Global warming: is weight loss a solution?

The current climate change has been most likely caused by the increased greenhouse gas emissions. We have looked at the major greenhouse gas, carbon dioxide (CO2), and estimated the reduction in the CO2 emissions that would occur with the theoretical global weight loss. The calculations were based on our previous weight loss study, investigating the effects of a low-carbohydrate diet on body weight, body composition and resting metabolic rate of obese volunteers with type 2 diabetes. At 6 months we observed decreases in weight, fat mass, fat free mass and CO2 production. We estimated that a 10 kg weight loss of all obese and overweight people would result in a decrease of 49.560 Mt of CO2 per year, which would equal to 0.2 % of the CO2 emitted globally in 2007. This reduction could help meet the CO2 emission reduction targets and unquestionably would be of a great benefit to the global health

Observations of the December 13 and 14, 2006, Solar Particle Events in the 80 MeV/n - 3 GeV/n range from space with PAMELA detector

We present the space spectrometer PAMELA observations of proton and helium fluxes during the December 13 and 14, 2006 solar particle events. This is the first direct measurement of the solar energetic particles in space with a single instrument in the energy range from $\sim$ 80 MeV/n up to $\sim$ 3 GeV/n. In the event of December 13 measured energy spectra of solar protons and helium were compared with results obtained by neutron monitors and other detectors. Our measurements show a spectral behaviour different from those derived from the neutron monitor network. No satisfactory analytical fitting was found for the energy spectra. During the first hours of the December 13 event solar energetic particles spectra were close to the exponential form demonstrating rather significant temporal evolution. Solar He with energy up to ~1 GeV/n was recorded on December 13. In the event of December 14 energy of solar protons reached ~600 MeV whereas maximum energy of He was below 100 MeV/n. The spectra were slightly bended in the lower energy range and preserved their form during the second event. Difference in the particle flux appearance and temporal evolution in these two events may argue for a special conditions leading to acceleration of solar particles up to relativistic energies.Comment: Accepted for publication on Astrophysical journa

Energy Landscape and Global Optimization for a Frustrated Model Protein

The three-color (BLN) 69-residue model protein was designed to exhibit frustrated folding. We investigate the energy landscape of this protein using disconnectivity graphs and compare it to a Go model, which is designed to reduce the frustration by removing all non-native attractive interactions. Finding the global minimum on a frustrated energy landscape is a good test of global optimization techniques, and we present calculations evaluating the performance of basin-hopping and genetic algorithms for this system.Comparisons are made with the widely studied 46-residue BLN protein.We show that the energy landscape of the 69-residue BLN protein contains several deep funnels, each of which corresponds to a different β-barrel structure

Design of Lightweight Structural Components for Direct Digital Manufacturing

The rapid growth in direct digital manufacturing technologies has opened the challenge of designing optimal micro-structures for high-performance components. Current topology optimization techniques do not work well for this type of problems and hence in this paper we propose a technique based on an implicit representation of the structural topology. The detailed microstructure is defined by a continuous variable, the size distribution field, defined over the design domain by chosen shape functions. We can optimize the structural topology by optimizing only the weights of the size distribution field and, for any given size distribution, we use standard meshing software to determine the actual detailed micro-structure. We have implemented the optimization loop using commercial CAD and FEA software, running under a genetic algorithm in MATLAB. Application this novel technique to the design of a sandwich beam has produced designs that are superior to any standard solid beam or even optimized truss structure

S.6.1 β-catenin is a central mediator in SSc

Background. β-catenin is the central integrator of canonical Wnt signalling. Since recent evidence suggests a central role of Wnts in fibrosis, we examined the β-catenin/Wnt pathway in SSc and focused on the role of β-catenin in fibroblast activation. Methods. We performed qPCR for several Wnt ligands and axin-2 to examine Wnt expression in SSc skin. We further studied protein levels of Wnt-1, -4, -10b and β-catenin by IHC. To establish the effects of β-catenin/Wnt signalling on collagen release, we created mice with fibroblast-specific stabilization of β-catenin (dEx3 β-catenin (wt/fl) × Col1a2; Cre-ER) as well as mice carrying fibroblast-specific deletion of β-catenin [Ctnnb1(fl/fl) × Col1a2; Cre-ER]. Summary of the results. We could demonstrate mRNA overexpression of Wnt-1, -2, -9a, -9b, -10a, -10b and -16 in SSc skin. Wnt-1, -4 and -10b consistently showed strong expression in SSc skin when compared with healthy skin. On protein level, however, Wnt-4 was indistinguishable between SSc patients and healthy controls, whereas Wnt-1 and Wnt-10b protein levels were increased in SSc skin. The overexpression of Wnt-1 and Wnt-10b resulted in a prominent nuclear accumulation of β-catenin in fibroblasts. Finally, increased mRNA levels of the target gene axin-2 confirmed the activation of canonical Wnt signalling. In dEx3 β-catenin (wt/ex) mice, we addressed the consequences of enhanced Wnt signalling and increased accumulation of β-catenin in SSc. We selectively targeted β-catenin in fibroblasts. Cre-activated dEx3 β-catenin (wt/fl) × Col1a2; Cre-ER mice showed massive and spontaneous dermal thickening even 2 weeks after Cre activation. Eight weeks after Cre-activation, skin thickening cumulated at 102.6% (P < 0.001). In line with the dermal thickening, hydroxyproline content and myofibroblast counts showed strong increases. To test the therapeutic potential of targeting β-catenin/Wnt signaling, we created Ctnnb1(fl/fl) x Col1a2;Cre-ER mice to specifically delete β-catenin in fibroblasts. After Cre activation and β-catenin deletion in fibroblasts, mice were challenged with bleomycin subcutaneously for 4 weeks. We found that Cre-activated Ctnnb1(fl/fl) × Col1a2; Cre-ER mice were protected from bleomycin-induced dermal with a reduction of skin thickening by 71% (P < 0.05). Conclusions. We demonstrated a prominent activation of canonical Wnt signalling in SSc with nuclear accumulation of β-catenin in fibroblasts and activation of the target gene axin-2. Our results showed that fibroblast-specific stabilization of β-catenin resulted in enhanced collagen release, whereas deletion of β-catenin potently reduced collagen production. Together, our findings highlight a key role of β-catenin in fibroblast activation and fibrosis. Thus, β-catenin may be promising molecular target for anti-fibrotic therapie

Covert action failure and fiasco construction: William Hague’s 2011 Libyan venture

In 2011 William Hague, then British Foreign Secretary, authorized a Special Forces team to enter Libya and attempt to contact rebels opposed to Muammar Gaddafi in the unfolding civil war. However, its members were detained by the rebels, questioned and ejected from the country. This article puts the literature on public policy failures into dialogue with that on covert action as a tool of foreign policy. It asks: why did this not develop into a fully-fledged policy fiasco when journalists and politicians alike judged it to have been a major error of judgement on Hague’s part? Using narrative analysis of the contemporary reporting of this incident, we argue that the government – possessing the advantage of information asymmetry accruing from operational secrecy – was ultimately able to win the battle of narratives in a frame contestation process. The study of information asymmetry can enhance the recently revivified research into foreign policy failures

Synthesis by High-Efficiency Liquid-Phase (HELP) Method of Oligonucleotides Conjugated with High-Molecular Weight Polyethylene Glycols (PEGs)

The chemical modification of synthetic oligonucleotides has recently been investigated to improve their pharmacological utilization. In addition to chemical alterations of the backbone and of the heterocyclic bases, their conjugation with amphiphylic moieties, such as the polyethylene glycol has been proposed. The large scale production of these molecules as demanded for commercial purposes is hampered by the heterogeneity of the solid-phase processes and by the low reactivity of high-molecular weight PEGs in solution. A new synthetic procedure based on the recently developed liquid-phase method (HELP), has been set up to overcome these limitations

Knowledge, science and death: the theory of brain-sign

In today’s paradigmatic climate, the possibility of knowledge, and therefore science, still depends upon our being conscious. However, no scientifically accepted account of consciousness exists. In recent years I have developed the theory of brain-sign which replaces consciousness as a wholly physical neural condition. The first tenet is that the brain is a causal organ, not a knowledge organ. The second is that brain-sign, used in inter-neural communication for uncertain or imprecise collective action, derives at each moment from the causal orientation of the brain. Signs are ubiquitous bio-physical entities. Thus there is no problematic dualism, consciousness and world. We now have two accounts of the brain phenomenon. The first (consciousness) is an inexplicable physical anomaly. The second (brain-sign) belongs in the physical universe, and fulfils a crucial neurobiological function. With brain-sign theory we even ‘discover’ that we do not know we are alive or will die

Structural representations: causally relevant and different from detectors

This paper centers around the notion that internal, mental representations are grounded in structural similarity, i.e., that they are so-called S-representations. We show how S-representations may be causally relevant and argue that they are distinct from mere detectors. First, using the neomechanist theory of explanation and the interventionist account of causal relevance, we provide a precise interpretation of the claim that in S-representations, structural similarity serves as a ‘‘fuel of success’’, i.e., a relation that is exploitable for the representation using system. Then, we discuss crucial differences between S-representations and indicators or detectors, showing that—contrary to claims made in the literature—there is an important theoretical distinction to be drawn between the two