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Die Versorgung schwangerer Traumapatientinnen stellt das gesamte medizinische Team vor eine besondere Herausforderung. Ziel unserer Studie war es, diese Daten zu erheben und die Unterschiede zu nichtschwangeren Traumapatientinnen zu ermitteln. Wir fuhrten eine retrospektive Datenanalyse aus dem TraumaRegister DGU® durch und verglichen 102 schwangere mit 3135 nichtschwangeren Patientinnen im gebarfahigen Alter (16–45 Jahre) aus den Jahren 2016–2018, welche in Traumazentren behandelt worden sind. Die Patientinnen sind jeweils uber den Schockraum aufgenommen und auf Intensivstation behandelt worden. In Deutschland, Osterreich und der Schweiz waren 3,2 % der Traumapatientinnen schwanger, d. h. 102 Frauen. Frauen im durchschnittlichen Alter von 29 Jahren erlitten am haufigsten ein Trauma infolge eines Verkehrsunfalls. Ein schweres Trauma („Injury Severity Score“ [ISS] ≥16 Punkte) erlitten 24,5 % der Schwangeren und 37,4 % der Nichtschwangeren. Bei schwangeren Patientinnen wurde nur in 32,7 % der Falle eine Computertomographie (Traumaspirale) durchgefuhrt – bei nichtschwangeren Frauen dagegen in 79,8 %. Infolge des Traumas verstarben 2,9 % der schwangeren und 3,5 % der nichtschwangeren Patientinnen. Die standardisierte Mortalitatsrate (SMR) hatte einen Wert bei Schwangeren von 0,42 und bei Nichtschwangeren von 0,63. Erstmalig liegen nun Daten fur die Lander Deutschland, Osterreich und Schweiz zu Inzidenz, Traumamechanismen, prahospitaler und innerklinischer Versorgungsphase sowie Intensivtherapiephase fur schwangere Traumapatientinnen vor. Weitere Untersuchungen zu Daten bezuglich des fetalen Outcomes und traumaassoziierten Verletzungen der schwangeren Traumapatientinnen waren wunschenswert. Gynakologen bzw. Geburtshelfer sollten hier im Bedarfsfall standardisiert in das Schockraumteam integriert werden konnen.

At the time of diagnosis, only about 20% of patients with pancreatic ductal adenocarcinoma (PDAC) have resectable disease. PDAC treatment necessitates a multidisciplinary approach, and adjuvant chemotherapy after upfront resection is an established means of preventing recurrence. Neoadjuvant chemotherapy (NAT), originally introduced to downstage tumor size, is nowadays more frequently used for selection of patients with favorable tumor biology and to control potential micrometastases. While NAT is routinely applied in locally advanced (LA) PDAC, there is increasing evidence demonstrating benefits of NAT in borderline resectable (BR) PDAC. The concept of NAT has recently been tested in resectable PDAC, but to date NAT has been restricted to clinical trials, as the data are limited and no clear benefits have yet been shown in this patient group. This review summarizes the current evidence for NAT in resectable, BR, and LA PDAC, with a focus on high-level evidence and randomized controlled trials.

BackgroundChimeric antigen receptor (CAR) T cell therapy has proven its clinical utility in hematological malignancies. Optimization is still required for its application in solid tumors. Here, the lack of cancer-specific structures along with tumor heterogeneity represent a critical barrier to safety and efficacy. Modular CAR T cells indirectly binding the tumor antigen through CAR-adaptor molecules have the potential to reduce adverse events and to overcome antigen heterogeneity. We hypothesized that a platform utilizing unique traits of clinical grade antibodies for selective CAR targeting would come with significant advantages. Thus, we developed a P329G-directed CAR targeting the P329G mutation in the Fc part of tumor-targeting human antibodies containing P329G L234A/L235A (LALA) mutations for Fc silencing.MethodsA single chain variable fragment-based second generation P329G-targeting CAR was retrovirally transduced into primary human T cells. These CAR T cells were combined with IgG1 antibodies carrying P329G LALA mutations in their Fc part targeting epidermal growth factor receptor (EGFR), mesothelin (MSLN) or HER2/neu. Mesothelioma, pancreatic and breast cancer cell lines expressing the respective antigens were used as target cell lines. Efficacy was evaluated in vitro and in vivo in xenograft mouse models.ResultsUnlike CD16-CAR T cells, which bind human IgG in a non-selective manner, P329G-targeting CAR T cells revealed specific effector functions only when combined with antibodies carrying P329G LALA mutations in their Fc part. P329G-targeting CAR T cells cannot be activated by an excess of human IgG. P329G-directed CAR T cells combined with a MSLN-targeting P329G-mutated antibody mediated pronounced in vitro and in vivo antitumor efficacy in mesothelioma and pancreatic cancer models. Combined with a HER2-targeting antibody, P329G-targeting CAR T cells showed substantial in vitro activation, proliferation, cytokine production and cytotoxicity against HER2-expressing breast cancer cell lines and induced complete tumor eradication in a breast cancer xenograft mouse model. The ability of the platform to target multiple antigens sequentially was shown in vitro and in vivo.ConclusionsP329G-targeting CAR T cells combined with antigen-binding human IgG1 antibodies containing the P329G Fc mutation mediate pronounced in vitro and in vivo effector functions in different solid tumor models, warranting further clinical translation of this concept.

The terrestrial flora and vegetation of Clipperton (La Passion) atoll, a very remote and small (170 ha of land) French island located in the North-Eastern Pacific Ocean, at ca. 1,000 km west of the Mexican coast, have dramatically changed during the past three centuries. This paper, based on historical testimonies, previously published floristic studies, and an extensive plant inventory conducted during the “International Scientific Expedition PASSION 2015”, show that the atoll has experienced particularly active and rapid vegetation dynamics with alternating plant cover expansion and regression phases. Our results provide the first comprehensive assessment of vegetation cover and vascular plant species distribution based on georeferenced data and mapped with GIS software, as well as the first record of two newly established non-native weeds. The current composition and abundance of native and alien vascular plant communities (15 species including only 4 native taxa) appear to depend not only on abiotic factors (e.g. substrate and climatic events) but also on biotic interactions with animal communities (e.g. native seabirds and crabs). Anthropogenic activities and disturbances (e.g. coconut palm, pig, rat and weed introductions) that have occurred in the past 100 years have also played an important role in explaining the past and current floristic changes.

We provide the first assessment for a coral reef fish population of a potentially threatened endemic species from a remote and isolated oceanic island. Based on a 3-dimensional (3D) numerical field model of the reef habitat and underwater visual censuses conducted by 2 different teams in February and May 2016, we show that the 3.7 km2 of the Clipperton Atoll reefs shallower than 30 m host >50000 ind. (average density of 0.02 ind. m-2) of the endemic Clipperton angelfish Holacanthus limbaughi. Based on limited submersible observations to 150 m, the population likely extends below the 30 m depth stratum, resulting in an even larger population size and providing a potential depth refuge against expected warming ocean temperatures.

Chimeric antigen receptor (CAR) T cells have shown promising results for the treatment of blood cancers and various CAR-T cell approaches are in development for use in different tumor indications. Universal or modular CARs do not directly recognize the tumor target antigen, but bind via an adaptor molecule to their respective tumor target. We describe the P329G-CAR-T platform as a novel modular CAR-T cell platform that recognizes the P329G mutation in the Fc portion of IgG1 antibodies, a mutation frequently applied to abolish the Fc immune effector function of therapeutic antibodies. In contrast to other adaptor CAR-T cell platforms this approach does not rely on haptens or artificial tags fused to the targeting antibody.The crystal structure analysis of the anti-P329G Fab fragment in complex with a P329G-Fc portion showed that the Fab fragment recognizes the Fc mutation with 1:1 binding stoichiometry. Surface plasmon resonance analysis determined the equilibrium binding affinity of the P329G antibody to the P329G Fc-portion to be 15 nM. Cell assays using Jurkat-NFAT reporter cell lines and primary T cells transduced with the P329G-CAR showed specific recruitment of P329G CAR-T cells by P329G-containing antibodies, and potent and dose dependent tumor cell killing accompanied by IFNg release and subsequent T cell activation for several unrelated tumor antigens including CD20, CD33, HER2, FOLR1 and mesothelin. Notably, P329G-CAR-T cell killing activity was comparable to the activity of the respective direct scFv-based CAR-T cells, both in terms of kinetics and absolute killing potency. Finally, comparable activity was determined in comparison to CD16 extracellular domain (ECD)-based CAR-T cells engaging the CAR-T cells via the Fc-CD16-ECD interaction. In summary, P329G-CAR-T cells mediate potent tumor cell killing in combination with various tumor targeting antibodies as adaptor molecules. The combination with tumor targeting antibodies enables control of CAR-T activity by adjusting the dose and schedule of the respective antibody adaptor molecule. Importantly, different from CD16-ECD-based CAR-T cells, P329G-CAR-T cells cannot be engaged by endogenous immunoglobulins. In vivo studies to investigate efficacy and safety of P329G CAR-T cells are currently being completed and will be reported. Citation Format: Diana Darowski, Mohamed-Reda Benmebarek, Christian Jost, Kay Stubenrauch, Uwe Wessels, Joerg Benz, Anne Freimoser-Grundschober, Ekkehard Moessner, Pablo Umana, Sebastian Kobold, Christian Klein. Developing a novel adaptor CAR-T cell platform based on the recognition of the P329G Fc mutation in therapeutic IgG1 antibodies for adoptive T cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 570.

International audience; The termite nest is one of the architectural wonders of the living world, built by the collective action of workers in a colony. Each nest has several characteristic structural motifs that allow for efficient ventilation, cooling, and traversal. We use tomography to quantify the nest architecture of the African termite Apicotermes lamani , consisting of regularly spaced floors connected by scattered linear and helicoidal ramps. To understand how these elaborate structures are built and arranged, we formulate a minimal model for the spatiotemporal evolution of three hydrodynamic fields—mud, termites, and pheromones—linking environmental physics to collective building behavior using simple local rules based on experimental observations. We find that floors and ramps emerge as solutions of the governing equations, with statistics consistent with observations of A. lamani nests. Our study demonstrates how a local self-reinforcing biotectonic scheme is capable of generating an architecture that is simultaneously adaptable and functional, and likely to be relevant for a range of other animal-built structures.

T-cell bispecific antibodies (TCBs) are a novel class of engineered immunoglobulins that unite monovalent binding to the T-cell receptor (TCR) CD3e chain and bivalent binding to tumor-associated antigens in order to recruit and activate T-cells for tumor cell killing. In vivo, T-cell activation is usually initiated via the interaction of the TCR with the peptide-HLA complex formed by the human leukocyte antigen (HLA) and peptides derived from intracellular proteins. TCR-like antibodies (TCRLs) that recognize pHLA-epitopes extend the target space of TCBs to peptides derived from intracellular proteins, such as those overexpressed during oncogenesis or created via mutations found in cancer. One challenge during lead identification of TCRL-TCBs is to identify TCRLs that specifically, and ideally exclusively, recognize the desired pHLA, but not unrelated pHLAs. In order to identify TCRLs suitable for TCRL-TCBs, large numbers of TCRLs have to be tested in the TCB format. Here, we propose a novel approach using chimeric antigen receptors (CARs) to facilitate the identification of highly selective TCRLs. In this new so-called TCRL-CAR-J approach, TCRL-candidates are transduced as CARs into Jurkat reporter-cells, and subsequently assessed for their specificity profile. This work demonstrates that the CAR-J reporter-cell assay can be applied to predict the profile of TCRL-TCBs without the need to produce each candidate in the final TCB format. It is therefore useful in streamlining the identification of TCRL-TCBs.

Adequate mechanical stimulation is essential for cellular health and tissue maintenance, including articular cartilage, which lines the articulating bones in joints. Chondrocytes, which are the sole cells found in articular cartilage, are responsible for matrix synthesis, maintenance and degradation. It is generally believed that chondrocytes require mechanical stimuli through daily physical activity for adequate cartilage homeostasis. However, to date, the molecular mechanisms of cellular force sensing (mechanotransduction) are not fully understood. Among other mechanisms, the cytoskeleton is thought to play a key role. Despite that gravity is a very small force at the cellular level, cytoskeletal adaptations have been observed under altered gravity conditions of a parabolic flight in multiple cell types. In this study, we developed a novel hardware which allowed to chemically fix primary bovine chondrocytes at 7 time points over the course of a 31-parabola flight. The samples were subsequently stained for the microtubules and vimentin network and microscopic images were acquired. The images showed a large heterogeneity among the cells in morphology as well as in the structure of both networks. In all, no changes or adaptions in cytoskeleton structure could be detected over the course of the parabolic flight., + ID der Publikation: hslu_78813 + Art des Beitrages: Wissenschaftliche Medien + Jahrgang: 2020 + Sprache: Englisch + Letzte Aktualisierung: 2020-09-08 15:15:01

PD-L1/PD-1 blocking antibodies have demonstrated therapeutic efficacy across a range of human cancers. Extending this benefit to a greater number of patients, however, will require a better understanding of how these therapies instigate anticancer immunity. Although the PD-L1/PD-1 axis is typically associated with T cell function, we demonstrate here that dendritic cells (DCs) are an important target of PD-L1 blocking antibody. PD-L1 binds two receptors, PD-1 and B7.1 (CD80). PD-L1 is expressed much more abundantly than B7.1 on peripheral and tumor-associated DCs in patients with cancer. Blocking PD-L1 on DCs relieves B7.1 sequestration in cis by PD-L1, which allows the B7.1/CD28 interaction to enhance T cell priming. In line with this, in patients with renal cell carcinoma or non-small cell lung cancer treated with atezolizumab (PD-L1 blockade), a DC gene signature is strongly associated with improved overall survival. These data suggest that PD-L1 blockade reinvigorates DC function to generate potent anticancer T cell immunity.

The availability of Ags on the surface of tumor cells is crucial for the efficacy of cancer immunotherapeutic approaches using large molecules, such as T cell bispecific Abs (TCBs). Tumor Ags are processed through intracellular proteasomal protein degradation and are displayed as peptides on MHC class I (MHC I). Ag recognition through TCRs on the surface of CD8+ T cells can elicit a tumor-selective immune response. In this article, we show that proteolysis-targeting chimeras (PROTACs) that target bromo- and extraterminal domain proteins increase the abundance of the corresponding target-derived peptide Ags on MHC I in both liquid and solid tumor–derived human cell lines. This increase depends on the engagement of the E3 ligase to bromo- and extraterminal domain protein. Similarly, targeting of a doxycycline-inducible Wilms tumor 1 (WT1)-FKBP12F36V fusion protein, by a mutant-selective FKBP12F36V degrader, increases the presentation of WT1 Ags in human breast cancer cells. T cell–mediated response directed against cancer cells was tested on treatment with a TCR-like TCB, which was able to bridge human T cells to a WT1 peptide displayed on MHC I. FKBP12F36V degrader treatment increased the expression of early and late activation markers (CD69, CD25) in T cells; the secretion of granzyme β, IFN-γ, and TNF-α; and cancer cell killing in a tumor-T cell coculture model. This study supports harnessing targeted protein degradation in tumor cells, for modulation of T cell effector function, by investigating for the first time, to our knowledge, the potential of combining a degrader and a TCB in a cancer immunotherapy setting.

ZusammenfassungMit einem kindlichen Trauma wird der Notarzt eher selten konfrontiert, und so fehlt häufig die Routine in diesen Notfallszenarien, verbunden mit Unsicherheit im Umgang mit Kindern. Nicht selten unterbleibt dann eine suffiziente Analgesie, Anxiolyse oder Sedierung. Dieser Beitrag stellt ein adäquates Konzept zur sicheren und suffizienten Analgesie und Sedierung von Kindern vor.

The second member of the human ErbB family of receptor tyrosine kinases, HER2/hErbB2, is regarded as an exceptional case: The four extracellular subdomains could so far only be found in one fixed overall conformation, designated "open" and resembling the ligand-bound form of the other ErbB receptors. It thus appears to be different from the extracellular domains of the other family members that show inter-subdomain flexibility and exist in a "tethered" form in the absence of ligand. For HER2, there was so far no direct evidence for such a tethered conformation on the cell surface. Nonetheless, alternative conformations of HER2 in vivo could so far not be excluded. We now demonstrate the rigidity of HER2 on the surface of tumor cells by employing two orthogonal approaches of protein engineering: To directly test the potential of the extracellular domain of HER2 to adopt a pseudo-tethered conformation on the cell surface, we first designed HER2 variants with a destabilized interface between extracellular subdomains I and III that would favor deviation from the "open" conformation. Secondly, we used differently shaped versions of a Designed Ankyrin Repeat Protein (DARPin) fusion, recognizing subdomain I of HER2, devised to work as probes for a putative pseudo-tethered extracellular domain of HER2. Combining our approaches, we exclude, on live cells and in vitro, that significant proportions of HER2 deviate from the "open" conformation.

We summarize our lattice QCD determinations of the pion-pion, pion-kaon and kaon-kaon s-wave scattering lengths at maximal isospin with a particular focus on the extrapolation to the physical point and the usage of next-to-leading order chiral perturbation theory to do so. We employ data at three values of the lattice spacing and pion masses ranging from around 230 MeV to around 450 MeV, applying Luescher's finite volume method to compute the scattering lengths. We find that leading order chiral perturbation theory is surprisingly close to our data even in the kaon-kaon case for our entire range of pion masses., 10 pages, 8 figures, Presented at the 9th International Workshop on Chiral Dynamics, Sept. 17-21, 2018, Duke University, Durham, NC, USA , submitted to PoS, (C18-09-17.6). Funding acknowledgements added in v2 replacement, comma added in abstract. In v3 replacement, corrected typo in equation 6.2 which was referring to the pion-kaon reduced mass instead of the pion mass

We present a lattice QCD investigation of the $$\rho $$ρ-meson with $$N_\mathrm{{f}}=2+1+1$$Nf=2+1+1 dynamical quark flavours for the first time. The calculation is performed based on gauge configuration ensembles produced by the ETM Collaboration with three lattice spacing values and pion masses ranging from 230 to 500 MeV. Applying the Lüscher method phase-shift curves are determined for all ensembles separately. Assuming a Breit–Wigner form, the $$\rho $$ρ-meson mass and width are determined by a fit to these phase-shift curves. Mass and width combined are then extrapolated to the chiral limit, while lattice artefacts are not detectable within our statistical uncertainties. For the $$\rho $$ρ-meson mass extrapolated to the physical point we find good agreement with experiment. The corresponding decay width differs by about two standard deviations from the experimental value.

Author-generated preprint; International audience; The nests of termites are amongst the most diverse and complex structures among the great diversity of those built by animals. Their intricate architectures and the manner in which termites make use of them have fascinated mankind for centuries, whether it is part of local agricultural practice, as a simple landscape feature, as an inspiration for societal collective building or as a scientific study object on its own. However, their nests remain relatively little understood compared to those of many ants, social wasps and social bees, especially honey bees and stingless bees since termites that actually build mounds or other conspicuous structures are of minor economic importance. The few termites that serve as structural pests-and so attract the most study-mostly live inside their food supply without constructing a distinctive nest. My purpose here is to build on the few earlier reviews with an emphasis on mound nests. Many recent advances have been possible thanks to new imaging technics such as Computer Tomography, photogrammetry or automatic tracking and behavior classification. Modelling and simulation techniques further help to link individual construction behavior to emerging architectures.

Monoclonal antibody-based therapeutics are an integral part of treatment of different human diseases, and the selection of suitable antibody candidates during the discovery phase is essential. Here, we describe a novel, cellular screening approach for the identification and characterization of therapeutic antibodies suitable for conversion into T cell bispecific antibodies using chimeric antigen receptor (CAR) transduced Jurkat-NFAT-luciferase reporter cells (CAR-J). For that purpose, we equipped a Jurkat-NFAT reporter cell line with a universal CAR, based on a monoclonal antibody recognizing the P329G mutation in the Fc-part of effector-silenced human IgG1-antibodies. In addition to scFv-based second generation CARs, Fab-based CARs employing the P329G-binder were generated. Using these anti-P329G-CAR-J cells together with the respective P329G-mutated IgG1-antibodies, we established a system, which facilitates the rapid testing of therapeutic antibody candidates in a flexible, high throughput setting during early stage discovery. We show that both, scFv- and Fab-based anti-P329G-CAR-J cells elicit a robust and dose-dependent luciferase signal if the respective antibody acts as an adaptor between tumor target and P329G-CAR-J cells. Importantly, we could demonstrate that functional characteristics of the antibody candidates, derived from the anti-P329G-CAR-J screening assay, are predictive for the functionality of these antibodies in the T cell bispecific antibody format.

Introduction: In the rapidly growing field of chimeric antigen receptor (CAR) engineered T cells new approaches aim to make CAR-T cell therapy safer and more effective. Recent, designs aim towards universal or modular CARs that do not directly recognize the target antigen itself, but instead facilitate contact to CAR-adaptor molecules, which in turn bind to the target antigen. Current CAR-adaptor molecules include human antibodies of the IgG1 isotype binding to CD16 or antibodies modified by peptide or hapten tags. We developed a modular CAR-T approach that recognizes the P329G mutation clinically used to silence the Fc effector function of therapeutic antibodies. These modular anti-P329G-CAR-T cells are only functional in the presence of antibodies that possess the P329G mutation. Methods: The anti-P329G interaction with P329G-containing Fc fragment was analyzed using surface plasmon resonance and co-crystallography. Lentivirus transfected anti-P329G CAR-T cells were characterized in vitro for their selectivity and potential to mediate antigen specific tumor cell lysis, cytokine secretion and proliferation. Immunological synapse formation was investigated using confocal microscopy. Results: Anti-P329G-CAR-T cells allow the precise recognition of the P329G mutation present in therapeutic IgG1 based adaptor-molecules. Crystal structure- and SPR-analysis revealed a 1:1 binding stoichiometry with low nanomolar affinity of the P329G-Fab fragment applied in the CAR for P329G-containing IgG1 antibodies. Potent tumor cell lysis was demonstrated for multiple tumor antigens e.g. CD20, HER2, FOLR1, EpCAM, FAP and others. For all tested antigens, a huIgG1 dose-dependent activation of anti-P329G-CAR-T cells as well as dose-dependent tumor cell lysis was observed. For selected antigens P329G-CAR-T activity was found comparable to the activity mediated by T cell bispecific antibodies recognizing the respective tumor antigen. Finally, the immunological synapse formed by P329-CAR-T cells was compared to the one formed by T cell bispecific antibodies in a 2+1 format. Conclusions: P329G-CAR-T cells mediate potent and specific tumor cell killing using various tumor targeted antibodies as adaptor molecules. Based on these data in vivo studies to investigate efficacy and safety of the approach are foreseen. Notably, this approach allows control of CAR-T activity and potential side effects by titrating the adaptor molecule, as well as the simultaneous targeting of more than one antigen at the same time with the goal to prevent tumor escape mechanisms. Combining the P329G-CAR with allogenic T-cells may provide a truly off-the-shelf P329G-CAR-T cell therapy approach. Citation Format: Diana Darowski, Christian Jost, Zeno Riester, Mohamed Benmebarek, Kay Stubenrauch, Anne Freimoser-Grundschober, Uwe Wessels, Jörg Benz, Ekkehard Mössner, Renier Myburgh, Floriana Cremasco, Mario Perro, Pablo Umana, Sebastian Kobold, Christian Klein. Anti-P329G-CAR-T cells as a novel universal CAR-T cell platform [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4229.

In this paper we explore the computation of topological susceptibility and ${\ensuremath{\eta}}^{\ensuremath{'}}$ meson mass in ${N}_{f}=2$ flavor QCD using lattice techniques with a physical value of the pion mass as well as larger pion mass values. We observe that the physical point can be reached without a significant increase in the statistical noise. The mass of the ${\ensuremath{\eta}}^{\ensuremath{'}}$ meson can be obtained from both fermionic two point functions and topological charge density correlation functions, giving compatible results. With the pion mass dependence of the ${\ensuremath{\eta}}^{\ensuremath{'}}$ mass being flat we arrive at ${M}_{{\ensuremath{\eta}}^{\ensuremath{'}}}=772(18)\text{ }\text{ }\mathrm{MeV}$ without an explicit continuum limit. For the topological susceptibility we observe a linear dependence on ${M}_{\ensuremath{\pi}}^{2}$, however, with an additional constant stemming from lattice artifacts.

Chimeric antigen receptor (CAR)-engineered T cells have a proven efficacy for the treatment of refractory hematological B cell malignancies. While often accompanied by side effects, CAR-T technology is getting more mature and will become an important treatment option for various tumor indications. In this review, we summarize emerging approaches that aim to further evolve CAR-T cell therapy based on combinations of so-called universal or modular CAR-(modCAR-)T cells, and their respective adaptor molecules (CAR-adaptors), which mediate the crosslinking between target and effector cells. The activity of such modCAR-T cells is entirely dependent on binding of the respective CAR-adaptor to both a tumor antigen and to the CAR-expressing T cell. Contrary to conventional CAR-T cells, where the immunological synapse is established by direct interaction of CAR and membrane-bound target, modCAR-T cells provide a highly flexible and customizable development of the CAR-T cell concept and offer an additional possibility to control T cell activity.

In this paper, we report on results for the $s$-wave scattering length of the $\ensuremath{\pi}\text{\ensuremath{-}}K$ system in the $I=3/2$ channel from ${N}_{f}=2+1+1$ lattice QCD. The calculation is based on gauge configurations generated by the European Twisted Mass Collaboration with pion masses ranging from about 230 to 450 MeV at three values of the lattice spacing. Our main result reads ${M}_{\ensuremath{\pi}}{a}_{0}^{3/2,\text{phys}}=\ensuremath{-}0.059(2)$. Using chiral perturbation theory we are also able to estimate ${M}_{\ensuremath{\pi}}{a}_{0}^{1/2,\text{phys}}=0.163(3)$. The error includes statistical and systematic uncertainties, and for the latter in particular errors from the extrapolation to the physical point.

We present results for the isospin-0 $\pi\pi$ s-wave scattering length calculated with Osterwalder-Seiler valence quarks on Wilson twisted mass gauge configurations. We use three $N_f = 2$ ensembles with unitary (valence) pion mass at its physical value (250$\sim$MeV), at 240$\sim$MeV (320$\sim$MeV) and at 330$\sim$MeV (400$\sim$MeV), respectively. By using the stochastic Laplacian Heaviside quark smearing method, all quark propagation diagrams contributing to the isospin-0 $\pi\pi$ correlation function are computed with sufficient precision. The chiral extrapolation is performed to obtain the scattering length at the physical pion mass. Our result $M_\pi a^\mathrm{I=0}_0 = 0.198(9)(6)$ agrees reasonably well with various experimental measurements and theoretical predictions. Since we only use one lattice spacing, certain systematics uncertainties, especially those arising from unitary breaking, are not controlled in our result., Comment: 21 pages, 5 figures, 6 tables

Termite mounds are often cited as an example of efficient thermoregulated structures. Nest thermal stability can be critical for insects that are particularly sensitive to heat and desiccation. Few studies have measured internal temperature of termite nests with respect to environmental parameters, especially in Neotropical species. In this study, we analyzed the thermal profiles of different parts of Procornitermes araujoi nests, a neotropical mound-building termite of the Brazilian cerrado. To read into our dataset we first used rasterization, a method that allows a quick-look assessment of time-series. Our results show that nest architecture efficiently buffers against environmental temperature fluctuations while at the same time maintaining a relatively high internal temperature in the core. This rather stable internal climate follows nevertheless the external temperature long-term averages. Using a novel numerical scheme, we further show that the heat transfer dynamics are well described by the classical heat equation, with an additional heat source whose origin is discussed.

We present physics results from simulations of QCD using Nf 1⁄4 2 dynamical Wilson twisted mass fermions at the physical value of the pion mass. These simulations are enabled by the addition of the clover term to the twisted mass quark action. We show evidence that compared to previous simulations without this term, the pion mass splitting due to isospin breaking is almost completely eliminated. Using this new action, we compute the masses and decay constants of pseudoscalar mesons involving the dynamical up and down as well as valence strange and charm quarks at one value of the lattice spacing, a ≈ 0.09 fm. Further, we determine renormalized quark masses as well as their scale-independent ratios, in excellent agreement with other lattice determinations in the continuum limit. In the baryon sector, we show that the nucleon mass is compatible with its physical value and that the masses of the Δ baryons do not show any sign of isospin breaking. Finally, we compute the electron, muon and tau lepton anomalous magnetic moments and show the results to be consistent with extrapolations of older ETMC data to the continuum and physical pion mass limits. We mostly find remarkably good agreement with phenomenology, even though we cannot take the continuum and thermodynamic limits.

International audience; La Polynésie française se caractérise par une immense zone économique exclusive, constituant la moitié de la zone maritime française, elle-même deuxième mondiale. Les enjeux de conservation et d'exploitation durable des océans et des ressources marines (objectif 14 de l'agenda onusien du développement durable) y sont considérables. Dans un contexte international marqué par une hausse de la demande en matières premières minérales et une "course à la mer", nouvelle frontière d'expansion territoriale, la question des ressources minérales profondes en Polynésie française suscite aujourd'hui un intérêt accru. L'État et la Polynésie française ont commandé à l'Institut de recherche pour le Développement (IRD) cette expertise collégiale sur les ressources minérales marines profondes en Polynésie française. Cette expertise, réalisée par un collège d'experts pluridisciplinaire (anthropologie, biologie, droit, économie, géographie, géologie, technologie), recense les connaissances actuelles et construit un diagnostic nuancé. Elle aboutit à une série de recommandations utiles aux décideurs politiques en matière de production de connaissances, de développement de technologies et de gouvernance, contribuant ainsi à la définition d'une stratégie de développement d'une filière minière sous-marine respectueuse des enjeux sociaux et environnementaux spécifiques à la Polynésie française. Contribution des auteurs