Towards a quantitative theory of epidermal calcium profile formation in unwounded skin

We propose and mathematically examine a theory of calcium profile formation in unwounded mammalian epidermis based on: changes in keratinocyte proliferation, fluid and calcium exchange with the extracellular fluid during these cells' passage through the epidermal sublayers, and the barrier functions of both the stratum corneum and tight junctions localised in the stratum granulosum. Using this theory, we develop a mathematical model that predicts epidermal sublayer transit times, partitioning of the epidermal calcium gradient between intracellular and extracellular domains, and the permeability of the tight junction barrier to calcium ions. Comparison of our model's predictions of epidermal transit times with experimental data indicates that keratinocytes lose at least 87% of their volume during their disintegration to become corneocytes. Intracellular calcium is suggested as the main contributor to the epidermal calcium gradient, with its distribution actively regulated by a phenotypic switch in calcium exchange between keratinocytes and extracellular fluid present at the boundary between the stratum spinosum and the stratum granulosum. Formation of the extracellular calcium distribution, which rises in concentration through the stratum granulosum towards the skin surface, is attributed to a tight junction barrier in this sublayer possessing permeability to calcium ions that is less than 15 nm/s in human epidermis and less than 37 nm/s in murine epidermis. Future experimental work may refine the presented theory and reduce the mathematical uncertainty present in the model predictions.

Cultural relativity as exchange : J.W. Lindt’s bush character and Aboriginal from The Grafton Album (circa 1872)

J.W.Lindt’s Colonial man and Aborigine image from the GRAFTON ALBUM: “On chemistry and optics all does not depend, art must with these in triple union blend” (text from J.W. Lindt’s photographic backing card)...

Optimal electricity distribution framework for public space: Assessing renewable energy proposals for Freshkills Park, New York City

Integrating renewable energy into public space is becoming more common as a climate change solution. However, this approach is often guided by the environmental pillar of sustainability, with less focus on the economic and social pillars. The purpose of this paper is to examine this issue in the speculative renewable energy propositions for Freshkills Park in New York City submitted for the 2012 Land Art Generator Initiative (LAGI) competition. This paper first proposes an optimal electricity distribution (OED) framework in and around public spaces based on relevant ecology and energy theory (Odum’s fourth and fifth law of thermodynamics). This framework addresses social engagement related to public interaction, and economic engagement related to the estimated quantity of electricity produced, in conjunction with environmental engagement related to the embodied energy required to construct the renewable energy infrastructure. Next, the study uses the OED framework to analyse the top twenty-five projects submitted for the LAGI 2012 competition. The findings reveal an electricity distribution imbalance and suggest a lack of in-depth understanding about sustainable electricity distribution within public space design. The paper concludes with suggestions for future research.

The neural correlates of justified and unjustified killing: An fMRI study

Despite moral prohibitions on hurting other humans, some social contexts allow for harmful actions such as the killing of others. One example is warfare, where killing enemy soldiers is seen as morally justified. Yet, the neural underpinnings distinguishing between justified and unjustified killing are largely unknown. To improve understanding of the neural processes involved in justified and unjustified killing, participants had to imagine being the perpetrator whilst watching “first-person perspective” animated videos where they shot enemy soldiers (‘justified violence’) and innocent civilians (‘unjustified violence’). When participants imagined themselves shooting civilians compared to soldiers, greater activation was found in the lateral orbitofrontal cortex (OFC). Regression analysis revealed that the more guilt participants felt about shooting civilians, the greater the response in the lateral OFC. Effective connectivity analyses further revealed an increased coupling between lateral OFC and the tempoparietal junction (TPJ) when shooting civilians. The results show that the neural mechanisms typically implicated with harming others, such as the OFC, become less active when the violence against a particular group is seen as justified. This study therefore provides unique insight into how normal individuals can become aggressors in specific situations.

The effect of BCMO1 gene variants on macular pigment optical density in young healthy Caucasians

Background Serum lutein (L) and zeaxanthin (Z) positively correlate with macular pigment optical density (MPOD), hence the latter is a valuable indirect tool for measuring L and Z content in the macula. L and Z have been attributed antioxidant capacity and protection from certain retinal diseases but their uptake within the eye is thought to depend on genetic, age and environmental factors. In particular gene variants within beta-carotene monooxygenase (BCMO1) are thought to modulate MPOD in the macula. Objectives: To determine the effect of BCMO1 single nucleotide polymorphisms (SNPs) rs11645428, rs6420424 and rs6464851 on macular pigment optical density (MPOD) in a cohort of young healthy participants of Caucasian origin with normal ocular health. Design In this cohort study, MPOD was assessed in 46 healthy participants (22 male and 24 female) with a mean age of 24 ± 4.0 years (range 19-33). The three SNPs, rs11645428, rs6420424, rs6564851 that have established associations with MPOD were determined using MassEXTEND (hME) Sequenom assay. One-way analysis of variance (ANOVA) was performed on groups segregated into homozygous and heterozygous BCMO1 genotypes. Correlations between body mass index (BMI), iris colour, gender, central retinal thickness (CRT), diet and MPOD were investigated. Results MPOD did not significantly vary with BCMO1 rs11645428 (F2,41 = 0.700, p = 0.503), rs6420424 (F2,41 = 0.210, p = 0.801) nor rs6464851 homozygous or heterozygous genotypes (F2,41 = 0,13, p = 0.88), in this young healthy cohort. The combination of these three SNPs into triple genotypes based on plasma conversion efficiency did not affect MPOD (F2,41 = 0.07, p = 0.9). There was a significant negative correlation with MPOD and central retinal thickness (r = - 0.39, p = 0.01) but no significant correlation between BMI, iris colour, gender and MPOD. Conclusion Our results indicate that macular pigment deposition within the central retina is not dependent on BCMO1 gene variants in young healthy people. We propose that MPOD is saturated in younger persons and/or other gene variant combinations determine its deposition.

Turbulence and Mixing in the Environment: Multi-Device Study in a Sub-tropical Estuary

In an estuary, mixing and dispersion result from a combination of large-scale advection and smallscale turbulence, which are complex to estimate. The predictions of scalar transport and mixing are often inferred and rarely accurate, due to inadequate understanding of the contributions of these difference scales to estuarine recirculation. A multi-device field study was conducted in a small sub-tropical estuary under neap tide conditions with near-zero fresh water discharge for about 48 hours. During the study, acoustic Doppler velocimeters (ADV) were sampled at high frequency (50 Hz), while an acoustic Doppler current profiler (ADCP) and global positioning system (GPS) tracked drifters were used to obtain some lower frequency spatial distribution of the flow parameters within the estuary. The velocity measurements were complemented with some continuous measurement of water depth, conductivity, temperature and some other physiochemical parameters. Thorough quality control was carried out by implementation of relevant error removal filters on the individual data set to intercept spurious data. A triple decomposition (TD) technique was introduced to access the contributions of tides, resonance and ‘true’ turbulence in the flow field. The time series of mean flow measurements for both the ADCP and drifter were consistent with those of the mean ADV data when sampled within a similar spatial domain. The tidal scale fluctuation of velocity and water level were used to examine the response of the estuary to tidal inertial current. The channel exhibited a mixed type wave with a typical phase-lag between 0.035π– 0.116π. A striking feature of the ADV velocity data was the slow fluctuations, which exhibited large amplitudes of up to 50% of the tidal amplitude, particularly in slack waters. Such slow fluctuations were simultaneously observed in a number of physiochemical properties of the channel. The ensuing turbulence field showed some degree of anisotropy. For all ADV units, the horizontal turbulence ratio ranged between 0.4 and 0.9, and decreased towards the bed, while the vertical turbulence ratio was on average unity at z = 0.32 m and approximately 0.5 for the upper ADV (z = 0.55 m). The result of the statistical analysis suggested that the ebb phase turbulence field was dominated by eddies that evolved from ejection type process, while that of the flood phase contained mixed eddies with significant amount related to sweep type process. Over 65% of the skewness values fell within the range expected of a finite Gaussian distribution and the bulk of the excess kurtosis values (over 70%) fell within the range of -0.5 and +2. The TD technique described herein allowed the characterisation of a broader temporal scale of fluctuations of the high frequency data sampled within the durations of a few tidal cycles. The study provides characterisation of the ranges of fluctuation required for an accurate modelling of shallow water dispersion and mixing in a sub-tropical estuary.

The largest Au deposits in the St Ives Goldfield (Yilgarn Craton, Western Australia) may be located in a major Neoarchean volcano-sedimentary depo-centre

The largest Neoarchean gold deposits in the world-class St Ives Goldfield, Western Australia, occur in an area known as the Argo-Junction region (e.g. Junction, Argo and Athena). Why this region is so well endowed with large deposits compared with other parts of the St Ives Goldfield is currently unclear, because gold deposits at St Ives are hosted by a variety of lithologic units and were formed during at least three different deformational events. This paper presents an investigation into the stratigraphic architecture and evolution of the Argo-Junction region to assess its implications for gold metallogenesis. The results show that the region's stratigraphy may be subdivided into five regionally correlatable packages: mafic lavas of the Paringa Basalt; contemporaneously resedimented feldspar-rich pyroclastic debris of the Early Black Flag Group; coarse polymictic volcanic debris of the Late Black Flag Group; thick piles of mafic lavas and sub-volcanic sills of the Athena Basalt and Condenser Dolerite; and the voluminous quartz-rich sedimentary successions of the Early Merougil Group. In the Argo-Junction region, these units have an interpreted maximum thickness of at least 7,130 m, and thus represent an unusually thick accumulation of the Neoarchean volcano-sedimentary successions. It is postulated that major basin-forming structures that were active during deposition and emplacement of the voluminous successions later acted as important conduits during mineralisation. Therefore, a correlation exists between the location of the largest gold deposits in the St Ives Goldfield and the thickest parts of the stratigraphy. Recognition of this association has important implications for camp-scale exploration.

The importance of connexin hemichannels during chondroprogenitor cell differentiation in hydrogel versus microtissue culture models

Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell-cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell-cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5'-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular chondrocytes and BM-MSCs. Therefore, reducing direct cell-cell contacts does not affect in vitro chondrogenesis. However, blocking gap junctions compromises cell differentiation, pointing to a prominent role for hemichannel function in this process. Therefore, scaffold design strategies that promote an increasing distance between single chondroprogenitor cells do not restrict their differentiation potential in tissue-engineered constructs.

Origins of Australian Football: Victoria's Early History. Volume 3: Covert 'Professionalism': The Power of the Wealthy Clubs 1886 to 1890

This volume continues the story of football in Marvellous Melbourne during the 1880s. At this time the VFA continued to expand as Melbourne’s boom continued apace. In 1886 Port Melbourne, Prahran, St Kilda, Footscray and South Williamstown joined the competition, and the Ballarat clubs Ballarat, Ballarat Imperial and South Ballarat were also contending for the VFA premiership. In 1886 matches were divided into four quarters, goal umpires waved two flags to announce a goal, and time clocks and bells were employed to mark the end of quarters. Victoria also played inter-colonial matches against New South Wales, Tasmania and South Australia. VFA secretary T.S. Marshall was at the forefront of fighting the game’s turn towards professionalism, but although it was illegal to pay players, the practice continued. The period 1886 to 1890 also set the stage for the eventual formation of the Victorian Football League, for by the end of the 1880s the Victorian Football Association had become in effect a two-tier competition. The most popular clubs in the VFA, South Melbourne, Geelong, Carlton and Essendon collected the lion’s share of the gate money, which they used to build their wealth and entrench their position as the dominant Victorian teams. The lower tier clubs had to make do with paltry gate money and season fixtures that advantaged the strong clubs. In these fixtures the strong clubs elected to play each other first to increase their gate money, and only deemed to play the poorer clubs at the start of the season. This led to an increasing divide between the VFA’s rich and poor, and by 1890 South Williamstown and Prahran merged with Williamstown and St Kilda respectively, University dropped out of senior ranks, and the Ballarat clubs were excluded from competing for the VFA premiership, which left 12 senior clubs until Collingwood’s emergence in 1892. At this time, no team was as powerful as South Melbourne, which experienced the greatest success in the club’s VFA and VFL history when it collected triple premiership crowns in 1888, 1889, and 1890. South Melbourne was a most ambitious club and spearheaded the move towards professionalism, although this could not be made public. The fine teams it produced at this time contained some of the greatest players of the era, such as Peter Burns, “Sonny” Elms and “Dinny” McKay, and it looked after players with health insurance, jobs, inter-colonial trips, and other incentives. Geelong’s premiership in 1886 was perhaps its greatest triumph, but this success was followed by a premiership drought that would last for 39 years. Carlton remained one of Victorian football’s power clubs, and after securing the premiership in 1887 continued to compete for top honours. As always, the game became ever more popular and world record crowds of over 30,000 attended matches between South Melbourne, Carlton, Geelong and Essendon.

Organic photovoltaics using thin gold film as an alternative anode to indium tin oxide

Indium Tin Oxide (ITO) is the most commonly used anode as a transparent electrode and more recently as an anode for organic photovoltaics (OPVs). However, there are significant drawbacks in using ITO which include high material costs, mechanical instability including brittleness and poor electrical properties which limit its use in low-cost flexible devices. We present initial results of poly(3-hexylthiophene): phenyl-C61-butyric acid methyl ester OPVs showing that an efficiency of 1.9% (short-circuit current 7.01 mA/cm2, open-circuit voltage 0.55 V, fill factor 0.49) can be attained using an ultra thin film of gold coated glass as the device anode. The initial I-V characteristics demonstrate that using high work function metals when the thin film is kept ultra thin can be used as a replacement to ITO due to their greater stability and better morphological control.

Race against time: The export of essential medicines to Rwanda

This article considers the significance of the first export of essential medicines under the WTO General Council Decision 2003. In July 2007, Rwanda became the first country to provide a notification under the WTO General Council Decision 2003 of its intent to import a fixed-dose, triple combination HIV/AIDS drug manufactured by the Canadian generic pharmaceuticalmanufacturer Apotex, Inc. In September 2007, Apotex was granted the first compulsory licence application under Canada's Access to Medicines Regime. This article considers the convoluted and protracted negotiations between the Government of Rwanda, Apotex and three patent holders, GlaxoSmithKline, Boehringer Ingleheim Canada and Shire BioChemical, Inc. It questions the efficiency of this process. This article considers the review of the Jean Chretien Pledge to Africa Act 2004 (Canada). It is critical of the refusal of the Conservative Government of Canada to make any amendments to the legislation to improve the cost-effective delivery of essential medicines. This article queries the proposed Hong Kong Amendment to the TRIPS Agreement 1994, given the concerns of the Africa Group. It is submitted that it is undesirable to codify the WTO General Council Decision 2003, given its failure to provide a speedy, efficient and cost-effective delivery of essential medicines.

Conceptualizing sustainable retirement villages in Australia

The Australian ageing society with baby boomers reaching retirement age has placed a lot of pressures on housing services. The retirement village is increasingly accepted as a suitable living arrangement for older people. Ecological theory of ageing emphasizes a match between environment and older peoples’ competences. As one response to this, creating village environment in a sustainable way is on the agenda. However, it is not very clear what kinds of sustainable features should be incorporated within the village environment to fit residents’ competences, in particular given that baby boomers who have unique requirements have become the main potential customers. In present paper, a sustainable retirement village framework is proposed by building on ecological theory of ageing and triple bottom line. A two-step inductive reasoning research method is adopted in this conceptualization process. The proposed sustainable retirement village framework contains four domains, including senior-oriented basic settings, financial affordability, age-friendly social environment and environmental sustainability. These four domains are interrelated, and a sustainable retirement village stresses a dynamic balance between different domains. This proposed framework not only gives implications for village developers on creating a suitable village environment to better accommodate residents, but also paves the way for future studies on housing older people in an age-friendly manner.

Two monoclonal antibodies to precisely the same epitope of type ii collagen select non-crossreactive phage clones by phage display: Implications for autoimmunity and molecular mimicry

Two monoclonal antibodies (mAb) CB268 and CII-C1 to type II collagen (CII) react with precisely the same conformational epitope constituted by the residues ARGLT on the three chains of the CII triple helix. The antibodies share structural similarity, with most differences in the complementarity determining region 3 of the heavy chain (HCDR3). The fine reactivity of these mAbs was investigated by screening two nonameric phage-displayed random peptide libraries. For each mAb, there were phage clones (phagotopes) that reacted strongly by ELISA only with the selecting mAb, and inhibited binding to CII only for that mAb, not the alternate mAb. Nonetheless, a synthetic peptide RRLPFGSQM corresponding to an insert from a highly reactive CII-C1-selected phagotope, which was unreactive (and non-inhibitory) with CB268, inhibited the reactivity of CB268 with CII. Most phage-displayed peptides contained a motif in the first part of the molecule that consisted of two basic residues adjacent to at least one hydrophobic residue (e.g. RRL or LRR), but the second portion of the peptides differed for the two mAbs. We predict that conserved CDR sequences interact with the basic-basic-hydrophobic motif, whereas non-conserved amino acids in the binding sites (especially HCDR3) interact with unique peptide sequences and limit cross-reactivity. The observation that two mAbs can react identically with a single epitope on one antigen (CII), but show no cross-reactivity when tested against a second (phagotope) indicates that microorganisms could exhibit mimics capable of initiating autoimmunity without this being evident from conventional assays.

Mimotopes identified by phage display for the monoclonal antibody CII- C1 to type II collagen

The characterization of B cell epitopes has been advanced by the use of random peptide libraries displayed within the coat protein of bacteriophage. This technique was applied to the monoclonal antibody (mAb) C1 to type II collagen (CII-C1). CII-C1 is known to react with a conformational epitope on type II collagen that includes residues 359-363. Three rounds of selection were used to screen two random nonameric phage libraries and 18 phagotopes were isolated. CII-C1 reacted by ELISA with 17 of the 18 phagotopes: one phagotope contained a stop codon. Of the eight most reactive phage, seven inhibited the reactivity by ELISA of CII-C1 with type II collagen. Of the 18 phage isolated, 11 encoded the motif F-G-x-Q with the sequence F-G-S-Q in 6, 2 encoded F-G-Q, and one the reverse motif Q-x-y-F. Most phagotopes that inhibited the reactivity of CII-C1 encoded two particular motifs consisting of two basic amino acid residues and a hydrophobic residue in the first part of the insert and the F-G-x-Q or F-G-Q motif ill the second part; phagotopes which contained only one basic residue in the first part of the sequence were less reactive. These motifs are not represented in the linear sequence of type II collagen and thus represent mimotopes of the epitope for CII-C1 on type II collagen. There were five phagotopes with peptide inserts containing the sequence RLPFG occurring in the Epstein-Barr virus nuclear antigen, EBNA- 1. This is of interest because EBV has been implicated in the initiation of rheumatoid arthritis (RA) by reason of increased reactivity to EBNA-1 in RA sera. In conclusion, the phage display technique disclosed mimotopes for a conformational epitope of type II collagen, and revealed an interesting homology with a sequence of the EBNA-1 antigen from Epstein Barr virus.

Crystal structures of the potassium and rubidium salts of (3,5-dichlorophenoxy)acetic acid: Two isotypic coordination polymers

The two-dimensional coordination polymeric structures of the hydrated potassium and rubidium salts of (3,5-dichlorophenoxy)acetic acid, (3,5-D) namely, poly[mu-aqua-bis[mu3-2-(3,5-dichlorophenoxy)acetato]potassium, [K2(C8H5Cl2O3)2 (H2O)]n (I) and poly[mu-aqua-bis[mu3-2-(3,5-dichlorophenoxy)acetato]dirubidium] [Rb2(C8H5Cl2O3)2 (H2O)]n (II), respectively have been determined and are described. The two compounds are isotypic and the polymer is based on centrosymmetric dinuclear bridged complex units. The irregular six-coordination about the metal centres comprises a bridging water molecule lying on a twofold rotation axis, the phenoxy O-atom donor and and a triple bridging carboxylate O-atom of the oxoacetate side chain of the 3,5-D ligand in a bidentate chelate mode, the second carboxy O-donor, also bridging. The K-O and Rb-O bond-length ranges are 2.7238(15)--2.9459(14) and 2.832(2)--3.050(2) \%A respectively and the K...K and Rb...Rb separations in the dinuclear unit are 4.0214(7) and 4.1289(6) \%A, respectively. Within the two-dimensional layers which lie parallel to (100), the coordinated water molecule forms an O---H...O hydrogen bond to the single bridging carboxylate O atom.