Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML

This study aimed to characterize different natural killer (NK) cell phenotypes on bone marrow and peripheral blood cells from acute myeloid leukemia (AML) patients and healthy donors (HDs). Our data show that CD56^dimCD16⁻ and CD56^brightCD16⁻ NK cells represent the predominant NK cell subpopulations in AML, while the CD56^dimCD16⁺ NK cells are significantly reduced compared to HDs. Moreover, TIGIT⁺ and PVRIG⁺ cells cluster on the CD56^dimCD16⁺ subset whereas CD39⁺ and CD38⁺ cells do so on CD56^brightCD16⁻ NK cells in AML. Furthermore, functional effects of (co-)blockade of TIGIT and CD39 or A2AR on NK cell functionality were analyzed. These experiments revealed that the single blockade of the TIGIT receptor results in an increased NK-92 cell-mediated killing of AML cells in vitro. Combined targeting of CD39 or A2AR significantly augments the anti-TIGIT-mediated lysis of AML cells. Our data indicate that distinct NK cell subsets in AML exhibit different immunosuppressive patterns (via the TIGIT/PVRIG receptors and the purinergic pathway). In summary, we conclude that TIGIT, CD39, and A2AR constitute relevant inhibitory checkpoints of NK cells in AML patients. A combinatorial blockade synergistically strengthens NK-92 cell-mediated cytotoxicity. As inhibitors of TIGIT, CD39, and A2AR are clinically available, studies on their combined use could be conducted in the near future.     

The experience curve,option value,and the energy paradox

This paper develops a model to explain the ‘energy paradox,’ the inclination of households and firms to require very high internal rates of return in order to make energy-saving investments. The model abstracts from many features of such investments to focus on their irreversibility, the uncertainty of their future payoff streams, and the investor's anticipation of future technological advance. In this setting, the decision to invest in energy-saving technology can be delayed, providing option value. In addition, delay allows the potential investor to cash in on future experience-curve effects: With the passage of time, firms gain practical knowledge in producing and installing the energy-saving technology, enabling them to reduce the technology's up-front cost per unit of energy saved. We incorporate these fundamentals into a stochastic model where the investment's discounted benefits follow geometric Brownian motion. To demonstrate the model's capabilities, we generate simulation results for photovoltaic systems that highlight the experience-curve effect as a fundamental reason why households and firms delay making energy-saving investments until internal rates of return exceed values of 50% and higher, consistent with observations in the economics literature. We also explore altruistic motivations for energy conservation and the model's implications for both “additionality” and the design of energy-conservation policy.     

Cultured beef: from small biopsy to substantial quantity

Cultured meat is an emerging technology with the potential to solve huge challenges related to the environmental, ethical, and health implications of conventional meat production. Establishing the basic science of cultured meat has been the primary focus of the last decade but it is now feasible that cultured meat products will enter the market within the next 3 to 4 years. This proximity to market introduction demands an evaluation of aspects of the cultured meat production process that have not yet been outlined or discussed in significant detail. For example, one technological approach for the production of cultured meat uses adult muscle stem cells, the limited proliferative capacity of which necessitates repeated collection of tissue samples via biopsies of living donor animals. The selection of donor animals and the details of biopsy processes must be optimized, as this is a key bottleneck in the cultured meat production process. The number of stem cells harvested from a biopsy, together with their proliferative capacity, determines a ‘multiplicity factor’ achieved by a cultured meat production process, thus dictating the reduction in number of animals required to produce a given quantity of meat. This article considers potential scenarios for these critical upstream steps, focusing on the production of cultured beef as an example. Considerations related to donor selection and details of the biopsy process are discussed in detail. The practicalities of various scenarios for cultured beef production, the health of donor animals, and regulatory issues associated with the safety of cultured meat for consumers are also considered. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Metabolic profile biomarkers of metal contamination in a sentinel terrestrial species are applicable across multiple sites

In this study, we addressed the question of whether an omic approach could genuinely be useful for biomarker profile analysis across different field sites with different physicochemical characteristics. We collected earthworms (Lumbricus rubellus) from seven sites with very different levels of metal contamination and prevailing soil type and analyzed tissue extracts by 1H nuclear magnetic resonance spectroscopy. Pattern recognition analysis of the data showed that both site- and contaminant-specific effects on the metabolic profiles could be discerned. Zinc was identified as the probable major contaminant causing a metabolic change in the earthworms. Individual sites could be resolved on the basis of NMR spectral profiles by principal component analysis; these site differences may also have been caused by additional abiotic factors such as soil pH. Despite an inevitable degree of confounding between site and contaminant concentrations, it was possible to identify metabolites which were correlated with zinc across all different sites. This study therefore acts as a proof of principle for the use of NMR-based metabolic profiling as a diagnostic tool for ecotoxicological research in polluted field soils.     

Conversion of waste polystyrene through catalytic degradation into valuable products

Waste expanded polystyrene (EPS) represents a source of valuable chemical products like styrene and other aromatics. The catalytic degradation was carried out in a batch reactor with a mixture of polystyrene (PS) and catalyst at 450 °C for 30 min in case of Mg and at 400 °C for 2 h both for MgO and MgCO₃ catalysts. At optimum degradation conditions, EPS was degraded into 82.20±3.80 wt%, 91.60±0.20 wt% and 81.80±0.53 wt% liquid with Mg, MgO and MgCO₃ catalysts, respectively. The liquid products obtained were separated into different fractions by fractional distillation. The liquid fractions obtained with three catalysts were compared, and characterized using GC-MS. Maximum conversion of EPS into styrene monomer (66.6 wt%) was achieved with Mg catalyst, and an increase in selectivity of compounds was also observed. The major fraction at 145 °C showed the properties of styrene monomer. The results showed that among the catalysts used, Mg was found to be the most effective catalyst for selective conversion into styrene monomer as value added product.     

Suspension and Mixing Characterization of Intermittent Agitation Modes in DASGIP Bioreactors

Intermittent agitation strategies have been increasingly used for a range of process development applications, i.e., to modulate physical cues, to improve stem cell differentiation yields, and to control hydrodynamic shear stresses in microcarrier suspension; however, there is a distinct lack of characterization. Both continuous and intermittent agitation modes in relation to suspension and mixing dynamics within a DASGIP bioreactor were characterized. Suspension dynamics were found to be affected by microcarrier porosity and the degree of settling was found to be more pronounced at the top of the bioreactor. Mixing time characterization showed a marked improvement in mixing efficiency for intermittent agitation, with an overall dependence on the timing of tracer insertion.     

On the importance of specific interface area in clay nanocomposites of PMMA filled with synthetic nano-mica

In clay nanocomposites, the specific interface area is the key factor determining potential improvements of properties. Nevertheless, in most systematic studies of nanocomposites little emphasis is put on assuring and characterizing dispersion quality. To probe the influence of dispersion quality, we compare nanocomposites filled with two layered silicates which were made by melt compounding and solution blending, respectively. Poly(methyl methacrylate) (PMMA) is chosen here as a thermoplastic model matrix which was compounded with a synthetic nano-mica (O-hect) and commercial Bentone with typical diameters of 5–7 μm and <300 nm, respectively.     

Development of active matrix LCD for use in high‐resolution adaptive headlights

Conventional adaptive driving beam headlamps are limited in achieving still higher quantities of switchable pixels by the number of LEDs and movable elements needed. In this paper, it is shown that by integrating an active matrix liquid crystal display module, it is possible to realize fully adaptive high‐resolution headlights without mechanical elements and a finite number of LED with 30 k switchable pixels.