Tandem B1 SINE retro-elements may provide a basis for natural antisense transcription in the Magi1 locus of the mouse (Mus musculus)

Transposable elements, which are DNA sequences that can move between different sites in genomes, comprise approximately 40% of the genome of mammals and are emerging as important contributors to biological diversity. Here we report a transcription unit lying within intron 1 of the murine Magi1 (membrane associated guanylate kinase inverted 1) gene that codes for a cell-cell junction scaffolding protein. The transcription unit, termed Magi1OS (Magi1 Opposite Strand), originates from a region with tandem B1 short interspersed nuclear elements (SINEs) and is an antisense gene to Magi1. Mag1OS transcription initiates in a proximal B1 element that shows only 4% divergence from the consensus sequence, indicating that it has been recently inserted into the mouse genome and could be replication competent. Moreover, a chimaeric transcript may result from intra-chromosomal interaction and trans-splicing of the Magi1 antisense transcript (Magi1OS) and Ghrl, which codes for the multifunctional peptide hormone ghrelin. These two genes are 20 megabases apart on chromosome 6 and are transcribed in opposite directions. We propose that the Magi1OS locus may serve as a useful model system to study exaptation and retrotransposition of B1 SINEs, as well as to examine the mechanisms of intra-chromosomal trans-splicing.

An alternate learning approach for destructive testing in civil engineering - Benefits from remote laboratory experimentation

An alternative learning approach for destructive testing of structural specimens in civil engineering is explored by using a remote laboratory experimentation method. The remote laboratory approach focuses on overcoming the constraints in the hands-on experimentation without compromising the understanding of the students on the concepts and mechanics of reinforced concrete structures. The goal of this study is to evaluate whether or not the remote laboratory experimentation approach can become a standard in civil engineering teaching. The teaching activity using remote-laboratory experimentation is presented here and the outcomes of this activity are outlined. The experience and feedback gathered from this study are used to improve the remote-laboratory experimentation approach in future years to other aspects of civil engineering where destructive testing is essential.

Managing Research Data: Mechanical testing and modelling of bone-implant constructs

Presentation by Dr Caroline Grant, Science & Engineering Faculty, IHBI, at Managing your research data seminar, 2012

Improved healing of large segmental defects in the rat femur by reverse dynamization in the presence of bone morphogenetic protein-2

Background Large segmental defects in bone do not heal well and present clinical challenges. This study investigated modulation of the mechanical environment as a means of improving bone healing in the presence of bone morphogenetic protein (BMP)-2. Although the influence of mechanical forces on the healing of fractures is well established, no previous studies, to our knowledge, have described their influence on the healing of large segmental defects. We hypothesized that bone-healing would be improved by initial, low-stiffness fixation of the defect, followed by high-stiffness fixation during the healing process. We call this reverse dynamization. Methods A rat model of a critical-sized femoral defect was used. External fixators were constructed to provide different degrees of stiffness and, importantly, the ability to change stiffness during the healing process in vivo. Healing of the critical-sized defects was initiated by the implantation of 11 mg of recombinant human BMP (rhBMP)-2 on a collagen sponge. Groups of rats receiving BMP-2 were allowed to heal with low, medium, and high-stiffness fixators, as well as under conditions of reverse dynamization, in which the stiffness was changed from low to high at two weeks. Healing was assessed at eight weeks with use of radiographs, histological analysis, microcomputed tomography, dual x-ray absorptiometry, and mechanical testing. Results Under constant stiffness, the low-stiffness fixator produced the best healing after eight weeks. However, reverse dynamization provided considerable improvement, resulting in a marked acceleration of the healing process by all of the criteria of this study. The histological data suggest that this was the result of intramembranous, rather than endochondral, ossification. Conclusions Reverse dynamization accelerated healing in the presence of BMP-2 in the rat femur and is worthy of further investigation as a means of improving the healing of large segmental bone defects. Clinical Relevance These data provide the basis of a novel, simple, and inexpensive way to improve the healing of critical-sized defects in long bones. Reverse dynamization may also be applicable to other circumstances in which bonehealing is problematic.

Design, characterisation and in vivo testing of a new, adjustable stiffness, external fixator for the rat femur

Very little is known about the infl uence of the mechanical environment on the healing of large segmental defects. This partly reflects the lack of standardised, well characterised technologies to enable such studies. Here we report the design, construction and characterisation of a novel external fixator for use in conjunction with rat femoral defects. This device not only imposes a predetermined axial stiffness on the lesion, but also enables the stiffness to be changed during the healing process. The main frame of the fi xator consists of polyethylethylketone with titanium alloy mounting pins. The stiffness of the fi xator is determined by interchangeable connection elements of different thicknesses. Fixators were shown to stabilise 5 mm femoral defects in rats in vivo for at least 8 weeks during unrestricted cage activity. No distortion or infections, including pin infections, were noted. The healing process was simulated in vitro by inserting into a 5 mm femoral defect, materials whose Young’s moduli approximated those of the different tissues present in regenerating bone. These studies confirmed that, although the external fixator is the major determinant of axial stiffness during the early phase of healing, the regenerate within the lesion subsequently dominates this property. There is much clinical interest in altering the mechanics of the defect to enhance bone healing. Our data suggest that, if alteration of the mechanical environment is to be used to modulate the healing of large segmental defects, this needs to be performed before the tissue properties become dominant.

Dilemmatic spaces : high-stakes testing and the possibilities of collaborative knowledge work to generate learning innovations

This paper examines collaborative researcher-practitioner knowledge work around assessment data in culturally diverse, low- socioeconomic school communities in Queensland, Australia. Specifically, the paper draws on interview accounts about the work of a bridging knowledge flows between a local university and a cluster of schools. We draw on Bernstein’s (2000) concept of recontextualisation to explore the processes of knowledge mediation in dialogues around student assessment data to design instructional innovations. We argue that critical policy studies need to explore the complex ways in which neoliberal education policies are enacted in local sites. Moreover, we suggest that an analysis of collaborative knowledge work designed to improve student learning outcomes in low-socioeconomic school communities necessitates attention to the principles regulating knowledge flows across boundaries. In addition, it necessitates attention to the ways in which mediators navigate dilemmatic spaces, anxieties and affects/feelings in order to generate innovative learning designs in the current global context of high-stakes national testing and accountability regimes.

Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Δ4-tibolone

Medroxyprogesterone acetate (MPA) has widely been used in hormone replacement therapy (HRT), and is associated with an increased risk of breast cancer, possibly due to disruption of androgen receptor (AR) signaling. In contrast, the synthetic HRT Tibolone does not increase breast density, and is rapidly metabolized to estrogenic 3α-OH-tibolone and 3β-OH-tibolone, and a delta-4 isomer (Δ4-TIB) that has both androgenic and progestagenic properties. Here, we show that 5α-dihydrotestosterone (DHT) and Δ4-TIB, but not MPA, stabilize AR protein levels, initiate specific AR intramolecular interactions critical for AR transcriptional regulation, and increase proliferation of AR positive MDA-MB-453 breast cancer cells. Structural modeling and molecular dynamic simulation indicate that Δ4-TIB induces a more stable AR structure than does DHT, and MPA a less stable one. Microarray expression analyses confirms that the molecular actions of Δ4-TIB more closely resembles DHT in breast cancer cells than either ligand does to MPA.

Performance-based structural fire design and testing of structures

Fire incident in buildings is common in Hong Kong and this could lead to heavy casualties due to its high population density, so the fire safety design of the framed structure is an important research topic. This paper describes a computer tool for determination of capacity of structural safety against various fire scenarios and the well-accepted second-order direct plastic analysis is adopted for simulation of material yielding and buckling. A computer method is developed to predict structural behaviour of bare steel framed structures at elevated temperatures but the work can be applied to structures made of other materials. These effects of thermal expansion and material degradation due to heating are required to be considered in order to capture the actual behavior of the structure under fire. Degradation of material strength with increasing temperature is included by a set of temperature-stress-strain curves according to BS5950 Part 8 mainly, which implicitly allows for creep deformation. Several numerical and experimental verifications of framed structures are presented and compared against solutions by other researchers. The proposed method allows us to adopt the truly performance-based structural fire analysis and design with significant saving in cost and time.

Physiological basis of salt stress tolerance in rice expressing the antiapoptotic gene SfIAP

Programmed cell death-associated genes, especially antiapoptosis-related genes have been reported to confer tolerance to a wide range of biotic and abiotic stresses in dicotyledonous plants such as tobacco (Nicotiana tabacum L.) and tomato (Solanum lycopersicum L.). This is the first time the antiapoptotic gene SfIAP was transformed into a monocotyledonous representative: rice (Oryza sativa L.). Transgenic rice strains expressing SfIAP were generated by the Agrobacterium-mediated transformation method and rice embryogenic calli, and assessed for their ability to confer tolerance to salt stress at both the seedling and reproductive stages using a combination of molecular, agronomical, physiological and biochemical techniques. The results show that plants expressing SfIAP have higher salt tolerance levels in comparison to the wild-type and vector controls. By preventing cell death at the onset of salt stress and maintaining the cell membrane’s integrity, SfIAP transgenic rice plants can retain plant water status, ion homeostasis, photosynthetic efficiency and growth to combat salinity successfully.

Base-induced decomposition of alkyl hydroperoxides in the gas phase. Part 3. Kinetics and dynamics in HO-+CH3OOH, C2H5OOH, and tert-C4H9OOH reactions

The E-CO(2) elimination reactions of alkyl hydroperoxides proceed via abstraction of an (x-hydrogen by a base: X- + (RRHCOOH)-R-1-H-2 -> HX + (RRC)-R-1-C-2=O + HO-. Efficiencies and product distributions for the reactions of the hydroxide anion with methyl, ethyl, and tert-butyl hydroperoxides are studied in the gas phase. On the basis of experiments using three isotopic analogues, HO- + CH3OOH, HO- + CD3OOH, and H18O- + CH3OOH. the overall intrinsic reaction efficiency is determined to be 80% or greater. The E(CO)2 decomposition is facile for these methylperoxide reactions, and predominates over competing proton transfer at the hydroperoxide moiety. The CH3CH2OOH reaction displays a similar E(CO)2 reactivity, whereas proton transfer and the formation of HOO- are the exclusive pathways observed for (CH3)(3)COOH, which has no (x-hydrogen. All results are consistent with the E-CO(2) mechanism, transition state structure, and reaction energy diagrams calculated using the hybrid density functional B3LYP approach. Isotope labeling for HO- + CH3OOH also reveals some interaction between H2O and HO- within the E(CO)2 product complex [H2O center dot center dot center dot CH2=O center dot center dot center dot HO-]. There is little evidence, however. for the formation of the most exothermic products H2O + CH2(OH)O-, which would arise from nuclephilic condensation of CH2=O and HO-. The results suggest that the product dynamics are not totally statistical but are rather direct after the E-CO(2) transition state. The larger HO- + CH3CH2OOH system displays more statistical behavior during complex dissociation.

Modeling nitrous oxide emissions from irrigated agriculture : testing DayCent with high-frequency measurements

A unique high temporal frequency dataset from an irrigated cotton-wheat rotation was used to test the agroecosystem model DayCent to simulate daily N2O emissions from sub-tropical vertisols under different irrigation intensities. DayCent was able to simulate the effect of different irrigation intensities on N2O fluxes and yield, although it tended to overestimate seasonal fluxes during the cotton season. DayCent accurately predicted soil moisture dynamics and the timing and magnitude of high fluxes associated with fertilizer additions and irrigation events. At the daily scale we found a good correlation of predicted vs. measured N2O fluxes (r2 = 0.52), confirming that DayCent can be used to test agricultural practices for mitigating N2O emission from irrigated cropping systems. A 25 year scenario analysis indicated that N2O losses from irrigated cotton-wheat rotations on black vertisols in Australia can be substantially reduced by an optimized fertilizer and irrigation management system (i.e. frequent irrigation, avoidance of excessive fertiliser application), while sustaining maximum yield potentials.

A query-basis approach to parametrizing novelty-biased cumulative gain

Novelty-biased cumulative gain (α-NDCG) has become the de facto measure within the information retrieval (IR) community for evaluating retrieval systems in the context of sub-topic retrieval. Setting the incorrect value of parameter α in α-NDCG prevents the measure from behaving as desired in particular circumstances. In fact, when α is set according to common practice (i.e. α = 0.5), the measure favours systems that promote redundant relevant sub-topics rather than provide novel relevant ones. Recognising this characteristic of the measure is important because it affects the comparison and the ranking of retrieval systems. We propose an approach to overcome this problem by defining a safe threshold for the value of α on a query basis. Moreover, we study its impact on system rankings through a comprehensive simulation.

Applying and testing design for intuitive interaction

Various tools have been developed to assist designers in making interfaces easier to use although none yet offer a complete solution. Through previous work we have established that intuitive interaction is based on past experience. From this we have developed theory around intuitive interaction, a continuum and a conceptual tool for intuitive use. We then trialled our tool. Firstly, one designer used the tool to design a camera. Secondly, seven groups of postgraduate students re-designed various products using our tool. We then chose one of these - a microwave – and prototyped the new and original microwave interfaces on a touchscreen. We tested them on three different age groups. We found that the new design was more intuitive and rated by participants as more familiar. Therefore, design interventions based on our intuitive interaction theory can work. Work is ongoing to develop the tool further.

Costs - solicitor's retainer on 'no win, no fee' basis - meaning of 'win' - solicitor not entitled to recover excess of costs over amount paid on settlement - no consideration for variation of oral retainer.

In Baker Johnson Lawyers v Jorgensen [2002] QDC 205 McGill DCJ considered the meaning of a 'no win, no fee' retainer and concluded that, in the absence of qualification by agreement, solicitors retained on that basis were not entitled to recover costs exceeding the amount of any judgment or settlement.