The origins of stability of spontaneous vesicles

Equilibrium unilamellar vesicles are stabilized by one of two distinct mechanisms depending on the value of the bending constant. Helfrich undulations ensure that the interbilayer potential is always repulsive when the bending constant, K, is of order kBT. When K ≫ kBT, unilamellar vesicles are stabilized by the spontaneous curvature that picks out a particular vesicle radius; other radii are disfavored energetically. We present measurements of the bilayer elastic constant and the spontaneous curvature, Ro, for three different systems of equilibrium vesicles by an analysis of the vesicle size distribution determined by cryo-transmission electron microscopy and small-angle neutron scattering. For cetyltrimethylammonium bromide (CTAB)/sodium octyl sulfonate catanionic vesicles, K = .7 kBT, suggesting that the unilamellar vesicles are stabilized by Helfrich-undulation repulsions. However, for CTAB and sodium perfluorooctanoate (FC7) vesicles, K = 6 kBT, suggesting stabilization by the energetic costs of deviations from the spontaneous curvature. Adding electrolyte to the sodium perfluorooctanoate/CTAB vesicles leads to vesicles with two bilayers; the attractive interactions between the bilayers can overcome the cost of small deviations from the spontaneous curvature to form two-layer vesicles, but larger deviations to form three and more layer vesicles are prohibited. Vesicles with a discrete numbers of bilayers at equilibrium are possible only for bilayers with a large bending modulus coupled with a spontaneous curvature.

An evaluation of the performance of cDNA microarrays for detecting changes in global mRNA expression

The cDNA microarray is one technological approach that has the potential to accurately measure changes in global mRNA expression levels. We report an assessment of an optimized cDNA microarray platform to generate accurate, precise and reliable data consistent with the objective of using microarrays as an acquisition platform to populate gene expression databases. The study design consisted of two independent evaluations with 70 arrays from two different manufactured lots and used three human tissue sources as samples: placenta, brain and heart. Overall signal response was linear over three orders of magnitude and the sensitivity for any element was estimated to be 2 pg mRNA. The calculated coefficient of variation for differential expression for all non-differentiated elements was 12–14% across the entire signal range and did not vary with array batch or tissue source. The minimum detectable fold change for differential expression was 1.4. Accuracy, in terms of bias (observed minus expected differential expression ratio), was less than 1 part in 10 000 for all non-differentiated elements. The results presented in this report demonstrate the reproducible performance of the cDNA microarray technology platform and the methods provide a useful framework for evaluating other technologies that monitor changes in global mRNA expression.

Nutraceutical approach to the modulation of cholesterol metabolism: in vitro and in vivo studies

Negli ultimi anni, si sono diffusi nuove strategie per il trattamento delle malattie cardiovascolari, che possano supportare una terapia medica, o in alcuni casi, sostituirla. Infatti, l’abbandono delle terapie è il più importante problema di salute pubblica del mondo occidentale, soprattutto per le malattie croniche. Ciò è dovuto alla complessità delle terapie farmacologiche e ai numerosi e in alcuni casi gravi effetti collaterali dei farmaci somministrati. Di conseguenza, una riduzione di questi effetti migliorerebbe le condizioni di vita del paziente e quindi diminuirebbe il rischio di abbandono della terapia. Per ottenere ciò, è possibile affiancare al trattamento farmacologico una terapia nutraceutica, consistente nella somministrazione di complessi molecolari o microorganismi, provenienti da piante, latte o cibi funzionali. Lo scopo generale di questo studio è indagare le attività ipolipidemizzanti di un composto nutraceutico e di un ceppo batterio specifico nel modello animale che presenta elevati alti livelli plasmatici di colesterolo. Inoltre, sono stati analizzati gli effetti del trattamento nutraceutico sui meccanismi fisiologici che contrastano la creazione della placca aterosclerotica come l’efflusso di colesterolo dalle “foam cells” presenti nell’ateroma, o la riduzione dell’assorbimento intestinale di colesterolo. La presente tesi è divisa in due parti. Nella prima parte, abbiamo analizzato la capacità dei Bifidobacteria di ridurre i livelli di colesterolo nel medium di crescita. Dall’analisi, si è osservato che vari ceppi del genere Bifidobacteria presentano un’ampia capacità di assimilazione del colesterolo all’interno della cellula batterica, in particolare il Bifidobacterium bifidum PRL2010. Le analisi di trascrittomica del Bb PRL2010 incubato in presenza di colesterolo, hanno rivelato un significativo aumento dei livelli di trascrizione di geni codificanti trasportatori e riduttasi, responsabili del meccanismo di accumulo all’interno della cellula batterica e della conversione del colesterolo in coprostanolo. L’attività ipolipidemizzante del Bb PRL2010 è stata poi valutata nel modello murino, mostrando la modificazione del microbiota dei topi trattati dopo somministrazione del batterio in questione. Nella seconda parte del progetto di ricerca, abbiamo indagato sugli effetti di un composto coperto da brevetto, chiamato “Ola”, sull’efflusso di colesterolo di criceti trattati con questo composto nutraceutico. L’efflusso di colesterolo è il primo step del meccanismo fisiologico noto come Trasporto Inverso del Colesterolo, che consente l’eliminazione del colesterolo dalle placche aterosclerotiche, attraverso l’interazione fra le HDL, presenti nella circolazione sanguigna, e specifici trasportatori delle foam cells, come ABCA1/G1 e SR-BI. In seguito, le lipoproteine rilasciano il colesterolo alle cellule epatiche, dove è metabolizzato ed escreto attraverso le feci. Per valutare l’effetto dell’Ola sul profilo lipidico dei criceti, sono state condotte analisi in vitro. I risultati mostrano un aumento dell’efflusso di colesterolo in cellule che esprimono il trasportatore ABCA1, comparato con il gruppo controllo. Questi due studi mostrano come l’approccio nutraceutico può essere un importante modo per contrastare l’aterosclerosi. Come mostrato in letteratura, gli effetti dei composti nutraceutici sull’aterosclerosi e su altre malattie croniche, hanno portato a un ampio uso come supporto alle terapie farmacologiche, ed in alcuni casi hanno rimpiazzato la terapia farmacologica stessa.

Effects of Institutional Factors on the Retention of Graduate Students of Color in Schools of Library and Information Science

The intent of the study was to understand the changes that have occurred over the last 25 years in library programs as far as enrollment and diversity of students, number and ethnicity of the faculty, program income and expenses, cost of attendance, and scholarship and fellowship aid, in an effort to better understand library programs granting the MLIS degree. The study also endeavored to identify institutional factors associated with the retention and productivity rates of White students and students of color in schools of library and information science. During the period studied, the proportional representation of White students decreased. For students of color, proportional representation was stable during the same time period. Results revealed a medium effect size of time with productivity rates for both groups declining over time. Retention rate differed significantly by time, with a small effect size with retention rate that initially increased over time, but is now decreasing. The final analyses were meta-regressions to determine if retention and productivity rates can be predicted by cost of attendance, scholarship and fellow aid, and program size. Results indicated that for students of color, program size in 2000 was significantly predictive of retention, cost of attendance was predictive in 2002, and scholarship and fellowship aid was predictive of retention in 2004. No variables were significantly predictive for retention of White students. The last analysis was to determine if productivity rate can be predicted by cost of attendance, scholarship and fellow aid, and program size. Results indicate that for White students in 2002, the cost of attendance was predictive of productivity rating. In 2003, scholarship and fellowship aid was predictive of productivity rate and in 2004, scholarship and fellowship aid was predictive of productivity rating. For students of color, results indicate that only scholarship and fellowship aid in 2005 was predictive of productivity rate. No other variables in any of the years studied showed any significant prediction of productivity rating for students of color.

The Power of the Placement of Public Sculpture

The Power of the Placement of Public Sculpture explores the aesthetic effects public sculpture has on the environment around it. The work presented includes a discussion of case studies in select American and international communities. Relevance is brought to the topic through the documentation of the placement of a fabricated eight-foot avocado sculpture displayed on the University of Denver campus. Reflection on the experience exposes additional questions and demonstrates the importance of the placement of a public sculpture.

Is the date of birth an advantage/ally to excel in handball?

The Relative Age Effect (RAE) has been analyzed in a population of Spanish international handball players (n=161) divided into four different levels: Senior, Junior, Juvenile and Promising Talents. The variables registered were quarter, half year and year of birth using the initial information of their date of birth. The data were collected from the Royal Spanish Handball Federation on-line data base. The statistical method used was the χ2 and the minimum level of significance was set at p<0.05. The total results on distribution by quarter show a significant difference (χ2= 21.68; p<0.01) with a greater frequency of players born in the first quarter (40.37%) compared to those born in the second (22.36%), third (16.15%) and fourth quarter (21.12%). The total results on the distribution of birth date by half year show a significant difference (χ2= 10.44; p<0.01) with a greater frequency of players born in the first half of the year (62.73%). With regard to the rate of births registered in an even numbered or odd numbered year there are significant differences when the rates for an even numbered year (64.60%) and an odd numbered year (35.40%) are compared with those of the general population (χ2= 13.72; p<0.001). Based on the data collected and analyzed it can be concluded that there is a RAE in the basic categories of the Spanish national men’s handball teams according to quarter, half year and year of birth (even or odd numbered), but there exists little knowledge about the causes and consequence which may be produced by, or derive from, this effect.

Applying model-driven engineering to the development of Rich Internet Applications for Business Intelligence

Business Intelligence (BI) applications have been gradually ported to the Web in search of a global platform for the consumption and publication of data and services. On the Internet, apart from techniques for data/knowledge management, BI Web applications need interfaces with a high level of interoperability (similar to the traditional desktop interfaces) for the visualisation of data/knowledge. In some cases, this has been provided by Rich Internet Applications (RIA). The development of these BI RIAs is a process traditionally performed manually and, given the complexity of the final application, it is a process which might be prone to errors. The application of model-driven engineering techniques can reduce the cost of development and maintenance (in terms of time and resources) of these applications, as they demonstrated by other types of Web applications. In the light of these issues, the paper introduces the Sm4RIA-B methodology, i.e., a model-driven methodology for the development of RIA as BI Web applications. In order to overcome the limitations of RIA regarding knowledge management from the Web, this paper also presents a new RIA platform for BI, called RI@BI, which extends the functionalities of traditional RIAs by means of Semantic Web technologies and B2B techniques. Finally, we evaluate the whole approach on a case study—the development of a social network site for an enterprise project manager.

The Impact of BIM on the Distribution of Cost and Return on Investment in UK Construction Projects

It has been widely documented that when Building Information Modelling (BIM) is used, there is a shift in effort to the design phase. Little investigation into the impact of this shift in effort has been done and how it impacts on costs. It can be difficult to justify the increased expenditure on BIM in a market that is heavily driven by costs. There are currently studies attempting to quantify the return on investment (ROI) for BIM for which these returns can be seen to balance out the shift in efforts and costs to the design phase. The studies however quantify the ROI based on the individual stakeholder’s investment without consideration for the impact that the use of BIM from their project partners may have on their own profitability. In this study, a questionnaire investigated opinions and experience of construction professionals, representing clients, consultants, designers and contractors, to determine fluctuations in costs by their magnitude and when they occur. These factors were examined more closely by interviewing senior members representing each of the stakeholder categories and comparing their experience in using BIM within environments where their project partners were also using BIM and when they were not. This determined the differences in how the use and the investment in BIM impacts on others and how costs are redistributed. This redistribution is not just through time but also between stakeholders and categories of costs. Some of these cost fluctuations and how the cost of BIM is currently financed are also highlighted in several case studies. The results show that the current distribution of costs set for traditional 2D delivery is hindering the potential success of BIM. There is also evidence that stakeholders who don’t use BIM may benefit financially from the BIM use of others and that collaborative BIM is significantly different to the use of ‘lonely’ BIM in terms of benefits and profitability.

The adoption of IPSASs in the Iberian Peninsula: the perspective of the standar-setters

The last decades have been fruitful in reforms in public sector accounting across the world, namely moving from cash-based into accrual-based regimes. In this process of bringing public sector accounting close to business accounting, International Public Sector Accounting Standards (IPSASs) have been developed and adopted in several countries. In the EU context, public sector harmonization among member-States is currently being considered, namely via the development of European Public Sector Accounting Standards (EPSASs). Both IPSASs and EPSASs are understood as, among other things, important to contribute for a more informative and transparent financial reporting of public sector entities and governments. Moreover they are expected to approximate public sector accounting and the National Accounts, hence allowing for more reliable information to monitor fiscal discipline among EU countries. The Iberian countries, after using accrual accounting in the public sector for more than twenty years (Spain from middle 1980s and Portugal from 1990s), have acknowledged the need to embark in an international harmonization process adopting IPSASs, particularly after the adoption of IFRSs in the business sector, which was creating some difficulties for consolidated accounts. Spain has passed the Chart of Accounts for the Public Sector through the Order EHA/1037/2010, which is adapted to IPSASs; Portugal has just passed Law-decree 192/2015, September 11, and is expecting to start implementation in 2017. In both countries a central role in this reform has been assumed by the national standard-setters for public sector accounting. Based on the “Actor Network Theory” to help understanding how and why organizations interact and how this interaction could have an impact on their choice of accounting policies, this paper aims to analyse, from the Iberian public sector accounting standard-setters perspective, how the adoption/adaptation of IPSASs has been considered and developed in these countries. Research questions to be considered are the following, which will be asked in interviews to the members of the standard-setting committees in both Portugal and Spain: • What were the driving forces leading to the decision to adopt and implement IPSASs? • Which other governmental bodies’ experiences, if any, were considered in the adoption of IPSASs? • What specific steps were/are being undertaken to prepare for the conversion from the existing system to IPSASs? • What were/are the institutional challenges faced/expected to face? • What assistance have been received from IFAC and/or IPSASB, or from other sources, if any, throughout the adoption/implementation? • How can the success of the adoption/implementation be characterised? • What benefits can/have the government derive/derived from the adoption and implementation of IPSASs? The paper is expected to contribute to the understanding of the issues underlying the process of embarking in public sector accounting reforms towards IPSASs.

Electricity without borders: a plan to make the internal market work. Bruegel Blueprint Series 20, 5 September 2013

The most straightforward European single energy market design would entail a European system operator regulated by a single European regulator. This would ensure the predictable development of rules for the entire EU, significantly reducing regulatory uncertainty for electricity sector investments. But such a first-best market design is unlikely to be politically realistic in the European context for three reasons. First, the necessary changes compared to the current situation are substantial and would produce significant redistributive effects. Second, a European solution would deprive member states of the ability to manage their energy systems nationally. And third, a single European solution might fall short of being well-tailored to consumers’ preferences, which differ substantially across the EU. To nevertheless reap significant benefits from an integrated European electricity market, we propose the following blueprint: First, we suggest adding a European system-management layer to complement national operation centres and help them to better exchange information about the status of the system, expected changes and planned modifications. The ultimate aim should be to transfer the day-to-day responsibility for the safe and economic operation of the system to the European control centre. To further increase efficiency, electricity prices should be allowed to differ between all network points between and within countries. This would enable throughput of electricity through national and international lines to be safely increased without any major investments in infrastructure. Second, to ensure the consistency of national network plans and to ensure that they contribute to providing the infrastructure for a functioning single market, the role of the European ten year network development plan (TYNDP) needs to be upgraded by obliging national regulators to only approve projects planned at European level unless they can prove that deviations are beneficial. This boosted role of the TYNDP would need to be underpinned by resolving the issues of conflicting interests and information asymmetry. Therefore, the network planning process should be opened to all affected stakeholders (generators, network owners and operators, consumers, residents and others) and enable the European Agency for the Cooperation of Energy Regulators (ACER) to act as a welfare-maximising referee. An ultimate political decision by the European Parliament on the entire plan will open a negotiation process around selecting alternatives and agreeing compensation. This ensures that all stakeholders have an interest in guaranteeing a certain degree of balance of interest in the earlier stages. In fact, transparent planning, early stakeholder involvement and democratic legitimisation are well suited for minimising as much as possible local opposition to new lines. Third, sharing the cost of network investments in Europe is a critical issue. One reason is that so far even the most sophisticated models have been unable to identify the individual long-term net benefit in an uncertain environment. A workable compromise to finance new network investments would consist of three components: (i) all easily attributable cost should be levied on the responsible party; (ii) all network users that sit at nodes that are expected to receive more imports through a line extension should be obliged to pay a share of the line extension cost through their network charges; (iii) the rest of the cost is socialised to all consumers. Such a cost-distribution scheme will involve some intra-European redistribution from the well-developed countries (infrastructure-wise) to those that are catching up. However, such a scheme would perform this redistribution in a much more efficient way than the Connecting Europe Facility’s ad-hoc disbursements to politically chosen projects, because it would provide the infrastructure that is really needed.

At any price: Russia is embarking on the construction of South Stream. OSW Commentary No. 98, 2012-12-07

Gazprom is determined to continue its efforts to build the South Stream gas pipeline regardless of the slump on the European gas market and the fact that there is sufficient capacity already in the existing transport infrastructure. The official inauguration of the maritime section of South Stream was held on 7 December this year, but the construction itself will commence in 2014. The agreements concluded so far, both intergovernmental and between corporations, are necessary for the launch of the construction of the new pipeline, but still do not guarantee that the project will be completed on time. First of all, some legal problems have yet to be resolved, such as the evaluation of the compliance of the planned actions with the ‘third energy package’ or the fact that ecological surveys required under European law need to be carried out. Secondly, given the present situation on the European gas market and medium-term forecasts, the high cost of implementation of this project and the maintenance expenses of existing pipelines – which are not being used to full capacity – the new project seems to be unfeasible. However, Gazprom’s determination in its efforts to build the pipeline proves that Russia is ready to take a high economic risk to maintain its dominant position on the European gas supply market; it will restrict the possibilities of alternative infrastructural projects being implemented (above all, the EU’s Southern Corridor) and use the construction of new pipelines as an instrument of political pressure on the present transit countries (especially Ukraine).

How EU Fiscal Norms Will Become a Safety Net for the Failure of National Golden Rules. European Policy Brief No. 6, January 2012

If introduced successfully, national Golden Rules will completely overturn fiscal governance in the eurozone. Golden Rules would almost always be more stringent than EU-level fiscal norms. EU fiscal norms will hence evolve into a safety net in case a Golden Rule fails. The possibility of such a failure is, indeed, not to be dismissed. Because of the severity of the Golden Rules, eurozone leaders should reflect on their design. There is a real risk that they will undercut public investment, which would be at the cost of the EU’s other long-term challenges.

On the Evaluation of a DSL for Architectural Consistency Checking

Software architecture erodes over time and needs to be constantly monitored to be kept consistent with its original intended design. Consistency is rarely monitored using automated techniques. The cost associated to such an activity is typically not considered proportional to its benefits. To improve this situation, we propose Dicto, a uniform DSL for specifying architectural invariants. This language is designed to reduce the cost of consistency checking by offering a framework in which existing validation tools can be matched to newly-defined language constructs. In this paper we discuss how such a DSL can be qualitatively and qualitatively evaluated in practice.

The Principle of Common Concern and Climate Change

Effective policies combating global warming and incentivising reduction of greenhouse gases face fundamental collective action problems. States defending short term interests avoid international commitments and seek to benefit from measures combating global warming taken elsewhere. The paper explores the potential of Common Concern as an emerging principle of international law, in particular international environmental law, in addressing collective action problems and the global commons. It expounds the contours of the principle, its relationship to common heritage of mankind, to shared and differentiated responsibility and to public goods. It explores its potential to provide the foundations not only for international cooperation, but also to justify, and delimitate at the same time, unilateral action at home and deploying extraterritorial effects in addressing the challenges of global warming and climate change mitigation. As unilateral measures mainly translate into measures of trade policy, the principle of Common Concern is inherently linked and limited by existing legal disciplines in particular of the law of the World Trade Organization.

Contributions to the history of science,

Each part also published separately, 1915 and 1916 respectively.