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Demyelinating disorders, with a particular focus on multiple sclerosis (MS), have a multitude of detrimental cognitive and physical effects on the patients. Current treatment options that involve substances promoting remyelination fail in the clinics due to difficulties in reaching the central nervous system (CNS). Here, the dual encapsulation of retinoic acid (RA) into lipid nanocapsules with a nominal size of 70 nm, and a low PdI of 0.1, coupled with super paramagnetic iron oxide nanoparticles (SPIONs) was accomplished, and joined by an external functionalization process with a transferrin-receptor binding peptide. This nanosystem showed a 3-fold improved internalization by endothelial cells compared to the free drug, ability to interact with oligodendrocyte progenitor cells and microglia, and improvements in the permeability through the blood-brain barrier by 5-fold. The lipid nanocapsules also induced the differentiation of oligodendrocyte progenitor cells into more mature, myelin producing oligodendrocytes, as evaluated by high-throughput image screening, by 3–5-fold. Furthermore, the ability to tame the inflammatory response was verified in lipopolysaccharide-stimulated microglia, suppressing the production of pro-inflammatory cytokines by 50–70%. Overall, the results show that this nanosystem can act in both the inflammatory microenvironment present at the CNS of affected patients, but also stimulate the differentiation of new oligodendrocytes, paving the way for a promising platform in the therapy of MS. [Display omitted] • Functionalized lipid nanocapsules are a versatile tool to encapsulate lipophilic drugs and ensure delivery to the brain • The lipid nanocapsules were able to significantly suppress the inflammatory phenotype of activated microglia; • Healthier, mature oligodendrocytes were stimulated when exposed to the lipid nanocapsules. [ABSTRACT FROM AUTHOR]

The central nervous system (CNS), namely the brain, still remains as the hardest area of the human body to achieve adequate concentration levels of most drugs, mainly due to the limiting behavior of its physical and biological defenses. Lipid nanocapsules emerge as a versatile platform to tackle those barriers, and efficiently delivery different drug payloads due to their numerous advantages. They can be produced in a fast, solvent-free and scalable-up process, and their properties can be fine-tuned for to make an optimal brain drug delivery vehicle. Moreover, lipid nanocapsule surface modification can further improve their bioavailability towards the central nervous system. Coupling these features with alternative delivery methods that stem to disrupt or fully circumvent the blood-brain barrier may fully harness the therapeutic advance that lipid nanocapsules can supply to current treatment options. Thus, this review intends to critically address the development of lipid nanocapsules, as well as to highlight the key features that can be modulated to ameliorate their properties towards the central nervous system delivery, mainly through intravenous methods, and how the pathological microenvironment of the CNS can be taken advantage of. The different routes to promote drug delivery towards the brain parenchyma are also discussed, as well as the synergetic effect that can be obtained by combining modified lipid nanocapsules with new/smart administration routes. Unlabelled Image [ABSTRACT FROM AUTHOR]

The blood brain barrier (BBB) is a well-established cell-based membrane that circumvents the central nervous system (CNS), protecting it from harmful substances. Due to its robustness and cell integrity, it is also an outstanding opponent when it comes to the delivery of several therapeutic agents to the brain, which requires the crossing through its highly-organized structure. This regulation and cell-cell communications occur mostly between astrocytes, pericytes and endothelial cells. Therefore, alternative ways to deliver drugs to the CNS, overcoming the BBB are required, to improve the efficacy of brain target drugs. Nanoparticles emerge here as a promising drug delivery strategy, due to their ability of high drug loading and the capability to exploit specific delivery pathways that most drugs are unable to when administered freely, increasing their bioavailability in the CNS. Thus, further attempts to assess the possible influence of non-endothelial may have on the BBB translocation of nanoparticles are here revised. Furthermore, the use of macrophages and/or monocytes as nanoparticle delivery cells are also approached. Lastly, the temporarily disruption of the overall organization and normal structure of the BBB to promote the penetration of nanoparticles aimed at the CNS is described, as a synergistic path. [ABSTRACT FROM AUTHOR]

Propagation of surface waves can occur with complex energy distribution amongst the various modes. It is shown that even simple V S (shear-wave velocity) profiles can generate velocity spectra that, because of a complex mode excitation, can be quite difficult to interpret in terms of modal dispersion curves. In some cases, Rayleigh waves show relevant differences depending on the considered component (radial or vertical) and the kind of source (vertical impact or explosive). Contrary to several simplistic assumptions often proposed, it is shown, both via synthetic and field datasets, that the fundamental mode of Rayleigh waves can be almost completely absent. This sort of evidence demonstrates the importance of a multi-component analysis capable of providing the necessary elements to properly interpret the data and adequately constrain the subsurface model. It is purposely shown, also through the sole use of horizontal geophones, how it can be possible to efficiently and quickly acquire both Love and Rayleigh (radial-component) waves. The presented field dataset reports a case where Rayleigh waves (both their vertical and radial components) appear largely dominated by higher modes with little or no evidence of the fundamental mode. The joint inversion of the radial and vertical components of Rayleigh waves jointly with Love waves is performed by adopting a multi-objective inversion scheme based on the computation of synthetic seismograms for the three considered components and the minimization of the whole velocity spectra misfits ( Full Velocity Spectra – FVS – inversion). Such a FVS multi-component joint inversion can better handle complex velocity spectra thus providing a more robust subsurface model not affected by erroneous velocity spectra interpretations and non-uniqueness of the solution. [ABSTRACT FROM AUTHOR]

ABSTRACT In recent years some authors have given a certain amount of attention to towed seismic reflection acquisition systems. Based on some of these works we sought to design and test a system making use of currently available geophones instead of specifically designed sensors as employed in some previous works. Thus, bearing in mind that the geophone's characteristics are achieved in the conditions that they are originally designed to be employed in, i.e., coupled with a spike driven into the ground, we devoted our attention to some of the variables involved in the geophone's performance, namely the total weight, the effect of a spikeless geophone and the surfaces on which the geophone is placed. Previously, we had experimentally verified some variations in the signal response due to coupling geophones in different surface materials, such as hard soil, asphalt and concrete pavement and we noticed that these surface materials were in fact an important factor in the overall response. Hence, these materials, or as we also called them coupling agents, could be employed as a base material in the construction of a mobile seismic acquisition device composed of blocks of a certain size, on which the geophone would be then inserted and thus making it into a spikeless surface towable system. Therefore, various materials were tested in order to select one that could maintain a similar fidelity to that of the spike coupled geophone and thus contribute towards building a more time efficient and towable geophone and block system. Pinging tests revealed variations in the coupling frequency and damping characteristics of each coupling agent and from all of these tested materials one was selected for field comparative tests with the normally planted geophones with spike coupling. Finally a seismic reflection profile was acquired simultaneously with both systems, i.e., spike coupling versus cement block coupled geophones. This field test showed similar results in terms of signal levels and frequency content and therefore it was possible to observe the presence of the same reflectors and other seismic events in either of the time sections. With this experiment we propose not only a system that allows a time efficient seismic field operation but we also aim to encourage more research into the response dependency of the coupling agent of which the towable base block is made of. [ABSTRACT FROM AUTHOR]

Abstract: Pirimicarb is considered a selective and effective insecticide for the control of aphids and whiteflies. Coccinella undecimpunctata L. is a euriphagous predator autochthonous to the Azores, which feeds preferentially on aphids. The voracity of 4th instars and adults (males and females) of C. undecimpunctata using Aphis fabae Scopoli or Aleyrodes proletella L. as preys was evaluated in laboratory, as well as the impact of pirimicarb on the feeding performance using A. fabae as prey. In the absence of chemical treatment and when the prey was A. proletella, satiation lower limits were estimated on a density of 200 individuals in a 24-h period, for 4th instars, adult females and males of C. undecimpunctata. With A. fabae, satiation was attained when 200, 150 and 100 aphids were provided to 4th instars, adult females and males, respectively. C. undecimpunctata exhibited a type II functional response for both prey species. Fourth instars displayed a lower handling time than the adults; handling times of the adults where higher when A. fabae was the prey and attack rates were sex-dependent, that is, attack rate of females was higher on A. fabae while of males was higher on A. proletella. Voracity of C. undecimpunctata was not significantly affected by pirimicarb; therefore, the use of this insecticide can constitute a complementary component for the integrated management of A. fabae. [Copyright &y& Elsevier]

The Geant4 Monte Carlo radiation transport toolkit provides the basic services and infrastructure required for the development of flexible simulation frameworks and applications, which ave found generalized use in high energy physics, nuclear physics, astrophysics, and medical physics research. Object-odented design provides the possibility to implement or modify any physics process in Geant4 without changing other parts of the code. This feature makes Geant4 open to extension of its physics modeling capabilities and to the implementation of alternative physics models. In this paper, the development of a simulation platform for performance studies and detector optimization of the Clear-PEM scanner, a high-performance positron emission mammography prototype, and the implementation of precise low energy bremsstrahlung angular generators for the Geant4 LowE category are described. [ABSTRACT FROM AUTHOR]

Due to the current energetic transition, new geological exploration technologies are needed to discover mineral deposits containing critical materials such as lithium (Li). The vast majority of European Li deposits are related to Li–Cs–Ta (LCT) pegmatites. A review of the literature indicates that conventional exploration campaigns are dominated by geochemical surveys and related exploration tools. However, other exploration techniques must be evaluated, namely, remote sensing (RS) and geophysics. This work presents the results of the INOVMINERAL4.0 project obtained through alternative approaches to traditional geochemistry that were gathered and integrated into a webGIS application. The specific objectives were to: (i) assess the potential of high-resolution elevation data; (ii) evaluate geophysical methods, particularly radiometry; (iii) establish a methodology for spectral data acquisition and build a spectral library; (iv) compare obtained spectra with Landsat 9 data for pegmatite identification; and (v) implement a user-friendly webGIS platform for data integration and visualization. Radiometric data acquisition using geophysical techniques effectively discriminated pegmatites from host rocks. The developed spectral library provides valuable insights for space-based exploration. Landsat 9 data accurately identified known LCT pegmatite targets compared with Landsat 8. The user-friendly webGIS platform facilitates data integration, visualization, and sharing, supporting potential users in similar exploration approaches. [ABSTRACT FROM AUTHOR]

Grounded in the Emotional Labour Theory, we aim to study the relationship between emotional demands (the expression of positive emotions and suppression of negative emotions) and work engagement in a sample of Portuguese police officers. We intend to explore the possible effects of these emotional demands on work engagement and ways of preventing and/or mitigating its impact. When analysing the studies conducted in the Portuguese police context, we found a gap regarding emotions and/or emotional regulation. Accordingly, a sample of 924 Portuguese police officers from the Public Security Police (PSP) answered the Emotion Work Requirements Scale and the Utrecht Work Engagement Scale voluntarily. Through correlation and multiple linear regression, we found a relationship between these emotional demands toward different interpersonal interactions and work engagement. We discuss these results, providing suggestions for field intervention and clues for future research. [ABSTRACT FROM AUTHOR]

Associated with the exploitation of metallic minerals in Europe during the 20th century, several mining areas were abandoned without adequate environmental intervention. Furthermore, these areas lack studies to characterize the impact of pollution on the hydrogeological system. The area surrounding the tungsten mine of Regoufe, in northern Portugal, is one such area exploited during the Second World War. The accumulation of sulfide-rich tailings may have caused an acid mine drainage (AMD), where the leaching processes caused by seepage water led to soil contamination, evidenced by its acid character and anomalous concentrations of some Potentially Toxic Elements (PTE) reported in previous studies. The present research proposes an innovative approach that seeks the integration of different geophysical techniques to characterize the impact of mining activity on the subsurface. Electrical resistivity (ER) and electromagnetic (EM) were used to measure subsurface electrical properties. In addition, seismic refraction and Multichannel Analysis of Surface Waves (MASW) were performed to characterize the geometry, depth, and geomechanical behavior of the soil and rock bodies. The integration of these techniques allowed the interpretation of hydrogeological sections and a 3D resistivity volume to gain insight into the distribution of potentially contaminating fluids and tailings material present in the mining valley. [ABSTRACT FROM AUTHOR]

Geophysical techniques can be successfully applied towards the detection of buried explosive devices, the ground-penetrating radar (GPR) being an example of one such method. This technology works through emission and reception of electromagnetic radio waves being thus able to detect the presence of a subsurface object fundamentally due to reflections from contrasting electromagnetic properties between the object and the surrounding medium (e.g., soil). Many factors can influence the success of a GPR survey (e.g., target type, soil type, environmental conditions, GPR antenna frequency, data processing techniques), being essential to know and understand their likely effects before performing GPR studies, mainly in real cases. In this paper, through the analysis of case studies related to the use of GPR technology towards the detection of buried explosive devices, we intend to arrange and layout the main prior knowledge that a forensic geophysical expert must have when dealing with this type of fieldwork. [ABSTRACT FROM AUTHOR]

Abstract: The suitability of Aphis fabae Scopoli, Myzus persicae Sulzer and Aleyrodes proletella L. as food sources for Coccinella undecimpunctata L. was evaluated by studying the impact of prey consumption on the predator’s population growth parameters and feeding parameters. Unlike A. proletella, A. fabae and M. persicae supported the development and reproduction of C. undecimpunctata. A. fabae and M. persicae were considered to be essential prey, whereas A. proletella was considered to be an alternative prey. Aphid species showed different degrees of suitability: M. persicae significantly decreased the pre-oviposition period and increased adult longevity, fecundity and fertility compared with A. fabae. Moreover, A. fabae represents a suitable diet for larval development, but is not a suitable food source for adult reproduction. The predator’s population growth parameters, R 0, r m and λ were increased with M. persicae, whereas T decreased. We found that the 4th instar larvae were the most voracious, particularly when fed on M. persicae; nevertheless, with this prey daily weight gain and feeding efficiency of 4th instar larvae were similar to that of individuals fed with A. fabae. [Copyright &y& Elsevier]

Although nanocarriers offer many advantages as drug delivery systems, their poor stability in circulation, premature drug release and nonspecific uptake in non-target organs have prompted biomimetic approaches using natural cell membranes to camouflage nanovehicles. Among them, erythrocytes, representing the most abundant blood circulating cells, have been extensively investigated for biomimetic coating on artificial nanocarriers due to their upgraded biocompatibility, biodegradability, non-immunogenicity and long-term blood circulation. Due to the cell surface mimetic properties combined with customized core material, erythrocyte-mimicking nanovehicles (EM-NVs) have a wide variety of applications, including drug delivery, imaging, phototherapy, immunomodulation, sensing and detection, that foresee a huge potential for therapeutic and diagnostic applications in several diseases. In this review, we summarize the recent advances in the biomedical applications of EM-NVs in cancer, infection, heart-, autoimmune- and CNS-related disorders and discuss the major challenges and opportunities in this research area. [Display omitted] [ABSTRACT FROM AUTHOR]

• NDT high-resolution methods in the characterization of heritage buildings. • Combined seismic transmission tomography and GPR. • Building materials and inner structure characterization of walls and columns. Rehabilitation, restoration and maintenance of monuments, heritage and buildings pose challenging tasks to engineers and architects, as any intervention must respect their architectural and constructive characteristics. Often these are unknown and sources of information have long been lost in time. Thus, there is a need to use methods capable of providing information on a wide range of aspects such as building foundations, construction characteristics and materials, alterations from the original layout, infrastructure mapping, pathologies, etc. These methods must respect the inherent structural delicacy and characteristics of ancient buildings and non-destructive methods, NDT such as geophysical methods, have been proposed to investigate these problems. It is common knowledge that a single geophysical method cannot provide full information on the problems to investigate. Thus, herein the combined use of Seismic Transmission Tomography and Ground Penetrating Radar – GPR - is demonstrated to provide important results in the investigation of the constructive elements (columns and walls) of a 14th century UNESCO monument. As demonstrated, high-resolution geophysical data obtained from both methods provide very good images of the interior of both walls and columns giving information on the quality and spatial distribution of the materials used in the construction of the monument. Finally, the results herein discussed prove the suitability and complementarity of these two methods to investigate, built heritage, monuments and buildings in general. [ABSTRACT FROM AUTHOR]

Geophysical experts aimed to establish a method to identify contamination by landfill leakage without chemically analyzing subsoil samples, which is time-consuming and expensive. To that end, researchers developed a software package that let the experts create 3D visualizations of geophysical data acquired around the landfill and apply statistical analysis to detect anomalous values. The data used, electrical resistivity, are typically sparse. So, the application employs kriging to interpolate the data and provide a volumetric representation of the subsoil resistivity. To avoid invalid conclusions, the visualization also represents uncertainty. The application enabled the experts to better understand the phenomenon and to develop and validate their method. Their evaluation of the application indicated that it helped them throughout the method's development and significantly eased their workload. [ABSTRACT FROM AUTHOR]

Mountains are often considered as the world's water towers. This paper presents a critical review on the research concerning the integrated assessment of groundwater resources of the mountain hydrogeologic system of Serra da Estrela Natural Park (central Portugal). The study area is the Zêzere river basin upstream of Manteigas village located at the Serra da Estrela Mountain in Central Portugal. It provides the source of strategic water resources for the Portuguese mainland, including normal groundwaters, thermomineral waters and surface waters. An integrated approach has been used to formulate a conceptual model for this complex mountain hydrogeological system by integrating the geological, morphotectonic, hydroclimatic, unsaturated soil zone, hydrogeological, hydrogeophysical, hydrogeochemical and isotopic data. This model has been useful to: i) evaluate the water resources; ii) provide the basis for a sustainable management of water resources, iii) design measures for groundwater exploitation and contamination control; and iv) set up land-use policies. [ABSTRACT FROM AUTHOR]

In a multidisciplinary approach, geological, geomorphologic, structural, hydrogeochemical and isotopic surveys were conducted on the Serra da Estrela groundwater system (central Portugal) in order to establish/develop a conceptual circulation model of the Caldas de Manteigas thermomineral system. A detailed study of the isotopic and geochemical composition of surface waters (e.g. Zêzere River), shallow groundwaters (cold dilute springs), and thermomineral waters was carried out to characterize the distribution of isotopes in waters of this mountainous region, and to determine the origin and possible recharge locations of the thermomineral system. Special attention was dedicated to isotopic tracers and their role in the definition of the thermomineral waters' conceptual model, considering: (1) the δO fractionation gradient; (2) the mean isotopic composition of the thermomineral waters in the region; and (3) the estimation of snowmelt contribution as a source of groundwater recharge at Serra da Estrela. The recharge of the thermomineral aquifer takes place on the more permeable zones of the granitic massif, associated with the main tectonic structures, whereas the recharge of the shallow aquifers seems to take place mostly in the plateaus, although another part of the recharge may occur in the slopes of the Zêzere River valley. [ABSTRACT FROM AUTHOR]

Abstract: In the framework of the Clear-PEM project for the construction of a high-resolution scanner for breast cancer imaging, a very compact and dense frontend electronics system has been developed for readout of multi-pixel S8550 Hamamatsu APDs. The frontend electronics are instrumented with a mixed-signal Application-Specific Integrated Circuit (ASIC), which incorporates 192 low-noise charge pre-amplifiers, shapers, analog memory cells and digital control blocks. Pulses are continuously stored in memory cells at clock frequency. Channels above a common threshold voltage are readout for digitization by off-chip free-sampling ADCs. The ASIC has a size of and was implemented in a AMS CMOS technology. In this paper the experimental characterization of the Clear-PEM frontend ASIC, reading out multi-pixel APDs coupled to LYSO:Ce crystal matrices, is presented. The chips were mounted on a custom test board connected to six APD arrays and to the data acquisition system. Six 32-pixel LYSO:Ce crystal matrices coupled on both sides to APD arrays were readout by two test boards. All 384 channels were operational. The chip power consumption is 660mW (3.4mW per channel). A very stable behavior of the chip was observed, with an estimated ENC of at APD gain 100. The inter-channel noise dispersion and mean baseline variation is less than 8% and 0.5%, respectively. The spread in the gain between different channels is found to be 1.5%. Energy resolution of 16.5% at 511keV and 12.8% at 662keV has been measured. Timing measurements between the two APDs that readout the same crystal is extracted and compared with detailed Monte Carlo simulations. At 511keV the measured single photon time RMS resolution is 1.30ns, in very good agreement with the expected value of 1.34ns. [Copyright &y& Elsevier]

Abstract: Clear-PEM is a dedicated PET scanner for breast and axilla cancer diagnosis, under development within the framework of the Crystal Clear Collaboration at CERN, aiming at the detection of tumors down to 2mm in diameter. The camera consists of two planar detector heads with active dimensions 16.0×14.5cm2. Each head has 96 Clear-PEM detector modules consisting of 32 LYSO:Ce pixels with dimensions 2×2×20mm3 packed in a 4×8 BaSO4 reflector matrix compressed between two Hamamatsu S8550 APD arrays in a double-readout configuration for Depth-of-Interaction (DoI) determination. The modules are individually measured and characterized before being grouped into Supermodules (comprised of 24 modules). Measured properties include photo-peak position, relative gain dispersion, energy resolution, cross-talk and DoI resolution. Optical inspection of matrices was also performed with the aid of a microscope, to search for pixel misalignments and matrix defects. Modules’ performance was thoroughly evaluated with a 511keV collimated beam to exactly determine DoI resolution. In addition, a fast quality control (QC) procedure using flood irradiations from a 137Cs source was applied systematically. The overall performance of the 24 detector modules complies with the design goals of the Clear-PEM detector, showing energy resolution around 15%, DoI resolution of about 2mm and gain dispersion among pixels of 15%. [Copyright &y& Elsevier]

Abstract: Clear-PEM is a Positron Emission Mammography (PEM) prototype being developed in the framework of the Crystal Clear Collaboration at CERN. This device is a dedicated PET camera for mammography, based on LYSO:Ce scintillator crystals, Avalanche PhotoDiodes (APD) and a fast, low-noise electronics readout system, designed to examine both the breast and the axillary lymph node areas, and aiming at the detection of tumors down to 2mm in diameter. The prototype has two planar detector heads, each composed of 96 detector modules. The Clear-PEM detector module is composed of a matrix of 32 identical 2×2×20mm3 LYSO:Ce crystals read at both ends by Hamamatsu S8550 APD arrays (4×8) for Depth-of-Interaction (DoI) capability. The APD arrays were characterized by the measurement of gain and dark current as a function of bias voltage, under controlled temperature conditions. Two independent setups were used. The full set of 398 APD arrays followed a well-defined quality control (QC) protocol, aiming at the rejection of arrays not complying within defined specifications. From a total of 398 arrays, only 2 (0.5%) were rejected, reassuring the trust in these detectors for prototype assembly and future developments. [Copyright &y& Elsevier]

Abstract: Experimental evaluation of the imaging system Clear-PEM for positron emission mammography, under development within the framework of the crystal clear collaboration at CERN, is presented in terms of its long-term stability. The detector modules and experimental setup are described. Time evolution results of signal yield, energy resolution, depth-of-interaction and inter-channel crosstalk for a reference detector module are reported. [Copyright &y& Elsevier]

The design and evaluation of the imaging system Clear-PEM for positron emission mammography, under development by the PEM Consortium within the framework of the Crystal Clear Collaboration at CERN, is presented. The proposed apparatus is based on fast, segmented, high atomic number radiation sensors with depth-of-interaction measurement capabilities, and state-of-the-art data acquisition techniques. The camera consists of two compact and planar detector heads with dimensions 16.5 × 14.5 cm² for breast and axilla imaging. Low-noise integrated electronics provide signal amplification and analog multiplexing based on a new data-driven architecture. The coincidence trigger and data acquisition architecture makes extensive use of pipeline processing structures and multi-event memories for high efficiency up to a data acquisition rate of one million events/s. Experimental validation of the detection techniques, namely the basic properties of the radiation sensors and the ability to measure the depth-of-interaction of the incoming photons, are presented. System performance in terms of detection sensitivity, count-rates and reconstructed image spatial resolution were also evaluated by means of a detailed Monte Carlo simulation and an iterative image reconstruction algorithm. [ABSTRACT FROM AUTHOR]