Double-walled poly-(D,l-lactide-co-glycolide) (plga) and poly(l-lactide) (plla) nanoparticles for the sustained release of doxorubicin

Funding Information: This research was funded by Funda??o para a Ci?ncia e a Tecnologia, Portugal, [grant numbers PTDC/QUE/EPR/119631/2010, SFRH/BD/48773/2008] and by the Associate Laboratory for Green Chemistry-LAQV which is financed by national funds from FCT/MCTES [UIDB/50006/2020 and UIDP/50006/2020] and co-financed by the ERDF [PT2020 Partnership Agreement POCI-01-0145-FEDER-007265].Double-walled nanoparticles (DWNPs), containing doxorubicin as a model drug, were produced using poly-(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by the solvent evaporation technique. Double-walled microparticles containing doxorubicin were also produced to make possible the examination of the inner morphology and drug distribution using optical and fluorescence microscopy. The produced microparticles present a double-walled structure with doxorubicin solubilized in the PLGA-rich phase. The DWNPs produced present very low initial burst values and a sustained DOX release for at least 90 days with release rates decreasing with the increase in the PLLA amount. Zero-order release kinetics were obtained after day 15. The results support that the PLLA layer acts as a rate control barrier and that the diffusion of doxorubicin from the drug-loaded inner PLGA core can be retarded by an increase in the thickness of the unloaded outer layer. The unloaded double-walled nanoparticles produced were used in in vitro tests with CHO cells and demonstrate that they are nontoxic, while the double-walled nanoparticles loaded with doxorubicin caused a great cellular viability and decreased when tested in vitro.publishersversionpublishe

A neural integrator model for planning and value-based decision making of a robotics assistant

Modern manufacturing and assembly environments are characterized by a high variability in the built process which challenges human–robot cooperation. To reduce the cognitive workload of the operator, the robot should not only be able to learn from experience but also to plan and decide autonomously. Here, we present an approach based on Dynamic Neural Fields that apply brain-like computations to endow a robot with these cognitive functions. A neural integrator is used to model the gradual accumulation of sensory and other evidence as time-varying persistent activity of neural populations. The decision to act is modeled by a competitive dynamics between neural populations linked to different motor behaviors. They receive the persistent activation pattern of the integrators as input. In the first experiment, a robot learns rapidly by observation the sequential order of object transfers between an assistant and an operator to subsequently substitute the assistant in the joint task. The results show that the robot is able to proactively plan the series of handovers in the correct order. In the second experiment, a mobile robot searches at two different workbenches for a specific object to deliver it to an operator. The object may appear at the two locations in a certain time period with independent probabilities unknown to the robot. The trial-by-trial decision under uncertainty is biased by the accumulated evidence of past successes and choices. The choice behavior over a longer period reveals that the robot achieves a high search efficiency in stationary as well as dynamic environments.The work received financial support from FCT through the PhD fellowships PD/BD/128183/2016 and SFRH/BD/124912/2016, the project “Neurofield” (PTDC/MAT-APL/31393/2017) and the research centre CMAT within the project UID/MAT/00013/2013

On the chronological structure of the solutrean in Southern Iberia

The Solutrean techno-complex has gained particular significance over time for representing a clear demographic and techno-typological deviation from the developments occurred during the course of the Upper Paleolithic in Western Europe. Some of Solutrean's most relevant features are the diversity and techno-typological characteristics of the lithic armatures. These have been recurrently used as pivotal elements in numerous Solutrean-related debates, including the chronological organization of the techno-complex across Iberia and Southwestern France. In Southern Iberia, patterns of presence and/or absence of specific point types in stratified sequences tend to validate the classical ordering of the techno-complex into Lower, Middle and Upper phases, although some evidence, namely radiocarbon determinations, have not always been corroborative. Here we present the first comprehensive analysis of the currently available radiocarbon data for the Solutrean in Southern Iberia. We use a Bayesian statistical approach from 13 stratified sequences to compare the duration, and the start and end moments of each classic Solutrean phase across sites. We conclude that, based on the current data, the traditional organization of the Solutrean cannot be unquestionably confirmed for Southern Iberia, calling into doubt the status of the classically defined type-fossils as precise temporal markers.Fundacao para a Ciencia e Tecnologia [PTDC/HAH/64184/2006, PTDC/HIS-ARQ/117540/2010, SFRH/BD/65527/2009, SFRH/BPD/96277/2013]; National Geographic Society [8045-06]; Wenner-Gren Foundation for Anthropological Research [8290

A stalagmite test of North Atlantic SST and Iberian hydroclimate linkages over the last two glacial cycles

Close coupling of Iberian hydroclimate and North Atlantic sea surface temperature (SST) during recent glacial periods has been identified through the analysis of marine sediment and pollen grains co-deposited on the Portuguese continental margin. While offering precisely correlatable records, these time series have lacked a directly dated, site-specific record of continental Iberian climate spanning multiple glacial cycles as a point of comparison. Here we present a high-resolution, multi-proxy (growth dynamics and delta C-13, delta O-18, and delta U-234 values) composite stalagmite record of hydroclimate from two caves in western Portugal across the majority of the last two glacial cycles (similar to 220 ka). At orbital and millennial scales, stalagmite-based proxies for hydroclimate proxies covaried with SST, with elevated delta C-13, delta O-18, and delta U-234 values and/or growth hiatuses indicating re-duced effective moisture coincident with periods of lowered SST during major ice-rafted debris events, in agreement with changes in palynological reconstructions of continental climate. While in many cases the Portuguese stalagmite record can be scaled to SST, in some intervals the magnitudes of stalagmite isotopic shifts, and possibly hydroclimate, appear to have been somewhat decoupled from SST.Agência financiadora / Número do subsídio Center for Global and Regional Environmental Research, Cornell College US National Science Foundation BCS-1118155 BCS-1118183 AGS-1804132 IGESPAR Associacao de Estudos Subterraneos e Defesa do Ambienteinfo:eu-repo/semantics/publishedVersio

A dynamic neural field approach to natural and efficient human-robot collaboration

A major challenge in modern robotics is the design of autonomous robots that are able to cooperate with people in their daily tasks in a human-like way. We address the challenge of natural human-robot interactions by using the theoretical framework of dynamic neural fields (DNFs) to develop processing architectures that are based on neuro-cognitive mechanisms supporting human joint action. By explaining the emergence of self-stabilized activity in neuronal populations, dynamic field theory provides a systematic way to endow a robot with crucial cognitive functions such as working memory, prediction and decision making . The DNF architecture for joint action is organized as a large scale network of reciprocally connected neuronal populations that encode in their firing patterns specific motor behaviors, action goals, contextual cues and shared task knowledge. Ultimately, it implements a context-dependent mapping from observed actions of the human onto adequate complementary behaviors that takes into account the inferred goal of the co-actor. We present results of flexible and fluent human-robot cooperation in a task in which the team has to assemble a toy object from its components.The present research was conducted in the context of the fp6-IST2 EU-IP Project JAST (proj. nr. 003747) and partly financed by the FCT grants POCI/V.5/A0119/2005 and CONC-REEQ/17/2001. We would like to thank Luis Louro, Emanuel Sousa, Flora Ferreira, Eliana Costa e Silva, Rui Silva and Toni Machado for their assistance during the robotic experiment

Territoriality and the organization of technology during the Last Glacial Maximum in southwestern Europe

Climate changes that occurred during the Last Glacial Maximum (LGM) had significant consequences in human eco-dynamics across Europe. Among the most striking impacts are the demographic contraction of modern humans into southern refugia and the potential formation of a population bottleneck. In Iberia and southern France transformations also included the occurrence of significant technological changes, mostly marked by the emergence of a diverse set of bifacially-shaped stone projectiles. The rapid dissemination of bifacial technologies and the geographical circumscription of specific projectile morphologies within these regions have been regarded as evidence for: (1) the existence of a system of long-distance exchange and social alliance networks; (2) the organization of human groups into cultural facies with well-defined stylistic territorial boundaries. However, the degree and modes in which cultural transmission have occurred within these territories, and how it may have influenced other domains of the adaptive systems, remains largely unknown. Using southern Iberia as a case-study, this paper presents the first quantitative approach to the organization of lithic technology and its relationship to hunter-gatherers' territorial organization during the LGM. Similarities and dissimilarities in the presence of morphological and metric data describing lithic technologies are used as a proxy to explore modes and degrees of cultural transmission. Statistical results show that similarities in technological options are dependent on the chronology and geographical distance between sites and corroborate previous arguments for the organization of LGM settlement in Southern Iberia into discrete eco-cultural facies.STSM COST action (ref. COST-STSM-TD0902-10855); FCT, contract ref. DL 57/2016/CP1361/ CT0026. Work at Vale Boi is funded by the project ALG-01-0145-FEDER-27833 - PTDC/HAR-ARQ/27833/2017.info:eu-repo/semantics/publishedVersio

The resilience of postglacial hunter-gatherers to abrupt climate change

Understanding the resilience of early societies to climate change is an essential part of exploring the environmental sensitivity of human populations. There is significant interest in the role of abrupt climate events as a driver of early Holocene human activity, but there are very few well-dated records directly compared with local climate archives. Here, we present evidence from the internationally important Mesolithic site of Star Carr showing occupation during the early Holocene, which is directly compared with a high-resolution palaeoclimate record from neighbouring lake beds. We show that-once established-there was intensive human activity at the site for several hundred years when the community was subject to multiple, severe, abrupt climate events that impacted air temperatures, the landscape and the ecosystem of the region. However, these results show that occupation and activity at the site persisted regardless of the environmental stresses experienced by this society. The Star Carr population displayed a high level of resilience to climate change, suggesting that postglacial populations were not necessarily held hostage to the flickering switch of climate change. Instead, we show that local, intrinsic changes in the wetland environment were more significant in determining human activity than the large-scale abrupt early Holocene climate events

Complete blood count parameters as biomarkers of retinopathy of prematurity: a Portuguese multicenter study

Purpose: To evaluate complete blood count (CBC) parameters in the first week of life as predictive biomarkers for the development of retinopathy of prematurity (ROP). Methods: Multicenter, prospective, observational study of a cohort of preterm infants born with gestational age (GA) < 32 weeks or birth weight < 1500 g in eight Portuguese neonatal intensive care units. All demographic, clinical, and laboratory data from the first week of life were collected. Univariate logistic regression was used to assess risk factors for ROP and then multivariate regression was performed. Results: A total of 455 infants were included in the study. The median GA was 29.6 weeks, and the median birth weight was 1295 g. One hundred and seventy-two infants (37.8%) developed ROP. Median values of erythrocytes (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin concentration (p < 0.001), lymphocytes (p = 0.035), and platelets (p = 0.003) of the group of infants diagnosed with ROP any stage were lower than those without ROP. Mean corpuscular volume (MCV) (p = 0.044), red blood cell distribution width (RDW) (p < 0.001), erythroblasts (p < 0.001), neutrophils (p = 0.030), neutrophils-lymphocytes ratio (p = 0.028), and basophils (p = 0.003) were higher in the ROP group. Higher values of MCV, erythroblasts, and basophils remained significantly associated with ROP after multivariate regression. Conclusion: In our cohort, the increase in erythroblasts, MCV, and basophils in the first week of life was significantly and independently associated with the development of ROP. These CBC parameters may be early predictive biomarkers for ROP.info:eu-repo/semantics/publishedVersio