Forces Shaping China's Interprovincial Inequality

China, regional development, production

Stochastic noise and synchronisation during Dictyostelium aggregation make cAMP oscillations robust

The molecular network, which underlies the oscillations in the concentration of adenosine 3′, 5′-cyclic monophosphate (cAMP) during the aggregation phase of starvation-induced development in Dictyostelium discoideum, achieves remarkable levels of robust performance in the face of environmental variations and cellular heterogeneity. However, the reasons for this robustness remain poorly understood. Tools and concepts from the field of control engineering provide powerful methods for uncovering the mechanisms underlying the robustness of these types of biological systems. Using such methods, two important factors contributing to the robustness of cAMP oscillations in Dictyostelium are revealed. First, stochastic fluctuations in the molecular interactions of the intracellular network, arising from random or directional noise and biological sources, play an important role in preserving stable oscillations in the face of variations in the kinetics of the network. Second, synchronisation of the aggregating cells through the diffusion of extracellular cAMP appears to be a key factor in ensuring robustness to cell-to-cell variations of the oscillatory waves of cAMP observed in Dictyostelium cell cultures. The conclusions have important general implications for the robustness of oscillating biomolecular networks (whether seen at organism, cell, or intracellular levels and including circadian clocks or Ca2+ oscillations, etc.), and suggest that such analysis can be conducted more reliably by using models including stochastic simulations, even in the case where molecular concentrations are very high

Taking Turing by Surprise? Designing Digital Computers for morally-loaded contexts

There is much to learn from what Turing hastily dismissed as Lady Lovelace s objection. Digital computers can indeed surprise us. Just like a piece of art, algorithms can be designed in such a way as to lead us to question our understanding of the world, or our place within it. Some humans do lose the capacity to be surprised in that way. It might be fear, or it might be the comfort of ideological certainties. As lazy normative animals, we do need to be able to rely on authorities to simplify our reasoning: that is ok. Yet the growing sophistication of systems designed to free us from the constraints of normative engagement may take us past a point of no-return. What if, through lack of normative exercise, our moral muscles became so atrophied as to leave us unable to question our social practices? This paper makes two distinct normative claims: 1. Decision-support systems should be designed with a view to regularly jolting us out of our moral torpor. 2. Without the depth of habit to somatically anchor model certainty, a computer s experience of something new is very different from that which in humans gives rise to non-trivial surprises. This asymmetry has key repercussions when it comes to the shape of ethical agency in artificial moral agents. The worry is not just that they would be likely to leap morally ahead of us, unencumbered by habits. The main reason to doubt that the moral trajectories of humans v. autonomous systems might remain compatible stems from the asymmetry in the mechanisms underlying moral change. Whereas in humans surprises will continue to play an important role in waking us to the need for moral change, cognitive processes will rule when it comes to machines. This asymmetry will translate into increasingly different moral outlooks, to the point of likely unintelligibility. The latter prospect is enough to doubt the desirability of autonomous moral agents

Structure, stability and elasticity of DNA nanotube

DNA nanotubes are tubular structures composed of DNA crossover molecules. We present a bottom up approach for construction and characterization of these structures. Various possible topologies of nanotubes are constructed such as 6-helix, 8-helix and tri-tubes with different sequences and lengths. We have used fully atomistic molecular dynamics simulations to study the structure, stability and elasticity of these structures. Several nanosecond long MD simulations give the microscopic details about DNA nanotubes. Based on the structural analysis of simulation data, we show that 6-helix nanotubes are stable and maintain their tubular structure; while 8-helix nanotubes are flattened to stabilize themselves. We also comment on the sequence dependence and effect of overhangs. These structures are approximately four times more rigid having stretch modulus of ~4000 pN compared to the stretch modulus of 1000 pN of DNA double helix molecule of same length and sequence. The stretch moduli of these nanotubes are also three times larger than those of PX/JX crossover DNA molecules which have stretch modulus in the range of 1500-2000 pN. The calculated persistence length is in the range of few microns which is close to the reported experimental results on certain class of the DNA nanotubes.Comment: Published in Physical Chemistry Chemical Physic

Monetary Convergence of the EU Candidates to the Euro: A Theoretical Framework and Policy Implications

A flexible approach to direct inflation targeting is a viable monetary policy choice for transition economies that is believed to facilitate both the economic transition and the monetary convergence to the euro. Following this assumption, an analytical model investigating the link between the inflation process and monetary variables in transition economies is advanced in this study. The empirical testing is conducted for Poland, the Czech Republic and Hungary. The analysis recommends that the monetary convergence begins with inflation targeting and concludes with a full-fledged euroization. It further advocates the application of flexible benchmarks of monetary convergence that would accommodate various non-monetary factors affecting inflation in transition economies.transition economies, European Union candidate countries, inflation targeting, inflation targeting, monetary convergence

Objective assessment of movement disabilities using wearable sensors

The research presents a series of comprehensive analyses based on inertial measurements obtained from wearable sensors to quantitatively describe and assess human kinematic performance in certain tasks that are most related to daily life activities. This is not only a direct application of human movement analysis but also very pivotal in assessing the progression of patients undergoing rehabilitation services. Moreover, the detailed analysis will provide clinicians with greater insights to capture movement disorders and unique ataxic features regarding axial abnormalities which are not directly observed by the clinicians

rational design of functionalized lipids with antioxidant and scavenging activity as components of innovative artificial tears

openDurante i tre anni di dottorato mi sono occupato del design razionale di lipidi funzionalizzati ad attività antiossidante da utilizzare per la formulazione di lacrime artificiali. Abbiamo scelto i liposomi per veicolare le molecole antiossidanti testate; siamo partiti utilizzando l’Edaravone (EDR), il quale è stato opportunamente funzionalizzato (EDR-C18), senza diminuire le proprietà antiossidanti della molecola. Abbiamo condotto studi sperimentali evidenziando che l’EDR-C18 mantiene elevate capacità antiossidanti, solo a questo punto abbiamo condotto simulazioni di dinamica molecolare utilizzando un sistemi lipidici puri contenti fosfatidilcolina (POPC), e differenti concentrazioni di EDR-C18. I dati di simulazione hanno evidenziato una elevata stabilità dell’EDR-C18 in membrana. Abbiamo quindi determinato la concentrazione ottimale al fine di ottenere una intatta fluidità del sistema e allo stesso tempo una elevata quantità di antiossidante. Partendo da questo modello di simulazione, abbiamo creato altri sistemi di simulazione in cui abbiam investigato l’effetto dei Sali. Abbiamo testato soluzioni saline già comunemente utilizzate nella formulazione di lacrime artificiali, ed abbiamo riscontrato nel CaCl2 il sale maggiormente utile per la nostra strategia. Tali sistemi sono estremamente promettenti per la formulazione di gocce oculari. Un’altra molecola testata è l’epigallocatechin3-Gallato (EGCG). Essa ha la capacità di interagire spontaneamente con sistemi lipidici, perciò non è stata funzionalizzata. Abbiamo condotto delle simulazioni di dinamica molecolare creando sistemi lipidici misti per indagare l’effetto della matrice sulla capacità di inglobamento dell’EGCG. Abbiamo inoltre modulato la concentrazione salina ed abbiamo individuato nel sistema lipidico anionico con una quantità di Magnesio pari a 5:1 in rapporto molare con EGCG, il sistema in cui tutto l’EGCG introdotto viene inglobato, aumentando la biodisponibilità della molecola al massimo possibile.During three years of my PhD course, I studied the rational design of functionalized lipid with antioxidant activity to be used for the formulation of artificial tears. We chosen the liposomes to carrier the antioxidant molecules that we studied; we started using the edaravone (EDR), which has been suitably functionalized (EDR-C18), without decrease the antioxidant properties of the molecule. For this purpose, we made experimental studies showing that the EDR-C18 maintains high antioxidant capacity, only at this point we carried out the molecular dynamics (MD) simulations using pure lipid systems containing POPC and different EDR-C18 concentrations. The simulation data showed a high EDR-C18 stability in the membrane. We determined the optimal concentration to obtain an intact fluidity of the system and at the same time a high amount of antioxidant. On the basis on this simulation model, we created other MD systems in which we have investigated the effects of salts. We tested salt solutions already commonly used in the formulation of artificial tears, and we found that CaCl2 is better salt to use for our strategy. Such systems are extremely promising for the formulation of eye drops. Another antioxidant that we studied is the epigallocatechin3-gallate (EGCG). It has the ability to interact spontaneously with lipid system, for this reason, it was not functionalized. We carried out MD simulations creating mixed lipid systems to investigate the effects of the matrix on the EGCG encapsulation. In addition, we modulated on salt concentration and we found that the best model is the anionic lipid system with an amount of magnesium equal to 5:1 in molar ratio with EGCG the system in which all the EGCG introduced is encapsulated, maximizing the bioavailability of the antioxidant compound, that is able to reach the lipid medium of lacrimal tear and to retain in it.SCIENZE DELLA VITA E DELL'AMBIENTEembargoed_20181001Laudadio, EmilianoLaudadio, Emilian

Exploring the conformational dynamics of alanine dipeptide in solution subjected to an external electric field: A nonequilibrium molecular dynamics simulation

In this paper, we investigate the conformational dynamics of alanine dipeptide under an external electric field by nonequilibrium molecular dynamics simulation. We consider the case of a constant and of an oscillatory field. In this context we propose a procedure to implement the temperature control, which removes the irrelevant thermal effects of the field. For the constant field different time-scales are identified in the conformational, dipole moment, and orientational dynamics. Moreover, we prove that the solvent structure only marginally changes when the external field is switched on. In the case of oscillatory field, the conformational changes are shown to be as strong as in the previous case, and non-trivial nonequilibrium circular paths in the conformation space are revealed by calculating the integrated net probability fluxes.Comment: 23 pages, 12 figure