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Heart disease is the leading cause of death globally, and delivery of therapeutic cargo (e.g., particles loaded with proteins, drugs, cells, or genes) through direct injection into the myocardium is a promising clinical intervention. However, retention of deliverables to the contracting myocardium is low, with as much as 60 – 90% of payload being lost within 24 hours. Commercially-available injectable hydrogels, including Matrigel, have been hypothesized to increase payload retention, but have not yielded significant improvements in quantified analyses. Here, we assess a recombinant hydrogel composed of chemically modified hyaluronan and elastin-like protein (HELP) as an alternative injectable carrier to increase cargo retention. HELP is crosslinked using dynamic covalent bonds, and tuning the hyaluronan chemistry significantly alters hydrogel mechanical properties including stiffness, stress-relaxation rate, and ease of injectability through a needle or catheter. These materials can be injected even after complete crosslinking, extending the time window for surgical delivery. We show that HELP gels significantly improve in vivo retention of microsphere cargo compared to Matrigel, both 1 day and 7 days post-injection directly into the rat myocardium. These data suggest that HELP gels may assist with the clinical translation of therapeutic cargo designed for delivery into the contracting myocardium by preventing acute cargo loss.

Intrinsically disordered proteins and regions (IDPs and IDRs) and their importance in biology are becoming increasingly recognized in biology, biochemistry, molecular biology and chemistry textbooks, as well as in current protein science and structural biology curricula. We argue that the sequence → dynamic conformational ensemble → function principle is of equal importance as the classical sequence → structure → function paradigm. To highlight this point, we describe the IDPs and/or IDRs behind the discoveries associated with 17 Nobel Prizes, 11 in Physiology or Medicine and 6 in Chemistry. The Nobel Laureates themselves did not always mention that the proteins underlying the phenomena investigated in their award-winning studies are in fact IDPs or contain IDRs. In several cases, IDP- or IDR-based molecular functions have been elucidated, while in other instances, it is recognized that the respective protein(s) contain IDRs, but the specific IDR-based molecular functions have yet to be determined. To highlight the importance of IDPs and IDRs as general principle in biology, we present here illustrative examples of IDPs/IDRs in Nobel Prize-winning mechanisms and processes.

Heart disease is the leading cause of death globally, and delivery of therapeutic cargo (e.g. cells, proteins, drugs) through direct injection into the myocardium is a promising clinical intervention. However, retention of deliverables to the contracting myocardium is low, with as much as 60 - 90% of payload being lost within 24 hours. Commercially-available injectable hydrogels, including Matrigel, have been hypothesized to increase payload retention, but have not yielded significant improvements in quantified analyses. Here, we assess a recombinant hydrogel composed of chemically modified hyaluronan and elastin-like protein (HELP) as an alternative injectable carrier to increase cargo retention. HELP is crosslinked using dynamic covalent bonds, and tuning the hyaluronan chemistry significantly alters hydrogel mechanical properties including stiffness, stress-relaxation rate, and ease of injectability through a needle or catheter. These materials can be injected even after complete crosslinking, extending the time window for surgical delivery. We show that HELP gels significantly improve in vivo retention of microsphere cargo compared to Matrigel, both 1 day and 7 days post-injection directly into the rat myocardium. These data suggest that HELP gels may assist with the clinical translation of therapeutic cargo designed for delivery into the contracting myocardium by preventing acute cargo loss.

Resumen: La expansión urbana ha ampliado las distancias y tiempos de viaje de las personas que viven y trabajan en las ciudades. En el Área Metropolitana de Santiago de Chile sus habitantes menos favorecidos enfrentan profundos desafíos, pues tanto sus ingresos como los territorios donde residen revelan una menguada disponibilidad de capitales de movilidad. La presente investigación busca calcular y entender los distintos costos de la movilidad expresados en tiempo y en dinero, a partir de los viajes al trabajo como expresión de las desigualdades urbanas existentes en la ciudad. Se utilizan para esto las Encuestas de Caracterización Socio Económica (CASEN) del Ministerio de Desarrollo Social de 2015 y 2017, que incorporan preguntas sobre la movilidad de las personas. Desde un enfoque cuantitativo, se definen los costos monetarios mensuales de la movilidad de los hogares determinando su porcentaje en el ingreso monetario del hogar y se realiza un análisis complementario considerando distintas variables socioeconómicas. Los resultados evidencian profundas desigualdades debidas al mayor peso del costo del transporte público en los ingresos de los más vulnerables, hecho que se condice con mayores tiempos de viaje debido a la lejanía entre su residencia y los centros laborales, mayor desempleo y menor motorización privada.

International audience; In this work we formulate a Stackelberg Security Game that coordinates resources in a border patrol problem. In this security domain, resources from different precincts have to be paired to conduct patrols in the border due to logistic constraints. Given this structure, models that enumerate the pure defender strategies scale poorly. We describe the set of mixed strategies using a polynomial number of variables but exponentially many constraints that come from the matching polytope. We then include this description in a mixed integer formulation to compute the Strong Stackelberg Equilibrium efficiently with a branch and cut scheme. Since the optimal patrol solution is a probability distribution over the set of exponential size, we also introduce an efficient sampling method that can be used to deploy the security resources every shift. Our computational results evaluate the efficiency of the branch and cut scheme developed and the accuracy of the sampling method.

Self-healing materials represent a paradigm shift from traditional materials development, enabling intrinsic repair of functionality (such as strength) after a catastrophic failure as opposed to part replacement. Several healing mechanisms have been demonstrated in polymeric and ceramic materials, but few in metallic systems. This study demonstrates a novel liquid-assisted self-healing metal-matrix composite (MMC) designed to be capable of over 90% strength recovery after a healing cycle. The aluminum (Al)-based matrix is reinforced with continuous nickel-titanium (NiTi) shape-memory alloy (SMA) reinforcements. Using a tailored heat treatment for healing, a paired effect of crack closure from the SMA reinforcement and partial liquefaction of the matrix occurs. These effects result in a compressive force across the crack surface, and, coupled with increased diffusion rates from the liquefied matrix, produces consolidation and healing in the composite structure. This work provides experimental and computational evidence for the healing mechanism under both tensile and fatigue conditions.

Upper Cretaceous intrusives of limited extent crop out in the Coastal Cordillera near of Valdivia (39°48' S), 100 km west of the main topographic divide of the Andean Cordillera. Given that plutonic rocks of the same age crop out at the same latitudes in the high Andes the coastal intrusives emplaced in a forearc position in the upper plate of a subduction setting. They correspond to hypabyssal intrusives displaying mainly porphyritic texture and lithological variations with microtonalites (minor), porphyritic microgranodiorites (main) and microgranites. They intrude the Upper Paleozoic-Triassic accretionary complex of the Bahia Mansa Metamorphic Complex. These intrusives, that comprise the Chaihuín Pluton and minor stocks of porphyritic felsic rocks, have calc-alkaline affinities with metaluminous and peraluminous character. They are geochemically similar to the contemporaneous main arc-related plutonic rocks of the Gualletué Plutonic Group. The microgranitoids and dacitic rocks from Los Boldos, the low and Loncoche are peculiar because they show an apparently adakitic affinity in Sr/Y and LaN/YbN discriminant diagrams; nevertheless Sr contents of these rocks (<

In the past 10 years, the concept of public space has gradually become a new key topic in Chile’s urban planning debate. Most often linked to sustainable urban growth and sustainable mobility, the concept arises in a context of legal changes aiming to reinforce the street as a public space dedicated to all type of mobilities, including active modes of transport (walking and cycling). These recent legal transformations represent an important shift in Chile’s urban planning, establishing guidelines for the future in order to encourage sustainable mobility and increase public space quality and access in Chile’s cities. This integrated approach to urban development represents a clear tendency to promote a more cohesive society in a context of increasing urban complexity and environmental challenges. It recognizes spatial, socio-economic and environmental issues and aims to articulate urban planning with mobility by seeking a balanced distribution of urban functions in Chilean cities. Although at first glance this new approach seems positive, it is important to analyse these changes through the lens of Chile’s urban production, especially in the case of intermediate Chilean cities that, due to their scale, still have the possibility to redirect their development towards a more sustainable growth. We propose a critical analysis of urban public space production in intermediate Chilean cities. By defining streets as public spaces and enabling specific social practices in line with specific urban contexts, we are able to define streets as a social space dedicated to mobilities. From this position, under what type of conditions are these public spaces planned and designed? What social consequences or conflicts emerge through their implementation? These processes will be illustrated through examples of public space projects and policies developed in intermediate Chilean cities these past few years.

Science fiction had anticipated the prediction of future occurrence of crimes. In fact, that prediction is actually possible. It can be done with some imprecision and by computer algorithms using available data from various sources. The prediction involves approximate time and risk maps of occurrence of certain type of felonies such as home burglaries, armed robberies and violent thefts. The police can then use this information for increasing their patrolling accordingly and thereby reducing the crime occurrence rate. We present a crime prediction solution developed for Chilean large cities. Its novel approach includes three independent software modules which make predictions based on different algorithms. The final prediction is the cooperative integration of the individual ones. The developed system has been tested on historical data and its performance has been considered acceptable for police field use. An interesting result is that the performance of each individual module is inferior to the joint performance, validating a hypothesis that different algorithms may exploit different features of the available data.

We present a decision support system to help plan preventive border patrols. The system represents the interaction between defenders and intruders as a Stackelberg security game (SSG) where the defender pools local resources to conduct joint preventive border patrols. We introduce a new SSG that constructs defender strategies that pair adjacent precincts to pool resources that are used to patrol a location within one of the two precincts. We introduce an efficient formulation of this problem and an efficient sampling method to construct an implementable defender strategy.