Structural effects of neutral lipids on the divalent cation-induced interactions of phosphatidylserine - containing bilayers

As Ca2+ and phosphatidylserine (PS) are known to induce the adhesion of bilayer vesicles and form collapsed multibilayer structures in vitro, it was the aim of this study to examine how that interaction and the resultant structures might be modified by neutral lipid species. X-ray diffraction data from multilamellar systems suggest that phosphatidylcholine (PC) and diacylglycerol (DG) might be in the collapsed phase up to a concentration of -30 mole % and that above this concentration these neutral lipids may modify Ca2+-induced bilayer interactions. Using large unilamellar vesicles and long incubations in excess Ca2+ to ensure equilibration, similar preliminary results were again obtained with PC, and also with phosphatidylethanolamine (PE). A combination of X-ray diffraction, thin-layer chromatography, density gradient centrifugation and freeze-fracture electron microscopy, used in conjunction with an osmotic stress technique, showed that (i) -30 mole % PC can be accomodated in the Ca(DOPS)2 phase; and (ii) higher PC levels modify Ca2+-induced bilayer interactions resulting in single lamellar phases of larger dimension and reduced tendency for REV collapse. Importantly, the data suggest that PC is dehydrated during the rapid collapse process leading. to Ca(DOPS)2 formation and exists with this dehydrated phase. Similar results were obtained using PS isolated from bovine brain. Preliminary studies using two different phosphatidylethanolamine (PE) species indicated accomodation by Ca(DOPS)2 of -25-30 mole 0/0 PE and bulk phase separation, of species favouring a non-bilayer phase, at higher levels. Significantly, all PS/PE vesicles appear to undergo a complete Ca2+-induced collapse, even with contents of up to 90 mole % PE. These data suggest that PE may have an important role in fusion mechanisms in vivo. In sum the data lend both structural and stoichiometric evidence for th~ existence of laterally segregated neutral lipid molecules within the same bilayers as PS domains exposed to Ca2+.

A influência do esgoto doméstico como fluido de saturação no colapso de um solo arenoso

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exploring the folding free energy surface of a three-helix bundle protein

The multidimensional free energy surface for a small fast folding helical protein is explored based on first-principle calculations. The model represents the 46-residue segment from fragment B of staphylococcal protein A. The relationship between collapse and tertiary structure formation, and the order of collapse and secondary structure formation, are investigated. We find that the initial collapse process gives rise to a transition state with about 30% of the native tertiary structure and 50–70% of the native helix content. We also observe two distinct distributions of native helix in this collapsed state (Rg ≈ 12 Å), one with about 20% of the native helical hydrogen bonds, the other with near 70%. The former corresponds to a local minimum. The barrier from this metastable state to the native state is about 2 kBT. In the latter case, folding is essentially a downhill process involving topological assembly. In addition, the order of formation of secondary structure among the three helices is examined. We observe cooperative formation of the secondary structure in helix I and helix II. Secondary structure in helix III starts to form following the formation of certain secondary structure in both helix I and helix II. Comparisons of our results with those from theory and experiment are made.

Loess as a Collapsible Soil: Some Basic Particle Packing

Loess is the most important collapsible soil; possibly the only engineering soil in which real collapse occurs. A real collapse involves a diminution in volume - it would be an open metastable packing being reduced to a more closely packed, more stable structure. Metastability is at the heart of the collapsible soils problem. To envisage and to model the collapse process in a metastable medium, knowledge is required about the nature and shape of the particles, the types of packings they assume (real and ideal), and the nature of the collapse process - a packing transition upon a change to the effective stress in a media of double porosity. Particle packing science has made little progress in geoscience discipline - since the initial packing paradigms set by Graton and Fraser (1935) - nevertheless is relatively well-established in the soft matter physics discipline. The collapse process can be represented by mathematical modelling of packing – including the Monte Carlo simulations - but relating representation to process remains difficult. This paper revisits the problem of sudden packing transition from a micro-physico-mechanical viewpoint (i.e. collapse imetan terms of structure-based effective stress). This cross-disciplinary approach helps in generalization on collapsible soils to be made that suggests loess is the only truly collapsible soil, because it is only loess which is so totally influenced by the packing essence of the formation process.

Branching processes and computational collapse of discretized unimodal mappings

In computer simulations of smooth dynamical systems, the original phase space is replaced by machine arithmetic, which is a finite set. The resulting spatially discretized dynamical systems do not inherit all functional properties of the original systems, such as surjectivity and existence of absolutely continuous invariant measures. This can lead to computational collapse to fixed points or short cycles. The paper studies loss of such properties in spatial discretizations of dynamical systems induced by unimodal mappings of the unit interval. The problem reduces to studying set-valued negative semitrajectories of the discretized system. As the grid is refined, the asymptotic behavior of the cardinality structure of the semitrajectories follows probabilistic laws corresponding to a branching process. The transition probabilities of this process are explicitly calculated. These results are illustrated by the example of the discretized logistic mapping.

Growth and demise of Permian biogenic chert along northwest Pangea: evidence for end-Permian collapse of thermohaline circulation

The Permian Chert Event (PCE) was a 30 Ma long episode of unusual chert accumulation along the northwest margin of Pangea, and possibly worldwide. The onset of the PCE occurred at about the Sakmarian-Artinskian boundary in the Sverdrup Basin, Canadian Arctic, where it coincides with a maximum flooding event, the ending of high-frequency/high-amplitude shelf cyclicity, the onset of massive biogenic chert deposition in deep-water distal areas, and a long-term shift from warm- to cool-water carbonate sedimentation in shallow-water proximal areas. A similar and coeval shift is observed from the Barents Sea to the northwestern USA. A landward and southward expansion of silica factories occurred during the Middle and Late Permian at which time warm-water carbonate producers disappeared completely from the northwest margin of Pangea. Biotically impoverished and increasingly narrow cold-water carbonate factories (characterised by non-cemented bioclasts of sponges, bryozoans, echinoderms and brachiopods) were then progressively replaced by silica factories. By Late Permian time, little carbonate sediments accumulated in the Barents Sea and in the Sverdrup Basin. where the deep- to shallow-water sedimentary spectrum was occupied by siliceous sponge spicules. By that time, biogenic silica sedimentation was common throughout the world. Silica factories collapsed in the Late Permian, abruptly bringing the PCE to an end. In northwest Pangea, the end- Permian collapse of the PCE was associated with a major transgression and with a return to much warmer oceanic and continental climatic conditions. Chert deposition resumed in the distal oceanic areas during the early Middle Triassic (Anisian) after a 8-10 Ma interruption (Early Triassic Chert Gap). The conditions necessary for the onset, expansion and zenith of the PCE were provided by the thermohaline circulation of nutrient-rich cold waters along the northwestern and western margin of Pangea, and possibly throughout the world oceans. These conditions provided an efficient transportation mechanism that constantly replenished the supply of silica in the area, created a nutrient- and oxygen-rich environment favouring siliceous biogenic productivity. established cold sea-floor conditions, hindering silica dissolution, while increasing calcium carbonate solubility, and provided conditions adverse to organic and inorganic carbonate production, The northwest margin of Pangea was, for nearly 30 Ma. bathed by cold waters presumably derived from the seasonal melting of northern sea ice, the assumed engine for thermohaline circulation. This process started near the Sakmarian-Artinskian boundary. intensified throughout Middle and Late Permian time and ceased suddenly in latest Permian time, It led to oceanic conditions much colder than normally expected from the palaeolatitudes. and the influence of cold northerly-derived water was felt as far south southern Nevada. The demise of silica factories was caused by the rapid breakdown of these conditions and the establishment of a much warmer marine environment accompanied by sluggish circulation and perhaps a reduced input of dissolved silica to the ocean. Complete thawing of northern sea ice would have ended thermohaline circulation and led to warm and sluggish oceanic conditions inimical to the production. accumulation and preservation of biogenic silica.

The Prize is more Peace: The EU should consolidate its enlargement process. CEPS Commentary, 8 November 2012

The sovereign debt crisis and the threat of financial collapse of some EU member states have triggered fierce debate about the economic, social and political finalité of the Union and curbed the appetite for further enlargement. The European Commission needs to find new ways to consolidate the enlargement agenda, gain full support of the member states for its implementation and assure a consistent application of the pre-accession requirements. Arguably, more time, more money and greater expertise are needed to pursue the vocation recognised by the Nobel Committee.

Effect of apparent viscosity on fluidized bed drying process parameters of guava pulp

Pressure drop and minimum fluidization velocity were experimentally studied in a vibro-fluidized bed of inert particles subjected to different vibration intensities during drying of guava pulp. Maltodextrin was added to the pulp in order to prevent stickiness between particles and the consequent bed collapse. Pulps were initially concentrated, resulting in pastes with different soluble solids content, and a constant fraction of maltodextrin was guaranteed in the final pulp samples. The pulp rheological behavior as affected by temperature and total soluble solids content, including maltodextrin, was evaluated and the effect of pulp apparent viscosity on pressure drop and minimum vibro-fluidization velocity were investigated. Two types of inert particles -3.6 mm glass beads and 3 mm Teflon cylinders were tested and, due to lower pressure drop presented by Teflon cylinders during operation of the dry vibro-fluidized bed, these particles were adopted for pulp drying process. Increasing pulp apparent viscosity caused a considerable increase in the vibro-fluidized bed pressure drop during pulp drying and, as a consequence resulted in a larger value of minimum vibro-fluidization velocity. on the other hand, the negative effect of increasing apparent viscosity could be attenuated by increasing the fluidized bed vibration intensity, which could prevent stickiness between particles. (c) 2006 Elsevier Ltd. All rights reserved.

Large heterogeneities in comet 67P as revealed by active pits from sinkhole collapse

Pits have been observed on many cometary nuclei mapped by spacecraft(1-4). It has been argued that cometary pits are a signature of endogenic activity, rather than impact craters such as those on planetary and asteroid surfaces. Impact experiments(5,6) andmodels(7,8) cannot reproduce the shapes of most of the observed cometary pits, and the predicted collision rates imply that few of the pits are related to impacts(8,9). Alternative mechanisms like explosive activity(10) have been suggested, but the driving process remains unknown. Here we report that pits on comet 67P/Churyumov-Gerasimenko are active, and probably created by a sinkhole process, possibly accompanied by outbursts. We argue that after formation, pits expand slowly in diameter, owing to sublimation-driven retreat of the walls. Therefore, pits characterize how eroded the surface is: a fresh cometary surface will have a ragged structure with many pits, while an evolved surface will look smoother. The size and spatial distribution of pits imply that large heterogeneities exist in the physical, structural or compositional properties of the first few hundred metres below the current nucleus surface.

Plastisol foaming process. Decomposition of the foaming agent, polymer behavior in the corresponding temperature range and resulting foam properties

The decomposition of azodicarbonamide, used as foaming agent in PVC—plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min−1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g−1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol−1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse.

The Political Logic of Disintegration: Seven Lessons from the Soviet Collapse. CEPS Essay (No. 1), September 2012

In short, the European Union, as we know it, no longer exists. The very foundations on which it was built are eroding. Shared memories of the Second World War have faded away – half the 15- and 16-year-olds in German high schools do not know that Hitler was a dictator, while a third believe that he protected human rights. The collapse of the Soviet Union has stripped away the geopolitical rationale for European unity. The democratic welfare state that was at the heart of the post-war political consensus is under siege by, among other things, sheer demographics. And the prosperity that bolstered the European project’s political legitimacy is vanishing. More than six out of ten Europeans believe that the lives of today’s children will be more difficult than those of people from their own generation. Against this background, how unthinkable is the EU’s disintegration? Should Europeans make the mistake of taking the Union for granted? Should they assume that the Union would not collapse because it should not collapse? Here, Europe’s capacity to learn from the Soviet precedent could play a crucial part. For the very survival of the EU may depend on its leaders’ ability to manage a similar mix of political, economic and psychological factors that were in play in the process of the Soviet collapse. The game of disintegration is primarily a political one driven much more by the perceptions and misperceptions of the political actors than simply by the constellation of the structural factors – institutional and economic.

Pharmaceutical process optimisation of bulk lyophilisates:implications of powder handling

Lyophilisation or freeze drying is the preferred dehydrating method for pharmaceuticals liable to thermal degradation. Most biologics are unstable in aqueous solution and may use freeze drying to prolong their shelf life. Lyophilisation is however expensive and has seen lots of work aimed at reducing cost. This thesis is motivated by the potential cost savings foreseen with the adoption of a cost efficient bulk drying approach for large and small molecules. Initial studies identified ideal formulations that adapted well to bulk drying and further powder handling requirements downstream in production. Low cost techniques were used to disrupt large dried cakes into powder while the effects of carrier agent concentration were investigated for powder flowability using standard pharmacopoeia methods. This revealed superiority of crystalline mannitol over amorphous sucrose matrices and established that the cohesive and very poor flow nature of freeze dried powders were potential barriers to success. Studies from powder characterisation showed increased powder densification was mainly responsible for significant improvements in flow behaviour and an initial bulking agent concentration of 10-15 %w/v was recommended. Further optimisation studies evaluated the effects of freezing rates and thermal treatment on powder flow behaviour. Slow cooling (0.2 °C/min) with a -25°C annealing hold (2hrs) provided adequate mechanical strength and densification at 0.5-1 M mannitol concentrations. Stable bulk powders require powder transfer into either final vials or intermediate storage closures. The targeted dosing of powder formulations using volumetric and gravimetric powder dispensing systems where evaluated using Immunoglobulin G (IgG), Lactate Dehydrogenase (LDH) and Beta Galactosidase models. Final protein content uniformity in dosed vials was assessed using activity and protein recovery assays to draw conclusions from deviations and pharmacopeia acceptance values. A correlation between very poor flowability (p<0.05), solute concentration, dosing time and accuracy was revealed. LDH and IgG lyophilised in 0.5 M and 1 M mannitol passed Pharmacopeia acceptance values criteria with 0.1-4 while formulations with micro collapse showed the best dose accuracy (0.32-0.4% deviation). Bulk mannitol content above 0.5 M provided no additional benefits to dosing accuracy or content uniformity of dosed units. This study identified considerations which included the type of protein, annealing, cake disruption process, physical form of the phases present, humidity control and recommended gravimetric transfer as optimal for dispensing powder. Dosing lyophilised powders from bulk was demonstrated as practical, time efficient, economical and met regulatory requirements in cases. Finally the use of a new non-destructive technique, X-ray microcomputer tomography (MCT), was explored for cake and particle characterisation. Studies demonstrated good correlation with traditional gas porosimetry (R2 = 0.93) and morphology studies using microscopy. Flow characterisation from sample sizes of less than 1 mL was demonstrated using three dimensional X-ray quantitative image analyses. A platinum-mannitol dispersion model used revealed a relationship between freezing rate, ice nucleation sites and variations in homogeneity within the top to bottom segments of a formulation.

Soviet and Western bloc competition in the less developed world and the collapse of Détente

The purpose of my dissertation was to examine the competition between the U.S.-led Western bloc and the Soviet bloc in the less developed world during Détente. I assessed whether or not the Soviet bloc pushed for strategic gains in the less developed world in the middle-to-late 1970's and whether this contributed to the U.S. decision to abandon Détente in 1979. I made the attempt to test the international relations theory of balance of threat realism (Walt, 1992). I accomplished the test in two ways. First, I measured the foreign aid allocations (military and economic) made by each respective bloc towards the Third World by using a quantitative approach. Second, I examined U.S. archives using the process-tracing/historical method. The U.S. archives gave me the ability to evaluate how U.S. decision-makers and U.S. intelligence agencies interpreted the actions of the Soviet bloc. They also gave me the chance to examine the U.S. response as we evaluated the policies that were pushed by key U.S. decision-makers and intelligence agencies. On the question of whether or not the Soviet bloc was aggressive, the quantitative evidence suggested that it was not. Instead, the evidence found the Western-bloc to have been more aggressive in the less developed world. The U.S. archives also showed Soviet actions to have been defensive. Key U.S. decision-makers and intelligence agencies attested to this. Finally, the archives show that U.S. officials pushed for aggressive actions against the Third World during the final years of Détente. Thus, balance of threat realism produced an incorrect assessment that U.S. aggression in the late 1970's was a response to Soviet aggression during Détente. The evidence suggests structural Marxism and domestic politics can better explain U.S./Western actions. The aggressive foreign aid allocations of the West, coupled with evidence of U.S. decision-makers/agencies vehemently concerned about the long-term prospects of the West, strengthened structural Marxism. Domestic politics can also claim to explain the actions of U.S. decision-makers. I found extensive archival evidence of bureaucratic inter-agency conflict between the State Department and other intelligence agencies in areas of strategic concern to the U.S.

Processes of social flourishing and their liminal collapse: elements to a genealogy of globalization

This article aims at exploring a long-term historical perspective on which contemporary globalization can be more meaningfully situated. A central problem with established approaches to globalization is that they are even more presentist than the literature on modernization was. Presentism not only means the ignoring of history, but also the unreflective application to history of concepts taken from the study of the modern world. In contrast, it is argued that contemporary globalization is not a unique development, but rather is a concrete case of a historical type. Taking as its point of departure the spirit, rather than the word, of Max Weber, this article extends the scope of sociological investigation into archaeological evidence. Having a genealogical design and introducing the concept of ‘liminality’, the article approaches the modern process of globalization through reconstructing the internal dynamics of another type of historical change called ‘social flourishing’. Taking up the Weberian approach continued by Eisenstadt in his writings on ‘axial age’, it moves away from situations of crisis as reference point, shifting attention to periods of revival by introducing the term ‘epiphany’. Through the case of early Mesopotamia, it shows how social flourishing can be transmogrified into globalizing growth, gaining a new perspective concerning the kind of ‘animating spirit’ that might have driven the shift from Renaissance to Reformation, the rise of modern colonialism, or contemporary globalization. More generally, it will retrieve the long-term historical background of the axial age and demonstrate the usefulness and importance of archaeological evidence for sociology.