Mass spectrometric studies of the oxocarbons CnOn (n=3-6)

The anion radicals CnOn-. (n = 3-6) can be generated by ionization of cyclic carbonyl compounds in the negative ion mode. The ions as well as the corresponding neutral counterparts are probed by means of different mass spectrometric techniques. The results suggest that oxocarbons, i.e. cyclic polyketones, are formed under conservation of the skeletons of the precursor molecules. At least for n = 3, however, the experimental findings indicate partial rearrangement of the expected cyclopropanetrione structure to an oxycarboxylate for the anion, i.e. O-.-C=C-CO2-. For n = 4 and 6 almost complete dissociation of the neutral polyones into carbon monoxide is found, whereas for n = 5 a distinct recovery signal indicates the generation of genuine cyclopentanepentaone.

Poly-[μ-aqua-μ5-[(2,3,6-trichlorophenyl)acetato)-caesium]

In the structure of the title complex [Cs(C8H4Cl3O2)(H2O)]n, the Cs salt of the commercial herbicide fenac [(2,3,6-trichlorophenyl)acetic acid], the irregular eight-coordination about Cs+ comprises a bidentate chelate (O:Cl) interaction involving a carboxyl O-atom and an ortho-related ring substituted Cl atom which is also bridging, a triple-bridging carboxyl O-atom and a bridging water molecule. A two-dimensional sheet polymer is generated, lying parallel to (100), within which there are water O---H...O(carboxyl) hydrogen-bonding interactions.

Contribution of fibroblast and mast cell (afferent) and tumor (efferent) IL-6 effects within the tumor microenvironment

Hyperactive inflammatory responses following cancer initiation have led to cancer being described as a 'wound that never heals'. These inflammatory responses elicit signals via NFκB leading to IL-6 production, and IL-6 in turn has been shown to induce epithelial to mesenchymal transition in breast cancer cells in vitro, implicating a role for this cytokine in cancer cell invasion. We previously have shown that conditioned medium derived from cancer-associated fibroblasts induced an Epithelial to Mesenchymal transition (EMT) in PMC42-LA breast cancer cells and we have now identify IL-6 as present in this medium. We further show that IL-6 is expressed approximately 100 fold higher in a cancer-associated fibroblast line compared to normal fibroblasts. Comparison of mouse-specific (stroma) and human-specific (tumor) IL-6 mRNA expression from MCF-7, MDA MB 468 and MDA MB 231 xenografts also indicated the stroma rather than tumor as a significantly higher source of IL-6 expression. Mast cells (MCs) feature in inflammatory cancer-associated stroma, and activated MCs secrete IL-6. We observed a higher MC index (average number of mast cells per xenograft section/average tumor size) in MDA MB 468 compared to MDA MB 231 xenografts, where all MC were observed to be active (degranulating). This higher MC index correlated with greater mouse-specific IL-6 expression in the MDA MB 468 xenografts, implicating MC as an important source of stromal IL-6. Furthermore, immunohistochemistry on these xenografts for pSTAT3, which lies downstream of the IL-6 receptor indicated frequent correlations between pSTAT3 and mast cell positive cells. Analysis of publically available databases for IL-6 expression in patient tissue revealed higher IL-6 in laser capture microdissected stroma compared to adjacent tissue epithelium from patients with inflammatory breast cancer (IBC) and invasive non-inflammatory breast cancer (non-IBC) and we show that IL-6 expression was significantly higher in Basal versus Luminal molecular/phenotypic groupings of breast cancer cell lines. Finally, we discuss how afferent and efferent IL-6 pathways may participate in a positive feedback cycle to dictate tumor progression.

Interleukin-6 is a potent inducer of S100P, which is up-regulated in androgen-refractory and metastatic prostate cancer

Elevated circulating interleukin-6 (IL6) and up-regulated S100P in prostate cancer (PCa) specimens correlate independently with progression to androgen-independent and metastatic PCa. The cause of up-regulated S100P levels in advanced PCa remains to be determined. We investigated the possibility that IL6 is an inducer of S100P. Determination of mRNA and protein levels by real-time PCR and Western blotting revealed that IL6 is a more potent inducer of S100P than the synthetic androgen, R1881, in the LNCaP/C4-2B model of PCa progression. IL6 did not require androgen to induce S100P in these cells, which express a functional androgen receptor (AR). Like R1881, IL6 was unable to induce S100P in PC3 cells that lack a functional AR. IL6 did not strongly induce the AR-dependent genes PSA and KLK2 and, contrary to R1881, down-regulated Cyr61/CCN1, a potential marker that is down-regulated in PCa. Epidermal growth factor (EGF), which like IL6 is a non-androgen activator of the AR, did not induce S100P. The data identifies a unique gene-induction profile for IL6 and suggests that IL6 may require a functional AR for S100P induction. A link between elevated IL6 and up-regulated S100P in androgen-refractory and metastatic PCa is postulated.

The impact of a congestion charging exemption on the demand for new low‐emission vehicles

Numerous initiatives have been employed around the world in order to address rising greenhouse gas (GHG) emissions originating from the transport sector. These measures include: travel demand management (congestion‐charging), increased fuel taxes, alternative fuel subsidies and low‐emission vehicle (LEV) rebates. Incentivizing the purchase of LEVs has been one of the more prevalent approaches in attempting to tackle this global issue. LEVs, whilst having the advantage of lower emissions and, in some cases, more efficient fuel consumption, also bring the downsides of increased purchase cost, reduced convenience of vehicle fuelling, and operational uncertainty. To stimulate demand in the face of these challenges, various incentive‐based policies, such as toll exemptions, have been used by national and local governments to encourage the purchase of these types of vehicles. In order to address rising GHG emissions in Stockholm, and in line with the Swedish Government’s ambition to operate a fossil free fleet by 2030, a number of policies were implemented targeting the transport sector. Foremost amongst these was the combination of a congestion charge – initiated to discourage emissions‐intensive travel – and an exemption from this charge for some LEVs, established to encourage a transition towards a ‘green’ vehicle fleet. Although both policies shared the aim of reducing GHG emissions, the exemption for LEVs carried the risk of diminishing the effectiveness of the congestion charging scheme. As the number of vehicle owners choosing to transition to an eligible LEV increased, the congestion‐reduction effectiveness of the charging scheme weakened. In fact, policy makers quickly recognized this potential issue and consequently phased out the LEV exemption less than 18 months after its introduction (1). Several studies have investigated the demand for LEVs through stated‐preference (SP) surveys across multiple countries, including: Denmark (2), Germany (3, 4), UK (5), Canada (6), USA (7, 8) and Australia (9). Although each of these studies differed in approach, all involved SP surveys where differing characteristics between various types of vehicles, including LEVs, were presented to respondents and these respondents in turn made hypothetical decisions about which vehicle they would be most likely to purchase. Although these studies revealed a number of interesting findings in regards to the potential demand for LEVs, they relied on SP data. In contrast, this paper employs an approach where LEV choice is modelled by taking a retrospective view and by using revealed preference (RP) data. By examining the revealed preferences of vehicle owners in Stockholm, this study overcomes one of the principal limitations of SP data, namely that stated preferences may not in fact reflect individuals’ actual choices, such as when cost, time, and inconvenience factors are real rather than hypothetical. This paper’s RP approach involves modelling the characteristics of individuals who purchased new LEVs, whilst estimating the effect of the congestion charging exemption upon choice probabilities and subsequent aggregate demand. The paper contributes to the current literature by examining the effectiveness of a toll exemption under revealed preference conditions, and by assessing the total effect of the policy based on key indicators for policy makers, including: vehicle owner home location, commuting patterns, number of children, age, gender and income. Extended Abstract Submission for Kuhmo Nectar Conference 2014 2 The two main research questions motivating this study were:  Which individuals chose to purchase a new LEV in Stockholm in 2008?; and,  How did the congestion charging exemption affect the aggregate demand for new LEVs in Stockholm in 2008? In order to answer these research questions the analysis was split into two stages. Firstly, a multinomial logit (MNL) model was used to identify which demographic characteristics were most significantly related to the purchase of an LEV over a conventional vehicle. The three most significant variables were found to be: intra‐cordon residency (positive); commuting across the cordon (positive); and distance of residence from the cordon (negative). In order to estimate the effect of the exemption policy on vehicle purchase choice, the model included variables to control for geographic differences in preferences, based on the location of the vehicle owners’ homes and workplaces in relation to the congestion‐charging cordon boundary. These variables included one indicator representing commutes across the cordon and another indicator representing intra‐cordon residency. The effect of the exemption policy on the probability of purchasing LEVs was estimated in the second stage of the analysis by focusing on the groups of vehicle owners that were most likely to have been affected by the policy i.e. those commuting across the cordon boundary (in both directions). Given the inclusion of the indicator variable representing commutes across the cordon, it is assumed that the estimated coefficient of this variable captures the effect of the exemption policy on the utility of choosing to purchase an exempt LEV for these two groups of vehicle owners. The intra‐cordon residency indicator variable also controls for differences between the two groups, based upon direction of travel across the cordon boundary. A counter‐hypothesis to this assumption is that the coefficient of the variable representing commuting across the cordon boundary instead only captures geo‐demographic differences that lead to variations in LEV ownership across the different groups of vehicle owners in relation to the cordon boundary. In order to address this counter‐hypothesis, an additional analysis was performed on data from a city with a similar geodemographic pattern to Stockholm, Gothenburg ‐ Sweden’s second largest city. The results of this analysis provided evidence to support the argument that the coefficient of the variable representing commutes across the cordon was capturing the effect of the exemption policy. Based upon this framework, the predicted vehicle type shares were calculated using the estimated coefficients of the MNL model and compared with predicted vehicle type shares from a simulated scenario where the exemption policy was inactive. This simulated scenario was constructed by setting the coefficient for the variable representing commutes across the cordon boundary to zero for all observations to remove the utility benefit of the exemption policy. Overall, the procedure of this second stage of the analysis led to results showing that the exemption had a substantial effect upon the probability of purchasing and aggregate demand for exempt LEVs in Stockholm during 2008. By making use of unique evidence of revealed preferences of LEV owners, this study identifies the common characteristics of new LEV owners and estimates the effect of Stockholm's congestion charging exemption upon the demand for new LEVs during 2008. It was found that the variables that had the greatest effect upon the choice of purchasing an exempt LEV included intra‐cordon residency (positive), distance of home from the cordon (negative), and commuting across the cordon (positive). It was also determined that owners under the age of 30 years preferred non‐exempt LEVs (low CO2 LEVs), whilst those over the age of 30 years preferred electric vehicles. In terms of electric vehicles, it was apparent that those individuals living within the city had the highest propensity towards purchasing this vehicle type. A negative relationship between choosing an electric vehicle and the distance of an individuals’ residency from the cordon was also evident. Overall, the congestion charging exemption was found to have increased the share of exempt LEVs in Stockholm by 1.9%, with, as expected, a much stronger effect on those commuting across the boundary, with those living inside the cordon having a 13.1% increase, and those owners living outside the cordon having a 5.0% increase. This increase in demand corresponded to an additional 538 (+/‐ 93; 95% C.I.) new exempt LEVs purchased in Stockholm during 2008 (out of a total of 5 427; 9.9%). Policy makers can take note that an incentive‐based policy can increase the demand for LEVs and appears to be an appropriate approach to adopt when attempting to reduce transport emissions through encouraging a transition towards a ‘green’ vehicle fleet.

Identifying the key sociocultural influences on drinking behavior in high and moderate binge-drinking countries and the public policy implications

Despite considerable state investment and initiatives, binge drinking is still a major behavioral problem for policy makers and communities in many parts of the world. Furthermore, the practice of bingeing on alcohol seems to be spreading to young people in countries traditionally considered to have moderate drinking behaviors. Using a sociocultural lens and a framework of sociocultural themes from previous literature to develop propositions from their empirical study, the authors examine binge-drinking attitudes and behaviors among young people from high and moderate binge-drinking countries. The authors then make proposals regarding how policy makers can use social marketing more effectively to contribute to behavior change. Qualitative interviews were conducted with 91 respondents from 22 countries who were studying in two high binge-drinking countries at the time. The results show support for three contrasting sociocultural propositions that identify influences on binge drinking across these countries.

6 versus 12 month performance of polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model

Introduction Well-designed biodegradable scaffolds in combination with bone growth factors offer a valuable alternative to the current gold standard autograft in spinal fusion surgery Yong et al. (2013). Here we report on 6- vs 12- month data set evaluating the longitudinal performance of a CaP coated polycaprolactone (PCL) scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within a large preclinical animal model. Methods Twelve sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels; (i) calcium phosphate (CaP) coated polycaprolactone based scaffold plus 0.54µg rhBMP-2, (ii) CaP coated PCL- based scaffold alone or (iii) autograft (mulched rib head). Fusion assessments were performed via high resolution clinical computed tomography and histological evaluation were undertaken at six (n=6) and twelve (n=6) months post-surgery using the Sucato grading system (Sucato et al. 2004). Results The computed tomography fusion grades of the 6- and 12- months in the rhBMP-2 plus PCL- based scaffold group were 1.9 and 2.1 respectively, in the autograft group 1.9 and 1.3 respectively, and in the scaffold alone group 0.9 and 1.17 respectively. There were no statistically significant differences in the fusion scores between 6- and 12- month for the rhBMP plus PCL- based scaffold or PCL – based scaffold alone group however there was a significant reduction in scores in the autograft group. These scores were seen to correlate with histological evaluations of the respective groups. Conclusions The results of this study demonstrate the efficacy of scaffold-based delivery of rhBMP-2 in promoting higher fusion grades at 6- and 12- months in comparison to the scaffold alone or autograft group within the same time frame. Fusion grades achieved at six months using PCL+rhBMP-2 are not significantly increased at twelve months post-surgery.

The molecular structure of the phosphate mineral kidwellite NaFe93+(PO4)6(OH)11⋅3H2O – a vibrational spectroscopic study

The mineral kidwellite, a hydrated hydroxy phosphate of ferric iron and sodium of approximate formula NaFe93+(PO4)6(OH)11⋅3H2O, has been studied using a combination of electron microscopy with EDX and vibrational spectroscopic techniques. Raman spectroscopy identifies an intense band at 978 cm−1 and 1014 cm−1. These bands are attributed to the PO43− ν1 symmetric stretching mode. The ν3 antisymmetric stretching modes are observed by a large number of Raman bands. The series of Raman bands at 1034, 1050, 1063, 1082, 1129, 1144 and 1188 cm−1 are attributed to the ν3 antisymmetric stretching bands of the PO43− and HOPO32− units. The observation of these multiple Raman bands in the symmetric and antisymmetric stretching region gives credence to the concept that both phosphate and hydrogen phosphate units exist in the structure of kidwellite. The series of Raman bands at 557, 570, 588, 602, 631, 644 and 653 cm−1are assigned to the PO43− ν2 bending modes. The series of Raman bands at 405, 444, 453, 467, 490 and 500 cm−1 are attributed to the PO43− and HOPO32− ν4 bending modes. The spectrum is quite broad but Raman bands may be resolved at 3122, 3231, 3356, 3466 and 3580 cm−1. These bands are assigned to water stretching vibrational modes. The number and position of these bands suggests that water is in different molecular environments with differing hydrogen bond distances. Infrared bands at 3511 and 3359 cm−1 are ascribed to the OH stretching vibration of the OH units. Very broad bands at 3022 and 3299 cm−1 are attributed to the OH stretching vibrations of water. Vibrational spectroscopy offers insights into the molecular structure of the phosphate mineral kidwellite.

Cholesterol regulates Syntaxin 6 trafficking at trans-Golgi network endosomal boundaries.

Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs). This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.

Predicting stock market returns and volatility with investor sentiment : evidence from eight developed countries

We test the predictive ability of investor sentiment on the return and volatility at the aggregate market level in the U.S., four largest European countries and three Asia-Pacific countries. We find that in the U.S., France and Italy periods of high consumer confidence levels are followed by low market returns. In Japan both the level and the change in consumer confidence boost the market return in the next month. Further, shifts in sentiment significantly move conditional volatility in most of the countries, and in Italy such impacts lead to an increase in returns by 4.7% in the next month.

Educating for the creative economy in emerging countries

In 1972, the United Nations (UN) Conference on the Human Environment expressed a growing realization that economic and social progress needed to be balanced with a concern for the environment and the stewardship of natural resources. The hard-to-grasp concept of "sustainable development" was first defined as "development that meets the needs of the present without compromising the ability of future generations to meet their needs" (World Commission on Environment and Development [WESDJ, 1987, p. 43). This definition contains two concepts: first, "human needs," with priority given to the world's poor, and, second, the environment's limits for meeting the state of technological and social organization (WESD, 1987, p. 43). At the 2002 World Summit on Sustainable Development (UN, 2002a), the focus on environmental protection broadened to encompass social justice and the fight against poverty as key principles of development that is sustainable. Three interdependent and mutually reinforcing "pillars" were recognized: economic development, social development, and environmental protection. These pillars must be established at local, national, and global levels. The complexity and interrelationship of critical issues such as poverty, wasteful consumption, urban decay, population growth, gender inequality, health, conflict, and the violation of human rights are addressed in all three pillars (Pigozzi, 2003, p. 3). Following the concept of sustainable development, we argue that the challenge for developing countries in contemporary society is to meet the very real need for economic development and opportunities for income generation, while avoiding the unintended and unwanted consequences of economic development and globalization. These consequences include social exclusion, loss of cultural heritage, and environmental and ecological problems.

Women, peace and security as an ASEAN priority

The Association of South East Asian Nations (ASEAN) Secretariat and its member states have repeatedly professed their commitment to the protection and advancement of women’s economic and human rights. Such commitments have included the Declaration on the Advancement of Women in ASEAN in 1988, the ASEAN Declaration on the Elimination of Violence Against Women in 2004, and the ASEAN Declaration of Human Rights in 2012, as well as the establishment of the ASEAN Committee on Women in 2002 and the ASEAN Commission on the Promotion and Protection of Women and Children in 2009. However, none of these regional commitments or institutions expressly take up the core concern of the Women, Peace and Security (WPS) agenda set out in United Nations Security Council (UNSC) Resolution 1325 in 2000. ASEAN has no 1325 regional action plan and amongst the ASEAN membership, the Philippines is the only state that has adopted a 1325 National Action Plan (NAP). We explore the possible reasons for lack of ASEAN institutional engagement with 1325, outline the case for regional engagement, and suggest specific roles for ASEAN Secretariat, donor governments and individual member states to commit to UNSCR 1325 as a regional priority.

The 1989 Comprehensive Plan of Action (CPA) and refugee policy in Southeast Asia : twenty years forward what has changed?

In 2012, the only South East Asian countries that have ratified the 1951 Convention relating to the Status of Refugees and the 1967 Protocol Relating to the Status of Refugees (hereafter referred to as the 1951 Convention and 1967 Protocol) is Philippines (signed 1954), Cambodia (signed 1995) and Timor Leste (signed 2001). Countries such as Indonesia, Malaysia and Thailand have annual asylum seeking populations from Myanmar, South Asia and Middle East, that are estimated to be at 15 000-20 000 per country (UNHCR 2012). The lack of a permanent and formal asylum processing process in these countries means that that asylum-seeking populations in the region are reliant on the local offices of the United Nations High Commission for Refugees based in the region to process their claims. These offices rely upon the good will of these governments to have a presence near detection camps and in capital cities to process claims of those who manage to reach the UNHCR representative office. The only burden sharing mechanism within the region primarily exists under the Bali Process on People Smuggling, Trafficking in Persons and Related Transnational Crime (the Bali Process), introduced in 2002. The Bali Process refers to an informal cooperative agreement amongst the states from the Asia-Pacific region, with Australia and Indonesia as the co-chairs, which discusses its namesake: primarily anti-people smuggling activities and migration protocols. There is no provision within this process to discuss the development of national asylum seeking legislation, processes for domestic processing of asylum claims or burden sharing in contrast to other regions such as Africa and South America (i.e. 2009 African Union Convention for the Protection and Assistance of the Internally Displaced, 1969 African Union Convention Governing the Specific Aspects of Refugee Problems in Africa and 1984 Cartagena Declaration on Refugees [Americas]) (PEF 2010: 19).

Asia Pacific Business Process Management

This book constitutes the proceedings of the Second Asia Pacific Conference on Business Process Management held in Brisbane, QLD, Australia, in July 2014. In all, 33 contributions from 12 countries were submitted. After each submission was reviewed by at least three Program Committee members, nine full papers were accepted for publication in this volume. These nine papers cover various topics that can be categorized under four main research focuses in BPM: process mining, process modeling and repositories, process model comparison, and process analysis.

A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands : challenges for malaria diagnostics in an elimination setting

Background Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting. Methods During the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs). The performances of these diagnostic methods were compared. Results A total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%. The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax. In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥38°C) at the time of the survey. A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/μL. There was an age correlation for the proportion of parasite density below 100/μL for P. vivax infections, but not for P. falciparum infections. PCR detected substantially more infections than microscopy (point prevalence of 8.71%), indicating a large number of subjects had sub-microscopic parasitemia. The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162) compared to P. falciparum (36/118). The malaria RDT detected the 12 microscopy and PCR positive P. falciparum, but failed to detect 12/13 microscopy and PCR positive P. vivax infections. Conclusion Asymptomatic malaria infections and infections with low and sub-microscopic parasite densities are highly prevalent in Temotu province where malaria transmission is low. This presents a challenge for elimination since the large proportion of the parasite reservoir will not be detected by standard active and passive case detection. Therefore effective mass screening and treatment campaigns will most likely need more sensitive assays such as a field deployable molecular based assay.