C2 and C3 alkanes are selectively adsorbed from mixtures over the corresponding alkenes on the zeolite imidazolate framework ZIF‐7 through a gate‐opening mechanism. As a result, the direct production ...of the pure alkene upon adsorption and the pure alkane upon desorption in packed columns is possible. Herein, a detailed investigation of the step‐wise adsorption and separation of alkanes and alkenes is presented, together with a rigorous performance assessment. A molecular picture of the gate‐opening mechanism underlying the unprecedented selectivity towards alkane adsorption is proposed based on DFT calculations and a thermodynamic analysis of the adsorption–desorption isotherms.
Going their separate ways: The separation of short‐chain alkanes and alkenes is accomplished by selective adsorption on the zeolite imidazolate framework ZIF‐7 through a gate‐opening mechanism. The difference in the partial pressure at which alkenes and alkanes are taken up by ZIF‐7 makes it an excellent candidate for the design of simpler alkane/alkene PSA‐based separation schemes, for which fewer cycles and less energy will be required.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose To investigate the prevalence of anatomical and surgical findings and complications in maxillary sinus floor elevation surgery, and to describe the clinical implications. Patients and Methods ...One hundred consecutive patients scheduled for maxillary sinus floor elevation were included. The patients consisted of 36 men (36%) and 64 women (64%), with a mean age of 50 years (range, 17 to 73 years). In 18 patients, a bilateral procedure was performed. Patients were treated with a top hinge door in the lateral maxillary sinus wall, as described by Tatum ( Dent Clin North Am 30:207, 1986). In bilateral cases, only the first site treated was evaluated. Results In most cases, an anatomical or surgical finding forced a deviation from Tatum's standard procedure. A thin or thick lateral maxillary sinus wall was found in 78% and 4% of patients, respectively. In 6%, a strong convexity of the lateral sinus wall called for an alternative method of releasing the trapdoor. The same method was used in 4% of cases involving a narrow sinus. The sinus floor elevation procedure was hindered by septa in 48%. In regard to complications, the most common complication, a perforation of the Schneiderian membrane, occurred in 11% of patients. In 2%, visualization of the trapdoor preparation was compromised because of hemorrhages. The initial incision design, ie, slightly palatal, was responsible for a local dehiscence in 3%. Conclusion To avoid unnecessary surgical complications, detailed knowledge and timely identification of the anatomic structures inherent to the maxillary sinus are required.
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GEOZS, NUK, OILJ, SBCE, UL
Two decades of clinical cancer research with dendritic cell (DC)-based vaccination have proved that this type of personalized medicine is safe and has the capacity to improve survival, but ...monotherapy is unlikely to cure the cancer. Designed to empower the patient's antitumor immunity, huge research efforts are set to improve the efficacy of next-generation DC vaccines and to find synergistic combinations with existing cancer therapies. Immune checkpoint approaches, aiming to breach immune suppression and evasion to reinforce antitumor immunity, have been a revelation in the immunotherapy field. Early success of therapeutic antibodies blocking the programmed death-1 (PD-1) pathway has sparked the development of novel inhibitors and combination therapies. Hence, merging immunoregulatory tumor-specific DC strategies with PD-1-targeted approaches is a promising path to explore. In this review, we focus on the role of PD-1-signaling in DC-mediated antitumor immunity. In the quest of exploiting the full potential of DC therapy, different strategies to leverage DC immunopotency by impeding PD-1-mediated immune regulation are discussed, including the most advanced research on targeted therapeutic antibodies, lessons learned from chemotherapy-induced immune activation, and more recent developments with soluble molecules and gene-silencing techniques. An overview of DC/PD-1 immunotherapy combinations that are currently under preclinical and clinical investigation substantiates the clinical potential of such combination strategies.
Genetic engineering of T cells with tumor specific T-cell receptors (TCR) is a promising strategy to redirect their specificity against cancer cells in adoptive T cell therapy protocols. Most studies ...are exploiting integrating retro- or lentiviral vectors to permanently introduce the therapeutic TCR, which can pose serious safety issues when treatment-related toxicities would occur. Therefore, we developed a versatile, non-genotoxic transfection method for human unstimulated CD8
T cells. We describe an optimized double sequential electroporation platform whereby Dicer-substrate small interfering RNAs (DsiRNA) are first introduced to suppress endogenous TCR α and β expression, followed by electroporation with DsiRNA-resistant tumor-specific
mRNA. We demonstrate that double sequential electroporation of human primary unstimulated T cells with DsiRNA and
mRNA leads to unprecedented levels of transgene TCR expression due to a strongly reduced degree of TCR mispairing. Importantly, superior transgenic TCR expression boosts epitope-specific CD8
T cell activation and killing activity. Altogether, DsiRNA and
mRNA double sequential electroporation is a rapid, non-integrating and highly efficient approach with an enhanced biosafety profile to engineer T cells with antigen-specific TCRs for use in early phase clinical trials.
The permeation and separation characteristics of an all-silica DDR zeolite tubular membrane have been studied in the temperature range of 303–773
K and feed pressures up to 500
kPa. The permeation ...experiments are complemented by single component adsorption isotherms.
The permeance of He, H
2, CO
2, CO and N
2 monotonically decreases with increasing temperature. This behaviour could be described accurately for all components by a surface diffusion mechanism. Only in case of N
2 and CO small deviations are observed above 600
K. Isobutane is not able to enter the DDR pores and passes only through a very small number of defects in the membrane.
The single component permeance is about equal to the permeance of this component in a binary mixture. Only below 473
K the H
2 permeance in a mixture with CO
2 or isobutane is reduced in comparison with its single component permeance. The ideal H
2/CO and CO
2/CO selectivities range from 3 to 12 and 10 to 2 between 303 and 673
K, respectively. These mixture selectivities where always below 5 and much lower than the ideal selectivities because of non-differential operation along the membrane tube. The ideal H
2/isobutane selectivity is >600 at 101
kPa feed pressure at all temperatures. The mixture selectivities at 101
kPa total feed pressure is ∼400 in an equimolar binary mixture.
The high selectivities, high H
2 and CO
2 fluxes and stable membrane operation, also at high temperatures, makes this membrane a potential candidate for high temperature (reactive) separations that involve removal of H
2 and CO
2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Adoptive immunotherapy is gaining momentum to fight malignancies, whereby γδ T cells have received recent attention as an alternative cell source as to natural killer cells and αβ T cells. The advent ...of γδ T cells is largely due to their ability to recognize and target tumor cells using both innate characteristic and T cell receptor (TCR)-mediated mechanisms, their capacity to enhance the generation of antigen-specific T cell responses, and their potential to be used in an autologous or allogeneic setting.
In this study, we explored the beneficial effect of the immunostimulatory cytokine interleukin (IL)-15 on purified γδ T cells and its use as a stimulatory signal in the ex vivo expansion of γδ T cells for adoptive transfer. The expansion protocol was validated both with immune cells of healthy individuals and acute myeloid leukemia patients.
We report that the addition of IL-15 to γδ T cell cultures results in a more activated phenotype, a higher proliferative capacity, a more pronounced T helper 1 polarization, and an increased cytotoxic capacity of γδ T cells. Moreover γδ T cell expansion starting with peripheral blood mononuclear cells from healthy individuals and acute myeloid leukemia patients is boosted in the presence of IL-15, whereby the antitumor properties of the γδ T cells are strengthened as well.
Our results support the rationale to explore the use of IL-15 in clinical adoptive therapy protocols exploiting γδ T cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The analysis of forest management strategies at landscape and regional levels forms a vital part of finding viable directions that will satisfy the many services expected of forests. This article ...describes the structure and content of a stand simulator, GAYA, which has been adapted to Swedish conditions. The main advantage of the GAYA implementation compared to other resources is that it generates a large number of management programmes within a limited time frame. This is valuable in cases where the management programmes appear as activities in linear programming (LP) problems. Two methods that are engaged in the projections, a climate change response function and a soil carbon model, are designed to complement other methods, offering transparency and computational effectiveness. GAYA is benchmarked against projections from the Heureka system for a large set of National Forest Inventory (NFI) plots. The long-term increment for the entire NFI set is smaller for GAYA compared with Heureka, which can be attributed to different approaches for modelling the establishment of new forests. The carbon pool belonging to living trees shows the same trend when correlated to standing volume. The soil carbon pool of GAYA increases with increased standing volume, while Heureka maintains the same amount over the 100-year projection period.
Pancreatic ductal adenocarcinoma (PDAC) is the 4
leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong ...desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC). The potency of IL-15 to promote NK cell-mediated killing was evaluated phenotypically and functionally. In addition, NK cell and immune checkpoint ligands on PSC were charted. We demonstrate that IL-15 activated NK cells kill both PCC and PSC lines (range 9-35% and 20-50%, respectively) in a contact-dependent manner and significantly higher as compared to resting NK cells. Improved killing of these pancreatic cell lines is, at least partly, dependent on IL-15 induced upregulation of TIM-3 and NKG2D. Furthermore, we confirm significant killing of primary PSC by IL-15 activated NK cells in an
autologous system. Screening for potential targets for immunotherapeutic strategies, we demonstrate surface expression of both inhibitory (PD-L1, PD-L2) and activating (MICA/B, ULBPs and Galectin-9) ligands on primary PSC. These data underscore the therapeutic potential of IL-15 to promote NK cell-mediated cytotoxicity as a treatment of pancreatic cancer and provide promising future targets to tackle remaining PSC.
Abstract Interleukin (IL)-15 is one of the most promising molecules to be used in antitumor immune therapy, as it is able to stimulate the main killer cells of both the innate and adaptive immune ...system. Although this cytokine can be used as a stand-alone immunotherapeutic agent, IL-15 will probably be most efficient in combination with other strategies to overcome high tumor burden, immune suppression of the tumor microenvironment and/or the short half-life of IL-15. In this review, we will discuss the combination strategies with IL-15 that have been tested to date in different animal tumor models, which include chemotherapy, other immunostimulatory cytokines, targeted therapy, adoptive cell transfer and gene therapy. In addition, we give an overview of IL-15 combination therapies that are currently tested in clinical studies to treat patients with hematological or advanced solid tumors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
ZnCl2 hydrate, the main molten salt used in biomass conversion, combined with low concentration HCl is an excellent solvent for the dissolution and hydrolysis of the carbohydrates present in ...lignocellulosic biomass. The most recalcitrant carbohydrate, cellulose, is dissolved in a residence time less than 1 h under mild conditions without significant degradation. This technology is referred to as BIOeCON-solvent technology. Separation of the sugars from the solution is the main challenge. The earlier conclusion regarding the potential of zeolite beta for selective adsorption has been used as the basis of a scale-up study. The technology of choice is continuous chromatographic separation (e.g., simulated moving bed, SMB). The sugar monomers are separated from the sugar oligomers, allowing the production of monosugars at high yield, using water as an eluent. Results of a pilot plant study are presented showing a stable operation at high selectivity. Several process designs are discussed, and the techno-economic performance of the BIOeCON-solvent technology is demonstrated by comparison with the state-of-the-art technology of NREL (National Renewable Energy Laboratory), which is based on enzymatic conversion of cellulose. It is concluded that the BIOeCON-solvent technology is technically and economically viable and is competitive to the NREL process. Because the BIOeCON-solvent process is in an early stage of development and far from fully optimized, it has the potential to outperform the existing processes.
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