A new urban freight distribution scheme and an optimization methodology for reducing its overall cost

The paper refers to an innovative urban freight distribution scheme, aimed at reducing the externalities connected with the freight delivery process. Both packages destined to commercial activities and to end consumers (e-commerce) are taken into account. Each package is characterized by an address and dimensions. In the proposed transport system, freight is firstly delivered to the UDC on the border of urban areas through trucks or trains which perform the long distance transport. After, freight is reorganized and consolidated into load units, i.e. the FURBOT boxes, according to packages dimensions and to the addresses of receivers. Each box is addressed to a temporary unloading bay and it is delivered there by a FURBOT vehicle. The receivers are in charge of collecting their packages in the related unloading bays where they have been delivered. The paper concerns a methodology for optimizing this freight transport system's performances. The overall methodology receives in input the actual freight demand and the road network, and finds the transport system parameters (number of required FURBOT boxes, their temporary unloading bay, the FURBOT fleet dimension and the FURBOT vehicle routing) that minimize the system overall cost. The overall cost is a sum of the users' cost, which depends on the distance they have to walk for collecting their packages in the FURBOT box, and of the operator's cost, which depends on the number of required boxes, the total distance travelled by the FURBOT vehicles and the required number of FURBOT vehicles. The overall procedure has been applied to the case study of Barreiro old town, a suburb of Lisbon, Portugal

Comparative study of paediatric prescription drug utilization between the spanish and immigrant population

<p>Abstract</p> <p>Background</p> <p>The immigrant population has increased greatly in Spain in recent years to the point where immigrants made up 12% of the infant population in 2008. There is little information available on the profile of this group with regard to prescription drug utilization in universal public health care systems such as that operating in Spain. This work studies the overall and specific differences in prescription drug utilization between the immigrant and Spanish population.</p> <p>Methods</p> <p>Use was made of the Aragonese Health Service databases for 2006. The studied population comprises 159,908 children aged 0-14 years, 13.6% of whom are foreign nationals. Different utilization variables were calculated for each group. Prescription-drug consumption is measured in Defined Daily Doses (DDD) and DDD/1000 persons/day/(DID).</p> <p>Results</p> <p>A total of 833,223 prescriptions were studied. Utilization is lower for immigrant children than in Spanish children for both DID (66.27 v. 113.67) and average annual expense (€21.55 v. €41.14). Immigrant children consume fewer prescription drugs than Spanish children in all of the therapy groups, with the most prescribed (in DID) being: respiratory system, anti-infectives for systemic use, nervous system, sensory organs. Significant differences were observed in relation to the type of drugs and the geographical background of immigrants.</p> <p>Conclusion</p> <p>Prescription drug utilization is much greater in Spanish children than in immigrant children, particularly with reference to bronchodilators (montelukast and terbutaline) and attention-disorder hyperactivity drugs such as methylphenidate. There are important differences regarding drug type and depending on immigrants' geographical backgrounds that suggest there are social, cultural and access factors underlying these disparities.</p

Increased cortical surface area and gyrification following long-term survival from early monocular enucleation

AbstractPurposeRetinoblastoma is typically diagnosed before 5 years of age and is often treated by enucleation (surgical removal) of the cancerous eye. Here, we sought to characterize morphological changes of the cortex following long-term survival from early monocular enucleation.MethodsNine adults with early right-eye enucleation (≤48 months of age) due to retinoblastoma were compared to 18 binocularly intact controls. Surface area, cortical thickness, and gyrification estimates were obtained from T1 weighted images and group differences were examined.ResultsEarly monocular enucleation was associated with increased surface area and/or gyrification in visual (i.e., V1, inferior temporal), auditory (i.e., supramarginal), and multisensory (i.e., superior temporal, inferior parietal, superior parietal) cortices compared with controls. Visual cortex increases were restricted to the right hemisphere contralateral to the remaining eye, consistent with previous subcortical data showing asymmetrical lateral geniculate nucleus volume following early monocular enucleation.ConclusionsAltered morphological development of visual, auditory, and multisensory regions occurs subsequent to long-time survival from early eye loss

Enzyme sequestration as a tuning point in controlling response dynamics of signalling networks

Signalling networks result from combinatorial interactions among many enzymes and scaffolding proteins. These complex systems generate response dynamics that are often essential for correct decision-making in cells. Uncovering biochemical design principles that underpin such response dynamics is a prerequisite to understand evolved signalling networks and to design synthetic ones. Here, we use in silico evolution to explore the possible biochemical design space for signalling networks displaying ultrasensitive and adaptive response dynamics. By running evolutionary simulations mimicking different biochemical scenarios, we find that enzyme sequestration emerges as a key mechanism for enabling such dynamics. Inspired by these findings, and to test the role of sequestration, we design a generic, minimalist model of a signalling cycle, featuring two enzymes and a single scaffolding protein. We show that this simple system is capable of displaying both ultrasensitive and adaptive response dynamics. Furthermore, we find that tuning the concentration or kinetics of the sequestering protein can shift system dynamics between these two response types. These empirical results suggest that enzyme sequestration through scaffolding proteins is exploited by evolution to generate diverse response dynamics in signalling networks and could provide an engineering point in synthetic biology applications

A Linear Framework for Time-Scale Separation in Nonlinear Biochemical Systems

Cellular physiology is implemented by formidably complex biochemical systems with highly nonlinear dynamics, presenting a challenge for both experiment and theory. Time-scale separation has been one of the few theoretical methods for distilling general principles from such complexity. It has provided essential insights in areas such as enzyme kinetics, allosteric enzymes, G-protein coupled receptors, ion channels, gene regulation and post-translational modification. In each case, internal molecular complexity has been eliminated, leading to rational algebraic expressions among the remaining components. This has yielded familiar formulas such as those of Michaelis-Menten in enzyme kinetics, Monod-Wyman-Changeux in allostery and Ackers-Johnson-Shea in gene regulation. Here we show that these calculations are all instances of a single graph-theoretic framework. Despite the biochemical nonlinearity to which it is applied, this framework is entirely linear, yet requires no approximation. We show that elimination of internal complexity is feasible when the relevant graph is strongly connected. The framework provides a new methodology with the potential to subdue combinatorial explosion at the molecular level