•Quantitative literature review on liquid air energy storage (LAES).•54 plant layouts are described and LAES techno-economic state-of-the-art presented.•Hot/cold recycle via thermal storage yields ...energy and exergy efficiency over 60%.•Challenges and opportunities for LAES integration in the energy system are discussed.•Advanced modelling is needed to understand LAES multi-service, multi-energy value.
Energy system decarbonisation pathways rely, to a considerable extent, on electricity storage to mitigate the volatility of renewables and ensure high levels of flexibility to future power grids. In this context, liquid air energy storage (LAES) has recently emerged as feasible solution to provide 10-100s MW power output and a storage capacity of GWhs. High energy density and ease of deployment are only two of the many favourable features of LAES, when compared to incumbent storage technologies, which are driving LAES transition from the concept proposed in 1977 to a real-life option. Two plants (350 kW and 5 MW) have been successfully built and demonstrated by Highview Power, and a 50 MW/250 MWh commercial plant is now under construction. Besides the commercial deployment, an ever-increasing body of literature on the topic proves the academic interest on LAES. However, literature heterogeneity in terms of the investigated concepts and plant layouts, working methodologies and study scope currently complicates the interpretation of outcomes. Few literature surveys have attempted to rationalise this landscape, yet leaving some key areas such as LAES integration practically unaddressed. The present article aims at filling these gaps and providing a holistic review of the LAES development. Uniquely in this review: i) we propose a new methodology for cross comparing the results from the literature and use it to harmonise techno-economic findings, ii) we review works where LAES operation in the energy system is considered and iii) we highlight promising LAES integration pathways and future research directions. More than 120 references on LAES have been processed according to the methodology. The results include once for all the state-of-the-art techno-economic performance of LAES, across all the concepts proposed, and propose necessary steps to further advance the LAES research. The need for more realistic LAES models for integration studies and a broader focus on LAES capabilities beyond electricity output, specifically for hybrid concepts, are highlighted.
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A great effort of research has been devoted in the last few years to developing new anti-HBV therapies of finite duration that also provide effective sustained control of virus replication and ...antigen production. Among the potential therapeutic strategies, immune-modulation represents a promising option to cure HBV infection and the adaptive immune response is a rational target for novel therapeutic interventions, in consideration of the key role played by T cells in the control of virus infections. HBV-specific T cells are severely dysfunctional in chronic HBV infection as a result of several inhibitory mechanisms which are simultaneously active within the chronically inflamed liver. Indeed, the liver is a tolerogenic organ harboring different non-parenchymal cell populations which can serve as antigen presenting cells (APC) but are poorly efficient in effector T cell priming, with propensity to induce T cell tolerance rather than T cell activation, because of a poor expression of co-stimulatory molecules, up-regulation of the co-inhibitory ligands PD-L1 and PD-L2 upon IFN stimulation, and production of immune regulatory cytokines, such as IL10 and TGF-β. They include resident dendritic cells (DCs), comprising myeloid and plasmacytoid DCs, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), hepatic stellate cells (HSCs) as well as the hepatocytes themselves. Additional regulatory mechanisms which contribute to T cell attrition in the chronically infected liver are the high levels of soluble mediators, such as arginase, indoleamine 2,3-dioxygenase (IDO) and suppressive cytokines, the up-regulation of inhibitory checkpoint receptor/ligand pairs, the expansion of regulatory cells, such as CD4+FOXp3+ Treg cells, myeloid-derived suppressor cells and NK cells. This review will deal with the interactions between immune cells and liver environment discussing the different mechanisms which contribute to T cell dysfunction in chronic hepatitis B, some of which are specifically activated in HBV infection and others which are instead common to chronic inflammatory liver diseases in general. Therapeutic interventions targeting dysregulated pathways and cellular functions will be also delineated.
Chronic hepatitis B virus (HBV) infection represents a worldwide public health concern with approximately 250 million people chronically infected and at risk of developing liver cirrhosis and ...hepatocellular carcinoma. Nucleos(t)ide analogues (NUC) are the most widely used therapies for HBV infection, but they often require long-lasting administration to avoid the risk of HBV reactivation at withdrawal. Therefore, there is an urgent need to develop novel treatments to shorten the duration of NUC therapy by accelerating virus control, and to complement the effect of available anti-viral therapies. In chronic HBV infection, virus-specific T cells are functionally defective, and this exhaustion state is a key determinant of virus persistence. Reconstitution of an efficient anti-viral T cell response may thus represent a rational strategy to treat chronic HBV patients. In this perspective, the enhancement of adaptive immune responses by a checkpoint inhibitor blockade, specific T cell vaccines, lymphocyte metabolism targeting, and autologous T cell engineering, including chimeric antigen receptor (CAR) and TCR-redirected T cells, constitutes a promising immune modulatory approach for a therapeutic restoration of protective immunity. The advances of the emerging immune-based therapies in the setting of the HBV research field will be outlined.
Energy storage is widely recognised as one of the key enablers for higher renewable energy penetration and future energy system decarbonisation. The term Carnot Battery refers to a set of storage ...technologies with electricity stored in the form of thermal energy, thus making them suitable not only for power balancing, but also for multi-vector energy management as a unique asset. With growing scientific literature on different Carnot Battery technologies and data from ongoing pilot and demonstration projects worldwide, this article aims to provide a review on the most recent developments in the area. More specifically, three complementary aspects are addressed: i) the collection and cross-comparison of quantitative techno-economic performance data of different Carnot Battery systems based on scientific literature findings; ii) the discussion of proposed applications for Carnot Batteries at the energy system scale, including power and thermal service provisions and retrofit opportunities; iii) the discussion of the most recent commercial developments in Carnot Battery technologies. Through this, we present the commonalities and discrepancies between scientific research and system implementation in ongoing projects. Our results show (a) a clear difference in the techno-economics of various Carnot Battery technologies; (b) a wide range of some performance metrics due to the absence of empirical evidence; and, interestingly, (c) a certain discrepancy between the systems and applications most addressed by the scientific community and the projects under development. The harmonisation of these discrepancies and the inclusion of location-specific integration considerations are proposed as a way forward for performance advancement and future deployment of Carnot Batteries.
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•Review of Carnot-Battery techno-economics, applications and ongoing projects•Data from 33 Carnot Batteries in the literature and 30+ demo/commercial projects•Significant techno-economic and size variation across Carnot Battery classes•Discrepancy between scientific/commercial evidence on plant layout and application•Location-specific constraints and retrofits to be considered for system deployment
Hepatitis C virus infection (HCV) represents a unique model to characterize, from early to late stages of infection, the T cell differentiation process leading to exhaustion of human CD8+ T cells. ...Here we show that in early HCV infection, exhaustion-committed virus-specific CD8+ T cells display a marked upregulation of transcription associated with impaired glycolytic and mitochondrial functions, that are linked to enhanced ataxia-telangiectasia mutated (ATM) and p53 signaling. After evolution to chronic infection, exhaustion of HCV-specific T cell responses is instead characterized by a broad gene downregulation associated with a wide metabolic and anti-viral function impairment, which can be rescued by histone methyltransferase inhibitors. These results have implications not only for treatment of HCV-positive patients not responding to last-generation antivirals, but also for other chronic pathologies associated with T cell dysfunction, including cancer.
Immune modulatory therapies are widely believed to represent potential therapeutic strategies for chronic hepatitis B infection (CHB). Among the cellular targets for immune interventions, Natural ...Killer (NK) cells represent possible candidates because they have a key role in anti-viral control by producing cytokines and by exerting cytotoxic functions against virus-infected cells. However, in patients with chronic hepatitis B, NK cells have been described to be more pathogenic than protective with preserved cytolytic activity but with a poor capacity to produce anti-viral cytokines. In addition, NK cells can exert a regulatory activity and possibly suppress adaptive immune responses in the setting of persistent viral infections. Consequently, a potential drawback of NK-cell targeted modulatory interventions is that they can potentiate the suppressive NK cell effect on virus-specific T cells, which further causes impairment of exhausted anti-viral T cell functions. Thus, clinically useful NK-cell modulatory strategies should be not only suited to improve positive anti-viral NK cell functions but also to abrogate T cell suppression by NK cell-mediated T cell killing. This review outlines the main NK cell features with a particular focus on CHB infection. It describes different mechanisms involved in NK-T cell interplay as well as how NK cells can have positive anti-viral effector functions and negative suppressive effects on T cells activity. This review discusses how modulation of their balance can have potential therapeutic implications.
To report a single-centre experience with the novel Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) technique and systematically review the related literature.
...Since January 2013, patients with extended primary or secondary liver tumors whose future liver remnant (FLR) was considered too small to allow hepatic resection were prospectively assessed for the ALPPS procedure. A systematic literature search was performed using PubMed, Scopus and the Cochrane Library Central.
Until July 2014 ALPPS was completed in 9 patients whose mean age was 60 ± 8 years. Indications for surgical resection were metastases from colorectal cancer in 3 cases, perihilar cholangiocarcinoma in 3 cases, intrahepatic cholangiocarcinoma in 2 cases and hepatocellular carcinoma without chronic liver disease in 1 case. The calculated FLR volume was 289 ± 122 mL (21.1 ± 5.5%) before ALPPS-1 and 528 ± 121 mL (32.2 ± 5.7%) before ALLPS-2 (p < 0.001). The increase in FLR between the two procedures was 96 ± 47% (range: 24-160%, p < 0.001). Additional interventions were performed in 4 cases: 3 patients underwent Roux-en-Y hepaticojejunostomy, and one case underwent wedge resection of a residual tumor in the FLR. The average time between the first and second step of the procedure was 10.8 ± 2.9 days. The average hospital stay was 24.1 ± 13.3 days. There was 1 postoperative death due to hepatic failure in the oldest patient of this series who had a perihilar cholangiocarcinoma and concomitant liver fibrosis; 11 complications occurred in 6 patients, 4 of whom had grade III or above disease. After a mean follow-up of 17.1 ± 8.5 months, the overall survival was 89% at 3-6 and 12 months. The recurrence-free survival was 100%, 87.5% and 75% at 3-6-12 months respectively. The literature search yielded 148 articles, of which 22 articles published between 2012 and 2015 were included in this systematic review.
The ALPPS technique effectively increased the resectability of otherwise inoperable liver tumors. The postoperative morbidity in our series was high in accordance with the data from the systematic review. Age, liver fibrosis and presence of biliary stenting were predisposing factors for postoperative morbidity and mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pancreatic resection still represents the only curative option for patients affected by pancreatic ductal adenocarcinoma (PDAC). However, the association with modern chemotherapy regimens is a key ...factor in improving the inauspicious oncological outcome. The benefit of neoadjuvant treatment (NAT) for borderline resectable/locally advanced PDAC has been demonstrated; this evidence raises the question of whether even resectable PDAC should undergo NAT rather than upfront surgery. NAT may avoid futile surgery because of undetected distant metastases or aggressive tumor biology, providing more effective systemic control of the disease, which is hampered when adjuvant chemotherapy is delayed or precluded. However, recent data show controversial results regarding the efficacy and safety of NAT in resectable PDAC compared to upfront surgery. Although several prospective studies and meta-analyses indicate better oncologic outcomes after NAT, there are some biases, such as the methodological approaches used to capture the events of interest, which could make these results hardly reproducible. For instance, per-protocol studies, considering only the postoperative outcomes, tend to overestimate the performance of NAT by excluding patients who will never be suitable for surgery due to the development of chemotoxicity or tumor progression. To draw reliable conclusions, the studies should capture the events of interest of both strategies (NAT/upfront surgery) from the time of allocation to a specific treatment in an intention-to-treat fashion. This critical review highlights the current literature data concerning the use of NAT in resectable PDAC, summarizing the results of high-quality studies and focusing on the methodological issues of the most recent pieces of evidence.
Coenzyme A (CoA) is a fundamental cofactor involved in a number of important biochemical reactions in the cell. Altered CoA metabolism results in severe conditions such as pantothenate ...kinase-associated neurodegeneration (PKAN) in which a reduction of the activity of pantothenate kinase isoform 2 (PANK2) present in CoA biosynthesis in the brain consequently lowers the level of CoA in this organ. In order to develop a new drug aimed at restoring the sufficient amount of CoA in the brain of PKAN patients, we looked at its turnover. We report here the results of two experiments that enabled us to measure the half-life of pantothenic acid, free CoA (CoASH) and acetylCoA in the brains and livers of male and female C57BL/6N mice, and total CoA in the brains of male mice. We administered (intrastriatally or orally) a single dose of a .sup.13 C.sub.3 -.sup.15 N-.sup.18 O-labelled coenzyme A precursor (fosmetpantotenate or .sup.13 C.sub.3 -.sup.15 N-pantothenic acid) to the mice and measured, by liquid chromatography-mass spectrometry, unlabelled- and labelled-coenzyme A species appearance and disappearance over time. We found that the turnover of all metabolites was faster in the liver than in the brain in both genders with no evident gender difference observed. In the oral study, the CoASH half-life was: 69 ± 5 h (male) and 82 ± 6 h (female) in the liver; 136 ± 14 h (male) and 144 ± 12 h (female) in the brain. AcetylCoA half-life was 74 ± 9 h (male) and 71 ± 7 h (female) in the liver; 117 ± 13 h (male) and 158 ± 23 (female) in the brain. These results were in accordance with the corresponding values obtained after intrastriatal infusion of labelled-fosmetpantotenate (CoASH 124 ± 13 h, acetylCoA 117 ± 11 and total CoA 144 ± 17 in male brain).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Unified techno-economic comparison of 6 thermo-mechanical energy storage concepts.•100 MW ACAES and LAES exhibit lower LCOS than Li-ion batteries above ∼ 4 h duration.•New technological concepts can ...meet cost target below 20 USD/kWh at 200 h duration.•Promising high-temperature thermochemical reactions for long-duration storage.•Identified material, device and system-level advancements needed to compete with H2.
The extent to which long-duration energy storage (LDES) will support grid decarbonisation by enabling large penetration of renewable generation is subject to the achievement of suitable technical and economic performance. This study investigates the potential of established and novel thermo-mechanical energy storage (TMES) technologies to meet LDES targets, benchmarks TMES current and future techno-economic performance and highlights critical research developments. Results justify the priority of ensuring low storage costs over high roundtrip efficiency for LDES, thus endorsing novel concepts based on thermochemical energy storage. Besides adiabatic compressed air energy storage, novel TMES using metal oxidation/reduction and CaO hydration/dehydration reactions can potentially already meet the 20 USD/kWh cost target at 200 h duration, with current technology performance. The need for suggested and wide-ranging enhancements at material, device and system level is discussed, which may lead to TMES costs below 14 USD/kWh – competitive with long-duration solutions like hydrogen for covering the energy balancing needs of future low-carbon energy systems.
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