1Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), Villejuif, France.
2INSERM Unit U1015, Villejuif, France.
3Université Paris Sud, Université Paris-Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France.
4INSERM Unit U981, Villejuif, France.
5Department of Medical Oncology, Villejuif, France.
6INSERM Unit U932, Institut Curie, Paris, France.
7Drug Development Department (DITEP), Villejuif, France.
9Metabolomics Platform, GRCC, Villejuif, France.
10Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France.
11Pôle de Biologie, Hôpital Européen Georges Pompidou, Paris, France.
12Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
13Université Pierre et Marie Curie, Paris, France.
14Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
15Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 507, Villejuif, France.
Address correspondence to: Laurence Zitvogel, Gustave Roussy Cancer Campus, 114 rue Edouard Vaillant, 94805 VILLEJUIF Cedex, France. Phone: 33.1.42.11.50.41; E-mail: laurence.zitvogel@gustaveroussy.fr.
J Clin Invest. 2016;126(4):1224–1232. https://doi.org/10.1172/JCI81137.
DC-derived exosomes (Dex) are nanometer-sized membrane vesicles that are secreted by the sentinel antigen-presenting cells of the immune system: DCs. Like DCs, the molecular composition of Dex includes surface expression of functional MHC-peptide complexes, costimulatory molecules, and other components that interact with immune cells. Dex have the potential to facilitate immune cell–dependent tumor rejection and have distinct advantages over cell-based immunotherapies involving DCs. Accordingly, Dex-based phase I and II clinical trials have been conducted in advanced malignancies, showing the feasibility and safety of the approach, as well as the propensity of these nanovesicles to mediate T and NK cell–based immune responses in patients. This Review will evaluate the interactions of Dex with immune cells, their clinical progress, and the future of Dex immunotherapy for cancer.
As the sentinel antigen-presenting cells (APCs) of the immune system, DCs play a central role in initiating antigen-specific immunity and tolerance (1). In cancer, DCs act as the initial link between oncogenesis and the host immune system, the first step of a cancer/immunity cycle that aims to eliminate cancer cells through the activation of T cells (2). Tumor-proximal DCs can capture neoantigens created and released during oncogenesis, which the DCs subsequently process and present to cognate T cells to generate antitumor T cell responses. However, such T cell responses can only be generated if certain additional conditions are met in the local environment (2). These conditions consist of locally present immunogenic signals, such as proinflammatory cytokines, danger-associated molecular patterns (DAMPs), or pathogen-associated molecular patterns (PAMPs). Such signals trigger DCs to present captured tumor-associated antigens (TAAs) via MHC class I (MHC-I) and MHC-II molecules to T cells in cooperation with costimulatory molecules such as CD80 and CD86, resulting in the priming and activation of TAA-specific effector T cells.
Therapies harnessing these properties of DCs to generate immune responses against tumors have great potential, though clinical progress of this application remains in its infancy. One notable exception is the success of the immunotherapy sipuleucel-T for early-stage, hormone-refractory prostate cancer. Sipuleucel-T is composed of autologous peripheral blood mononuclear cells (PBMCs) including APCs (such as DCs and their precursors) that have been stimulated ex vivo with a fusion protein consisting of the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF), which drives DC differentiation and activation, combined with a prostate antigen (3). Nonetheless, DC-based immunotherapy is challenging to practice in clinical settings. Implementing such therapies across large populations is costly, requires dedicated expertise, and requires monitoring of well-defined quality control parameters. Furthermore, it is difficult to store DCs over long periods of time while maintaining their efficacy (4).
The use of DC-derived exosomes (Dex) has been heralded as a solution to many of the technical challenges associated with DC-based immunotherapy (see Table 1) because they maintain the essential immunostimulatory faculties of DCs (e.g., sharing the ability to present antigens to T cells), while the stable nature of exosomal membranes allows their frozen storage for at least 6 months (5). As biologics, Dex are also more amenable to a strictly regulated and monitored manufacturing process (e.g., their composition and MHC-I and MHC-II content can be easily defined), and they lack the risks associated with viable cellular or viral therapies such as the risk of in vivo replication (6). Finally, treatment with cell-free Dex may be more resistant to immunomodulatory events that occur in tumors than other anticancer vaccines; such events can downregulate costimulatory molecules on DCs and impede stimulation of T cell responses (7).
As discussed in detail in other sections of this review series, DCs are one of the many cell types able to secrete membrane vesicles, such as exosomes, into the extracellular environment. This manner of signaling can modulate recipient cells, such as immune cells or cancer cells, to a level beyond classical ligand/receptor signaling pathways and can create complex cellular modifications that may play a substantial role in how tumor development or immune responses proceed. Moreover, detection of circulating, cancer cell–derived exosomes can serve as a noninvasive diagnostic and screening tool to detect early stages of cancer, facilitating deployment of therapeutic interventions (8) (discussed elsewhere in this review series; refs. 9, 10, 11). Secreted membrane vesicles consist of a surrounding lipid bilayer containing various transmembrane proteins; the bilayer encloses various cytosolic components and molecules (e.g., proteins, lipids, and nucleic acids) from the donor cell. While several different subtypes of membrane vesicles have been characterized, such as apoptotic bodies and the microvesicles that directly bud from the plasma membrane (12), the focus of this review will be on the exosomes secreted by DCs, which have progressed to the stage of clinical testing.
The molecular composition of Dex allows functionality as an immunotherapy. Similarly to all other exosomes, Dex have a size of 30–100 nm and are initially formed within the cell by the inward budding of endosomal membranes. The resulting endosome formed by this process with its content of intraluminal vesicles is referred to as a multivesicular body (MVB) (13). If MVBs are not targeted for lysosomal degradation, they may fuse with the cell surface membranes of DCs to allow release of their intraluminal vesicles as exosomes (13, 14). The first studies of the Dex proteome revealed a unique molecular composition that allowed for strong immunostimulatory functionality (15, 16). Dex were found to possess MHC-I and MHC-II molecules, which could potentially stimulate CD8+ and CD4+ T cells, respectively, as well as costimulatory molecules (15–18) (see below). Dex possess a variety of surface membrane proteins, including the integrin α and β chains (αMβ2), the immunoglobulin family member ICAM-1, and milk fat globule EGF factor 8 (MFG-E8), which allow for effective targeting and docking to recipient cells (12, 15, 16). MFG-E8 is an abundant protein constituent of Dex membranes that can bind externalized phosphatidylserine on the Dex outer membrane and facilitate uptake of exosomes by linking Dex with αvβ3 or αvβ5 integrins present on the receiving cell (16). The tetraspanin family of proteins, including CD9, CD63, and CD81, are also well-defined constituents of the Dex surface membrane (15, 16). These and other membrane microdomain organizing proteins are postulated to participate in exosome/acceptor cell interactions (15, 16).
Various cytosolic proteins derived from the donor DC are present on the Dex outer membrane. These proteins appear to be related to Dex biogenesis from DC endocytic compartments (e.g., annexins, RAB proteins, and tumor susceptibility gene 101 [TSG101]) or are participants in signal transduction pathways (e.g., G proteins and kinases). The heat shock cognate protein HSC73 makes up a significant fraction of the cytosolic proteins found in Dex (16). This HSP70 family member, together with members of the HSP90 family that are also present within Dex, may add to Dex immunogenicity, since these proteins can activate various immune cells and have significant roles as antigen chaperones and in MHC loading (18). In addition to these protein families, exosomes also contain mRNA and small RNA (including miR) molecules, which they can transfer between cells (19, 20). RNA transfer via Dex has been shown as a means of communication and posttranscriptional modification between DCs, since exosome-delivered miRs were demonstrated to repress target mRNAs of Dex-accepting DCs (21). These findings could have wide implications for Dex immunotherapy, as they suggest that particular RNA profiles of Dex (or, more specifically, those of the donor DC) could influence Dex immunogenicity through posttranscriptional modifications of acceptor APCs.
Direct and indirect molecular interactions between Dex and T cells. Perhaps the most important attributes of Dex surface membranes, which also set them apart from exosomes secreted by other immune cells, is their possession of DC-originating molecules involved in antigen processing and presentation. It was initially discovered that exosomes derived from B cells possess functional peptide/MHC-II complexes upon their surface membranes and that they could induce antigen-specific MHC-II–restricted T cell responses (22). Dex also have abundant MHC-I molecules (16, 14), which are similarly able to induce T cell responses (23, 24). Importantly, Dex derived from tumor peptide–stimulated DCs were able to prime tumor-specific cytotoxic T lymphocyte (CTL) responses in vivo, and a single intradermal injection of this preparation resulted in tumor growth delay or, in some cases, a complete eradication of established murine tumors (17). The presence of the potent costimulatory molecule CD86 on the surface of Dex may also have contributed to T cell priming and activation (17).
Several mechanisms have been proposed for how Dex present antigens via their MHC molecules to stimulate T cell responses (Figure 1), presumably within lymph nodes. Dex have been shown to stimulate T cells directly in vitro, though it appears that this mechanism operates most efficiently as a restimulation of activated T cells, memory T cells, or T cell lines, clones, and hybrids (14, 22, 23). Direct Dex-to–T cell stimulation appears to be inefficient in priming naive T cells (25) and is unlikely to occur to a significant extent in vivo (26). Furthermore, Dex appear to be less efficient in directly stimulating T cell responses when compared with the T cell stimulatory capacity of the donor DCs (27), but stimulation may be improved if Dex are immobilized or if their concentration is increased in vitro (14, 27).
Dex interactions with immune cells. Dex may stimulate T cells by direct and indirect routes. The presence of MHC-I and MHC-II molecules on the surface of Dex gives them the potential to directly stimulate CTLs and CD4+ T cells, respectively. Dex surface costimulatory molecules aid this process. A more likely route for Dex stimulation of T cells occurs indirectly via bystander DCs through two possible mechanisms. The first involves Dex internalization and transfer of antigenic peptides to MHC molecules of the DC. These MHC/peptide complexes may then be transported to the DC surface for presentation to T cells. The second mechanism involves Dex transfer of MHC/peptide complexes directly to the DC surface, a process termed cross-dressing. It has been suggested that Dex may also transfer MHC/peptide complexes to tumor cell surfaces, enabling tumor cell targeting by host T cells. Additionally, Dex have been shown to possess BAG6, NKG2D-L, and the IL-15/IL-15Rα complex, which can each result in NK cell activation.
Rather than a direct Dex/T cell route of stimulation, evidence suggests that Dex or other APC-derived exosomes stimulate T cell responses far more efficiently via indirect antigen presentation through transfer of antigenic peptide/MHC complexes to bystander APCs (Figure 1 and refs. 14, 27–30). Furthermore, priming of naive T cells has been shown to occur only if APCs are present (25, 26, 28). The constituents of exosome surface membranes, such as integrins and ICAMs, facilitate their binding to and uptake by APCs to enable indirect antigen presentation. Interestingly, the efficiency of indirect T cell stimulation appears to be highly dependent upon the activation status of the donor APC from which exosomes are derived. For example, the exosomes released from DCs treated with LPS or IFN-γ (mature DCs) have increased surface expression of ICAM-1 that presumably enhances their uptake by DCs and increased expression of MHC molecules and CD86, which contribute to T cell activation (31–33). Consistent with their topography, these mature exosomes have a greater capacity to stimulate T cells compared with exosomes derived from immature DCs (24, 31–33).
Following binding to bystander APCs, some of the Dex — but not all individual Dex molecules — are internalized by phagocytosis or macropinocytosis, with the remaining Dex likely retained on the DC surface. The proportion of internalized exosomes is dependent upon the maturation status of the accepting APC. It has been shown that immature DCs internalize exosomes more efficiently than mature DCs, whereas mature DCs are likely to retain more Dex on their surfaces, although presumably surface-retained Dex still interact with T cells (26). Following internalization, Dex peptide/MHC complexes can be reprocessed via endosomal pathways within the APC, resulting in the transfer of antigenic peptides from Dex MHCs to APC MHCs (14, 26, 34). These MHC/peptide complexes can then be transported back to the DC surface for presentation to T cells.
A second mechanism for Dex-mediated indirect antigen presentation to T cells is a process known as cross-dressing where, following binding to APCs, Dex merge with the acceptor APC surface membrane, thereby transferring their peptide/MHC complexes (Figure 1 and refs. 28, 35). This would potentially allow immediate recognition of MHC-presented peptides by T cells without the need for antigen processing and could enable the Dex-transferred antigen presentation machinery to benefit from additional costimulatory molecules and factors present on the accepting APC. In support of this paradigm, Dex can activate T cells only if mature CD8α– DCs are present, even when mature DCs are deficient for MHC-II (28), suggesting Dex-to-DC cross-dressing of MHC/peptide complexes. Expression of the costimulatory molecules CD80 and CD86 on the presenting DCs was required for T cell activation (28). However, Dex MHC-I cross-dressing of bystander DCs does not appear to induce ovalbumin-specific (OT-I) CD8+ T cell proliferation in an ovalbumin experimental model but instead occurs through Dex internalization and reprocessing of Dex-derived antigen onto MHC molecules of the recipient DC (30).
A third indirect route through which Dex could activate T cells may occur via tumor cells. In a recent study, treatment of human breast adenocarcinoma cells with Dex was sufficient to restimulate previously primed T cells, inducing significantly higher percentages of IFN-γ–secreting T cells compared with exposure to non–Dex-treated adenocarcinoma cells (36). This suggests that incorporation of Dex by tumor cells can potentially convert tumor cells into stronger immunogenic targets, opening a new avenue of therapeutic strategies to increase immune targeting of tumors.
In view of the high potential and benefits of Dex as an immunotherapy, Dex have been developed for clinical use as cell-free cancer vaccines. Two phase I clinical trials (37, 38) and one phase II trial (39) using Dex have now been completed in advanced cancer patients (see Table 2).
Technical considerations. The manufacturing steps for Dex preparation and purification are detailed in Figure 2. More than 100 individual Dex preparations have been made so far, as the process of vaccine generation is feasible from cells derived from a single leukapheresis. Quality control parameters include the determination of tetraspanins (CD81, CD82, and CD63), high levels of HLA-DR, costimulatory molecules, and exosomal hallmarks such as TSG101 and HSP70 (31). Verification of peptide loading can be performed by incubating Dex with or without HLA-A2– APCs (DCs) and a peptide-specific T cell clone. In this setting, indirect Dex loading of MHC-I-restricted peptides (i.e., loaded onto the donor IFN-γ–treated DCs on day 4 of culture) appears to be as effective as direct peptide loading for stimulation of antigen-specific T cell clones when short peptides were loaded (31). Activation of the latter relative to negative controls confirms functional T cell stimulatory capacity of Dex. For the phase II trial, Dex batch release depended upon a high ratio of tetraspanins and HLA-DR (MHC-II) when compared with control (31, 39). In the phase I trials, Dex MHC-I natural epitopes were acid eluted, whereas no prior elution was performed in the Dex phase II trial. This discontinuation of peptide elution was based on the capacity of high-affinity peptides to compete against and/or coexist with natural epitopes on exosomal surfaces, as shown using ex vivo functional assays with melan-A–specific (MART1-specific) CTL clones (31, 39).
The GMP manufacturing of Dex immunotherapy. Leukapheresis is performed for advanced cancer patients who will undergo Dex therapy. Within a cell therapy unit GMP (good manufacturing practices) laboratory, monocytes are isolated following elutriation, and these are differentiated to immature DCs (iDC) by addition of GM-CSF and IL-4 in culture. iDCs may then undergo a quality control (QC) check before loading of MHC-I– and MHC-II–binding peptides in the presence of IFN-γ to generate mDC. Peptide-loaded exosomes from culture supernatants can then be isolated and concentrated by a process of centrifugation, diafiltration, and finally ultracentrifugation over a D2O sucrose gradient. QC testing of immunological characteristics (e.g., tetraspanin content of Dex, MHC-II and costimulatory molecule levels) and immunostimulatory capacity (e.g., ability to stimulate a peptide-cognate T cell clone) is then performed for each preparation to determine whether a given batch can be released. Released batches may then be stored (–80°C) for therapeutic administration through intradermal (i.d.) injections. Production of Dex for immunotherapy takes approximately three weeks from the initial leukapheresis (this includes time for Dex manufacturing, QC testing, and treatment of the patient with metronomic cyclophosphamide).
Phase I trials. The initial phase I trials used Dex produced from autologous monocyte-derived DC cultures loaded with antigenic HLA-presented peptides of melanoma-associated antigen (MAGE). The patients in the two studies received four vaccinations with Dex at weekly intervals.
In the first of these phase I studies (38), nine patients with MAGE-expressing pretreated advanced non–small cell lung cancers (NSCLC) were eligible to receive Dex therapy (Table 2). Three patients who did not exhibit reactivity to MAGE prior to immunization showed systemic MAGE-sensitive immune responses one week following the last Dex injection, as determined by delayed-type hypersensitivity (DTH) response. Increases in T cell activity were detected by enzyme-linked immunospot (ELISPOT) assay to MAGE peptides in one of five tested patients. Treg suppression was postulated as a reason for this low rate of T cell activation, since Tregs (defined as CD4+CD25+ T cells) as a percentage of total CD4+ T cells were increased in two of three patients after Dex therapy compared with baseline levels. Interestingly, a potential increase in NK cell lysis ability was also observed in two of four analyzable samples. A good safety profile was the main clinical outcome for the NSCLC phase I study, with disease stability observed in two patients who had disease progression at the start of the study and continued disease stability over 12 months in two of four initially stable patients (38).
The second phase I study enrolled 15 patients with MAGE3+ advanced malignant melanoma (MM), all of whom received Dex (Table 2 and ref. 37). Of these patients, one patient exhibited a partial response to Dex immunotherapy and developed a halo of depigmentation around naevi and disappearance of arterial neovasculature, concomitant with tumor shrinkage. This patient was given continuation therapy with Dex for 4 months, during which time there was stabilization of disease without toxicity. Disease stabilization for up to 24 months was also achieved for another patient who received continued Dex therapy. The overall clinical outcome was two stable diseases, one minor response, one partial response, and one mixed response at skin or lymph node sites, with some of these responses occurring in patients with progressive disease who had previously received other biotherapies or alternative antitumor vaccinations. However, similarly to the other trial, neither MAGE-specific CD4+ and CD8+ T cell responses nor DTH responses could be detected in peripheral blood (37).
A third phase I clinical trial used ascites-derived exosomes (Aex) in combination with GM-CSF to treat 40 advanced colorectal carcinoma (CRC) patients with Aex alone or Aex plus GM-CSF. The patients received four immunizations at weekly intervals (Table 2 and ref. 40). Exosomes were prepared from malignant ascites of the patients and were found to be enriched in MHC-I and MHC-II molecules, costimulatory molecules, and ICAMs. They were also shown to contain the immunogenic carcinoembryonic antigen (CEA) of CRC. A good safety profile was observed for Aex; however, no detectable therapeutic responses were observed except in one patient with stable disease and a second patient who exhibited a minor response after treatment with Aex plus GM-CSF. Interestingly, and in contrast with the low-level stimulation of T cell responses in the Dex clinical studies, Aex plus GM-CSF could induce CEA-specific antitumor CTL responses (40). The majority of the Aex were believed to be derived from CRC cells, although the ascites used in this study likely contained other immune or mesothelial cell–derived nanoparticles or microvesicles. A greater level of TAAs present in Aex compared with Dex may have also been responsible for the greater T cell responses observed in this study as compared with the two Dex phase I trials. However, given findings that tumor-derived exosomes can possess immunosuppressive properties and can facilitate tumor growth, metastasis, and development of drug resistance, care should be taken to distinguish the exact exosome composition of Aex and similar preparations, with a view to removing potentially adverse tumor-derived exosomes when such technologies become available (8, 41).
Interpretation of the immunological findings from the phase I trials: Dex stimulate NK cell functions. The phase I studies confirmed the safety of Dex administration in patients and highlighted the feasibility of large-scale Dex production. Somewhat surprisingly, given the encouraging results from preclinical studies, Dex were apparently poor stimulators of T cell responses. However, Dex were found to stimulate NK cells.
Following the MM phase I trial, it has been shown that Dex derived from human immature DCs possess killer cell lectin–like receptor subfamily K, member 1 ligands (NKG2D-L) upon their surface, which can directly engage NKG2D present on NK cells, leading to their activation (42). By using samples from the MM clinical trial, it was found that the number of circulating NK cells significantly increased after 4 weekly vaccinations with Dex. Additionally, NKG2D expression levels and cytotoxicity of NK cells were restored after Dex vaccination in 50% of MM patients presenting with NK cell defects at diagnosis (42). Further investigations of Dex/NK cell interactions in vivo revealed that Dex promote IL-15Rα–dependent NK cell proliferation and an NKG2D-mediated activation of NK cells. These Dex-mediated pro-NK cell effects coincided with improved metastatic control by NK1.1+ cells in C57BL/6 mice inoculated i.v. with B16F10 melanoma cells (42). Dex derived from immature human DCs (and exosomes derived from 293T cells) also express BCL2-associated athanogene 6 (BAG6, also known as BAT3) on their surface (43), which has been identified as a ligand for natural cytotoxicity triggering receptor 3 (NKp30) receptors on NK cells (44). Exosomal BAG6 expression levels were shown to directly correlate with NK cell cytokine release (43). Additionally, Dex surface expression of TNF induces NK cell IFN-γ production (45).
Phase II trial. The poor capacity of Dex to stimulate T cell responses in the initial phase I studies encouraged new approaches to improve the interactions of Dex with the adaptive arm of the host immune response. As previously described, the use of exosomes derived from LPS- or IFN-γ–matured DCs (mDex) has been one such new approach, following discoveries that mDex can induce greater T cell stimulation than Dex derived from immature DCs (24, 31, 33). Application of these findings to human DC cultures led to a clinical-grade manufacturing process for Dex vaccines (31) in which IFN-γ stimulation of human DC cultures induces the expression of costimulatory molecules and ICAMs on Dex, yielding a second-generation Dex with enhanced immunostimulatory properties (31, 46). A phase II clinical trial was launched using second-generation Dex in advanced NSCLC patients, with the aim of investigating whether IFN-γ–Dex used as maintenance immunotherapy can ameliorate the rate of progression-free survival (PFS) at 4 months after platinum-based chemotherapy (39).
Twenty-two advanced NSCLC patients who had received four cycles of a first-line platinum-based chemotherapy were eligible to receive IFN-γ–Dex (39). Patients were administered metronomic oral cyclophosphamide (CTX) ahead of IFN-γ–Dex maintenance therapy based upon preclinical (47–49) and clinical evidence (48, 50) demonstrating that this regimen reduces Treg function and stimulates dual IFN-γ/IL-17–producing T cells, thereby facilitating Dex-mediated T cell priming and restoring T cell and NK cell functions. Seven patients (32%) exhibited stable disease after nine injections with IFN-γ–Dex, and these patients continued receiving Dex therapy every three weeks. Consequently, the primary endpoint of the trial, a PFS of 50%, was not reached. No objective response was recorded in the trial, although one patient experienced a long-term stabilization that allowed tumor debulking surgery, a downgrading of disease status by pathologists, and eligibility for local adjuvant thoracic and vertebral radiotherapy.
Regarding the immunological readouts, IFN-γ–Dex immunotherapy again failed to show evidence of TAA-specific T cell immune responses in the patient cohort (39) despite multiepitope loading and the CTX adjuvant. The immunostimulatory capacity of IFN-γ–Dex was instead apparently manifested through augmentation of NKp30-related NK cell functions. Despite low expression levels of NKp30 on stage IV NSCLC patient NK cells, NKp30-stimulated production of IFN-γ and TNF-α by circulating NK cells was increased after four IFN-γ–Dex vaccinations, as compared with the start of the study. Importantly, this increased NKp30-elicited NK cell activation correlated with longer PFS (39).
With regard to a potential mechanism for Dex stimulation of NK cells, it was found that the Dex vaccine preparations possessed the aforementioned membrane-associated NKp30 ligand BAG6, which may have been responsible for activating NK cells of patients in an NKp30-dependent fashion. In support of this hypothesis, BAG6 levels correlated with the MHC-II concentrations of Dex inocula and NKp30-dependent NK cell functions. This differs from the finding of the previous MM phase I study in which NKG2D (and potentially IL-15/IL-15Rα) signaling was responsible for Dex-mediated NK cell activation (37, 42). Because the Dex immunotherapies utilized in this previous study were not derived from IFN-γ–mDCs in which IFN-γ can upregulate BAG6 expression (51), NKG2D-L–mediated NK cell stimulation presumably featured more prominently in the absence of BAG6/NKp30 signaling.
The early clinical testing of Dex as cancer vaccines has shown limited clinical efficacy in advanced cancer patient cohorts, although cases of disease stabilization were observed in each study. The limited efficacy in the trials might be explained by poor stimulation of adaptive immunity in these patients, potentially due to several factors. A conceivable explanation is the heterogeneity and small size of the patient cohorts, which had received previous anticancer treatments before enrollment. More importantly, systemic and local immunoregulatory mechanisms (e.g., programmed death ligand-1 [PD-L1] expression in NSCLC cells associated with programmed death-1 [PD-1] upregulation by tumor-infiltrating lymphocytes [TILs], Treg, and myeloid-derived suppressor cell [MDSC] activity) at play in these advanced-stage patients may have also significantly limited this immunotherapy. Another possibility is that the Dex MHC-I– and MHC-II–restricted antigens employed in these advanced patient cohorts were insufficient to drive tumor-targeted T cell responses. The potential of mutated neoepitopes to drive high-avidity T lymphocytes could be exploited for NSCLC patient exosomes (52, 53). Additionally, the in vivo trafficking and fate of Dex in patients is unknown. Instead of reaching the T cell zones of secondary lymphoid organs in sufficient numbers, Dex may be transported to subcapsular sinus macrophages or lymphatic sinus DCs to encounter innate lymphocytes (54). Lastly, it remains to be determined whether Dex express functional PD-L1 or PD-L2 molecules that may restrict T cell responses.
Future strategies for development of Dex as an immunotherapy. Given the problems encountered within a clinical setting, it will be necessary to develop strategies to enhance Dex activity to create a successful immunotherapy. Dex can be engineered to enhance particular immunostimulatory characteristics; therefore, it is certainly possible to further improve upon the most recent second-generation Dex. Engineering Dex to have a greater surface expression of various costimulatory molecules, with lower expression of immunoregulatory molecules (e.g., immune checkpoint molecules like PD-L1) may enhance Dex activity. The choice of TAAs adopted in the Dex clinical trials might also be improved upon, perhaps including several different TAAs or mutated neoantigens to combat tumor evolution (2, 53, 55). Increasing the delivered quantity of such TAAs or the addition of GM-CSF to Dex immunotherapies may also help stimulate T cell responses, given the CTL activation observed in the Aex phase I trial (40). Moreover, recent findings have suggested that the design of Dex immunotherapies to stimulate B cell responses alongside T cell stimulation may optimize their immunogenicity (56, 57). Vaccination of mice with protein-loaded Dex, but not T cell peptide–loaded Dex, induced CD8+ T cell responses and control of tumor growth, and these effects depended on the presence of both B cells and CD4+ T cells (56).
Dex immunotherapies may also benefit from the addition of TLR ligand adjuvants. CpG and polyinosinic:polycyctidylic acid — which activate TLR9 and TLR3, respectively — induced efficient tumor rejection and Dex-mediated CD8+ T cell priming in a melanoma model using HLA-A2 transgenic mice (58). Thus, the inherent capability of Dex to bind TLR ligands, thereby activating bystander DCs (59), could be implemented to enhance their immunogenicity. In addition to their immunostimulatory capacity, Dex therapies could be engineered to target tumor cells directly (36, 45). Indeed, expression of TNF, FasL, and TRAIL on Dex surface membranes directly triggers caspase activation and apoptosis in tumor cells (45). Engineering Dex to transfer mRNAs encoding relevant neoantigen peptides, or miRs or mRNAs that modulate distinct signaling pathways in immune cells or cancer cells, are other possibilities (20, 21, 60, 61).
Potential next steps for the clinical testing of Dex as an immunotherapy. Dex immunotherapy may be most effective as part of a combinatorial treatment regime. Firstly, combining CTX chemotherapy with Dex vaccines in vivo significantly enhanced tumor- or peptide-induced CD8+ T cell recall responses, leading to a synergistic effect against preestablished tumors (47). However, CTX combination therapy only allowed efficient T cell priming by Dex in humans if genuine adjuvants were present. It is likely that the therapeutic effects seen in this scenario were due to a Dex/CTX therapy retuning of tumor-induced tolerance toward tumor-induced immunogenicity, since CTX can attenuate the suppressive function of Tregs (47, 50, 62, 63). The phase II Dex clinical trial similarly employed CTX to inhibit Tregs prior to Dex immunotherapy (39, 46), although the clinical efficacy of this combination would be more evident in a less advanced cohort. Secondly, combining Dex with PD-1/PD-L1 blockade (or coblockade with anti-CTLA4 therapy) could reduce TIL suppression and enhance T cell priming. Thirdly, a major disadvantage of dealing with NSCLC patients is that the current standard chemotherapeutic regimen does not induce immunogenic cell death (64). Combining Dex with immunogenic cytotoxic drugs would be a suitable option in other malignancies (65, 66). Lastly, it is conceivable that Dex- and NK cell–based immunotherapies (such as anti–killer cell immunoglobulin–like receptor Ab [anti-KIR Ab]; refs. 67–69) may have synergistic effects against NK cell–dependent malignancies such as gastrointestinal stromal tumors, neuroblastomas, leukemias, and kidney cancers (70–72).
Notwithstanding the many strategies to develop Dex immunotherapy, the predominant reason for the limited efficacy of Dex immunotherapies achieved in clinical trials thus far could be due to the small, advanced cancer–stage patient cohorts used and to the lack of preselection criteria (37, 38). Nonetheless, our phase II Dex trial (39) revealed that patients with detectable serum BAG6 (most probably associated with NKp30 functional defects) are most likely to benefit from Dex therapy. Indeed, patients destined to best respond to Dex appear to be those presenting with defective NK cell receptor expression or functions (notably NKG2D or NKp30), with the predominantly targeted NK receptor dependent upon the specific Dex preparation (e.g., immature versus mature Dex) (39, 42). In prospective clinical studies, these parameters (e.g., killer activated receptors [KARs] and their circulating ligands) should be followed with comprehensive immunomonitoring analyses. Careful patient monitoring for potential immune-related adverse events is also necessary in future trials involving Dex, despite Dex immunotherapy showing a strong safety profile thus far. This, alongside careful patient screening and selection, will be particularly important for future studies investigating potential combinatorial regimes with Dex (e.g., Dex combined with immune checkpoint inhibitors).
Despite the challenges encountered thus far, the prospect of Dex immunotherapy as a novel cancer treatment remains highly promising. Dex are adept mediators of immune responses and the relative technical ease in manipulating their immunostimulatory characteristics (via the donor DC), along with the advantages over cell-based therapies, ensures their future therapeutic uses. Although Dex immunotherapies produce an encouraging stimulatory effect upon NK cells, which likely contributed to the cases where improved clinical outcome was observed (39), it is clear that improved strategies to overcome the apparent lack of T cell responses are necessary. Focus on this hurdle, as well as on less understood Dex components and functions — such as mRNAs, miRs, transported cytokines, production of lipid mediators (73), and mechanisms through which each of these factors interact with acceptor immune cells — will help Dex immunotherapies to reach their full potential.
We thank Association de Recherche Contre le Cancer for supporting the phase II trial and J.M. Pitt. We are indebted to private philanthropy, namely Mrs. Badinter and Mrs. Agnès b. for their generous support of clinical trials. We thank N. Chaput and V. Lapierre for their work in the cell facility, as well as patients and their families for continuous support.
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Last week Spencer and I visited my sister in Chicago to see Aladdin in the theater district. While there we stayed in an ultra urban River North hotel. The Kinzie Hotel has windows sweeping nearly floor to ceiling. Located right next you can find the famous Harry Caray's. It's also just a five minute walk to the theater district. Or in my case a very inexpensive Uber since my shoes were not comfortable.
I'll admit the lobby was a bit confusing because it wasn't the typical large desk greeting. We walked in and there were small office desks set up and we were afraid we'd stepped in to the real estate side. We were checked in quite quickly once a host became available. The entire lobby staff was friendly and helpful. But on top of that they were fun. Jason offered us a lot of suggestions for things to do, places to eat and see and I can't wait to visit him again. The bell hop gentleman were always laughing and making the lobby feel warm.
Speaking of the lobby, it is quite small but comfortable. Art is the big draw with all different mediums hung throughout the lobby and hotel. If you pay attention you'll even see a life size horse. I've included pictures of my favorite pieces which includes their lighting. If you are in the area you should come in and take a look.
The Kinzie Hotel was another one of the hotels that I deem "too cool for me" but I still loved every second of our one night stay. We kicked back in the King Suite on the 4th floor. The room is more than spacious enough for 3 or 4 people but the pull out sofa may only hold one adult comfortably. The sitting area was a full sized living room with gorgeous windows curving across the walls in both rooms. Although the view is mostly of other buildings it is still mind-blowing when you have never seen a city like this. Spencer thought it was absolutely the coolest thing ever that there was a button on the wall to control the shades.
The bathroom offers H2O products which are one of my favorites. I've purchased them myself many times. If you really want to relax the shower has two shower heads and strong water pressure. The towels are fluffy soft and there are 2 robes with the King Suite. But don't forget to put one on before you walk out into those open windows. I wrapped up in a towel and then realized hundreds of eyes could be on me!
One of my favorite features of this River North hotel was the wallpaper behind the king sized bed in the bedroom which was a giant map of Chicago. Jackie commented on it right away as well, so it is probably popular with all guests. A welcomed treat was the Serta Perfect Sleeper Pillow Top Mattress after a long night. Jackie and I both snore and this incredibly comfortable mattress allowed us to sleep through the night. A small sitting area for chatting is also available which we took advantage of more than once.
Spencer appreciated that there were two televisions in the suite. Or maybe Jackie appreciated it since she dislikes kid's television shows. The USB ports and electric outlets next to the bed were a big relief for me. The continental breakfast each morning, which is included in your price, is on your own floor. That's right, each floor has a breakfast table of their own. It held us over until we could move on with our day. Cereals, pastries, fruit and donuts. If it begins to run low don't hesitate to call downstairs, they'll replenish until 10am.
Next time you visit Chicago and need a hotel in River North, The Kinzie Hotel is a wonderful choice. I forgot to mention the hotel hosts a happy hour each night between 5-8pm and even offer you a free drink. It's a great way to get to know other people in the hotel. So stop in, say hi to Jason and consider staying a few nights.
If stay at hotel, stay with Blue Beaker Bong, Nice work!


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Nel electrolyzer
Products Nel Hydroge
With more than 3,500 reliable, cost efficient electrolysers installed around the globe, Nel Hydrogen is the recognized industry leader of Alkaline and Proton Exchange Membrane (PEM) water electrolysis. Since our founding in 1927, sustained R&D efforts have contributed to continual improvement of electrolyser technology, setting the benchmark in the. With more than 3,500 reliable, cost efficient electrolysers installed around the globe, Nel Hydrogen is the recognized industry leader of Alkaline and Proton Exchange Membrane (PEM) water electrolysis
Water electrolysers / hydrogen generators Nel Hydroge
imal maintenance and siting requirements, M Series electrolysers can produce up to 5,000 Nm 3 /h of hydrogen gas at 99.9995% purity on-demand. Featuring a scalable modular design that can be containerized, these systems offer solutions that are well-suited for a variety of industrial, fueling and renewable energy applications
imal maintenance. Typical applications include renewable energy storage, industrial process gas, and hydrogen fueling
PHOENIX (JUNE 3, 2020) -- Nikola Corporation who becomes publicly traded on June 4, 2020 on the Nasdaq (NKLA), signed a purchase order with Nel ASA (Nel, OSE: NEL), for 85-megawatt alkaline electrolyzers supporting five of the world's first 8 ton per day hydrogen fueling stations
Nel is the largest hydrogen electrolyzer manufacturer in the world. This puts it in a great position to profit from green hydrogen growth. It wants to achieve $1.5/kg green hydrogen in 2025. This..
Nel ASA ist ein global operierendes, norwegisches Unternehmen mit Sitz in Oslo, das Lösungen für die Herstellung von Wasserstoff aus elektrischer Energie, sowie dessen Speicherung und Verteilung liefert. Das Unternehmen ist im OBX Index der Börse Oslo gelistet
About Nel: Nel is a global, dedicated hydrogen company, delivering optimal solutions to produce, store, and distribute hydrogen from renewable energy. We serve industries, energy, and gas companies with leading hydrogen technology Hoeller Electrolyzer GmbH. Alter Holzhafen 17 b. 23966 Wismar │ Germany . Tel.: +49 3841 38901 0. Fax: +49 3841 38901 99. E-Mail: info@hoeller-electrolyzer.co Nel ASA (Nel) reported revenues of NOK 229.1 million in the fourth quarter of 2020, up from NOK 175.9 million in the same quarter of 2019 and an EBITDA of negative NOK 96.2 million (Q4 2019: -41.7.
The water-splitting reaction in a PEM electrolyzer gleans its electrolytes from a catalyst that is applied to a polymeric membrane. Alkaline electrolysis is the more established technology, and alkaline electrolyzers typically are more affordable, but PEM electrolyzers bring some added value via a more rapid response to changes in power Eigentlich will Nel als bevorzugter Partner in großem Stil Wasserstoff-Tankstellen und Elektrolyseure an Nikola liefern. Deren Chef hat dann auch via Twitter bestätigt, dass es bei den Plänen.. Nel Hydrogen Electrolyser Nel ASA Q3 2017 1 electrolyzer (2.2MW) 6 electrolyzers (~13MW) 24 electrolyzers (~50MW) 176 electrolyzers (~400MW) A-SERIES Scalable and modular Built for future expansion up to any capacity size A-SERIES-C Highest efficiency 9 A-Series-C150 (~0.7MW) A-Series-C300 (~1.4MW May 7, 2019, 12:38 PM PDT. Nel Launches Containerized Large-Scale PEM Electrolyzer Nel Hydrogen Electrolyser, a subsidiary of Nel ASA, today officially launched the M Series containerized Proton.
Norwegian electrolyser maker Nel has unveiled plans to cut the cost of its electrolysers by about 75% in a new 2GW factory — set to be the world's largest — and to reduce the price of green hydrogen to $1.50 per kg by 2025, roughly the same cost as grey H 2 derived from unabated fossil fuels The method known as alkaline electrolysis has been in commercial use since the middle of the 20th century. It uses a cell with a cathode, an anode and an electrolyte based on a solution of caustic salts. When voltage is applied, water decomposes in the alkaline solution. Hydrogen is formed at the cathode and oxygen at the anode Press release - MarketReportsOnline - Impact of Covid-19 on Hydrogen Electrolyzer Market (Alkaline, PEM & Solid Oxide) 2021-2025 ? Siemens AG, ITM Power, NEL ASA, FuelCell Energy, Air Liquide and.
•Nel awarded contract as part of Nikola's development of a hydrogen station infrastructure owned and operated by Nikola in the U.S. •Multi-billion NOK 1 000 MW electrolyzer and fueling station contract, to be deployed from 2021 -largest electrolyzer contract ever awarded •Nikola and Nel A visit to Nel ASA's website shows that it sells an atmospheric alkaline electrolyzer that has capacities that range from a hydrogen production of 150 Nm³/h to 3,880 Nm³/h. The biggest electrolyzer..
Nel Hydrogen US has received a purchase order for a 1 MW containerized Proton PEM (Proton Exchange Membrane) electrolyzer from Trillium Transportation Fuels (image courtesy Nel). According to a statement, the electrolyzer will be used to produce hydrogen for a fleet of fuel cell electric buses in Urbana, Illinois (IL) Nel aus Norwegen beispielsweise beliefert das HYBRIT-Projekt mit einem Elektrolyseur. Laut HYBRIT verursacht die Stahl-Industrie weltweit sieben Prozent der gesamten CO2-Emissionen. In Schweden..
PEM Electrolyser Nel Hydroge
Electrolyzer Hydrogen storage Station module Dispensers 27 35MPa 70MPa 35MPa. Hyon AS, a one-stop-shop for complete hydrogen energy solutions •Joint venture between Nel ASA, Hexagon Composites ASA and PowerCell Sweden AB •Utilizes each partner's respective world-leading technologies and competencies to manage and develop projects for effectively integrating and optimize zero-emission.
The Norwegian manufacturer Nel is planning the construction of what they claim to become the world's largest electrolyser factory with an annual capacity of 360 MW. The facility is directly related to the major order that Nel received from the U.S. startup Nikola Motor. At the start of July, it was announced that Nikola had [
In 2006 at Hannover Messe, the business unveiled its Inergon ® (see HZwei issue from August 2006), a PEM electrolyzer Nel acquires Proton OnSite. On Feb. 27, 2017, Nel announced that it intended to buy Proton OnSite. It said that there was a non-binding agreement between both partners. The price of the acquisition, which could be completed during the second quarter of 2017, is reported to match the current market value of Proton Energy Systems of USD 70 million, of which.
The 4.5MW alkaline electrolyzer solution from Nel Hydrogen, will be part of this pilot. The pilot plant for fossil free steel production will operate in Luleå, Sweden, from 2021 until 2024, then the project enters a demonstration phase with the goal to have an industrial process in place by 2035
ate compression costs, increasing ammonia production efficiency. lower footprint, relates to plant size, supporting modular design and low-cost delivery; overall higher efficency is what will make green ammonia, produced from air and water using electricity, competitive with fossil ammonia. In.
NEL contributes its self-developed pressurized alkaline electrolyzer, which, with the help of electric current, produces a chemical reaction, a material conversion, which is needed for fertilizer production. The focus is on the development of efficient and environmentally friendly solutions for ammonia and fertilizer production together with Yara
Nel electrolyser. Hybrit Development, a joint venture between SSAB, LKAB and Vattenfall, has ordered a hydrogen generation electrolyzer solution from Nel Hydrogen to the pilot plant in Luleå, Sweden. HYBRIT, an initiative supported by the Swedish Energy Agency, plans to replace coal with fossil free electricity and hydrogen The electrolyzer from Nel Hydrogen has a higher daily production capacity than the truck's expected daily energy demand. This will allow for the storage of excess fuel during downtimes. If the program is successful, Anglo American will convert all of its trucks at the mine and expand the program to its other mining operations. More Sustainable Mining . Under the announced agreement, Nel.
Containerized PEM Electrolyser Nel Hydroge
Press Releases. Electrolyzer Market to Reach $0.9 Bn, Globally, by 2027 at 24.6% CAGR: Allied Market Research. May 18, 2021. Nel ASA: Receives Purchase Order for 2 MW PEM Electrolyser. May 5, 2021.
Nel Hydrogen Electrolyser, a subsidiary of Nel ASA, launched the M Series containerized Proton PEM electrolyzer. We have spent considerable effort over the last year to finalize the design of our M Series Proton PEM electrolyzer in a containerized version. It is a pleasure to now officially include this product..
Nel ASA: Awarded multi-billion NOK electrolyzer and fueling station contract by Nikola Published June 28, 2018 (Oslo, 28 June 2018) Nel ASA (Nel, OSE: NEL) has been awarded a contract for delivery of 448 electrolyzers and associated fueling equipment to Nikola Motor Company (Nikola) as part of Nikola's development of a hydrogen station infrastructure in the US for truck and passenger vehicles
g competitive with SMR OpEx: Renewable energy already enables fossil parity for hydrogen d d Source:Pareto Securities, Lazard EUR/USD:1:1.2 5.4 5.0 2.6 2.3.
NEL Aktie im Überblick: Realtimekurs, Chart, Fundamentaldaten, sowie aktuelle Nachrichten und Meinungen
The electrolyzer will be built by ITM Linde Electrolysis GmbH, a joint venture between Linde and ITM Power, using high-efficiency PEM technology. The plant is due to start production in the second half of 2022. Clean hydrogen is a cornerstone of the German and EU strategies to address the challenge of climate change. It is part of the solution to help reduce carbon dioxide emissions across.
Giner ELX electrolyzer systems incorporate our world-leading PEM electrolyzer stack technology. They deliver pure hydrogen (99.9995%) safely, cleanly, noiselessly and efficiently at pressures up to 40 barg or 580 psi. Applications include: Energy storage: storage of surplus electric energy—particularly of stranded solar or wind energy—as hydrogen for later use: to power fuel cell vehicles.
Nikola Orders Enough Electrolysis Equipment From Nel to
Nel Project (PD155) PI: K. Ayers. High Efficiency PEM Water Electrolysis. ANL Project (PD157) PI: D.J. Liu. PGM-free OER Catalyst: MOF, M - ZIF, Porous Nano-Network Electrode (PNNE) Univ. Oregon (PD187) PI: S. Boettcher. Precious Metal-free LTE. of Dirty Water. Georgia Tech (PD185) PI: P. Kohl. Engineering Durable Low. Cost AEM Electrolyzers. Discussed in PEC, P148A. Discussed here in LTE. Nel ASA Nel ASA operates business under three segments, which include hydrogen fueling, hydrogen solutions, and hydrogen electrolyzer. The company's key offering include Atmospheric Alkaline. Global $400+ Billion Hydrogen Electrolyzer (Alkaline, PEM & Solid Oxide) Market Insights & Forecast to 2025 Featuring Siemens AG, ITM Power, NEL ASA, FuelCell Energy, Air Liquide and Plug Powe
We offer electrolyzer's tailored solutions for hydrogen houses, businesses, farmers, refineries, green transport, energy storage solutions, gold and diamond mining, food processing, power station cooling and we aim at ensuring that as many applications of our hydrogen generator units use renewable energy. Each of our electrolyser product is unique and built to your needs all with the latest. Spanish energy company Iberdrola and Norwegian electrolyzer manufacturer Nel, through its subsidiary Nel Hydrogen Electrolyser, have signed an agreement to develop large electrolyzers and promote. Oslo— Nel Hydrogen Electrolyser, a subsidiary of Nel ASA (Nel, OSE:NEL), today officially launched the MC250 and MC500 containerized Proton PEM electrolysers. We are proud to officially launch the MC250 and MC500, representing automated MW-class on-site hydrogen generators utilizing a modular containerized design for ease of installation and integration Fig. 10.4 retrieved for Saba et al. (2017), which was derived from NEL (2015), shows the CAPEX of large-scale alkaline electrolyzer systems from 1 to 41 MW capacity. Information on the methodology used by NEL to derive this curve was not available. It can be assumed that probably a fixed cost for a 250 kW system was used as the base line The first electrolyzer subsequently appeared in 1800, when Nicholson and Carlisle induced a static charge into water. More than 200 years later, Cummins is continuing to evolve these fundamental discoveries. Electrolyte type Electrolysis cells are characterized by their electrolyte type. Cummins works with two types of low-temperature electrolysis:.
Nel ASA: The Road To Affordable Green Hydrogen (OTCMKTS
The world's largest PEM electrolyser factory. Electrolyser systems for Hydrogen generation. Find Out More. With the largest Electrolyser manufacturing facility in the world, ITM Power manufactures integrated hydrogen energy solutions to enhance the utilisation of renewable energy that would otherwise be wasted
And the hydrogen company Nel last month announced a joint project with ammonia producer Yara that will involve integration of a Nel electrolyzer into Yara's ammonia production process. According to an August 23 Ammonia Energy story, the partners hope that, by working together to develop Nel's 'next generation' electrolyzer technology and test it in an industrial setting, they can.
Nel Hydrogen Electrolyser, a subsidiary of Nel ASA, today officially launched the A1000 alkaline electrolyzer. After working with large-scale solutions for our alkaline electrolyzers, we have now designed a new medium scale, 2 ton/day solution. It is a pleasure to now officially include this product in our electrolyzer offering, says.
Hydrogen from water electrolysis is clean and green. It is a solution for renewable variability and values excess energy supply. The electrolyzer used at the..
Overview. We are developing a range of large electrolyzer stacks to address the nascent power to gas and Power 2 MobilityTM markets. Giner's Kennebec stacks span the range from 60 kg/day to 2200 kg/day (5 MW nominal input). Giner is driving PEM electrolyzer technology forward to meet the needs of tomorrow's green hydrogen economy Manufacturers are scaling up their electrolyzer offerings, and double-digit megawatt projects are being built. Only 1%-4% of hydrogen is produced with electrolyzers in 2019. However, with greater emphasis on decarbonization, increasing renewables integration, and decreasing capital costs of electrolyzers, Guidehouse Insights expects significant growth in the electrolyzer market. While most. The electrolyzer, model H 2 IGen 300/1/25, was manufactured by Vandenborre Hydrogen Systems (now acquired by Hydrogenics) and is shown in Fig. 14.15. The device is of the advanced alkaline type and uses an aqueous solution of KOH at 30 wt% to maximize ionic conductivity at the rated operating temperature of 65 °C. The electrolysis module is formed by 22 circular cells, 300 cm 2 each. Oslo— Nel ASA (Nel, OSE:NEL) announces preliminary findings from safety consultancy Gexcon regarding the incident at the Kjørbo hydrogen station on June 10, 2019. Based on what we have seen at the site, we can conclude that neither the electrolyzer nor the dispenser used by customers had anything to do with this incident
Nel ASA - Wikipedi
The growing number of large-scale electrolyzer projects will spur competition between suppliers. In Europe, suppliers include ThyssenKrupp, McPhy, Hydrogenics, NEL, SOEC, ITM Power and Siemens. To date, much of the electrolyzer development has revolved around chlorine production. Technologies differ between supplier and include alkaline electrolysis, polymer electrolyte membranes (PEMs) and. The Electrolyzer market was valued at Million US$ in 2017 and is projected to reach Million US$ by 2025, at a CAGR of during the forecast period. In this study, 2017 has been considered as the base year and 2018 to 2025 as the forecast period to estimate the market size for Electrolyzer. The following manufacturers are covered in this report: McPhy Energy S.A. NEL Acta ITM Power SwissHydrogen.
Nel ASA: Order for four additional H2Station™ hydrogen
(Oslo, 9 December 2019) Nel Hydrogen Electrolyser AS, a subsidiary of Nel ASA (Nel, OSE:NEL) has received a purchase order, following a previously announced contract, for a 3.5 MW electrolyser from ENGIE. The electrolyser is an element of ENGIE's hydrogen solution to produce renewable hydrogen for the world's largest fuel cell electric mining haul truck for Anglo American, a global mining. Die Nel-Aktie erholte sich daraufhin von den Tagestiefen, die in Oslo bei 7,45 Kronen markiert wurden, auf 8,20 Kronen. Damit blieben sie jedoch weiter unter dem Tageshoch bei 8,90 Euro. Im.
Video: HOELLER Electrolyze
NEL ASA (NEL.OL) Stock Price, News, Quote & History ..
At this stage, Nel - as a small player outside the niche electrolyzer space - is relying heavily on partnerships to get to a respectable scale. It is positioning itself as a preferred partner to. Nel Hydrogen Electrolyser, a subsidiary of Nel ASA, today officially launched the M Series containerized Proton® PEM electrolyzer. Print. OSLO, Norway-Wednesday 8 May 2019 [ AETOS Wire ] ( BUSINESS WIRE )-- Nel ASA (OSE:NEL): We have spent considerable effort over the last year to finalize the design of our M Series Proton PEM electrolyzer.
The electrolyzer efficiency is calculated in the same way as a fuel cell. The fuel cell efficiency is given by the formula: And the inverse of this formula is the efficiency of the electrolyzer: The losses in electrolyzers are the same as fuel cells, and typical values for Vcell and Vel_cell are 1.6 - 2.0 V depending upon the current density. The stack efficiency should also include the. Top Key Players Are: NEL Acta ITM Power SwissHydrogen SA Siemens. Electrolyzer Market research is an intelligence report with meticulous efforts undertaken to study the right and valuable information. The data which has been looked upon is done considering both, the existing top players and the upcoming competitors. Electrolyzer Market is growing at a +35% CAGR during the forecast period. The electrolyzer technology provides a means to address one of the largest dilemmas in the renewable energy industry, which is how to store the energy when it's not in demand. Cummins' PEM electrolyzers, like Douglas County PUD's electrolyzer plant, enables utilities to store the excess energy that they would typically sell off to the market at a financial loss, or not harness at all. The global electrolyzer market size was USD 321.65 million in 2019. The global impact of COVID-19 has been unprecedented and staggering, with the product type witnessing a negative demand shock across all regions amid the pandemic. Based on our analysis, the market will exhibit a decline of -5.31% in 2020
Nel ASA announces the construction of the world's largest fully automated electrolyzer manufacturing plant with a capacity of 360 MW/year Electrolyzer. Tube Truck. System to be modeled. Optimization framework. Research aims: • Explore electrolysis-based hydrogen production cost, optimizing retail rates • Improve competitiveness of hydrogen technologies. NATIONAL RENEWABLE ENERGY LABORATORY 7 Electric utility rates: Retail tariff structure (Faruqui et al. 2010) Energy and demand charges: Energy charges are associated with the. Electrolyzer P. I. Hoon T. Chung Los Alamos National Laboratory 4-30-2019 Project ID p158 This presentation does not contain any proprietary, confidential, or otherwise restricted information . Project Overview Project Partners Hoon T. Chung, Los Alamos National Laboratory Barr Zulevi, Pajarito Powder, LLC Project Vision The key challenge in anion exchange membrane (AEM) electrolyzer is to. Worldwide Market Reports has publicized the addition of a new market intelligence report, titled Global Hydrogen Electrolyzer Market.The report gives an elaboration on the key drivers, restraints, emerging trends, opportunities, prominent business, and recent technological progress.The research presents a comprehensive insight into the share and size of the various types, profitable avenues. In Hanover, ITM exhibited two container units replete with electrolyzer technology. Graham Cooley, ITM's CEO, said Norwegian-based Nel Hydrogen - which celebrated its 90-year anniversary in Hanover - and US-based Proton OnSite had two separate booths despite the former having acquired the latter at the beginning of this year. Nel.
Electrolyzer Technologies for Green Hydrogen - Chemical
Nel ASA: Secured location for low-cost electrolyzer manufacturing with infrastructure allowing for more than 1 GW/year capacity Wed, Aug 28, 2019 06:34 CET The new location at Herøya provides a number of benefits, including a potential to further expand capacity to more than 1 GW/year Nel-Partner Nikola Motor: Das Start-up hat Großes vor. -3,81 %. Nel. Nel. Nikola Motor. Wasserstoff. Nikola Motor hat vor Kurzem mit der geplanten Fusion mit VectoIQ und einem damit verbundenen. NEW YORK, May 17, 2021 /PRNewswire/ -- The hydrogen electrolyzers market is set to reach USD 79.90 million and registers an accelerating CAGR of over 6% during 2020-2024. The report offers an up. About Press Copyright Contact us Creators Advertise Developers Terms Privacy Policy & Safety How YouTube works Test new features Press Copyright Contact us Creators.
Seite 1267 der Diskussion 'NEL ASA - Elektrolyse-Spezialist aus Norwegen' vom 26.11.2015 im w:o-Forum 'Grüne Aktien' Seite 1180 der Diskussion 'NEL ASA - Elektrolyse-Spezialist aus Norwegen' vom 26.11.2015 im w:o-Forum 'Grüne Aktien'
Nel verdaut Nikola-Schock: 50 Prozent Kurspotenzial - DER
Polymer electrolyte membrane (PEM) electrolysis is the electrolysis of water in a cell equipped with a solid polymer electrolyte (SPE) that is responsible for the conduction of protons, separation of product gases, and electrical insulation of the electrodes. The PEM electrolyzer was introduced to overcome the issues of partial load, low current density, and low pressure operation currently.
Beginning with the necessity of hydrogen technologies, in the 'Green Hydrogen Production: Electrolyzer Markets 2021-2031' report, IDTechEx started to analyse the actual necessity of the so-called hydrogen economy, providing a comparison with battery solutions. Following with an explanation of the European EU-ETS carbon pricing method, its.
Nel Hydrogen Announces $350/kW Electrolyser. Bye-bye Royal Dutch Shell, Total, BP, Exxon and what have you. Nel Hydrogen has just sold 5 x 17 = 85 MW worth of electrolysers to US truck startup Nikola Motors for ca. $30 million. PHOENIX (JUNE 3, 2020) — Nikola Corporation who becomes publicly traded on June 4, 2020 on the Nasdaq (NKLA), signed.
Nel's plan is to have the factory up and running by early 2020. Today, we confirm our leadership position within electrolyzer manufacturing, which will enable us to offer complete solutions at a benchmark price
NEL Hydrogen is a Norwegian company that has created the P60 electrolyzer for H2 production. Some of the key uses of the P60 include power to gas, hydrogen fueling stations and industrial applications. I would like to talk about the first two uses of the NEL P60. In regard to power to gas the P60 can use renewable energy along with an alkaline.
Nel has started construction of an electrolyzer plant at Notodden, Norway with an annual capacity of 360MW. Nel's new plant will be an extension of its current facility at Notodden and will be a fully automated plant, which can deliver highly efficient electrolyzers at low cost, the company stated ProtonOnsite (Proton) and Nel Hydrogen Solutions, divisions of Nel ASA, have received a purchase order of $8.3 million on a combined hydrogen PEM electrolyzer and H2Station fueling solution for SunLine Transit Agency (SunLine) in California. The combined solution will have a hydrogen capacity of up to 900 kg/day, making it the world's largest combined hydrogen production and fueling facility.
Nel ASA: Awarded multi-billion NOK electrolyzer and fueling station contract by Nikola (Oslo, 28 June 2018) Nel ASA (Nel, OSE: NEL) has been awarded a contract for delivery of 448 electrolyzers and associated fueling equipment to Nikola Motor Company (Nikola) as part of Nikola's development of a hydrogen station infrastructure in the US for truck and passenger vehicles. Under the multi.
First Solar and Nel Hydrogen Electrolyser AS will initially develop an integrated power plant control and SCADA system, as part of a broader plan to build integrated photovoltaic/hydrogen power.
Nel's 8 ton/day (18 MW) electrolyzer plant provides the hydrogen production for each station site. New factory in Norway will enable 40% reduction in stack cost. Created Date: 1/16/2020 8:18:16 AM.
05/04. NEL ASA : 1st quarter results. CO. 05/03. NEL ASA : Receives purchase order for 2 MW PEM electrolyser. AQ. 05/03. NEL ASA : Enters collaboration with First Solar. AQ
PEM ELECTROLYSIS STACKS. PEM ELECTROLYSERS: Electrolyser ME 100/350. Electrolyser ME 450/1400. Applications. Markets. Power Gap Filler Project. eFarm Sector Integration. Ellhöft Wind Farm Augmented McLyzer: The next-generation alkaline electrolyzer range for the 20 and 100 MW models and beyond. Our cutting-edge Augmented McLyzer electrolyzers combine reliability and maturity of alkaline technology with high flexibility. Production capacity is doubled in relation to market standards thanks to the unique combination of McPhy's high-pressure alkaline electrolysis solutions (30. Trillium Transportation Fuels, LLC has ordered a 1 megawatt containerized Proton PEM electrolyzer from Nel Hydrogen US, a subsidiary of Nel ASA. The electrolyzer will be used to produce hydrogen for a fleet of fuel cell electric buses in Urbana, Illinois. Trillium will produce green hydrogen for a fleet of.. Oslo-Nel Hydrogen US, a subsidiary of Nel ASA (Nel, OSE:NEL), has received a purchase order for a 1 megawatt containerized Proton PEM® electrolyzer from Trillium Transportation Fuels, LLC (Trillium). The electrolyser will be used to produce hydrogen for a fleet of fuel cell electric buses in Urbana, Illinois, USA. We're proud to have received a purchase order for a megawatt scale.
Nel Launches Containerized Large-Scale PEM Electrolyzer
NEL will supply the electrolyser under a EUR 7.25 million contract with delivery scheduled to start late 2021. Everfuel is responsible for the EPC-work (engineering, procurement and construction), including storage and distribution facilities. When fully operational in mid-2022, the Fredericia facility will have a production capacity up to 8 tons per day of green hydrogen, made from primarily.
The electrolyzer, nearly a century old technology that was made uncompetitive by the low cost of fossil energy, would be brought back into play. An electrolyzer produces hydrogen from water using electricity and Nel is developing their next generation electrolyzer where the prototype will be tested at Porsgrunn. The capacity of the electrolyzer will be 5 MW corresponding to 1% of the hydrogen.
Oslo-based Nel Hydrogen Electrolyser, a division of Nel ASA, announced on Monday that it has received a purchase order for a 2 MW, fully containerized MC400 electrolyzer from Switzerland-focused.
Hydrogen - fuel of the future. Renewable energy is playing an increasingly important role worldwide. It's the backbone of a sustainable, CO 2  free energy sector, and thus a key technology for achieving decarbonization by the year 2100. Its share in global power generation is growing daily
Nel Hydrogen Electrolyser, a subsidiaryNorway-headed hydrogen technology provider Nel has launched. its M Series containerized Proton PEM electrolyzer (image courtesy Nel). The containerized version of the M Series Polymer Electrolyte Membrane/Proton Exchange Membrane (PEM) electrolyser will be delivered as standard 1 and 2 MW (200 and 400 Nm3.
Nel Hydrogen. April 8 at 11:04 PM ·. We're happy to announce we've entered into a strategic collaboration agreement with global consulting & engineering company, Wood. Together, we'll collaborate to develop & deliver large-scale, complex, green #renewable #hydrogen projects in select regions across the world
Nel to slash cost of electrolysers by 75%, with green
Nel Hydrogen US, a subsidiary of Nel ASA (Nel, OSE:NEL), has received a purchase order for a containerized 2.5 megawatt Proton PEM® electrolyzer from a customer in Europe Nel ASA has been awarded a contract for delivery of 448 electrolyzers and associated fueling equipment to Nikola Motor Company (Nikola) as part of Nikola's development of a hydrogen station infrastructure in the US for truck and passenger vehicles.. Under the multi-billion NOK (1 NOK = US$0.12) contract, to be deployed from 2020, Nel will deliver up to 1 GW of electrolysis plus fueling. Nel Hydrogen is also working to establish a 20-megawatt electrolyzer at a Shell oil refinery in Fredericia, Denmark. The electrolyzer will be ready to increase capacity to one-gigawatt in the future. Netherlands. The Netherlands Port of Rotterdam is partnering with BP and Nouryon to produce wind-sourced renewable hydrogen.. Norwa Hydrogen Electrolyzer Market Report provides a compressed list of market opportunities, challenges, drivers and market trends. Additionally, it provides market share for the Hydrogen Electrolyzer.
Electrolyzer overview: Lowering the cost of hydrogen and
This report benefited from input and review of the following experts: Katherine Ayers and Egil Rasten (NEL), Karan Bagga (ThyssenKrupp), Bart Biebuyck and Mirela Atanasiu (FCH JU), Luigi Crema and Martina Trini (Bruno Kessler Foundation), Tim Karlsson (IPHE), Ruud Kempener (European Commission), Francesco Massari (XBEC), Corky Mittelsteadt (Giner ELX), Samir Rachidi (IRESEN), Jan-Justus. Norwegian firm Nel Hydrogen Electrolyser is supplying the electrolyzer technology. Nel has also been named as the supplier for the 200 MW project, which will be located at Palos de la Frontera in.
It is an electrolyzer that uses green power, carbon dioxide (CO 2), and water to produce a synthesis gas consisting of carbon monoxide (CO) and hydrogen. From there, a tube runs past instruments and control displays to an eight-meter high steel cylinder in an adjacent hall. In the cylinder, bacteria convert the gas into chemical substances such as hexanol and butanol. For sure, that's not. cost of 1-MW electrolyzer, including stack and balance of plant, could also be reduced through manufacturing economies of scale - from $561/kW (±10%) at 10 units/year to $265/kW (±10%) at 1,000 units/year. The base year for the analysis is 2015, so all cost numbers presented in this report are expressed in 2015 dollars. In terms of the effect of the electrolysis system capital cost on. ELOGEN SAS, 8 avenue du Parana 91940 LES ULIS, takes care to ensure that the collection and processing of your personal data comply with applicable legislation (GDPR and the French Data Protection Act, etc.) Nel Vendor supplier for 1MW PEM electrolyzer unit. Providing support for prototype electrolyzer testing INL Development of front end controller, dynamic operation of prototype electolyzer NREL Development of front end controller, dynamic operation of prototype electolyzer ANL Analysis for scaled-up hydrogen production, hydrogen market analysis. 9 Proposed Future work 1. DOE reporting a) AMR. Siemens Energy and Air Liquide to develop a large scale electrolyzer partnership for sustainable hydrogen production. Both companies to initiate a European ecosystem for electrolysis and hydrogen technology ; Franco-German cooperation supported by French and German Governments ; Large hydrogen projects identified to lay the ground for industrial scale electrolyzer systems, one of these.
Nel launches MC250/MC500 PEM electrolysers, MW-class hydrogen generators utilizing modular containerized design for easy installation and integration We would also like to cordially thank Eric Dabe from NEL and Lucas Bertrand and Marcus Newborough from ITM Power for sharing their CAPEX data within the Task 38 effort. Recommended articles Citing articles (0) References. A. Butler, H. Spliethoff. Current status of water electrolysis for energy storage, grid balancing and sector coupling via power-to-gas and power-to-liquids: a review . Renew. The HOGEN C-series is the first to be listed to the international water electrolyzer standard ISO 22734-1. All NEL Proton PEM commercial hydrogen generators are designed and test-verified to be installed in ventilated, non-classified areas and to not cause the area to become classified. This is accomplished by virtue of an extremely low internal inventory of hydrogen that is well below any.
Impact of Covid-19 on Hydrogen Electrolyzer Market (Alkaline
Nel ASA: Constructing the world's largest electrolyzer manufacturing plant Wed, Aug 22, 2018 14:43 CET (Oslo, 22 August 2018) Nel ASA (Nel) today announces the construction of the world's largest electrolyzer plant, fully automated and able to deliver the most efficient electrolyzers at a game changing cost The Electrolyzer Market is expected to grow at a CAGR of 6.6% and is poised to reach US$3.3 Billion by 2027 as compared to US$1.2 Billion in 2020. The factors leading to this extraordinary growth is attributed to various market dynamics discussed in the report Our experts have examined the market from a 360 degree perspective thereby producing a report which is definitely going to impact your. Find the latest NEL ASA (NEL.OL) stock quote, history, news and other vital information to help you with your stock trading and investing
The $7.2 million project is one of 29 projects the Department of Energy (DOE) on Aug. 15 selected to receive up to $40 million in fiscal year 2019 federal funding to advance the H2@Scale concept. Combining solar and wind can increase electrolyzer capacity factor -particularly for off-grid applications. Depending of site location -wind production typically happens during night and solar during day. Optimization of solar/wind and electrolyzer capacity may enable up to 65% electrolyzer utilization off-grid At current electrolyzer effi ciencies, to produce hydrogen at less than $3.00/kg, electricity costs must be lower than 4 ¢ to 5.5 ¢ per kWh. For an ideal system operating at 100% effi ciency, electricity costs must be below 7.5 ¢ per kWh. This analysis demonstrates that regardless of any additional cost elements, electricity costs will be a major contributor to the price of hydrogen. Global electrolyzer market was valued at $0.2 billion in 2019, and is anticipated to generate $0.9 billion by 2027.The market is projected to experience growth at a CAGR of 24.6% from 2020 to 2027. The electrolyzers are used for electrolysis of water. Through electrolysis, water is split into hydrogen and oxygen, which are further collected. Now, NEL Hydrogen Electrolyser is to develop the electrolyser technology for water-based hydrogen production adapted to the use of various renewable energy sources from water, wind and sun, and to test this technology together with Yara. Fantastic support scheme to build a new generation of factories. Lorentsen commends the PILOT-E scheme that provides financing for Norwegian business and.
In May 2019, Nel ASA launched M-Series containerized large-scale PEM electrolyzer with 1 and 2 MW configurations with higher reliability with easier and flexible installation. In March 2019, H-TEC Systems launched Megawatt PEM Electrolyzer ME 450/1400 with the potential of producing 450 kgs of hydrogen per day Advanced alkaline water electrolysis. Based on thyssenkrupp Uhde Chlorine Engineers' robust and efficient chlor-alkali technologies we are developing our own advanced alkaline water electrolysis technology. Identifying the need for a low-CAPEX, low-OPEX technology to keep the electricity grid in balance in the future and to provide a. Alkaline electrolyzer dominated the market share, whereas, PEM electrolyzer is expected to grow at higher CAGR during the forecast period. By capacity, the market is bifurcated into less than 500.
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Diddy can now add television network owner to his resume.
The rapper, fashion designer and overall entrepreneur will launch his new lifestyle cable network, Revolt, in July.
According to reports, "the revolution" will be distributed through Comcast and feature art, music, fashion, culture and film content for an African-American audience.
Diddy's been getting the news out through his new social media campaign. Check out a YouTube clip below and then click through to read 5 tips he can take from Oprah's experience of launching OWN.


When it comes to developing and delivering learning, Europe's diversity can be a liability and an asset. But as learning modalities grow in sophistication and flexibility, it's increasingly viewed as a competitive advantage.
On the surface, Europe and the United States have much in common. But look deeper, and a number of striking dissimilarities emerge. For one thing, Europe contains more than 40 separate languages, and if you accept the most popular sociological view, some 80 separate cultures.
Amid talk of the world becoming a "global village" as technology develops and allows us to communicate with almost anyone anywhere in the world almost instantly, it is Europeans who already have many years of experience tackling the language and cultural issues that such communications raise.
Europe's multicultural publishers have been living with and making a living from this complex ecosystem for centuries. Over the years, they have learned that being successful as a publisher of multicultural learning materials, in all forms, involves a great deal more than merely translating text across languages.
"You don't just communicate with the words on a screen within, say, an e-learning program. There are also explicit and implicit messages contained in any screen of information, and different cultures interpret these messages in different ways," said Fabrizio Cardinali, co-chair of the European Learning Industry Group (ELIG), a consortium of international players in the e-marketplace that includes IT, content publishing and service provision for the e-learning market.
ELIG provides industry thought leadership and policy input to the European Commission (EC) and national governments within the European Union and, at the same time, functions as a networking and partnering platform for its members.
It used to be said that one of the advantages of e-learning over conventional learning is that, unlike courses in which the personality of a tutor or instructor colors the experience, it provides consistency of message. This is true even, or perhaps especially, when the message is being distributed to a geographically dispersed audience. Nowadays, learning technologists and designers recognize this is only partly true.
Thankfully, advances in technology coupled with advances in understanding of the process of learning are helping replace one-size-fits-all e-learning programs with materials that take into account not only the learner's needs and preferences but also the location and the way the learner needs to access the content. Increasingly, the traditional e-learning experience is enhanced by providing, for example, mobile access to the learning materials.
In terms of the personalization of learning, the IMS ePortfolio specification — an international standard created to make ePortfolios interoperable across different systems and institutions — is a parameter that needs to be taken into account when producing and packaging content for an e-learning program.
EPortfolios are now being used as tools for personal development planning, lifelong learning and learning in the workplace. Among other things, the ePortfolio specification supports the advancement of lifelong learning and makes exchanging portfolios from, for example, school-to-work transitions easier.
"When it comes to the contextualization of learning materials, you need to understand the users and where they are, both spiritually and physically," Cardinali explained. "This should enable you to compile a learning experience that is just in time, just enough and just for the learner. There is no longer any room for a monolithic approach. Instead, there must be learning solutions that are personalized to take into account the learner's background, preferred learning style, precise learning needs and so on. Then you also have to consider the medium by which the learner receives the learning materials. Increasingly, this could be via PDA, BlackBerry, Nintendo, smartphone and so on. Finally, you have to consider the learner's location.
"So today's learning platform should not be a single turnkey platform, but rather, it should be a learning services architecture, where, in addition to the learning content creation and delivery, you can read and write people's portfolios encompassing their backgrounds, competencies, the learning objects they need and so on. This means that you can use this architecture to engage in talent management by spotting and then plugging the gaps in people's knowledge, skills and competencies in order for them to progress and meet their organization's needs.
Consequently, Cardinali argues for the adoption of international standards to bring interoperability of systems and software, thus providing a common "information space" into which learners could tap. He also advocates the value of inclusion in human terms, as well as the benefits of innovation in learning technologies. He explained: "Since everyone in our society has valuable knowledge, skills and abilities, we shouldn't write off anyone. This means that we need to make learning opportunities available to all in order for them to develop to their fullest capabilities, and this raises accessibility issues where learning is concerned.
The growth of the Asian economies, together with changes in the structure of Europe's national economies that see manufacturing and extractive industry declining while the services sector forges ahead, is giving rise to the development of the knowledge workers, who have unique expertise and experience. If their knowledge and skills are harnessed correctly, they will maintain Europe as a key player on the world's economic stage. If this fails to happen, Europe could find itself left behind in terms of economic development for the first time in centuries.
Consequently, developing user-centered learning solutions that can be adapted to individuals' learning needs is a key objective for the EC and its constituent states. In the past year or so, European learning-delivery technologists have developed mobile learning via wearable computers; enabled the interaction of learners with remote coaches via mobile technology and virtual worlds; and made increasing use of serious games and simulations. At the Online Educa conference in Berlin at the end of 2007, Volkswagen, IKEA, Ericsson and Schlumberger were among the presenters of innovative, as well as more traditional, e-learning solutions to foster EU industries' greater competitiveness in worldwide markets.
Cardinali believes that Europe, with its history and lengthy experience of multiculturalism, is well-placed to cope with variations in languages and cultures and so will be able to rapidly up-skill its workforces to gain a competitive edge in world markets. Moreover, it is well-positioned to use this experience to communicate effectively with other cultures around the world and compete in those markets, too.
"One key message that we have learned in Europe is that we must be global, but we must also protect diversity within that global approach," Cardinali said. "Over the centuries, we have learned the value of multicultural societies. So we need to take account of these multicultural societies and protect our regional differences.
At present, each country within Europe maintains its own curricula and defines its own skill sets and competencies. Yet, Cardinali believes that these divisions along national lines need to be aligned with each other, if not combined, to present a consistent message across international borders in today's global village.
"We need to bring curricula and skills in the various countries within Europe into line with each other so that the criteria that define a baker in, say, Italy also define a baker in, say, the Netherlands," he said.
Far from handicapping its competitiveness in world markets, Europe's ostensible fragmentation — as a collection of nation states, with many languages, cultures and subcultures — has spurred it to harness the latest learning technologies' capabilities to help its designers produce materials that offer a consistent message to learners, whatever their personal circumstances, culture and learning preferences.


The NEC is the UK's most accessible venue no matter how you choose to travel.
Here you will find all the information you need to help plan your trip plus access to travel and parking discounts.
With 16,500 spaces available there is plenty of room for you. Follow the electronic signage or directions provided by The NEC traffic team to get you to the right car park area for your event. Once you've parked you can either take a free shuttle bus or walk to the halls using our sign posted footpaths. More Information.
The NEC food and beverage is operated by Amadeus, part of the NEC Group of companies and there is plenty of great food available to you during your visit. Amadeus work with a number of service partners to give you the best selection in food and drink when visiting the NEC. The selection includes: JD Wetherspoons, Subway, Starbucks, Pasty Presto, The Oak Kitchen, Jimmy Spices The Damn Fine Sandwich Company and FCB Artisan Espresso Bars. More Information.
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We have teamed up with EventexpressUK who have negotiated some excellent rates at local hotels to the NEC please Click Here to see the options and prices available.