TGF-β-responsive CAR-T cells promote anti-tumor immune function.

A chimeric antigen receptor (CAR) that responds to transforming growth factor beta (TGF-β) enables the engineering of T cells that convert this immunosuppressive cytokine into a potent T-cell stimulant. However, clinical translation of TGF-β CAR-T cells for cancer therapy requires the ability to productively combine TGF-β responsiveness with tumor-targeting specificity. Furthermore, the potential concern that contaminating, TGF-β?producing regulatory T (Treg) cells may preferentially expand during TGF-β CAR-T cell manufacturing and suppress effector T (Teff) cells demands careful evaluation. Here, we demonstrate that TGF-β CAR-T cells significantly improve the anti-tumor efficacy of neighboring cytotoxic T cells. Furthermore, the introduction of TGF-β CARs into mixed T-cell populations does not result in the preferential expansion of Treg cells, nor do TGF-β CAR-Treg cells cause CAR-mediated suppression of Teff cells. These results support the utility of incorporating TGF-β CARs in the development of adoptive T-cell therapy for cancer

Tethers in Space Handbook

A new edition of the Tethers in Space Handbook was needed after the last edition published in 1989. Tether-related activities have been quite busy in the 90's. We have had the flights of TSSI and TSSI-R, SEDS-1 and -2, PMG, TIPS and OEDIPUS. In less than three years there have been one international Conference on Tethers in Space, held in Washington DC, and three workshops, held at ESA/Estec in the Netherlands, at ISAS in Japan and at the University of Michigan, Ann Harbor. The community has grown and we finally have real flight data to compare our models with. The life of spaceborne tethers has not been always easy and we got our dose of setbacks, but we feel pretty optimistic for the future. We are just stepping out of the pioneering stage to start to use tethers for space science and technological applications. As we are writing this handbook TiPs, a NRL tether project is flying above our heads. There is no emphasis in affirming that as of today spacebome tethers are a reality and their potential is far from being fully appreciated. Consequently, a large amount of new information had to be incorporated into this new edition. The general structure of the handbook has been left mostly unchanged. The past editors have set a style which we have not felt needed change. The section on the flights has been enriched with information on the scientific results. The categories of the applications have not been modified, and in some cases we have mentioned the existence of related flight data. We felt that the section contributed by Joe Carroll, called Tether Data, should be maintained as it was, being a "classic" and still very accurate and not at all obsolete. We have introduced a new chapter entitled Space Science and Tethers since flight experience has shown that tethers can complement other space-based investigations. The bibliography has been updated. Due to the great production in the last few years %e had to restrict our search to works published in refereed journal. The production, however, is much more extensive. In addition, we have included the summary of the papers presented at the last International Conference which was a forum for first-hand information on all the flights

Temporal integration for amplitude modulation in childhood: Interaction between internal noise and memory

It is still unclear whether the gradual improvement in amplitude-modulation (AM) sensitivity typically found in children up to 10 years of age reflects an improvement in “processing efficiency” (the central ability to use information extracted by sensory mechanisms). This hypothesis was tested by evaluating temporal integration for AM, a capacity relying on memory and decision factors. This was achieved by measuring the effect of increasing the number of AM cycles (2 vs 8) on AM-detection thresholds for three groups of children aged from 5 to 11 years and a group of young adults. AM-detection thresholds were measured using a forced-choice procedure and sinusoidal AM (4 or 32 Hz rate) applied to a 1024-Hz pure-tone carrier. All age groups demonstrated temporal integration for AM at both rates; that is, significant improvements in AM sensitivity with a higher number of AM cycles. However, an effect of age is observed as both 5–6 year olds and adults exhibited more temporal integration compared to 7–8 and 10–11 year olds at both rates. This difference is due to: (i) the 5–6 year olds displaying the worst thresholds with 2 AM cycles, but similar thresholds with 8 cycles compared to the 7–8 and 10–11 year olds, and, (ii) adults showing the best thresholds with 8 AM cycles but similar thresholds with 2 cycles compared to the 7–8 and 10–11 year olds. Computational modelling indicated that higher levels of internal noise combined with poorer short-term memory capacities in children accounted for the developmental trends. Improvement in processing efficiency may therefore account for the development of AM detection in childhood

CONSTRUCTAL THEORY APPLIED TO THE GEOMETRIC OPTIMIZATION OF ELLIPTICAL CAVITIES INTO A SOLID CONDUCTING WALL

This work reports, according to Bejan’s Constructal theory, the geometric optimization of an elliptical cavity that intrudes into a solid conducting wall. The objective is to minimize the global thermal resistance between the solid and the cavity. There is uniform heat generation on the solid wall. The cavity is optimized for two sets of thermal conditions: isothermal cavity and cavity bathed by a steady stream of fluid. The solid conducting wall is isolated on the external perimeter. The total volume and the elliptical cavity volume are fixed while the geometry of the cavity is free to vary. The results show that the optimized geometrical shapes are relatively robust, i.e., insensitive to changes in some of the design parameters: the cavity shape is optimal when penetrates the conducting wall almost completely

Tether Transportation System Study

The projected traffic to geostationary earth orbit (GEO) is expected to increase over the next few decades. At the same time, the cost of delivering payloads from the Earth's surface to low earth orbit (LEO) is projected to decrease, thanks in part to the Reusable Launch Vehicle (RLV). A comparable reduction in the cost of delivering payloads from LEO to GEO is sought. The use of in-space tethers, eliminating the requirement for traditional chemical upper stages and thereby reducing the launch mass, has been identified as such an alternative. Spinning tethers are excellent kinetic energy storage devices for providing the large delta vee's required for LEO to GEO transfer. A single-stage system for transferring payloads from LEO to GEO was proposed some years ago. The study results presented here contain the first detailed analyses of this proposal, its extension to a two-stage system, and the likely implementation of the operational system

On the total order of reducibility of a pencil of algebraic plane curves

In this paper, the problem of bounding the number of reducible curves in a pencil of algebraic plane curves is addressed. Unlike most of the previous related works, each reducible curve of the pencil is here counted with its appropriate multiplicity. It is proved that this number of reducible curves, counted with multiplicity, is bounded by d^2-1 where d is the degree of the pencil. Then, a sharper bound is given by taking into account the Newton's polygon of the pencil

In-Space Transportation with Tethers

The annual report covers the research conducted on the following topics related to the use of spaceborne tethers for in-space transportation: ProSEDS tether modeling (current collection analyses, influence of a varying tether temperature); proSEDS mission analysis and system dynamics (tether thermal model, thermo-electro-dynamics integrated simulations); proSEDS-tether development and testing (tether requirements, deployment test plan, tether properties testing, deployment tests); and tethers for reboosting the space-based laser (mission analysis, tether system preliminary design, evaluation of attitude constraints)

Factors influencing the first thousand days of life

The first 1,000 days is a vulnerable phase in which parents, institutions and health professionals should create early interventions for the proper development and promotion of good health

A time‐course study of the expression level of synaptic plasticity‐associated genes in un‐lesioned spinal cord and brain areas in a rat model of spinal cord injury: A bioinformatic approach

open8noFunding: This research was funded by the POR-FESR 2019-21, project “Mat2Rep”, Emilia Romagna Region (L.C.) and by the Cluster Tecnologici Nazionali, project IRMI, MIUR (L.C.). Marco Sanna is receiving a fellowship from the program “Alte Competenze” by Emilia Romagna Region. The contribution of “Fondazione Montecatone”, Imola (Italy) is also gratefully acknowledged.“Neuroplasticity” is often evoked to explain adaptation and compensation after acute lesions of the Central Nervous System (CNS). In this study, we investigated the modification of 80 genes involved in synaptic plasticity at different times (24 h, 8 and 45 days) from the traumatic spinal cord injury (SCI), adopting a bioinformatic analysis. mRNA expression levels were analyzed in the motor cortex, basal ganglia, cerebellum and in the spinal segments rostral and caudal to the lesion. The main results are: (i) a different gene expression regulation is observed in the Spinal Cord (SC) segments rostral and caudal to the lesion; (ii) long lasting changes in the SC includes the extracellular matrix (ECM) enzymes Timp1, transcription regulators (Egr, Nr4a1), second messenger associated proteins (Gna1, Ywhaq); (iii) long‐lasting changes in the Motor Cortex includes transcription regulators (Cebpd), neurotransmitters/neuromodulators and receptors (Cnr1, Gria1, Nos1), growth factors and related receptors (Igf1, Ntf3, Ntrk2), second messenger associated proteins (Mapk1); long lasting changes in Basal Ganglia and Cerebellum include ECM protein (Reln), growth factors (Ngf, Bdnf), transcription regulators (Egr, Cebpd), neurotransmitter receptors (Grin2c). These data suggest the molecular mapping as a useful tool to investigate the brain and SC reorganization after SCI.openBaldassarro V.A.; Sanna M.; Bighinati A.; Sannia M.; Gusciglio M.; Giardino L.; Lorenzini L.; Calzà LauraBaldassarro V.A.; Sanna M.; Bighinati A.; Sannia M.; Gusciglio M.; Giardino L.; Lorenzini L.; Calzà Laur