mRNA-LNP vaccines tuned for systemic immunization induce strong antitumor immunity by engaging splenic immune cells

mRNA vaccines have recently proved to be highly effective against SARS-CoV-2. Key to their success is the lipid-based nanoparticle (LNP), which enables efficient mRNA expression and endows the vaccine with adjuvant properties that drive potent antibody responses. Effective cancer vaccines require long-lived, qualitative CD8 T cell responses instead of antibody responses. Systemic vaccination appears to be the most effective route, but necessitates adaptation of LNP composition to deliver mRNA to antigen-presenting cells. Using a design-of-experiments methodology, we tailored mRNA-LNP compositions to achieve high-magnitude tumor-specific CD8 T cell responses within a single round of optimization. Optimized LNP compositions resulted in enhanced mRNA uptake by multiple splenic immune cell populations. Type I interferon and phagocytes were found to be essential for the T cell response. Surprisingly, we also discovered a yet unidentified role of B cells in stimulating the vaccine-elicited CD8 T cell response. Optimized LNPs displayed a similar, spleen-centered biodistribution profile in non-human primates and did not trigger histopathological changes in liver and spleen, warranting their further assessment in clinical studies. Taken together, our study clarifies the relationship between nanoparticle composition and their T cell stimulatory capacity and provides novel insights into the underlying mechanisms of effective mRNA-LNP-based antitumor immunotherapy

Schoolgerelateerde fysieke activiteit en het bewegingsgedrag tijdens de vrije tijd bij adolescenten in Vlaanderen

status: publishe

The Diels-Alder reaction : doomed to academic praise only?

The Diels-Alder reaction is universally acknowledged for its atom-efficient and simple access to molecular complexity. This textbook example of a green reaction forms one of the most efficient routes towards six-membered rings. However, a large gap is noticed between the relevance and versatility in the academic world, implying a small scale, and industrial use. Obviously, the current developed Diels-Alder procedures are failing to make their way into industry. This perspective paper will gave a critical overview of the most important bottlenecks of Diels-Alder reactions. Flow chemistry, a key research area for green engineering, is a powerful tool to facilitate a safe transfer of Diels Alder processes to the industrial environment

Counting Steps in Institutionalized Older Adults During Daily Life Activities: the Validation of Two Motion Sensors

The primary purpose of this study was to assess the validity of two motion sensors in measuring steps in institutionalized older adults during daily life activities. Sixty-eight nursing home residents (85.8 ± 5.6 years) were equipped with a hip-worn and ankle-worn piezoelectric pedometer (New Lifestyles 2000) and with an arm-mounted multisensor (Sensewear Mini). The actual steps were tallied by an investigator with a hand counter. The results revealed that the multisensor and hip- and ankle-worn pedometer significantly underestimated step counts (89.6 ± 17.2%, 72.9 ± 25.8% and 20.8 ± 24.6%, respectively). Walking speed accounted for 41.6% of the variance in percent error of the ankle-worn pedometer. The threshold value for accurate step counting was set at 2.35 km/h, providing percent error scores within ±5%. The ankle-worn piezoelectric pedometer can be useful for accurate quantification of walking steps in the old and old-old walking faster than 2.35km/h.status: publishe

Are cycle ergometers effective to promote physical activity and physical function among older adults? Short-term effects of a 10-week structured versus need-supportive physical activity program in assisted living facilities

status: publishe

Theory versus practice : a closer look at transactional and interpersonal stance in English electronic complaint refusal notifications

In this paper, we investigate the attention given to and the impact of interpersonal, people-oriented and transactional, problem-oriented stance in English complaint refusals in business correspondence. The analysis is based on a sample analysis of English e-mail sequences from a Belgian multinational as well as experimental research that probes into the effect of interpersonal strategies on customer outcomes. The sample analysis shows a sharp contrast between theory and practice: while the need for supportive language and interpersonal attention are standard items in textbook instructions, the data show little alignment with the customer through expressions of regret, gratitude, or empathy. The experiment, in its turn, shows a positive impact of interactional stance on interactional justice but little to no impact on satisfaction, perceived professionalism, and loyalty. This raises a number of questions regarding best practice and best practice models

Improving the efficiency of the Diels-Alder process by using flow chemistry and zeolite catalysis

The industrial application of the Diels-Alder reaction for the atom-efficient synthesis of (hetero) cyclic compounds constitutes an important challenge. Safety and purity concerns, related to the instability of the polymerization prone diene and/or dienophile, limit the scalability of the production capacity of Diels-Alder products in a batch mode. To tackle these problems, the use of a high-pressure continuous microreactor process was considered. In order to increase the yields and the selectivity towards the endo-isomer, commercially available zeolites were used as a heterogeneous catalyst in a microscale packed bed reactor. As a result, a high conversion (>= 95%) and endo-selectivity (89 : 11) were reached for the reaction of cyclopentadiene and methyl acrylate, using a 1 : 1 stoichiometry. A throughput of 0.87 g h(-1) during at least 7 h was reached, corresponding to a 3.5 times higher catalytic productivity and a 14 times higher production of Diels-Alder adducts in comparison to the heterogeneous lab-scale batch process. Catalyst deactivation was hardly observed within this time frame. Moreover, complete regeneration of the zeolite was demonstrated using a straightforward calcination procedure

Short- and long-term effects of 10-week cycle ergometer interventions for older adults in assisted living facilities

status: accepte

Efficient continuous-flow bromination of methylsulfones and methanesulfonates and continuous synthesis of hypobromite

An efficient continuous-flow procedure for the synthesis of tribromomethylsulfones and tribromomethanesulfonates has been developed starting from the corresponding methylsulfones or methanesulfonates and potassium hypobromite using a biphasic reaction. Two different continuous-flow systems were used and compared for the bromination reaction. Different derivatives were synthesized in excellent isolated yields in very short reaction times using a small excess of potassium hypobromite. Hypobromite can be synthesized continuously leading to the continuous production of the brominated derivates. With the optimized flow conditions, a throughput of up to 53 g/day was obtained. The bromination reaction in flow has significant advantages compared to the corresponding batch process