38 research outputs found

    A simulation-based analysis of photovoltaic thermal hybrid solar collectors with a new TRNSYS type model

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    Nowadays buildings are responsible of 36% of CO2emissions and space heating and cooling alone accounts for 40% of the final energy consumption at European level. In this context, solar-assisted systems represent an important solution to support the decarbonisation pathways in residential sector. In this work, a novel lumped parameter simulation model for photovoltaic thermal hybrid solar collectors developed by Authors as a type of Transient System Simulation (TRNSYS) software is used to carry out computer simulations in different climatic conditions. The model is based on the electrical analogy method to solve the transient heat transfer problem and considers the effect of the thermal capacitances of the elements composing the photovoltaic thermal collector. The simulation tool was also validated with the experimental data in terms of both electrical and thermal power. In this work, a simulation-based analysis is carried out considering three climatic zones in order to evaluate the thermal performance of photovoltaic thermal hybrid solar collectors under different operating conditions

    Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome patients leads to functional correction

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    Wiskott–Aldrich syndrome (WAS) is an X-linked primary immunodeficiency with a median survival below the age of 20 due to infections, severe hemorrhage, and lymphomas. Transplantation of hematopoietic stem cells from HLA-identical sibling donors is a resolutive treatment, but is available for a minority of patients. Transplantation of genetically corrected autologous hematopoietic stem cells or T cells could represent an alternative treatment applicable to all patients. We investigated whether WAS gene transfer with MMLV-based oncoretroviral and HIV-based lentiviral vectors could restore normal functions of patients' T cells. T cells transduced either with lentiviral vectors expressing the WAS protein (WASP) from the ubiquitous PGK promoter or the tissue-specific WASP promoter or with an oncoretroviral vector expressing WASP from the LTR, reached normal levels of WASP with correction of functional defects, including proliferation, IL-2 production, and lipid raft upregulation. Lentiviral vectors transduced T cells from WAS patients at higher rates, compared to oncoretroviral vectors, and efficiently transduced both activated and naive WAS T cells. Furthermore, a selective growth advantage of T cells corrected with the lentiviral vectors was demonstrated. The observation that lentiviral vector-mediated gene transfer results in correction of T cell defects in vitro supports their application for gene therapy in WAS patients

    IL-3 or IL-7 Increases ex Vivo Gene Transfer Efficiency in ADA-SCID BM CD34 + Cells while Maintaining in Vivo Lymphoid Potential

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    To improve maintenance and gene transfer of human lymphoid progenitors for clinical use in gene therapy of adenosine deaminase (ADA)-deficient SCID we investigated several gene transfer protocols using various stem cell-enriched sources. The lymphoid differentiation potential was measured by an in vitro clonal assay for B/NK cells and in the in vivo SCID-hu mouse model. Ex vivo culture with the cytokines TPO, FLT3-ligand, and SCF (T/F/S) plus IL-3 or IL-7 substantially increased the yield of transduced bone marrow (BM) CD34+ cells purified from ADA-SCID patients or healthy donors, compared to T/F/S alone. Moreover, the use of IL-3 or IL-7 significantly improved the maintenance of in vitro B cell progenitors from ADA-SCID BM cells and allowed the efficient transduction of B and NK cell progenitors. Under these optimized conditions transduced CD34+ cells were efficiently engrafted into SCID-hu mice and gave rise to B and T cell progeny, demonstrating the maintenance of in vivo lymphoid reconstitution capacity. The protocol based on the T/F/S + IL-3 combination was included in a gene therapy clinical trial for ADA-SCID, resulting in long-term engraftment of stem/progenitor cells. Remarkably, gene-corrected BM CD34+ cells obtained from one patient 4 and 11 months after gene therapy were capable of repopulating the lymphoid compartment of SCID-hu hosts

    IL-7 and IL-15 allow the generation of suicide gene–modified alloreactive self-renewing central memory human T lymphocytes

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    Abstract Long-term clinical remissions of leukemia, after allogeneic hematopoietic stem cell transplantation, depend on alloreactive memory T cells able to self-renew and differentiate into antileukemia effectors. This is counterbalanced by detrimental graft-versus-host disease (GVHD). Induction of a selective suicide in donor T cells is a current gene therapy approach to abrogate GVHD. Unfortunately, genetic modification reduces alloreactivity of lymphocytes. This associates with an effector memory (TEM) phenotype of gene-modified lymphocytes and may limit antileukemia effect. We hypothesized that alloreactivity of gene-modified lymphocytes segregates with the central memory (TCM) phenotype. To this, we generated suicide gene–modified TCM lymphocytes with a retroviral vector after CD28 costimulation and culture with IL-2, IL-7, or a combination of IL-7 and IL-15. In vitro, suicide gene–modified TCM cells self-renewed upon alloantigen stimulation and resisted activation-induced cell death. In a humanized mouse model, only suicide gene–modified T cells cultured with IL-7 and IL-15 persisted, differentiated in TEM cells, and were as potent as unmanipulated lymphocytes in causing GVHD. GVHD was halted through the activation of the suicide gene machinery. These results warrant the use of suicide gene–modified TCM cells cultured with IL-7 and IL-15 for the safe exploitation of the alloreactive response against cancer

    Molecular purging of multiple myeloma cells by ex-vivo culture and retroviral transduction of mobilized-blood CD34+ cells

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    <p>Abstract</p> <p>Background</p> <p>Tumor cell contamination of the apheresis in multiple myeloma is likely to affect disease-free and overall survival after autografting.</p> <p>Objective</p> <p>To purge myeloma aphereses from tumor contaminants with a novel culture-based purging method.</p> <p>Methods</p> <p>We cultured myeloma-positive CD34<sup>+ </sup>PB samples in conditions that retained multipotency of hematopoietic stem cells, but were unfavourable to survival of plasma cells. Moreover, we exploited the resistance of myeloma plasma cells to retroviral transduction by targeting the hematopoietic CD34<sup>+ </sup>cell population with a retroviral vector carrying a selectable marker (the truncated form of the human receptor for nerve growth factor, ΔNGFR). We performed therefore a further myeloma purging step by selecting the transduced cells at the end of the culture.</p> <p>Results</p> <p>Overall recovery of CD34<sup>+ </sup>cells after culture was 128.5%; ΔNGFR transduction rate was 28.8% for CD34<sup>+ </sup>cells and 0% for CD138-selected primary myeloma cells, respectively. Recovery of CD34<sup>+ </sup>cells after ΔNGFR selection was 22.3%. By patient-specific Ig-gene rearrangements, we assessed a decrease of 0.7–1.4 logs in tumor load after the CD34<sup>+ </sup>cell selection, and up to 2.3 logs after culture and ΔNGFR selection.</p> <p>Conclusion</p> <p>We conclude that <it>ex-vivo </it>culture and retroviral-mediated transduction of myeloma leukaphereses provide an efficient tumor cell purging.</p

    The use of a P. falciparum specific coiled-coil domain to construct a self-assembling protein nanoparticle vaccine to prevent malaria.

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    The parasitic disease malaria remains a major global public health concern and no truly effective vaccine exists. One approach to the development of a malaria vaccine is to target the asexual blood stage that results in clinical symptoms. Most attempts have failed. New antigens such as P27A and P27 have emerged as potential new vaccine candidates. Multiple studies have demonstrated that antigens are more immunogenic and are better correlated with protection when presented on particulate delivery systems. One such particulate delivery system is the self-assembling protein nanoparticle (SAPN) that relies on coiled-coil domains of proteins to form stable nanoparticles. In the past we have used de novo designed amino acid domains to drive the formation of the coiled-coil scaffolds which present the antigenic epitopes on the particle surface. Here we use naturally occurring domains found in the tex1 protein to form the coiled-coil scaffolding of the nanoparticle. Thus, by engineering P27A and a new extended form of the coiled-coil domain P27 onto the N and C terminus of the SAPN protein monomer we have developed a particulate delivery system that effectively displays both antigens on a single particle that uses malaria tex1 sequences to form the nanoparticle scaffold. These particles are immunogenic in a murine model and induce immune responses similar to the ones observed in seropositive individuals in malaria endemic regions. We demonstrate that our P27/P27A-SAPNs induce an immune response akin to the one in seropositive individuals in Burkina Faso. Since P27 is highly conserved among different Plasmodium species, these novel SAPNs may even provide cross-protection between Plasmodium falciparum and Plasmodium vivax the two major human malaria pathogens. As the SAPNs are also easy to manufacture and store they can be delivered to the population in need without complication thus providing a low cost malaria vaccine

    Semen molecular and cellular features: these parameters can reliably predict subsequent ART outcome in a goat model

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    Currently, the assessment of sperm function in a raw or processed semen sample is not able to reliably predict sperm ability to withstand freezing and thawing procedures and in vivo fertility and/or assisted reproductive biotechnologies (ART) outcome. The aim of the present study was to investigate which parameters among a battery of analyses could predict subsequent spermatozoa in vitro fertilization ability and hence blastocyst output in a goat model. Ejaculates were obtained by artificial vagina from 3 adult goats (Capra hircus) aged 2 years (A, B and C). In order to assess the predictive value of viability, computer assisted sperm analyzer (CASA) motility parameters and ATP intracellular concentration before and after thawing and of DNA integrity after thawing on subsequent embryo output after an in vitro fertility test, a logistic regression analysis was used. Individual differences in semen parameters were evident for semen viability after thawing and DNA integrity. Results of IVF test showed that spermatozoa collected from A and B lead to higher cleavage rates (0 < 0.01) and blastocysts output (p < 0.05) compared with C. Logistic regression analysis model explained a deviance of 72% (p < 0.0001), directly related with the mean percentage of rapid spermatozoa in fresh semen (p < 0.01), semen viability after thawing (p < 0.01), and with two of the three comet parameters considered, i.e tail DNA percentage and comet length (p < 0.0001). DNA integrity alone had a high predictive value on IVF outcome with frozen/thawed semen (deviance explained: 57%). The model proposed here represents one of the many possible ways to explain differences found in embryo output following IVF with different semen donors and may represent a useful tool to select the most suitable donors for semen cryopreservation

    Integrated heat pump and Multi-Source Energy System modeling for sustainable heating and cooling in buildings

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    Negli ultimi decenni, il patrimonio edilizio è stato identificato come una delle aree di intervento più significative per ridurre il consumo di energia e decarbonizzare l'approvvigionamento energetico. Negli edifici nuovi ed esistenti, la sfida ambientale consiste nel ridurre al minimo le perdite termiche attraverso l'involucro, migliorare l'efficienza energetica dei sistemi di generazione ed aumentare la quota rinnovabile. In questo contesto, le pompe di calore giocano un ruolo chiave nel settore della climatizzazione, rappresentando una soluzione flessibile che può essere integrata in sistemi elettrici più o meno complessi e combinata con tecnologie rinnovabili. Gli obiettivi di aumento dell'efficienza energetica e di riduzione delle emissioni di gas serra possono essere raggiunti in diversi modi utilizzando le pompe di calore. Questo lavoro presenta alcune possibilità, tra cui lo studio di cicli di pompe di calore non convenzionali e di nuove configurazioni di sistema, l'uso di refrigeranti naturali e a basso GWP e l'integrazione delle pompe di calore in sistemi energetici a più fonti energetiche rinnovabili. I modelli dettagliati delle pompe di calore sono di grande importanza per la progettazione, l'ottimizzazione del controllo e l'analisi del funzionamento del sistema con diverse condizioni al contorno. Per questo motivo, in questo lavoro il software TRNSYS viene utilizzato per eseguire simulazioni dinamiche di sistemi energetici a pompa di calore. Viene presentato un modello flessibile di una pompa di calore sviluppato in ambiente TRNSYS e la sua applicazione a diversi casi di studio. Il nuovo componente viene utilizzato per modellare diverse configurazioni di pompe di calore e un collegamento interno a REFPROP consente di ottenere le proprietà termodinamiche dei fluidi refrigeranti nei punti principali del ciclo a compressione di vapore. Viene valutata l'integrazione di sistemi a pompa di calore e fonti di energia rinnovabili. Viene discussa e affrontata la questione della progettazione delle pompe di calore geotermiche. L'obiettivo è quello di fornire ai progettisti modelli di pompe di calore geotermiche semplificati ed accurati per il calcolo del calore scambiato con il terreno, partendo dai dati del produttore della pompa di calore. La ricerca include alcune analisi e ottimizzazioni di sistemi energetici multi-sorgente, concentrandosi sull'accoppiamento di pompe di calore con scambiatori di calore a terra, collettori solari termici e pannelli fotovoltaici-termici. In conclusione, nell’ottica di studiare distretti residenziali più sostenibili e “smart”, questo lavoro propone un modello di rete di teleriscaldamento e teleraffrescamento a bassa temperatura altamente integrato ed efficiente dal punto di vista energetico, basato sul concetto di comunità energetica.In the last decades, building stock has been identified as one of the significant areas of intervention to lower energy use and decarbonize the energy supply. In new and existing buildings, the environmental challenge consists of minimizing the thermal losses through the envelope, enhancing the energy efficiency of the generation systems, and increasing the renewable share. In this context, heat pumps play a key role in the air conditioning sector, representing a flexible solution that can be integrated into full electric systems and combined with renewable energy technologies. The goals of increasing energy efficiency and reducing greenhouse gas emissions can be achieved in several ways using heat pumps. This work presents some possibilities, including the study of non-conventional heat pump cycles and novel system configurations, the use of natural and low-GWP refrigerants, and the integration of heat pumps into multi-source energy systems. Detailed models of heat pumps are of great importance in heat pump design, control optimization, and analysis of the system operations with different boundary conditions. For this reason, in this work, TRNSYS is used to perform dynamic simulations of heat pump energy systems. A flexible TRNSYS model of a reversible heat pump and its application to different case studies is presented. The new component is utilized to model several heat pump configurations, and an internal link to REFPROP allows obtaining the thermodynamic properties of the refrigerant fluids in the main points of the vapor compression cycle. The integration of heat pump systems and renewable energy sources is evaluated. The issue concerning the design of ground-source heat pumps is discussed and addressed. The aim is to provide the designers with simplified and acceptably accurate water-source heat pump models for calculating heat exchanged with the ground, starting from heat pump manufacturer’s data. The research includes some analysis and optimization of multi-source energy systems, focusing on the coupling of heat pumps with ground heat exchangers, solar thermal collectors, and photovoltaic-thermal panels. In conclusion, toward more sustainable and smart districts, this work proposes a model of a highly integrated and energy-efficient ultra-low temperature district heating and cooling network based on the concept of energy communities
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