised to explore the detailed processes of particle formation for different printing scenarios, including warm-up, normal printing, and printing without toner. The results indicated that polymerisation may have occurred on the surface of the generated particles to produce thermoplastic polymers, which may account for the expandable characteristics of some particles. Furthermore, toner and other particle residues on the idling belt from previous print jobs were a very clear contributing factor in the formation of laser printer-emitted particles. In summary, this study not only improves scientific understanding of the nature of printer-generated particles, but also provides significant insight into the formation and ageing mechanisms of SOAs in the indoor environment. The outcomes will also be beneficial to governments, industry and individuals.

Effective adsorption of sodium dodecylsulfate (SDS) by hydrocalumite (CaAl-LDH-Cl) induced by self-dissolution and re-precipitation mechanism

Hydrocalumite (CaAl-LDH-Cl) were synthesized through a rehydration method involving a freshly prepared tricalcium aluminate (C3A) with CaCl2 solution. To understand the intercalation behaviour of sodium dodecylsulfate (SDS) with CaAl-LDH-Cl, X-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), inductively coupled plasma-atomic emission spectrometer (ICP) and elemental analysis have been undertaken. The sorption isotherms with SDS reveal that the maximum sorption amount of SDS by CaAl-LDH-Cl could reach 3.67 mmol•g-1. The results revealed that CaAl-LDH-Cl holds a self-dissolution property, about 20-30% of which is dissolved. And the dissolved Ca2+, Al3+ ions are combined with SDS to form CaAl-SDS or Ca-SDS precipitation. It has been highlighted that the composition of resulting products is strongly dependent upon the SDS concentration. With increasing SDS concentrations, the main resulting product changes from CaAl-SDS to Ca-SDS, and the value of interlayer spacing increased to 3.27 nm.

Enforceable undertakings : a new mechanism for minimum labour standards’ enforcement

Regulatory commentators have identified the need for more responsive regulation to allow enforcement agencies to respond to different types and degrees of non-compliance. One tool considered to support responsive enforcement is the Enforceable Undertaking (EU). EUs are used extensively by Australian regulators in decisions that forego litigation in exchange for offenders promising to (amongst other things) correct behaviour and comply in the future. This arguably allows regulatory agencies greater flexibility in how they obtain compliance with regulations. EUs became an additional enforcement tool for the Fair Work Ombudsman (FWO) under the Fair Work Act 2009. This paper is a preliminary exploration of the comparative use of EUs by the Australian Competition and Consumer Commission and the FWO to assess their effectiveness for the minimum labour standards' environment.

The legal framework for Australia's carbon pricing mechanism : a critique

As part of the Australian Government’s Clean Energy Plan, the Government has attempted to harness the legal innovation of the tradeable emissions unit, within a capped carbon trading system, to reduce greenhouse gas emissions. Such an approach promises to send a price signal to the market which will influence emitting behaviours and reduce our emissions in a cost-effective manner. However, if the carbon trading scheme is to successfully achieve cost-effective emissions reductions then the carbon market must be supported by an appropriate legal framework. This paper will consider the key features of the Australian Carbon Pricing Mechanism, including the Carbon Farming Initiative, and critique whether it has all the hallmarks of an effective legal framework to reduce Australia’s net greenhouse gas emissions. The likely future of the trading scheme, following the 2013 elections, will also be addressed.