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The cross-talk between T cells and astrocytes occurring under physiological and, even more, neuroinflammatory conditions may profoundly impact the generation of adaptive immune responses in the nervous tissue. In this study, we used a standardized in vitro co-culture assay to investigate the immunomodulatory properties of astrocytes differing for age, sex, and species. Mouse neonatal astrocytes enhanced T cell vitality but suppressed T lymphocyte proliferation in response to mitogenic stimuli or myelin antigens, regardless of the Th1, Th2 or Th17 T cell phenotype. Studies comparing glia cells from adult and neonatal animals showed that adult astrocytes were more efficient in inhibiting T lymphocyte activation than neonatal astrocytes, regardless of their sex. Differently from primary cultures, mouse and human astrocytes derived from reprogrammed fibroblasts did not interfere with T cell proliferation. Overall, we describe a standardized astrocyte-T cell interaction in vitro assay and demonstrate that primary astrocytes and iAstrocytes may differ in modulating T cell function. [ABSTRACT FROM AUTHOR]

Demyelination is a key pathogenic feature of multiple sclerosis (MS). Here, we evaluated the astrocyte contribution to myelin loss and focused on the neurotrophin receptor TrkB, whose up-regulation on the astrocyte finely demarcated chronic demyelinated areas in MS and was paralleled by neurotrophin loss. Mice lacking astrocyte TrkB were resistant to demyelination induced by autoimmune or toxic insults, demonstrating that TrkB signaling in astrocytes fostered oligodendrocyte damage. In vitro and ex vivo approaches highlighted that astrocyte TrkB supported scar formation and glia proliferation even in the absence of neurotrophin binding, indicating TrkB transactivation in response to inflammatory or toxic mediators. Notably, our neuropathological studies demonstrated copper dysregulation in MS and model lesions and TrkB-dependent expression of copper transporter (CTR1) on glia cells during neuroinflammation. In vitro experiments evidenced that TrkB was critical for the generation of glial intracellular calcium flux and CTR1 up-regulation induced by stimuli distinct from neurotrophins. These events led to copper uptake and release by the astrocyte, and in turn resulted in oligodendrocyte loss. Collectively, these data demonstrate a pathogenic demyelination mechanism via the astrocyte release of copper and open up the possibility of restoring copper homeostasis in the white matter as a therapeutic target in MS. [ABSTRACT FROM AUTHOR]

Hepatocyte nuclear factor 4 α (HNF4α), a transcription factor (TF) essential for embryonic development, has been recently shown to regulate the expression of inflammatory genes. To characterize HNF4a function in immunity, we measured the effect of HNF4α antagonists on immune cell responses in vitro and in vivo. HNF4α blockade reduced immune activation in vitro and disease severity in the experimental model of multiple sclerosis (MS). Network biology studies of human immune transcriptomes unraveled HNF4α together with SP1 and c-myc as master TF regulating differential expression at all MS stages. TF expression was boosted by immune cell activation, regulated by environmental MS risk factors and higher in MS immune cells compared to controls. Administration of compounds targeting TF expression or function demonstrated non-synergic, interdependent transcriptional control of CNS autoimmunity in vitro and in vivo. Collectively, we identified a coregulatory transcriptional network sustaining neuroinflammation and representing an attractive therapeutic target for MS and other inflammatory disorders. • HNF4α supports monocyte and T cell function. • HNF4α, SP1 and c-myc are shared transcription factor network hubs among MS stages. • Hub levels are higher in MS immune cells and regulated by environmental risk factors. • Hubs exert non-synergic, interdependent control of CNS autoimmunity in vivo. [ABSTRACT FROM AUTHOR]

Production activities of modern economies are ultimately sustained by depletion of non-renewable fossil fuels. In the perspective of non-renewables displacement, an accurate evaluation of energy embodied in goods and services is crucial in order to select among alternative products or policies. Economic-based Input-Output models are widely used for this purpose: however, due to the increasing amount of international trades of products, definition of appropriate methods to account for the energy embodied in trades is nowadays crucial. In this paper, international trades treatment methods in Input-Output analysis are comprehensively formalized and applied to a case study based on the World Input-Output Database (WIOD). Energy embodied in final demand and in detailed products of key national energy sectors have been evaluated for the WIOD countries according to Single-Region and Multi-Regional models. It is found that an inappropriate use of international trades treatment models may produce very inaccurate estimations of numerical values of embodied energy. Three country groups has been identified, characterized by different ranges of fractions of imported/exported primary fossil fuels: Single-Region method A returns best results for countries of Group 1, with high values of fossil exports and low values of fossil imports; Multi-Regional method C is to be preferred for countries of Group 2, with high values of fossil imports and low values of fossil exports; finally, Single-Region method B returns lower deviations compared to other methods for countries of group 3, with low values of fossil imports and exports. This paper aims at supporting researchers in the field of Life Cycle Assessment in the application of Environmentally extended Input-Output analysis, finding the best trade-off between the efforts due to data collection and the accuracy of results. [ABSTRACT FROM AUTHOR]

The fixed dome digester design is the most deployed small scale biogas technology in sub-Sahara Africa (SSA). This design is deployed on mono-feedstock-wet anaerobic digestion (WAD) principle. Little or nothing has been reported in the literature on the sustainability in terms of the actual field operation and performance of this design within the SSA context. This study aims at bridging this gap and bringing additional insights to the scientific literature by investigating the sustainability of the Nepali–type fixed dome digester within the context of rural Cameroon. The investigations were evaluated in terms of operating parameters, biogas production, production rate and productivity of the digester. In addition the local investment cost of the design was analyzed. The design was operated on multiple-locally-available feedstock mixed with water at an average of 3:1 ratio resulting in a higher than design TS of 16%. The design, thus was operated towards the dry anaerobic digestion principle, highlighting insufficient mono-feedstock and water scarcity for a sustainable operation of the design within the context of rural SSA. The average biogas production was 1.2 m 3 biogas /day, giving average volumetric production rate of 0.16 m 3 biogas /m 3 digester day −1 and yields of 0.18 m 3 biogas /kg VS respectively. This low performance compared with the potential mesophilic biogas production rate of 0.27 m 3 biogas /m 3 digester day −1 could be linked to insufficient mixing of digester content and low operating temperatures. Gas storage facility (dome), skilled labour and cement made significant contributions to the investment cost of the digester. The Levelized cost of Energy from the digester was less than 1 € cents/MJ. [ABSTRACT FROM AUTHOR]

One of the most controversial topics in energy analysis consists in the internalization of the effects of human labor in the embodied energy requirements of goods and services. In this paper, the Bioeconomic Input-Output model is proposed to address such issue: it consists in a partially closed Hybrid Input-Output model in which the production of human labor is internalized within the economy as a new productive sector. The human labor sector absorbs a portion of the national final demand, while it produces working hours in order to sustain the national economic activities. The Bioeconomic model causes a reallocation of the total energy embodied in the production of goods and services due to two overlapping effects: a change in the national production technology due to the definition of the human labor sector, and a reduction in the available final demand for the consumptions of the households. The Bioeconomic and the standard Input-Output models are comparatively applied for the analysis of (1) the energy embodied in goods and services produced by the Italian economy in 2010, and (2) the primary energy requirements of alternative dishwashing solutions in Italy. Specific embodied energy in Italian products increases by less than 5% for mining and energy industries, by 5–15% for manufacturing industries and by 15–70% for tertiary sectors. On the other hand, the energy embodied in total production from each sector may be lower or greater (from −20% to +50%) with respect to results of the standard Input-Output model. Moreover, it is found that the energy embodied in dishwashing by hand and by dishwasher in Italy increases respectively by 62% and by 35% if the Bioeconomic model is adopted. Based on these results, Authors argue that human labor should methodically be included alongside the supply chain of goods and services in both embodied energy analysis and life-cycle assessment. [ABSTRACT FROM AUTHOR]

Astrocytes are crucial regulators of innate and adaptive immune responses in the injured central nervous system. Depending on timing and context, astrocyte activity may exacerbate inflammatory reactions and tissue damage, or promote immunosuppression and tissue repair. Recent literature has unveiled key factors and intracellular signaling pathways that govern astrocyte behavior during neuroinflammation. Here we have re-visited in vivo studies on astrocyte signaling in neuroinflammatory models focusing on evidences obtained from the analysis of transgenic mice where distinct genes involved in ligand binding, transcriptional regulation and cell communication have been manipulated in astrocytes. The integration of in vivo observations with in vitro data clarifies precise signaling steps, highlights the crosstalk among pathways and identifies shared effector mechanisms in neuroinflammation. [ABSTRACT FROM AUTHOR]

Most energy conversion systems, and especially electricity generation plants, do not operate at nominal conditions throughout their useful life: periodic, semi-periodic and stochastic changes in the availability of the resource affect solar (thermal and PV), wind, hydraulic, and geothermal plants, which in reality operate at off-design conditions for most of their life. To a smaller extent, fossil-fuelled plants may also be plagued by fuel availability problems and no longer easily predictable demand oscillation. In spite of the ever growing net connectivity, since the demand curve in even larger geographic regions displays a typical quasi-sinusoidal shape, fleet load modulation is unavoidable. Naturally, off-design operation and load cycling affect the cost of the generated kWh. This paper presents a general thermoeconomic method to evaluate the economic and environmental effects of energy system integration, taking into account life cycle concerns (supply chains) and the effect of inefficiencies due to off-design operation of the systems. The method here is applied to a realistic case study of an Italian regional utility: an analysis of the implications of the variation of the productive mix between a photovoltaic power plant (PV) and a standard commercial, non-cogenerating gas turbine plant (GT) on the final cost of the electrical kWh. The demand curve is prescribed, and the effect of different mixes is assessed, both on the monetary and on the exergy cost of the electricity. The economic cost assessment is performed by standard thermoeconomic techniques, whereas the exergy costs are evaluated using both the Extended Exergy Accounting (EEA) and the Thermo-Ecological Cost (TEC) methods. The results show that a purely monetary cash flow accounting and thermo-economics lead to contrasting results, and also that the EEA and TEC cost indicators generate different rankings among the studied alternative GT/PV mixes. [ABSTRACT FROM AUTHOR]

Objective Although astrocytes participate in glial scar formation and tissue repair, dysregulation of the NFκB pathway and of nitric oxide (NO) production in these glia cells contributes to neuroinflammation and neurodegeneration. Here we investigated the role of the crosstalk between sphingosine-1-phosphate (S1P) and cytokine signaling cascades in astrocyte activation and inflammation-mediated neurodegeneration, and addressed the effects of fingolimod on astrocyte-neuron interaction and NO synthesis in vivo. Methods Immunohistochemistry, immunofluorescence, and confocal microscopy were used to detect S1P receptors, interleukin (IL) 1R, IL17RA, and nitrosative stress in multiple sclerosis (MS) plaques, experimental autoimmune encephalomyelitis (EAE) spinal cord, and the spinal cord of fingolimod-treated EAE mice. An in vitro model was established to study the effects of S1P, IL1, and IL17 stimulation on NFkB translocation and NO production in astrocytes, on spinal neuron survival, and on astrocyte-neuron interaction. Furthermore, fingolimod efficacy in blocking astrocyte-mediated neurodegeneration was evaluated. Results We found coordinated upregulation of IL1R, IL17RA, S1P1, and S1P3 together with nitrosative markers in astrocytes within MS and EAE lesions. In vitro studies revealed that S1P, IL17, and IL1 induced NFκB translocation and NO production in astrocytes, and astrocyte conditioned media triggered neuronal death. Importantly, fingolimod blocked the 2 activation events evoked in astrocytes by either S1P or inflammatory cytokines, resulting in inhibition of astrocyte-mediated neurodegeneration. Finally, therapeutic administration of fingolimod to EAE mice hampered astrocyte activation and NO production. Interpretation A neuroprotective effect of fingolimod in vivo may result from its inhibitory action on key astrocyte activation steps. Ann Neurol 2014;76:325-337 [ABSTRACT FROM AUTHOR]

Sphingosine 1-phosphate (S1P) is a potent bioactive sphingolipid binding to specific G protein-coupled receptors expressed in several organs. The relevance of S1P-S1P receptor axis in the pathophysiology of immune and nervous systems has encouraged the development of S1P receptor modulators for the treatment of neurological, autoimmune and/or inflammatory disorders. Currently, four S1P receptor modulators are approved drugs for multiple sclerosis (MS), an inflammatory disorder of the central nervous system. As main pharmacologic effect, these treatments induce lymphopenia due to the loss of responsiveness to S1P gradients guiding lymphocyte egress from lymphoid organs into the bloodstream. Recent data point to immunological effects of the S1P modulators beyond the inhibition of lymphocyte trafficking. Further, these drugs may cross the blood-brain barrier and directly target CNS resident cells expressing S1P receptors. Here we review the role of S1P signalling in neuroimmunology at the light of the evidences generated from the study of the mechanism of action of S1P receptor modulators in MS and integrate this information with findings derived from neuroinflammatory animal models and in vitro observations. These insights can direct the application of therapeutic approaches targeting S1P receptors in other disease areas. [ABSTRACT FROM AUTHOR]

Highlights: [•] The model proposed aims at minimizing local impact of energy systems. [•] The model is meant to minimize the impact starting from system thermodynamics. [•] The formulation combines exergy analysis and quantitative risk analysis. [•] The approach of the model is dual to Thermoeconomics. [ABSTRACT FROM AUTHOR]

Nucleophosmin (NPM) is a nucleolar phosphoprotein that binds the tumor suppressors p53 and p19Arf and is thought to be indispensable for ribogenesis, cell proliferation, and survival after DNA damage. The NPM gene is the most frequent target of genetic alterations in leukemias and lymphomas, though its role in tumorigenesis is unknown. We report here the first characterization of a mouse NPM knockout strain. Lack of NPM expression results in accumulation of DNA damage, activation of p53, widespread apoptosis, and mid-stage embryonic lethality. Fibroblasts explanted from null embryos fail to grow and rapidly acquire a senescent phenotype. Transfer of the NPM mutation into a p53-null background rescued apoptosis in vivo and fibroblast proliferation in vitro. Cells null for both p53 and NPM grow faster than control cells and are more susceptible to transformation by activated oncogenes, such as mutated Ras or overexpressed Myc. In the absence of NPM, Arf protein is excluded from nucleoli and is markedly less stable. Our data demonstrate that NPM regulates DNA integrity and, through Aft, inhibits cell proliferation and are consistent with a putative tumor-suppressive function of NPM. [ABSTRACT FROM AUTHOR]

Nucleophosmin (NPM) is a ubiquitously expressed nucleolar phosphoprotein that continuously shuttles between the nucleus and cytoplasm. It has been proposed to function in ribosomal protein assembly and transport, and also as a molecular chaperone that prevents proteins from aggregating in the crowded environment of the nucleolus. The NPM gene is involved in several tumour-associated chromosome translocations, which have resulted in the formation of fusion proteins that retain the amino terminus of NPM, including NPM?ALK, NPM?RAR and NPM?MLF1 (ref. 6). It is generally thought that the NPM component is not involved in the transforming potential of these fusion proteins, but instead provides a dimerization interface for the oligomerization and the oncogenic conversion of the various NPM partners (ALK, RAR, MLF1). Here we show that NPM interacts directly with the tumour suppressor p53, regulates the increase in stability and transcriptional activation of p53 after different types of stress, and induces p53-dependent premature senescence on overexpression in diploid fibroblasts. These findings indicate that NPM is a crucial regulator of p53 and suggest that alterations of the NPM function by NPM fusion proteins might lead to deregulation of p53 in tumours. [ABSTRACT FROM AUTHOR]

Astrocytes greatly participate to inflammatory and neurotoxic reactions occurring in neurodegenerative diseases and are valuable pharmacological targets to support neuroprotection. Here we used human astrocytes generated from reprogrammed fibroblasts as a cellular model to study the effect of the compound Laquinimod and its active metabolite de-Laquinimod on astrocyte functions and the astrocyte–neuron interaction. We show that human iAstrocytes expressed the receptor for the inflammatory mediator IL1 and responded to it via nuclear translocation of NFκB, an event that did not occur if cells were treated with Laquinimod, indicating a direct anti-inflammatory activity of the drug on the human astrocyte. Similarly, while exposure to IL1 downregulated glial glutamate transporters GLAST and GLT1, treatment with Laquinimod supported maintenance of physiological levels of these proteins despite the inflammatory milieu. Laquinimod also induced nuclear translocation of the aryl hydrocarbon receptor (AHR), suggesting that drug action was mediated by activation of the AHR pathway. However, the drug was effective despite AHR inhibition via CH223191, indicating that AHR signaling in the astrocyte is dispensable for drug responses. Finally, in vitro experiments with rat spinal neurons showed that laquinimod did not exert neuroprotection directly on the neuron but dampened astrocyte-induced neurodegeneration. Our findings indicate that fibroblast-derived human astrocytes represent a suitable model to study astrocyte–neuron crosstalk and demonstrate indirect, partial neuroprotective efficacy for laquinimod. [ABSTRACT FROM AUTHOR]

Abstract: The neurotrophin receptor p75NTR is a marker for human differentiation-prone muscle satellite cells and regulates myogenesis. Here, we wondered whether inflammation could modify p75NTR expression on muscle precursor cells in vitro and in vivo. In vitro experiments on human primary skeletal myoblasts demonstrated that exposure to IFN-γ or IL-1α decreased transcript and protein levels of p75NTR. Furthermore, histological investigations showed a reduction in the pool of p75NTR expressing satellite cells in inflammatory myopathy biopsies. These data suggest a link between muscle inflammation and reduction of p75NTR expression on precursor cells. [Copyright &y& Elsevier]

Whether Clonal Hematopoiesis (CH) represents a risk factor for severity of the COVID-19 disease remains a controversial issue. We report the first high- sensitivity analysis of CH in COVID-19 patients (threshold of detection at 0.5% vs 1 or 2% in previous studies). We analyzed 24 patients admitted to ICU for COVID-19 (COV-ICU) and 19 controls, including healthy subjects and asymptomatic SARS-CoV2-positive individuals. Despite the significantly higher numbers of CH mutations identified (80% mutations with <2% variant allele frequency, VAF), we did not find significant differences between COV-ICU patients and controls in the prevalence of CH or in the numbers, VAF or functional categories of the mutated genes, suggesting that CH is not overrepresented in patients with COVID-19. However, when considering potential drivers CH mutations (CH-PD), COV-ICU patients showed higher clonal complexity, in terms of both mutation numbers and VAF, and enrichment of variants reported in myeloid neoplasms. However, we did not score an impact of increased CH-PD on patient survival or clinical parameters associated with inflammation. These data suggest that COVID-19 influence the clonal composition of the peripheral blood and call for further investigations addressing the potential long-term clinical impact of CH on people experiencing severe COVID-19. We acknowledge that it will indispensable to perform further studies on larger patient cohorts in order to validate and generalize our conclusions. Moreover, we performed CH analysis at a single time point. It will be necessary to consider longitudinal approaches with long periods of follow-up in order to assess if the COVID-19 disease could have an impact on the evolution of CH and long-term consequences in patients that experienced severe COVID-19. [ABSTRACT FROM AUTHOR]

Long-read sequencing allows analyses of single nucleic-acid molecules and produces sequences in the order of tens to hundreds kilobases. Its application to whole-genome analyses allows identification of complex genomic structural-variants (SVs) with unprecedented resolution. SV identification, however, requires complex computational methods, based on either read-depth or intra- and inter-alignment signatures approaches, which are limited by size or type of SVs. Moreover, most currently available tools only detect germline variants, thus requiring separate computation of sample pairs for comparative analyses. To overcome these limits, we developed a novel tool (Germline And SOmatic structuraL varIants detectioN and gEnotyping; GASOLINE) that groups SV signatures using a sophisticated clustering procedure based on a modified reciprocal overlap criterion, and is designed to identify germline SVs, from single samples, and somatic SVs from paired test and control samples. GASOLINE is a collection of Perl, R and Fortran codes, it analyzes aligned data in BAM format and produces VCF files with statistically significant somatic SVs. Germline or somatic analysis of 30 × sequencing coverage experiments requires 4–5 h with 20 threads. GASOLINE outperformed currently available methods in the detection of both germline and somatic SVs in synthetic and real long-reads datasets. Notably, when applied on a pair of metastatic melanoma and matched-normal sample, GASOLINE identified five genuine somatic SVs that were missed using five different sequencing technologies and state-of-the art SV calling approaches. Thus, GASOLINE identifies germline and somatic SVs with unprecedented accuracy and resolution, outperforming currently available state-of-the-art WGS long-reads computational methods. [ABSTRACT FROM AUTHOR]

Abstract To support the ongoing transition towards smart and decarbonised energy systems, energy models need to expand their scope and predictive capabilities. To this end, this study proposes a multi-layer modelling methodology that soft-links (i) a stochastic bottom-up load curves estimation model, (ii) a technology-rich energy system optimisation model (Calliope) and (iii) a Multi-Regional Input-Output model (Exiobase v.3), and applies it to investigate the economic and environmental consequences entailed by a massive replacement of traditional gas-fired kitchens with induction kitchens within the Italian residential sector. Two scenarios are considered for the analysis: (i) business as usual (BAU, 2015 energy system configuration), and (ii) national energy strategy (SEN, configuration prospected in 2030). The results show how the intervention produces positive net effects on the primary energy balance of the energy sector only when sustained by adequate shares of renewables, as in the SEN (−1.5 TWh∙y−1); otherwise, increased operation of fossil-fuel plants offsets gas savings (BAU, +2 TWh∙y−1). Nonetheless, feedbacks on other productive sectors entail additional energy consumption and emissions, thus counterpoising positive effects obtained within the energy sector even in the SEN scenario. Still, higher renewables penetration reduces overall additional emissions from 2.07 Mton∙y−1 for BAU to 0.88 Mton∙y−1 for the SEN. Highlights • A multi-layer methodology to link energy models and input-output models is proposed. • Italian electricity demand due to massive electrification of cooking devices is assessed. • Change in the Italian power production mix is assessed based on Calliope energy model. • The related economic/environmental implications are assessed with the Exiobase model. [ABSTRACT FROM AUTHOR]

Improved Cooking Stoves (ICSs) represent the most commonly promoted solution to alleviate the burden associated with the use of traditional biomass in a short-term perspective. However, criticism is raising about the methodologies used for assessing their performance, with a particular focus on laboratory-based testing protocols. One of the key weaknesses of current protocols consists in the inaccurate and biased approach adopted for reporting and statistically analysing test results, which can lead to misleading conclusions about the actual improvements ensured by ICSs. This study proposes a robust procedure to deal with the statistical analysis of small sample sizes, and subsequently verify it through its application to an experimental comparison – based on the Water Boiling Test – between three models of stove. The results show that the current practice based on 3 or 5 replicates often produces biases in the analyses, as at least 13 replicates might be needed to achieve reliable results. Moreover, the study shows how the t-test is in most cases improperly applied, while the proposed procedure allows to deal both with normally and of non-normally distributed data sets in a robust way. In one case, the apparent improvement of an ICS model as compared to the three-stone fire, is refuted by the application of our procedure. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented describing necrotizing fasciitis, an infection of the subcutaneous tissue and the superficial fascia.

Faults and malfunctions occurring in engineering systems may cause additional resources consumptions and economic expenditures, thus their detection and isolation is of great practical significance. The procedure to discover faults is known as diagnosis , and it can be based on different techniques, depending on the purpose of the analysis: to predict the failure time of the component, or to quantify the inefficiencies of the system due to the anomaly. Among the existing approaches adopted to diagnose the energy systems, Thermoeconomic diagnosis provides useful information to detect the anomalies and to quantify its negative impacts. However, this method does not allow to identify possible strategies useful to reduce the inefficiencies caused by anomalies, which could be a crucial need for the system operator. To face this issue, this article proposes a method to perform Thermoeconomic diagnosis of energy systems that enables the analyst to understand the interdependencies between the components, and decomposing the main indicator resulting from Thermoeconomic diagnosis, known as malfunction. The method provides useful information for the system operators to define practical strategies to reduce the negative effects of malfunctions. This approach is also formalized and applied to the CGAM benchmark to highlight the practical achievements of this approach with numerical values. It is found that the proposed approach provides useful insight about the effects of malfunctions, and it may be helpful for system operators to reduce the negative impacts of the anomaly by pinpointing the component with higher contribution in total inefficiency of the system. In this specific case, proper intervention on the pinpointed component mitigated the total inefficiency of the system by almost 40%, and recovered the reference efficiency of the system. [ABSTRACT FROM AUTHOR]

Understanding the energy metabolism of national economies is nowadays crucial for policymakers in order to define effective policies and to properly set energy efficiency targets. Energy accountings based on the traditional Production-based accounting method (PBA) allows to understand how primary energy is directly extracted, traded, transformed and used within each economy. On the other hand, Consumption-based accounting method (CBA) allows to understand the ultimate economic purposes of such energy flows. The information provided by the joint application of these approaches may provide useful and complementary insight on the national energy metabolism, allowing to identify hotspots for potential interventions from both the supply and demand side. This paper reviews PBA and CBA energy accounting methods, presenting a possible way for the joint use of their results, consistently represented by means of one unique Sankey diagram. This will be useful to have a comprehensive insight on the energy metabolism of national economies, supporting analysts and policymakers in the identification of energy efficiency hotspots. The method is applied to South Africa and to the neighbor country of Botswana, based on data provided by IEA energy statistics and the EORA26 Multi-Regional Input-Output model, taking into account non-renewable fossil energy (raw coal, crude oil and natural gas) and considering the reference year 2013. Results suggest that the joint use of PBA and CBA methods may provide useful information on the hidden energy links among national economies, helping analysts and policymakers in defining alternative energy efficiency policies. For this reason, the Authors argue that results of CBA should be provided alongside energy statistics based on the traditional PBA approach. [ABSTRACT FROM AUTHOR]

Laboratory protocols based on water heating procedures represent the most widespread tool for the evaluation of Improved Cooking Stoves (ICSs) thermal performance. Nevertheless, the performance of the cooking system can vary substantially when the boundary conditions – ambient conditions, burn sequence – differ from those experienced in a specific lab. Consequently, we developed and experimentally validated a Cooking Stoves Thermal Performance Simulator (Cook-STePS), based on a 1-D heat and mass transfer model and implemented in an Excel ® and VBA environment, in order to provide additional information about how the performance of a cooking system would change, in selected conditions, as compared to the baseline laboratory performance. The study shows how the tool can be effectively applied to a generic cooking system through a two-steps procedure, based on (i) a preliminary set of experimental tests in controlled conditions and (ii) the simulation of performance in the desired conditions. [ABSTRACT FROM AUTHOR]

In the last decades, thermoeconomic analysis emerged as a combination of exergy analysis and cost accounting principles, widely used for multiple purposes: to account for the exergy and economic costs of energy systems products, to derive the structures of such costs for the design optimization purpose, and to perform system diagnosis quantifying the source and the impact of malfunctions and dysfunctions within the analyzed process. Traditionally, thermoeconomic analysis is referred to as Exergy Cost Analysis or Exergoeconomic Cost Analysis. The former is based on the so-called Exergy Cost Theory, focused on the evaluation of exergy cost of the system products, while the latter is focused on the evaluation of monetary cost following the same theory. Currently, many practical approaches are available in the literature for the application of thermoeconomic analysis and Exergy Cost Theory to energy conversion systems, while a comprehensive classification, benchmarking and comparison of such approaches is missing. This paper aims to fill this gap through the following activities: first of all, a brief but comprehensive literature review related to the theoretical developments and applications of thermoeconomic analysis method is performed. Secondly and for the purpose of benchmarking, the main practical approaches identified for the application of Exergy Cost Theory are presented and formalized, including the fundamental aspects related to the definition of auxiliary relations and the reallocation of the exergy cost of the residues. Finally, the identified approaches are comparatively applied to the standard CGAM problem, and the advantages and drawbacks of each approach are discussed. It is found that the definition of the functional diagram and the numerical solution of the system through input-output analysis seem to be more straightforward with respect to the other approaches, leading also to the formalization of an unambiguous method to reallocate the exergy cost of the residual flows. [ABSTRACT FROM AUTHOR]

Aberrant DNA methylation at CpG dinucleotides is a cancer hallmark that is associated with the emergence of resistance to anti cancer treatment, though molecular mechanisms and biological significance remain elusive. Genome scale methylation maps by currently used methods are based on chemical modification of DNA and are best suited for analyses of methylation at CpG rich regions (CpG islands). We report the first high coverage whole-genome map in cancer using the long read nanopore technology, which allows simultaneous DNA-sequence and -methylation analyses on native DNA. We analyzed clonal epigenomic/genomic evolution in Acute Myeloid Leukemias (AMLs) at diagnosis and relapse, after chemotherapy. Long read sequencing coupled to a novel computational method allowed definition of differential methylation at unprecedented resolution, and showed that the relapse methylome is characterized by hypermethylation at both CpG islands and sparse CpGs regions. Most differentially methylated genes, however, were not differentially expressed nor enriched for chemoresistance genes. A small fraction of under-expressed and hyper-methylated genes at sparse CpGs, in the gene body, was significantly enriched in transcription factors (TFs). Remarkably, these few TFs supported large gene-regulatory networks including 50% of all differentially expressed genes in the relapsed AMLs and highly-enriched in chemoresistance genes. Notably, hypermethylated regions at sparse CpGs were poorly conserved in the relapsed AMLs, under-represented at their genomic positions and showed higher methylation entropy, as compared to CpG islands. Analyses of available datasets confirmed TF binding to their target genes and conservation of the same gene-regulatory networks in large patient cohorts. Relapsed AMLs carried few patient specific structural variants and DNA mutations, apparently not involved in drug resistance. Thus, drug resistance in AMLs can be mainly ascribed to the selection of random epigenetic alterations at sparse CpGs of a few transcription factors, which then induce reprogramming of the relapsing phenotype, independently of clonal genomic evolution. DNA methylation patterns from Acute Myeloid Leukemia patients highlight sparse CpG regions as drivers for chemoresistance. [ABSTRACT FROM AUTHOR]

Exergy Life Cycle Assessment (ELCA) is proposed by literature to account for the exergy embodied in products of energy systems. In order to make results of ELCA comparable, supply chains that support the life cycle of the system should be analyzed through a unified model: this is one of the main concerns related to Life Cycle Assessment and Industrial Ecology disciplines. In this paper, Hybrid Input-Output analysis is proposed as the computational structure of ELCA: according to this method, national supply chains are modeled through the Monetary Input Output Tables (MIOTs) of national economies, a constantly updated and freely available data source. Then, the adopted national MIOT is expanded to include the detailed model of the considered energy system, hence defining a Hybrid Input-Output model. The (non-renewable) exergy embodied in electricity production and the Exergy Return on Investment (ExROI) are defined as the appropriate performance indicators based on ELCA. The introduced model is here adopted for the analysis of a Waste-to-Energy (WtE) power plant currently operating in the Italian context. It is found that the primary non-renewable exergy embodied in electricity produced by the analyzed WtE is non-negligible for both the construction (127.1 toe) and the operation phases (11.6 toe/y). Nonetheless, the plant is able to produce a net amount of electricity that pays back such primary non-renewable resources requirements about a hundred times. Finally, the joint application of Exergy Analysis and ELCA lead to improve the overall thermodynamic performances of the WtE system, increasing its exergy efficiency by 1%, and reducing the non-renewable exergy embodied in electricity production by 7938 toe. [ABSTRACT FROM AUTHOR]

The latest developments in solar technologies demonstrated that the solar central receiver configuration is the most promising application among concentrated solar power (CSP) plants. In CSPs solar-heated air can be used as the working fluid in a Brayton thermal cycle and as the heat transfer fluid for a Rankine thermal cycle as an alternative to more traditional working fluids thereby reducing maintenance operations and providing the power section with a higher degree of flexibility To supply thermal needs when the solar source is unavailable, an auxiliary burner is requested. This configuration is adopted in the Julich CSP (J-CSP) plant, operating in Germany and characterized by a nominal power of 1.5 MW, the heat transfer fluid (HTF) is air which is heated in the solar tower and used to produce steam for the bottoming Rankine cycle. In this paper, the J-CSP plant with thermal energy storage has been compared with a hybrid CSP plant (H-CSP) using air as the working fluid. Thermodynamic and economic performances of all the simulated plants have been evaluated by applying both exergy analysis and thermoeconomic analysis (TA) to determine the yearly average operation at nominal conditions. The exergy destructions and structure as well as the exergoeconomic costs of products have been derived for all the components of the plants. Based on the obtained results, the thermoeconomic design evaluation and optimization of the plants has been performed, allowing for improvement of the thermodynamic and economic efficiency of the systems as well as decreasing the exergy and exergoeconomic cost of their products. [ABSTRACT FROM AUTHOR]

Off-grid renewable systems can play a pivotal role in the process of rural electrification, thus promoting local development. Moreover, scientific literature is increasingly addressing this issue through the concept of sustainability and appropriate technologies. With regards to this topic, we present a sizing methodology which better relates the results and the sizing process itself to the local context. Specifically, we address the research area of sizing methodologies for off-grid PV systems. Typically, the Loss of Load Probability (LLP) is a key parameter in these methodologies, but is difficult to set as regards the specific context. The proposed methodology employs the concept of Levelized Cost of Supplied and Lost Energy, it is based on the estimate of an economic Value of Lost Load, and eventually, the LLP results to be an output of the process. Therefore, the methodology uses only data characterizing the local situation and results better fit with population conditions. We also propose a simple approach to compute the Value of Lost Load and we apply the methodology for a rural area of Uganda. The results show that the methodology identifies a reliable system which supplies electricity with a fair cost while minimizing the energy bill of the consumers. [ABSTRACT FROM AUTHOR]

Less than 15% of rural areas of Cameroon have access to grid electricity. Only 53% of the population has access to grid electricity. Notwithstanding, Cameroon has a huge hydropower potential which could be harnessed. Mini grids, powered by pico and micro hydropower plants, are a relatively new rural electrification strategy in Cameroon. Several of such mini grids have been realized in the mountain regions of the country. Some of these systems have been more successful than others. This paper aims to share the experiences of community-based pico and micro hydropower schemes for rural electrification in Cameroon. The paper provides insight to the challenges that three of such mini grid systems powered by pico and micro hydropower plants had encountered and it attempts to identify issues related to their performances. The study was based on personal experience, field visits, participant observations, interviews and focus group discussions with key members of the beneficiary communities and documentations from the local NGO which implemented the schemes. Key findings of this study relate to the description of the main aspects about: planning of a robust system design, organizational aspects, like social cohesion at all levels of scheme management, community leadership and ownership of the system and involvement of the beneficiaries at all stages of the project cycle. These aspects were particularly addressed within the context of rural communities in Cameroon. [ABSTRACT FROM AUTHOR]

The coexistence of the need to improve economic conditions and the conscious use of environmental resources plays a central role in today's sustainable development challenge. In this study, a novel integrated framework to evaluate the impact of new technological interventions is presented and an application to smallholder coffee farms and their supply chains in Kenya is proposed. This methodology is able to combine multiple information through the joint use of three approaches: supply chain analysis, input-output analysis, and energy system modeling. Application to the context of the Kenyan coffee sector enables framework validation: shading management measures, the introduction of eco-pulpers, and the exploitation of coffee waste biomass for power generation were compared within a holistic high-level perspective. The implementation of shading practices, carried out with fruit trees, shows the most relevant effects from the economic point of view, providing farmers with an additional source of income and generating $903 of work for every million of local currency (about $9k) invested in this solution. The same investment would save up to 1.46 M m3 of water per year with the eco-pulpers technology. Investing the same amount in coffee-biomass power plants would displace a small portion of production from heavy-duty oil and avoid importing a portion of fertilizer, saving up to 11 tons of CO2 and around $4k per year. The results suggest the optimal allocation of a $100m budget, which can be affected by adding additional constraints on minimum environmental or social targets in line with sustainable development goals. [ABSTRACT FROM AUTHOR]

Oligodendrocytes are the primary target of demyelinating disorders, and progressive neurodegenerative changes may evolve in the CNS. DNA damage and oxidative stress are considered key pathogenic events, but the underlying molecular mechanisms remain unclear. Moreover, animal models do not fully recapitulate human diseases, complicating the path to effective treatments. Here we report that mice with cell-autonomous deletion of the nuclear COP9 signalosome component CSN5 (JAB1) in oligodendrocytes develop DNA damage and defective DNA repair in myelinating glial cells. Interestingly, oligodendrocytes lacking JAB1 expression underwent a senescence-like phenotype that fostered chronic inflammation and oxidative stress. These mutants developed progressive CNS demyelination, microglia inflammation, and neurodegeneration, with severe motor deficits and premature death. Notably, blocking microglia inflammation did not prevent neurodegeneration, whereas the deletion of p21CIP1 but not p16INK4a pathway ameliorated the disease. We suggest that senescence is key to sustaining neurodegeneration in demyelinating disorders and may be considered a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Russia's invasion of Ukraine fuelled an energy crisis, which considerably impacted Europe given its heavy reliance on Russian natural gas imports. This study uses an ensemble of four global integrated assessment models, which are further soft-linked to two sectoral models, and explores the synergies and trade-offs among three approaches to living without Russian gas in Europe: (a) replacing with other gas imports, (b) boosting domestic energy production, and (c) reducing demand and accelerating energy efficiency. We find that substituting Russian gas from other trade partners would miss an opportunity to accelerate decarbonisation in end-use sectors while risking further fossil-fuel lock-ins, despite featuring the lowest gas price spikes and potentially reducing heating costs for end-users in the near term. Boosting domestic, primarily renewable, energy production on the other hand would instead require considerable investments, potentially burdening consumers. Energy demand reductions, however, could offer considerable space for further emissions cuts at the lowest power-sector investment costs; nonetheless, an energy efficiency-driven strategy would also risk relocation of energy-intensive industries, an aspect of increasing relevance to EU policymakers. • Three 'corner' strategies to replacing Russian natural gas in the EU are explored. • EU climate targets can still be reached in all three strategies, but costs increase. • Promoting energy efficiency or domestic renewables can boost end-use decarbonisation. • An 'energy efficiency first' response may save millions € in annual electricity costs. • Southern Europe is the most vulnerable to high electricity prices across strategies. [ABSTRACT FROM AUTHOR]

In state-of-the-art energy systems modelling, reservoir hydropower is represented as any other thermal power plant: energy production is constrained by the plant's installed capacity and a capacity factor calibrated on the energy produced in previous years. Natural water resource variability across different temporal scales and the subsequent filtering effect of water storage mass balances are not accounted for, leading to biased optimal power dispatch strategies. In this work, we aim at introducing a novelty in the field by advancing the representation of reservoir hydropower generation in energy systems modelling by explicitly including the most relevant hydrological constraints, such as time-dependent water availability, hydraulic head, evaporation losses, and cascade releases. This advanced characterization is implemented in an open-source energy modelling framework. The improved model is then demonstrated on the Zambezi River Basin in the South Africa Power Pool. The basin has an estimated hydropower potential of 20,000 megawatts (MW) of which about 5,000 MW has been already developed. Results show a better alignment of electricity production with observed data, with a reduction of estimated hydropower production up to 35% with respect to the baseline Calliope implementation. These improvements are useful to support hydropower management and planning capacity expansion in countries richly endowed with water resource or that are already strongly relying on hydropower for electricity production. [ABSTRACT FROM AUTHOR]

Energy access projects in remote off-grid areas would benefit from the adoption of a multi-energy system perspective, addressing all energy needs – not only lighting and power appliances, but also water-heating and cooking – by means of a mix of energy vectors. However, multi-energy analyses in remote areas are hindered by a lack of models allowing for the generation of multi-energy load profiles based on interview-based information characterised by high uncertainty. This study proposes a novel open-source bottom-up stochastic model specifically conceived for the generation of multi-energy loads for systems located in remote areas. The model is tested and validated against data obtained from a real system, showing a very good approximation of measured profiles, with percentage errors consistently below 2% for all the selected indicators, and an improved accuracy compared to existing approaches. In particular, some innovative features – such as the possibility to define and modulate throughout the day appliances' duty cycles – seem to be determinant in marking a difference with previous approaches. This might arguably be even more beneficial for case studies characterised by a larger penetration of appliances that are subject to complex and unpredictable duty cycle behaviour. • A model for generating load profiles for systems located in remote areas is designed. • The model is stochastic, open-source and conceived for multi-energy analyses. • Innovative features allow to model also complex and variable duty-cycles. • Validation against measured profiles proves consistent model accuracy. • Open-source nature allows customisability and context adaptability. [ABSTRACT FROM AUTHOR]

Abstract The production of Liquefied Natural Gas (LNG) from natural gas reservoirs with high content of acidic compounds is expected to be a strategic and crucial issue for the development of the natural gas market in future decades. Therefore, the identification of alternative suitable processes for the synergistic natural gas purification and LNG production, when the amount of CO 2 in the raw gas feed is high, and their comparative thermodynamic assessment, is necessary to foster a cleaner and efficient production of LNG. In this paper, the energy intensity of the classical chemical absorption units using aqueous solutions of Methyldiethanolamine (MDEA) and the novel Dual Pressure Low-Temperature Distillation process (DPD) operating in different national contexts is assessed by means of the Net Equivalent Methane analysis and the Energy Life Cycle Assessment. These methods return respectively the equivalent methane and the embodied non-renewable energy invoked by the two alternative processes in one operating year. In general, the primary energy required by the construction phases of both the systems results negligible compared to the operation phase, and most of the latter is due to the consumption of energy utilities, which is strongly dependent by the considered national context. According to the results obtained by means of both the methodologies, the DPD process is generally less energy intensive compared to MDEA: the DPD process results to be an efficient and promising technique to perform the synergistic natural gas purification and LNG production. Highlights • Exploitation of acidic natural gas reserves and LNG production will play key role in future decades. • Two alternative processes for acid natural gas purification and LNG production are introduced. • Net Equivalent Methane method and Energy LCA of the processes are comparatively applied. • Both the methods confirm that Dual Pressure Low-Temperature Distillation has the lowest energy intensity. [ABSTRACT FROM AUTHOR]

Abstract Rural electricity plans are usually designed by relying on top-down rough and aggregated estimations of the electricity demand, which may fail to capture the real dynamics of local contexts. This study aims at soft-linking a bottom-up approach for short- and long-term forecasts of load profiles with an energy optimisation model in a more comprehensive rural energy planning procedure. The procedure is applied to a small Indian community, and it is based on three blocks: (i) a bottom-up model to project households' electrical appliances, which adopts socio-economic indicators to make long-term projections; (ii) a stochastic load profile generator, which employs correlations and users' habits for assessing the coincidence and load factors; (ii) an energy optimisation model based on OSeMOSYS to find the economic optimum. The simulations show that demand models based on socio-economic indicators lead to more structured and less arbitrary scenarios. The soft-link with the energy optimisation model confirms that when accounting for short- and long-term variabilities of electricity demand together, the optimal capacities and costs can vary up to 144% and 50% respectively. Integrating optimisation tools to bottom-up models based on socio-economic indicators for forecasting electricity demand is therefore pivotal to set more reliable investments plans in rural electrification. Graphical abstract Image 1 Highlights • A bottom-up model for local electricity demand in rural India is revised. • A stochastic model accounts for short-term uncertainty. • Using socio-economic indicators leads to less arbitrary demand scenarios. • A soft-link with a long-term rural energy optimisation model is developed. • The optimal planning is very sensitive to short- and long-term demand variations. [ABSTRACT FROM AUTHOR]

Abstract In this article, the economic and environmental implications due to the projected evolution of the power sector in Egypt until 2040 are assessed and discussed. The Reference Energy System (RES) of the Egyptian power sector has been defined and implemented in the Open Source Energy Modelling System (OSeMOSYS), based on two different energy scenarios. To increase the accuracy of the analysis, the discount rate on capital investments for the energy technologies has been imposed as a time dependent exogenous variable. Moreover, the robustness of the obtained results has been tested through a sensitivity analysis on the main exogenous parameters. It is found that Combined Cycles, Wind, and Photovoltaic rooftop systems are compatible technologies to be included in the future Egypt's power generation mix. In particular, based on the abundant Egypt's renewables resources endowments, wind power technology comes first in achieving the proposed target on renewables penetration in the country's generation mix, and it might be a feasible alternative to replace a part of the natural gas share. Moreover, the significant impact of discount rate on capitals on the final results is highlighted: low values of discount rate would skew generation mix to include higher investment cost technologies and vice versa. Highlights • Implications of future energy scenarios in Egypt have analyzed based on OSeMOSYS. • Sensitivity analysis has performed on relevant techno-economic scenario parameters. • Combined cycles, wind and PV are key technologies in future Egypt's power mix. • Efficiency of combined cycles is relevant in reducing power cost and emissions. • Wind technology may replace a part of natural gas share in the electricity mix. [ABSTRACT FROM AUTHOR]

Alternative fuel policies need accurate and transparent methods to find the embedded carbon intensity of individual refinery products. This study investigates different ways of allocating greenhouse gases emissions deriving from refining and upstream crude oil supply. Allocation methods based on mass, energy content, economic value and, innovatively, added-value, are compared with the marginal refining emissions calculated by CONCAWE’s linear-programming model to the average EU refinery, which has been adopted as reference in EU legislation. Beside the most important transportation fuels (gasoline, diesel, kerosene/jet fuel and heavy fuel oil), the analysis extends to petroleum coke and refinery hydrogen. Moreover, novel criteria, based on the implications due to hydrogen usage by each fuel pathway, have been introduced to test the consistency of the analyzed approaches. It is found that only two economic-based allocation methods are consistent with the introduced criteria. These two methods also give negative refinery emissions for heavy products, which is coherent with the marginal emissions calculated through the CONCAWE refinery model. The recommended allocation methods are transparent and use only publicly available statistical data, so they may be useful not only for future EU legislation, but also in jurisdictions where a representative refinery model is not available. [ABSTRACT FROM AUTHOR]

Here, we propose an approach for supporting the design and performance evaluation phase of solar cooking technologies, to assess their eventual appropriateness for remote rural contexts, before proposing them for local field tests. The approach is based on (1) local context description and analysis, (2) design and construction of the solar cookers, and (3) thermodynamic performance evaluation. We used the approach to analyse 3 cookers for the area of Mutoyi, Burundi: a parabolic, a panel, and a box cooker. From phases 1 and 2, only panel and box cookers emerged as the technically viable solutions: They were sized, optimized, built, and tested. In phase 3, the thermodynamic evaluation indicated that the box cooker is inappropriate, since water does not reach high enough temperature. Instead, the panel cooker shows a Standardized Cooking Power of 46.85 W and a stagnation temperature higher than 75°C, which is able to bring the water to the boil when the environmental temperature is higher than 25°C. The thermal efficiency of the cooker resulted equal to 8.13%, while the mean integral temperature T m remained around 60°C for all the lab test replicates, higher than the minimum internal temperature to cook legumes. The results of the procedure applied to the case study indicate that the panel cooker can be proposed for local field tests with local food and cooking practices, for assessing its final appropriateness on the field. [ABSTRACT FROM AUTHOR]

Around 2.7 billion people rely on biomass fuelled inefficient devices for cooking and heating. Improved Cooking Stoves are promoted as a means to mitigate the economic, environmental and social implications of this practice. However, their diffusion is hindered by a number of factors, including in particular the lack of agreement on performance evaluation methodologies. Laboratory protocols are designed to give useful indications to cookstoves developers, in order to improve their performance under controlled conditions, while field protocols provide the assessment of real performance of a cookstove in a given context. However, due to high time and finance requirements of the latter, lab results are often used also for stoves selection, also because of a general misunderstanding regarding their correct utilisation. In this work, we provide a review of all lab protocols officially published to date, comparing conceptual and technical aspects. We find that no protocol takes into account all the relevant factors at once. As a result, lab tests carry little information about real field performance, and can be misleading regarding stoves optimisation. Therefore, the analysis reveals the need to define better standards, regarding: (i) repeatability, metrics and statistical analysis of results; (ii) burn sequences calibrated from time to time according to the specific user. [ABSTRACT FROM AUTHOR]

Due to the rapid increase of the World’s primary energy demand of the last decades, low-temperature processes for the purification of natural gas streams with high carbon dioxide content has gained interest, since they allow to make profitable exploitation of low-quality gas reserves. Low temperature purification processes allow the direct production of a methane stream at high purity and at low-temperature, suitable conditions for the direct synergistic integration with natural gas cryogenic liquefaction processes, while CO 2 is obtained in liquid phase and under pressure. In this way, it can be pumped for transportation, avoiding significant compression costs as for classical CO 2 capture units (where carbon dioxide is discharged in gas phase and at atmospheric pressure), and further uses such as Enhanced Oil Recovery (EOR) or underground storage. In this paper, the three most common natural gas low-temperature purification techniques have been modelled and their performances have been evaluated through energy and exergy analyses. Specifically, the dual pressure low-temperature distillation process, the anti-sublimation process and a hybrid configuration have been considered. It is found that the dual pressure low-temperature distillation scheme reach the highest thermodynamic performances, resulting in the best values of exergy efficiency and equivalent methane requirements with respect to the other configurations. This is mainly due to the distributed temperature profile along a distillation column, resulting in a less irreversible heat exchanging process. [ABSTRACT FROM AUTHOR]

Ischemic stroke is the leading cause of disability, but effective therapies are currently widely lacking. Recovery from stroke is very much dependent on the possibility to develop treatments able to both halt the neurodegenerative process as well as to foster adaptive tissue plasticity. Here we show that ischemic mice treated with neural precursor cell (NPC) transplantation had on neurophysiological analysis, early after treatment, reduced presynaptic release of glutamate within the ipsilesional corticospinal tract (CST), and an enhancedNMDAmediated excitatory transmission in the contralesional CST. Concurrently, NPC-treated mice displayed a reduced CST degeneration, increased axonal rewiring, and augmented dendritic arborization, resulting in long-term functional amelioration persisting up to 60 d after ischemia. The enhanced functional and structural plasticity relied on the capacity of transplanted NPCs to localize in the periischemic and ischemic area, to promote the upregulation of the glial glutamate transporter 1 (GLT-1) on astrocytes and to reduce peri-ischemic extracellular glutamate. The upregulation of GLT-1 induced by transplanted NPCs was found to rely on the secretion of VEGF by NPCs. Blocking VEGF during the first week after stroke reduced GLT-1 upregulation as well as long-term behavioral recovery in NPC-treated mice. Our results show that NPC transplantation, by modulating the excitatory-inhibitory balance and stroke microenvironment, is a promising therapy to ameliorate disability, to promote tissue recovery and plasticity processes after stroke. [ABSTRACT FROM AUTHOR]

Access to electric power supply has always had a significant role in promoting improvements in all the society sectors, nevertheless nowadays 1.3 billion of people still do not have electricity access. Moreover, most of them live in rural areas of developing countries which are often isolated, scattered populated and characterized by poor infrastructure and services. In this situation, the growing consideration towards the target of universal access to energy has emphasized the role of rural electrification, and off-grid small-scale generation represents one of the most appropriate options. As a consequence, the scientific literature has devoted attention to this topic with a large number of papers. In this frame, the present analysis focuses on off-grid systems for rural electrification and provides a general framework to this topic and an analytical review of the literature. The work is based on the review of more than 350 papers mainly published from 2000 to 2014 within selected journals, and it is organized in two sections. In the first one we describe the role of small-scale generation systems throughout the process of electrification, the main features of rural areas and their typical energy uses, and we propose a new comprehensive taxonomy for off-grid systems for rural electrification. In the second one we develop an extensive review of the selected literature according to the proposed classification and to five main research areas: Technology: layout and components; Models and methods for simulation and sizing; Techno-economic feasibility analyses and sustainability analyses; Case studies analyses; Policy analyses. The work results in a comprehensive review which organizes and capitalizes the main fundamentals of the addressed topic and provides elements to get acquainted with the literature. [ABSTRACT FROM AUTHOR]

This paper proposes an exergy-based well-to-wheels analysis to compare different passenger vehicles, based on three key indicators: petroleum energy use, CO 2 emissions, and economic cost. A set of fuel pathways, including petroleum-based fuels, compressed natural gas, biofuels, and electricity are considered in five representative national energy mixes, namely Brazil, China, France, Italy, and the United States of America. Results show no fundamental difference in the fossil fuel pathways among the five scenarios considered. Compressed natural gas vehicles and electric vehicles can completely displace oil consumption in the personal transportation sector. Compressed natural gas vehicles also reduce CO 2 emissions by over 20% compared to gasoline vehicles. Emissions from electric vehicles greatly vary depending on the electricity mix. In low-carbon electricity mixes electric vehicles reach almost-zero CO 2 emissions, while the use of biofuels leads to the lowest CO 2 emissions in carbon-intensive electricity generation mixes, where vehicles running on E85 could reduce CO 2 emission by over 50% compared to gasoline vehicles. Hybrid electric vehicles show the lowest overall economic cost, due to improved efficiency and low cost of petroleum-based fuels. Vehicles running on electricity are characterized by significantly higher capital cost and lower operating costs. Thus, different electricity generation costs impact minimally the overall cost. These results can be used to inform decision-makers regarding the multi-dimensional impact of passenger vehicles, including environmental impact, economic cost, and depletion of primary energy resources, with particular focus on petroleum. [ABSTRACT FROM AUTHOR]