New interleukin-15 superagonist (IL-15SA) significantly enhances graft-versus-tumor activity.

Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors. Herein, we evaluated the effects of IL-15SA in recipients of allogeneic hematopoietic stem cell transplantation. Weekly administration of IL-15SA to transplant recipients significantly increased the number of CD8+ T cells (specifically CD44+ memory/activated phenotype) and NK cells. Intracellular IFN-γ and TNF-α secretion by CD8+ T cells increased in the IL-15SA-treated group. IL-15SA also upregulated NKG2D expression on CD8+ T cells. Moreover, IL-15SA enhanced proliferation and cytokine secretion of adoptively transferred CFSE-labeled T cells in syngeneic and allogeneic models by specifically stimulating the slowly proliferative and nonproliferative cells into actively proliferating cells.We then evaluated IL-15SA\u27s effects on anti-tumor activity against murine mastocytoma (P815) and murine B cell lymphoma (A20). IL-15SA enhanced graft-versus-tumor (GVT) activity in these tumors following T cell infusion. Interestingly, IL-15 SA administration provided GVT activity against A20 lymphoma cells in the murine donor leukocyte infusion (DLI) model without increasing graft versus host disease. In conclusion, IL-15SA could be a highly potent T- cell lymphoid growth factor and novel immunotherapeutic agent to complement stem cell transplantation and adoptive immunotherapy

In vitro cryopreservation of date palm caulogenic meristems

Cryopreservation is the technology of choice not only for plant genetic resource preservation but also for virus eradication and for the efficient management of large-scale micropropagation. In this chapter, we describe three cryopreservation protocols (standard vitrification, droplet vitrification, and encapsulation vitrification) for date palm highly proliferating meristems that are initiated from vitro-cultures using plant growth regulator-free MS medium. The positive impact of sucrose preculture and cold hardening treatments on survival rates is significant. Regeneration rates obtained with standard vitrification, encapsulation-vitrification, and droplet-vitrification protocols can reach 30, 40, and 70%, respectively. All regenerated plants from non-cryopreserved or cryopreserved explants don't show morphological variation by maintaining genetic integrity without adverse effect of cryogenic treatment. Cryopreservation of date palm vitro-cultures enables commercial tissue culture laboratories to move to large-scale propagation from cryopreserved cell lines producing true-to-type plants after clonal field-testing trials. When comparing the cost of cryostorage and in-field conservation of date palm cultivars, tissue cryopreservation is the most cost-effective. Moreover, many of the risks linked to field conservation like erosion due to climatic, edaphic, and phytopathologic constraints are circumvented. (Résumé d'auteur

Double Haploidentical Hematopoietic Stem Cell Transplantation Results in Successful Engraftment of Bone Marrow from Both Donors without Graft-versus-Host or Graft-versus-Graft Effects

We established double-haploidentical (DH) hematopoietic stem cell transplantation (HSCT) murine models to explore competitive engraftment, graft-versus-graft effect and graft-versus-host disease (GVHD). T cell–depleted (TCD) bone marrow (BM) cells from B6SJF1 (donor 1 [D1]) and B6D2F1 (donor 2 [D2]) mice achieved >90% donor engraftment when transplanted into B6CBAF1 mice. B6CBAF1 recipients survived without evidence of GVHD when undergoing HSCT with TCD-BM from 2 haploidentical donors, D1 and D2. DH-HSCT recipients had significantly higher leukocyte and neutrophil counts than single-haploidentical HSCT recipients from either D1 or D2. DH recipients consistently showed successful mixed chimerism in both BM and spleen. Two other DH-HSCT models, B6D2F1 + C3D2F1→B6C3F1 and B6CBAF1 + B6SJLF1→B6D2F1, showed similar engraftment patterns. Low-dose T cell infusion from both D1 and D2 increased the degree of early engraftment of the respective donors in BM and spleen; however, this early engraftment pattern did not determine long-term engraftment dominance. In the long term, minimally engrafted D1 BM recovered and comprised >50% of all donor- derived B, T, and natural killer cells. We conclude that early BM engraftment is determined by donor T cell immunodominance, but long-term engraftment is related to the engraftment potential of stem cells after DH-HSCT

Recent JET Experiments on Alfvén Eigenmodes with Intermediate Toroidal Mode Numbers: Measurements and Modelling with the TAEFL code

This paper reports the results of recent experiments performed on the JET tokamak on Alfven eigenmodes (AEs) with toroidal mode number (n) in the range n=3—15. The stability properties of these medium-n AEs are investigated experimentally using a new set of compact in-vessel antennas, providing a direct and real-time measurement of the frequency, damping rate and amplitude for each individual toroidal mode number. We report here the quantitative analysis of the measurements of the damping rate for stable n=3 toroidal AEs as a function of the edge plasma elongation, and the theoretical analysis of these data with the TAEFL code. The TAEFL results are in excellent qualitative agreement with the measurements, reproducing well the experimental scaling of increasing damping rate versus increasing edge elongation, and in many cases are also quantitatively correct, with a difference with respect to the measurements below 30%, particularly for magnetic configurations that have a larger edge magnetic shear

Measurement of the Damping Rate of High-n Toroidal Alfven Eigenmodes in JET

A new set of compact in-vessel antennas has been built and installed in JET to provide for the first time the direct measurement of the damping rate (/) of stable Alfvén Eigenmodes (AEs) with toroidal mode number (n) in the range n=3-15. This paper reports the first quantitative analysis of the measurements of the damping rate for these modes as function of the edge plasma elongation (95). We find that the scaling of / vs. 95 for medium-n Toroidal AEs, with n=3-7, follows the same trend previously measured and explained theoretically for the n=1 and n=2 modes. This confirms the possibility of using the edge shape parameters as a real-time actuator for control of the stability of alpha-particles driven AEs in burning plasma experiments, such as ITER

Physical activity through sustainable transport approaches (PASTA): protocol for a multi-centre, longitudinal study

BACKGROUND: Physical inactivity is one of the leading risk factors for non-communicable diseases, yet many are not sufficiently active. The Physical Activity through Sustainable Transport Approaches (PASTA) study aims to better understand active mobility (walking and cycling for transport solely or in combination with public transport) as an innovative approach to integrate physical activity into individuals' everyday lives. The PASTA study will collect data of multiple cities in a longitudinal cohort design to study correlates of active mobility, its effect on overall physical activity, crash risk and exposure to traffic-related air pollution. METHODS/DESIGN: A set of online questionnaires incorporating gold standard approaches from the physical activity and transport fields have been developed, piloted and are now being deployed in a longitudinal study in seven European cities (Antwerp, Barcelona, London, Oerebro, Rome, Vienna, Zurich). In total, 14000 adults are being recruited (2000 in each city). A first questionnaire collects baseline information; follow-up questionnaires sent every 13 days collect prospective data on travel behaviour, levels of physical activity and traffic safety incidents. Self-reported data will be validated with objective data in subsamples using conventional and novel methods. Accelerometers, GPS and tracking apps record routes and activity. Air pollution and physical activity are measured to study their combined effects on health biomarkers. Exposure-adjusted crash risks will be calculated for active modes, and crash location audits are performed to study the role of the built environment. Ethics committees in all seven cities have given independent approval for the study. DISCUSSION: The PASTA study collects a wealth of subjective and objective data on active mobility and physical activity. This will allow the investigation of numerous correlates of active mobility and physical activity using a data set that advances previous efforts in its richness, geographical coverage and comprehensiveness. Results will inform new health impact assessment models and support efforts to promote and facilitate active mobility in cities

The Dependence of the Damping Rate of Medium-n Toroidal Alfvén Eigenmodes on the Edge Plasma Elongation in JET

This paper reports the first quantitative analysis of the measurements of the damping rate (gamma/omega) for stable Alfvén Eigenmodes (AEs) with toroidal mode number (n) in the range |n|=3-15 as function of the edge plasma elongation (kappa95). We find that the damping rate gamma/omega vs. kappa95 for medium-n Toroidal AEs, with n=3 and n=7, increases for increasing elongation, i.e. its scaling vs. kappa95 follows the same trend previously measured and explained theoretically for the n=1 and n=2 TAE modes. Theoretical analysis of the measurements for the n=3 TAEs has been performed using the LEMan code. The results are in good agreement (within a factor 2) for all the magnetic configurations where there is only a very minor up/down asymmetry in the poloidal cross-section of the plasma. These experimental results further confirm the possibility of using the edge shape parameters as a real-time actuator for control of the stability of alpha-particles driven AEs in burning plasma experiments, such as ITER

Transport mode choice and body mass index: Cross-sectional and longitudinal evidence from a European-wide study.

BACKGROUND: In the fight against rising overweight and obesity levels, and unhealthy urban environments, the renaissance of active mobility (cycling and walking as a transport mode) is encouraging. Transport mode has been shown to be associated to body mass index (BMI), yet there is limited longitudinal evidence demonstrating causality. We aimed to associate transport mode and BMI cross-sectionally, but also prospectively in the first ever European-wide longitudinal study on transport and health. METHODS: Data were from the PASTA project that recruited adults in seven European cities (Antwerp, Barcelona, London, Oerebro, Rome, Vienna, Zurich) to complete a series of questionnaires on travel behavior, physical activity levels, and BMI. To assess the association between transport mode and BMI as well as change in BMI we performed crude and adjusted linear mixed-effects modeling for cross-sectional (n = 7380) and longitudinal (n = 2316) data, respectively. RESULTS: Cross-sectionally, BMI was 0.027 kg/m2 (95%CI 0.015 to 0.040) higher per additional day of car use per month. Inversely, BMI was -0.010 kg/m2 (95%CI -0.020 to -0.0002) lower per additional day of cycling per month. Changes in BMI were smaller in the longitudinal within-person assessment, however still statistically significant. BMI decreased in occasional (less than once per week) and non-cyclists who increased cycling (-0.303 kg/m2, 95%CI -0.530 to -0.077), while frequent (at least once per week) cyclists who stopped cycling increased their BMI (0.417 kg/m2, 95%CI 0.033 to 0.802). CONCLUSIONS: Our analyses showed that people lower their BMI when starting or increasing cycling, demonstrating the health benefits of active mobility

AN ALGORITHM FOR THE REAL-TIME, BLIND DETECTION, DECOMPOSITION AND TRACKING OF THE INDIVIDUAL COMPONENTS IN A DEGENERATE, MULTI-HARMONICS SPECTRUM

In this work we report the successful application of an innovative method, based on the Sparse Representation of signals, to perform a real-time, unsupervised detection of the individual components in a frequency degenerate, multi-harmonic spectrum, using a small number of data un-evenly sampled in the spatial domain. This method has been developed from its original applications in astronomy, and is now routinely used in the JET thermonuclear fusion experiment to obtain the decomposition of a spectrum of high-frequency (~10-500kHz range) magnetic instabilities with a sub-ms time resolution, allowing the real-time tracking of its individual components as the plasma background evolves. This work opens a path towards developing real-time control tools for electro-magnetic instabilities in future fusion devices aimed at achieving a net energy gain. More generally, the speed and accuracy of this algorithm is recommended for instances of physics measurements and control engineering where an unsupervised, real-time decomposition of a degenerate signal is required from a small number of data