Microstructural evolution and grain boundary sliding in a superplastic magnesium AZ31 alloy

Tensile experiments on a fine-grained single-phase Mg–Zn–Al alloy (AZ31) at 673 K revealed superplastic behavior with an elongation to failure of 475% at 1 × 10−4 s−1 and non-superplastic behavior with an elongation to failure of 160% at 1 × 10−2 s−1; the corresponding strain rate sensitivities under these conditions were 0.5 and 0.2, respectively. Measurements indicated that the grain boundary sliding (GBS) contribution to strain ξ was 30% under non-superplastic conditions; there was also a significant sharpening in texture during such deformation. Under superplastic conditions, ξ was 50% at both low and high elongations of 20% and 120%; the initial texture became more random under such conditions. In non-superplastic conditions, deformation occurred under steady-state conditions without grain growth before significant flow localization whereas, under superplastic conditions, there was grain growth during the early stages of deformation, leading to strain hardening. The grains retained equiaxed shapes under all experimental conditions. Superplastic deformation is attributed to GBS, while non-superplastic deformation is attributed to intragranular dislocation creep with some contribution from GBS. The retention of equiaxed grain shapes during dislocation creep is consistent with a model based on local recovery related to the disturbance of triple junctions.

Inhibition of self-quenching in thioketones by micellar compartmentalization

The technique of micellar compartmentalization has been used to inhibit the diffusion-controlled self-quenching process in thioketones. By adjusting the ratio of the bulk concentration of the thioketone solute to the bulk concentration of micelles multiple occupancy of the micelles was avoided. Under these conditions enhanced phosphorescence intensity was observed in nitrogen-purged micellar solutions compared with that in acetonitrile solutions, indicating that the thioketone triple was indeed protected from deactivation by a ground statet

Oncolytic Adenoviruses for Gynecologic Cancer

Gene therapy is a promising novel approach for treating cancers resistant to or escaping currently available modalities. Treatment approaches are based on taking advantage of molecular differences between normal and tumor cells. Various strategies are currently in clinical development with adenoviruses as the most popular vehicle. Recent developments include improving targeting strategies for gene delivery to tumor cells with tumor specific promoters or infectivity enhancement. A rapidly developing field is as well replication competent agents, which allow improved tumor penetration and local amplification of the anti-tumor effect. Adenoviral cancer gene therapy approaches lack cross-resistance with other treatment options and therefore synergistic effects are possible. This study focused on development of adenoviral vectors suitable for treatment of various gynecologic cancer types, describing the development of the field from non-replicating adenoviral vectors to multiple-modified conditional replicating viruses. Transcriptional targeting of gynecologic cancer cells by the use of the promoter of vascular endothelial growth factor receptor type 1 (flt-1) was evaluated. Flt-1 is not expressed in the liver and thus an ideal promoter for transcriptional targeting of adenoviruses. Our studies implied that the flt-1 promoter is active in teratocarcinomas.and therefore a good candidate for development of oncolytic adenoviruses for treatment of this often problematic disease with then poor outcome. A tropism modified conditionally replicating adenovirus (CRAd), Ad5-Δ24RGD, was studied in gynecologic cancers. Ad5-Δ24RGD is an adenovirus selectively replication competent in cells defective in the p16/Rb pathway, including many or most tumor cells. The fiber of Ad5-Δ24RGD contains an integrin binding arginine-glycine-aspartic acid motif (RGD-4C), allowing coxackie-adenovirus receptor independent infection of cancer cells. This approach is attractive because expression levels of CAR are highly variable and often low on primary gynecological cancer cells. Oncolysis could be shown for a wide variety of ovarian and cervical cancer cell lines as well as primary ovarian cancer cell spheroids, a novel system developed for in vitro analysis of CRAds on primary tumor substrates. Biodistribution was evaluated and preclinical safety data was obtained by demonstrating lack of replication in human peripheral blood mononuclear cells. The efficicacy of Ad5-Δ24RGD was shown in different orthotopic murine models including a highly aggressive intraperitoneal model of disseminated ovarian cancer cells, where Ad5-Δ24RGD resulted in complete eradication of intraperitoneal disease in half of the mice. To further improve the selectivity and specificity of CRAds, triple-targeted oncolytic adenoviruses were cloned, featuring the cyclo-oxygenase-2 (cox-2) promoter, E1A transcomplementation and serotype chimerism. Those viruses were evaluated on ovarian cancer cells for specificity and oncolytic potency with regard to two different cox2 versions and three different variants of E1A (wild type, delta24 and delta2delta24). Ad5/3cox2Ld24 emerged as the best combination due to enhanced selectivity without potency lost in vitro or in an aggressive intraperitoneal orthotopic ovarian tumor model. In summary, the preclinical therapeutic efficacy of the CRAds tested in this study, taken together with promising biodistribution and safety data, suggest that these CRAds are interesting candidates for translation into clinical trials for gynecologic cancer.

Social Procurement and New Public Governance

Taking a critically informed approach, this innovative text examines emerging approaches to social procurement within the context of New Public Government (NPG), and examines the practices of social procurement across Europe, North America and Australia. Considering both the possibilities and limitations of social procurement, and the types of value it can generate, this book also provides empirically driven insights into the practicalities of 'triple bottom line' procurement, the related challenges of measuring social value and the management of both the strategic and operational dimensions of procurement processes. As such it will be invaluable reading for all those interest in social services, public governance and social enterprise.

Drivers' ability to absorb information from co-located signs along motorways

The paper presents initial findings from an Austroads funded project NT1782 Ability to Absorb Information through Electronic and Static Signs. The paper aims to investigate how easily messages displayed on co-located signs can be absorbed, and if drivers can absorb messages and take appropriate action without any adverse impact on the safety and efficiency of driving. Co-location of three types of signs under motorway conditions was investigated: direction signs (DS), variable message signs (VMS) and variable speed limits/lane control signs (VSL/LCS). The authors reviewed global wide practices and research evidence on different types of sign co-locations. It was found that dual co-location of VSL/LCS, VMS and/or DS is a practical arrangement which has been widely practised overseas and in Australia. Triple co-location of VSL/LCS, VMS and DS is also practised overseas but is still new to the Australian driving community. The NT1782 project also employed an advanced driving simulator (ADS) to further investigate the possible impacts of sign co-location on drivers’ responses in an emergency situation and there were no obviously adverse impacts have been identified from the ADS study. The authors consolidated all findings and concluded that although there is no clear evidence showing that triple co-location gives rise to riskier behaviour, this proposition should be viewed with caution. Further evaluation of triple co-location in a real-life setting is called for.

High Resoulution Electron Microscopy of Chloritoid Minerals From Different Geological Melieu

Structural defects of three chloritoid minerals from distinet geologic melieu have been investigated by high resolution electron microscopy. X-ray powder and electron diffraction patterns indicate that the chloritoid from one geological source (A) is2M 1+2M2 monoclinic variant while those from another geological source (B) are 2M 2 monoclinic variants. In a typical one-dimensional lattice image of a crystal from sourceA, the 2M 2 matrix is broken by insertion of triclinic inter-growths. Another crystal with the 2M 2 matrix showed single, triple, quadruple and quintuple layers displaying an unusually high degree of disorder. Lattice images of 2M 2 monoclinic variants from sourceB yielded more homogeneous micrographs. The important finding from the present studies is that the chloritoid from sourceA is a severely disordered low-temperature intermediate phase in the conversion of the triclinic chloritoid to the high-temperature ordered monoclinic variants of sourceB. Severely disordered chloritoids, marking the beginning of low grade metamorphism, are generated as intermediates between the state of complete disordered arrangement towards the end of low grade metamorphism within the narrow stability range of 400°–500°C.

A hypothesis on the role of hydroxyproline in stabilizing collagen structure

The possibility of hydroxyproline residues stabilizing the collagen triple-helical structure by the formation of additional hydrogen bonds through their γ-hydroxyl group has been studied from structural considerations. It is not possible for this hydroxyl group to form a direct hydrogen bond with a suitable group in a neighbouring chain of the triple-helical protofibril. However, in the modified one-bonded structure, which is stabilized by additional hydrogen bonds being formed through water molecules as intermediaries (put forward in 1968 by Ramachandran, G. N. and Chandrasekharan, R.), it is found that the γ-hydroxyl group of hydroxyproline can form a good hydrogen bond with the water oxygen as acceptor, the hydrogen bond length being 2.82 Å. It is proposed that, in addition to stabilizing the collagen triple-helical structure due to the stereochemical properties of the pyrrolidine ring, hydroxyproline gives added stability by the formation of an extra hydrogen bond. Experimental studies on the determination of shrinkage and denaturation temperatures of native collagen and its synthetic analogues, as a function of their hydroxyproline content, are being undertaken to test this hypothesis.

Classical solitons with no quantum counterparts and their supersymmetric revival

We demonstrate the phenomenon stated in the title, using for illustration a two-dimensional scalar-field model with a triple-well potential {fx837-1}. At the classical level, this system supports static topological solitons with finite energy. Upon quantisation, however, these solitons develop infinite energy, which cannot be renormalised away. Thus this quantised model has no soliton sector, even though classical solitons exist. Finally when the model is extended supersymmetrically by adding a Majorana field, finiteness of the soliton energy is recovered.

Stabilization of the collagen structure by hydroxyproline residues

The molecular structure of collagen is now accepted to be based on a triple-stranded coiled-coil, in which the three strands are held together predominantly by hydrogen bonds. Recent experimental evidence has shown that the presence of hydroxyproline residues in the third position of the repeating tripeptide unit lends additional stability to the collagen structure. In this paper, we report a model structure, which is supported by these observations. In a model structure proposed earlier, there are two hydrogen bonds per tripeptide unit, one of which is a direct interchain hydrogen bond, while the second hydrogen bond can be formedvia a water molecule. It has now been shown that the same water molecule can also form a hydrogen bond with the oxygen of theγ-hydroxyl group of hydroxyproline in the third position in the sequence (Gly-R2-R3). This hydroxyl group can also take part in an inter-triple-helix hydrogen bond. Our studies thus show the role played by hydroxyproline residues in the structure and stability of collagen.

Steroechemistry of the Pyrrolidine rings in the collagen structure

In the collagen triple-helical structure, large side groups occuring at location 3 in the repeating triplet sequences (Gly-Rz-Rz)n are appreciably constrained if a proline residue occurs as Rz in a neighbouring chain. The severity of the steric hindrance depends on the geometry of the prolyl ring. In this paper we propose two different puckerir.gs for the proline ring, the first one being energetically favorable for most types of residue sequences commonly found in collegen while the second is preferable when an amino acid residue with a large side group occurs at location 3 in a neighbouring chain. The puckering of the pyrrolidine ring of hydroxyproline, as proposed earlier, is quite favorable from energy as well as stereochemical considerations.

Optimisation of in-cell accelerated solvent extraction technique for the determination of organochlorine pesticides in river sediments

Organochlorine pesticides (OCPs) are ubiquitous environmental contaminants with adverse impacts on aquatic biota, wildlife and human health even at low concentrations. However, conventional methods for their determination in river sediments are resource intensive. This paper presents an approach that is rapid and also reliable for the detection of OCPs. Accelerated Solvent Extraction (ASE) with in-cell silica gel clean-up followed by Triple Quadrupole Gas Chromatograph Mass Spectrometry (GCMS/MS) was used to recover OCPs from sediment samples. Variables such as temperature, solvent ratio, adsorbent mass and extraction cycle were evaluated and optimised for the extraction. With the exception of Aldrin, which was unaffected by any of the variables evaluated, the recovery of OCPs from sediment samples was largely influenced by solvent ratio and adsorbent mass and, to some extent, the number of cycles and temperature. The optimised conditions for OCPs extraction in sediment with good recoveries were determined to be 4 cycles, 4.5 g of silica gel, 105 ᴼC, and 4:3 v/v DCM: hexane mixture. With the exception of two compounds (α-BHC and Aldrin) whose recoveries were low (59.73 and 47.66 % respectively), the recovery of the other pesticides were in the range 85.35 – 117.97% with precision < 10 % RSD. The method developed significantly reduces sample preparation time, the amount of solvent used, matrix interference, and is highly sensitive and selective.

Structural and Functional Studies on Trimeric Autotransporters

Trimeric autotransporters are a family of secreted outer membrane proteins in Gram-negative bacteria. These obligate homotrimeric proteins share a conserved C-terminal region, termed the translocation unit. This domain consists of an integral membrane β-barrel anchor and associated α-helices which pass through the pore of the barrel. The α-helices link to the extracellular portion of the protein, the passenger domain. Autotransportation refers to the way in which the passenger domain is secreted into the extracellular space. It appears that the translocation unit mediates the transport of the passenger domain across the outer membrane, and no external factors, such as ATP, ion gradients nor other proteins, are required. The passenger domain of autotransporters contains the specific activities of each protein. These are usually related to virulence. In trimeric autotransporters, the main function of the proteins is to act as adhesins. One such protein is the Yersinia adhesin YadA, found in enteropathogenic species of Yersinia. The main activity of YadA from Y. enterocolitica is to bind collagen, and it also mediates adhesion to other molecules of the extracellular matrix. In addition, YadA is involved in serum resistance, phagocytosis resistance, binding to epithelial cells and autoagglutination. YadA is an essential virulence factor of Y. enterocolitica, and removal of this protein from the bacteria leads to avirulence. In this study, I investigated the YadA-collagen interaction by studying the binding of YadA to collagen-mimicking peptides by several biochemical and biophysical methods. YadA bound as tightly to the triple-helical model peptide (Pro-Hyp-Gly)10 as to native collagen type I. However, YadA failed to bind a similar peptide that does not form a collagenous triple helix. As (Pro-Hyp-Gly)10 does not contain a specific sequence, we concluded that a triple-helical conformation is necessary for YadA binding, but no specific sequence is required. To further investigate binding determinants for YadA in collagens, I examined the binding of YadA to a library of collagen-mimicking peptides that span the entire triple-helical sequences of human collagens type II and type III. YadA bound promiscuously to many but not all peptides, indicating that a triple-helical conformation alone is not sufficient for binding. The high-binding peptides did not share a clear binding motif, but these peptides were rich in hydroxyproline residues and contained a low number of charged residues. YadA thus binds collagens without sequence specificity. This strategy of promiscuous binding may be advantageous for pathogenic bacteria. The Eib proteins from Escherichia coli are immunoglobulin (Ig)-binding homologues of YadA. I showed conclusively that recombinant EibA, EibC, EibD and EibF bind to IgG Fc. I crystallised a fragment of the passenger domain of EibD, which binds IgA in addition to IgG. The structure has a YadA-like head domain and an extended coiled-coil stalk. The top half of the coiled-coil is right-handed with hendecad periodicity, whereas the lower half is a canonical left-handed coiled-coil. At the transition from right- to left-handedness, a small β-sheet protrudes from each monomer. I was able to map the binding regions for IgG and IgA using truncations and site-directed mutagenesis to the coiled-coil stalk and identified residues critical for Ig binding.

Stereochemical restrictions on the occurrence of amino acid residues in the collagen structure

The primary structure of collagen is characterized by the repeating tripeptide sequence (Gly-R2-R3)n. The results of theoretical studies, carried out using contact criteria to compute the stereochemically allowed orientations for various side chains at locations 2 and 3, are reported here. It is found that side chains with only γ-atoms, as in valine, serine and threonine, or with only one δ-methyl group, as in isoleucine, can occur equally well at locations 2 and 3, as is actually the case in collagen. Side chains with two Cδ-atoms, as in leucine and phenyl-alanine, can also be accommodated at both positions. However, if they occur as R3 their freedom of orientation is severely restricted in the presence of a proline residue as R2 in a neighbouring chain. If water molecules bound to the chains of the triple helix are assumed to be present, then location 3 is virtually impossible for leucine and phenylalanine residues. Location 2 is, however, unaffected, and their presence as R2 can help to shield the water molecules from disturbance by the solvent medium. This may be the reason for the preferential occurrence of Leu and Phe residues in location 2 in the collagen triplets, although the polypeptides (Gly-Pro-Leu)n and (Gly-Pro-Phe)n form collagen-like structures.

Positional Preferences of Polypurine/Polypyrimidine Tracts in Saccharomyces cerevisiae Genome: Implications for cis Regulation of Gene Expression

The complete genome of the baker's yeast S. cerevisiae was analyzed for the presence of polypurine/polypyrimidine (poly[pu/py]) repeats and their occurrences were classified on the basis of their location within and outside open reading frames (ORFs). The analysis reveals that such sequence motifs are present abundantly both in coding as well as noncoding regions. Clear positional preferences are seen when these tracts occur in noncoding regions. These motifs appear to occur predominantly at a unit nucleosomal length both upstream and downstream of ORFs. Moreover, there is a biased distribution of polypurines in the coding strands when these motifs occur within open reading frames. The significance of the biased distribution is discussed with reference to the occurrence of these motifs in other known mRNA sequences and expressed sequence tags. A model for cis regulation of gene expression is proposed based on the ability of these motifs to form an intermolecular triple helix structure when present within the coding region and/or to modulate nucleosome positioning via enhanced histone affinity when present outside coding regions.

Exploring the role of lean thinking in sustainable business practice

A large and growing body of literature has explored corporate environmental sustainability initiatives and their impacts locally, regionally and internationally. While the initiatives provide examples of environmental stewardship and cleaner production, a large proportion of the organisations considered in this literature have ‘sustainable practice’, ‘environmental stewardship’ or similar goals as add-ons to their core business strategy. Furthermore, there is limited evidence of organizations embracing and internalising sustainability principles throughout their activities, products or services. Many challenges and barriers impede outcomes as whole system design or holistic approach to address environmental issues, with some evidence to suggest that targeted initiatives could be useful in making progress. ‘Lean management’ and other lean thinking strategies are often put forward as part of such targeted approaches. Within this context, the authors have drawn on current literature to undertake a review of lean thinking practices and how these influence sustainable business practice, considering the balance of environmental and economic aspects of triple bottom line in sustainability. The review methodology comprised firstly identifying theoretical constructs to be studied, developing criteria for categorising the literature, evaluating the findings within each category and considering the implications of the findings for areas for future research. The evaluation revealed two main areas of consideration: - a) lean manufacturing tools and environmental performance, and; - b) integrated lean and green models and approaches. However the review highlighted the ad hoc use of lean thinking within corporate sustainability initiatives, and established a knowledge gap in the form of a system for being able to consider different categories of environmental impacts in different industries and choose best lean tools or models for a particular problem in a way to ensure holistic exploration. The findings included a specific typology of lean tools for different environmental impacts, drawing from multiple case studies. Within this research context, this paper presents the findings of the review; namely the emerging consensus on the relationships between lean thinking and sustainable business practice. The paper begins with an overview of the current literature regarding lean thinking and its documented role in sustainable business practice. The paper then includes an analysis of lean and green paradigms in different industries; and describes the typology of lean tools used to reduce specific environmental impacts and, integrated lean and green models and approaches. The paper intends to encourage industrial practitioners to consider the merits and potential risks with using specific lean tools to reduce context-specific environmental impacts. It also aims to highlight the potential for further investigation with regard to comparing different industries and conceptualising a generalizable system for ensuring lean thinking initiatives build towards sustainable business practice.