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This document defines the inputs and processes used to calibrate the raw images returned by the Didymocs Reconnaissance and Asteroid Camera for OpNav (DRACO) instrument flown aboard the Double Asteroid Redirection Test (DART) mission.

Type 2 immunity is associated with adipose tissue (AT) homeostasis and infection with parasitic helminths, but whether AT participates in immunity to these parasites is unknown. We found that the fat content of mesenteric AT (mAT) declined in mice during infection with a gut-restricted helminth. This was associated with the accumulation of metabolically activated, interleukin-33 (IL-33), thymic stromal lymphopoietin (TSLP), and extracellular matrix (ECM)–producing stromal cells. These cells shared transcriptional features, including the expression of Dpp4 and Pi16 , with multipotent progenitor cells (MPC) that have been identified in numerous tissues and are reported to be capable of differentiating into fibroblasts and adipocytes. Concomitantly, mAT became infiltrated with resident T helper 2 (T H 2) cells that responded to TSLP and IL-33 by producing stromal cell–stimulating cytokines, including transforming growth factor β1 (TGFβ 1 ) and amphiregulin. These T H 2 cells expressed genes previously associated with type 2 innate lymphoid cells (ILC2), including Nmur1 , Calca , Klrg1 , and Arg1 , and persisted in mAT for at least 11 months after anthelmintic drug–mediated clearance of infection. We found that MPC and T H 2 cells localized to ECM-rich interstitial spaces that appeared shared between mesenteric lymph node, mAT, and intestine. Stromal cell expression of epidermal growth factor receptor (EGFR), the receptor for amphiregulin, was required for immunity to infection. Our findings point to the importance of MPC and T H 2 cell interactions within the interstitium in orchestrating AT remodeling and immunity to an intestinal infection.

Type 2 immunity is associated with adipose tissue (AT) homeostasis and infection with parasitic helminths, but whether AT participates in immunity to these parasites is unknown. We found that the fat content of mesenteric AT (mAT) declined in mice during infection with a gut-restricted helminth. This was associated with the accumulation of metabolically activated, interleukin-33 (IL-33), thymic stromal lymphopoietin (TSLP), and extracellular matrix (ECM)-producing stromal cells. These cells shared transcriptional features, including the expression of

Surge motion of a floating wind turbine can lead to conditions where the rotor moves backwards faster than the wind, leading to propeller-like conditions or vortex ring state (VRS). The effect of surge on the thrust of a floating turbine was investigated with OpenFOAM for conditions favourable to propeller and vortex ring state. Due to lower blade velocities and larger blade twists, a region of negative thrust is shown to extend spanwise from the blade root towards the tip signifying propeller state. Predictions that strong waves with low/moderate wind speeds leads to propeller-like conditions were confirmed for a representative surging simulation with a 9.4 m amplitude in waves with an 8.1 s period and 7 m/s wind speed. A negative thrust for the entire rotor, through the combination of an inboard region of negative and outboard region of small but still positive thrust, was observed during the expected part of the surging cycle. VRS was observed with blade tip-vortex interaction and root vortex recirculation due to the duration with a negative relative rotor velocity being similar to the blade passing period, inhibiting vortex advection downstream. This work explains and demonstrates the causes of propeller state and VRS for floating turbines.

Infection with helminth parasites can affect adiposity, but underlying mechanisms that regulate this process are unclear. We found that fat content of mesenteric adipose tissue (mAT) declined in mice during infection with gut-restricted parasitic worms. This was associated with the accumulation of metabolically activated, immunostimulatory cytokine- and extracellular matrix-secreting multipotent stromal cells, which had potential to differentiate into preadipocytes. Concomitantly, mAT became infiltrated with Th2 lymphocytes that took up long-term residence and responded to signals from stromal cells by producing stromal cell-stimulating cytokines, including Amphiregulin. Signals delivered by Amphiregulin to stromal cells were required for immunity to infection. Our findings reveal intricate intercellular communication between Th2 cells and adipocyte progenitors and link immunity to intestinal infection to T cell-dependent effects on the adipocyte lineage.

This document defines the inputs and processes used to calibrate the raw images returned by the Didymocs Reconnaisance and Asteroid Camera for OpNav (DRACO) instrument flown aboard the Double Asteroid Redirection Test (DART) mission.

Experimental and numerical studies are carried out employing the counterflow configuration to advance understanding of nonpremixed combustion of hydrocarbon fuels. The motivation for performing these studies is to increase the knowledge and accuracy of the parameters associated with the transport and chemical-kinetic rate processes of combustion. The counterflow configuration is a very useful tool in elucidating and inferring these parameters for using in numeric or analytical models of real combustion systems. First, a new counterflow burner was constructed for carrying out experiments on high molecular weight hydrocarbon fuels and jet fuels, in particular JP-8, at elevated pressures up to 2.5 MPa. Many of these fuels are liquids at room temperature and pressure. Previously, the U.S. Army Research Office (ARO) funded the design and construction of a High Pressure Combustion Experimental Facility (HPCEF) at the University of California, San Diego. The main pressure chamber with optical access from that project is used, and this new burner is placed inside the chamber. The "extinction top'", or the apparatus used to inject an oxidizing stream onto the fuel surface is also used from the previous work. The new burner is used to measure critical conditions of extinction for hydrocarbon fuels at elevated pressures. In the research previously supported by ARO, experiments were performed at elevated pressures on fuels that are gases at room temperature. Construction of the new liquid pool counterflow burner has extended the scope and quality of that research because it is now possible to characterize combustion of fuels that are liquids at room temperature and atmospheric pressure. An experimental study of nonpremixed combustion of a number of hydrocarbon fuels under moderate pressures is carried out. Fuels and blends used in this study include n-heptane, cyclo-hexane, n- octane, iso-octane, JP-8, Jet-A, and two surrogate blends. Next, experiments and numerical computations are completed to characterize mixtures of dimethyl ether and n-heptane at atmospheric pressures. Dimethyl ether is being studied as an oxygen-rich fuel additive or replacement for diesel fuel in compression-ignition engines due to its high cetane number, negligible global warming potential, it's ability to be produced from multiple sources, and it's high well-to-wheel efficiency. The research focuses on combining the well-validated and detailed LLNL DME mechanism with other hydrocarbon mechanisms to study blends of these fuels. Critical limits of extinction and autoignition of various blends are reported. Using a combined mechanism developed at RWTH Aachen, the extinction limits are very well predicted numerically. A formulation for calculating reactant mass fractions fixing stoichiometric mixture fraction and adiabatic flame temperature is described, which can be easily adapated for two-component blends of fuels with non-unity, unequal Lewis numbers. Experiments and computations both show that dimethyl ether enhances reactivity of blends of dimethyl ether and heptane. Ignition limits for blends are also reported, with numerical predictions overpredicting experimental ignition temperature by approximately 50-70 K, but otherwise predicting ignition temperatures well. Finally, in order to understand the gas-phase combustion characteristics of nitramine monopropellants, a number of subsystems of reactions among the major intermediate products are studied. This work considers the effect of the intermediate product nitrous oxide (N₂O) on the autoignition temperature of ethane (C₂H6). An improved understanding of the combustion taking place in this subsystem is required to model the combustion of nitramines. Here an experimental and computational study is carried out to determine the autoignition temperature of nonpremixed ethane flames with added (N₂O). The oxidi

Fever can provide a survival advantage during infection. Metabolic processes are sensitive to environmental conditions, but the effect of fever on T cell metabolism is not well characterized. We show that in activated CD8+ T cells, exposure to febrile temperature (39°C) augmented metabolic activity and T cell effector functions, despite having a limited effect on proliferation or activation marker expression. Transcriptional profiling revealed an up-regulation of mitochondrial pathways, which was consistent with increased mass and metabolism observed in T cells exposed to 39°C. Through in vitro and in vivo models, we determined that mitochondrial translation is integral to the enhanced metabolic activity and function of CD8+ T cells exposed to febrile temperature. Transiently exposing donor lymphocytes to 39°C prior to infusion in a myeloid leukemia mouse model conferred enhanced therapeutic efficacy, raising the possibility that exposure of T cells to febrile temperatures could have clinical potential.

The adoption of Warburg metabolism is critical for the activation of macrophages in response to lipopolysaccharide. Macrophages stimulated with lipopolysaccharide increase their expression of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD⁺ salvage, and loss of NAMPT activity alters their inflammatory potential. However, the events that lead to the cells' becoming dependent on NAD⁺ salvage remain poorly defined. We found that depletion of NAD⁺ and increased expression of NAMPT occurred rapidly after inflammatory activation and coincided with DNA damage caused by reactive oxygen species (ROS). ROS produced by complex III of the mitochondrial electron-transport chain were required for macrophage activation. DNA damage was associated with activation of poly(ADP-ribose) polymerase, which led to consumption of NAD⁺. In this setting, increased NAMPT expression allowed the maintenance of NAD⁺ pools sufficient for glyceraldehyde-3-phosphate dehydrogenase activity and Warburg metabolism. Our findings provide an integrated explanation for the dependence of inflammatory macrophages on the NAD⁺ salvage pathway.

The COVID-19 pandemic temporarily stopped executions in the United States and played a part in a record low number of death sentences handed down in 2020. While many newspapers reported on the pandemic-related disruption of individual executions and court proceedings, little attention has been given to understanding whether other crises in American history have similarly disrupted the death penalty. This paper examines execution data from several major crises in American history – wars, economic downturns, and pandemics – to assess whether COVID-19’s disruption of the American death penalty represents an anomaly among pandemics and other crises. As we will show, the death penalty has shown remarkable resiliency. Through all manner of national disruptions, with the exception of the first months of the COVID-19 pandemic, America’s execution machinery has kept on running. This fact is one indication of this nation’s attachment to capital punishment.

Significance T helper 2 (Th2) cells are defined by their ability to produce the hallmark cytokine IL-4. However, to mediate allergic inflammation in tissues, Th2 cells must secrete additional cytokines including IL-13 and IL-5. We used IL-4 and IL-13 dual-reporter mice to show that naive CD4+ T cells cultured in the presence of IL-4 and thymic stromal lymphopoietin (TSLP) generate a population of IL-4negIL-13pos Th2 cells that develop from IL-4neg precursors and express the Th2 effector cytokines IL-5 and IL-9. In vivo, high TSLP levels promote the development of a similar population of IL-4negIL-13pos T cells that also express Gata3, Il5, and Il3 transcripts. Thus, TSLP drives the early differentiation of a distinct population of effector Th2 cells with pro-inflammatory properties., T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen exposure primes IL-4+ Th2 cells in lymph node, but production of effector cytokines including IL-5 and IL-13 is thought to require additional signals from antigen and the environment. Here we report that a substantial proportion of naive CD4+ T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of naive CD4+ T cells in anti-(a)CD3, aCD28, and TSLP-supplemented Th2 conditions enabled the development of a unique population of IL-13-single positive (IL-13-SP) CD4+ T cells; TSLP and Th2 conditions were both required for their development. Sorting experiments revealed that IL-13-SP Th2 cells originated from IL-4-negative precursors and coexpressed transcripts for the Th2 cytokines IL-5 and IL-9. In vivo, high TSLP levels acted directly on CD4+ T cells to induce the development of IL-13-SP and IL-4+IL-13+ double-positive populations in lymph node. These cells were phenotypically similar to Th2 effector cells and were CXCR5lowPD1low and expressed low levels of Bcl6 and Il21 transcripts and high levels of Gata3, Il3, and Il5. Our findings suggest a role of TSLP in directly promoting Th2 cell effector function and support the notion of TSLP as a key driver of Th2 inflammation.

Summary How cells adapt metabolism to meet demands is an active area of interest across biology. Among a broad range of functions, the polyamine spermidine is needed to hypusinate the translation factor eukaryotic initiation factor 5A (eIF5A). We show here that hypusinated eIF5A (eIF5AH) promotes the efficient expression of a subset of mitochondrial proteins involved in the TCA cycle and oxidative phosphorylation (OXPHOS). Several of these proteins have mitochondrial targeting sequences (MTSs) that in part confer an increased dependency on eIF5AH. In macrophages, metabolic switching between OXPHOS and glycolysis supports divergent functional fates stimulated by activation signals. In these cells, hypusination of eIF5A appears to be dynamically regulated after activation. Using in vivo and in vitro models, we show that acute inhibition of this pathway blunts OXPHOS-dependent alternative activation, while leaving aerobic glycolysis-dependent classical activation intact. These results might have implications for therapeutically controlling macrophage activation by targeting the polyamine-eIF5A-hypusine axis., Graphical Abstract, Highlights • The polyamine synthesis pathway and hypusinated eIF5A modulate mitochondrial OXPHOS • Hypusinated eIF5A maintains TCA cycle and ETC integrity in macrophages • Some mitochondrial enzymes depend on eIF5AH for efficient expression • Inhibition of hypusinated eIF5A blunts macrophage alternative activation, Puleston et al. show that polyamine biosynthesis modulates mitochondrial metabolism through eIF5A hypusination (eIF5AH). They find that inhibiting the polyamine-eIF5A-hypusine pathway blocks OXPHOS-dependent macrophage alternative activation, while leaving aerobic glycolysis-dependent macrophage classical activation intact. These results might have implications for therapeutically controlling macrophage activation by targeting the polyamine-eIF5A-hypusine axis.

Summary: Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation to the surrounding microenvironment is therefore key for maintaining appropriate cell function. For instance, cancer cells use acetate as a substrate alternative to glucose to fuel metabolism and growth. Here, we show that acetate rescues effector function in glucose-restricted CD8+ T cells. Mechanistically, acetate promotes histone acetylation and chromatin accessibility and enhances IFN-γ gene transcription and cytokine production in an acetyl-CoA synthetase (ACSS)-dependent manner. Ex vivo acetate treatment increases IFN-γ production by exhausted T cells, whereas reducing ACSS expression in T cells impairs IFN-γ production by tumor-infiltrating lymphocytes and tumor clearance. Thus, hyporesponsive T cells can be epigenetically remodeled and reactivated by acetate, suggesting that pathways regulating the use of substrates alternative to glucose could be therapeutically targeted to promote T cell function during cancer. : Qiu et al. show that acetate enhances histone acetylation, chromatin accessibility, and effector function in glucose-restricted CD8+ T cells. The authors find that manipulation of acetate-handling pathways influences cytokine production of tumor-infiltrating CD8+ T cells, which could have therapeutic implications for activating CD8+ T cell effector function in the tumor microenvironment. Keywords: tumor-infiltrating lymphocytes, chromatin remodeling, T cells, acetate, acetyl-CoA synthetase, T cell exhaustion, T cell hyporesponsiveness, tumor immunity, effector functions

Summary Mitochondria constantly adapt to the metabolic needs of a cell. This mitochondrial plasticity is critical to T cells, which modulate metabolism depending on antigen-driven signals and environment. We show here that de novo synthesis of the mitochondrial membrane-specific lipid cardiolipin maintains CD8+ T cell function. T cells deficient for the cardiolipin-synthesizing enzyme PTPMT1 had reduced cardiolipin and responded poorly to antigen because basal cardiolipin levels were required for activation. However, neither de novo cardiolipin synthesis, nor its Tafazzin-dependent remodeling, was needed for T cell activation. In contrast, PTPMT1-dependent cardiolipin synthesis was vital when mitochondrial fitness was required, most notably during memory T cell differentiation or nutrient stress. We also found CD8+ T cell defects in a small cohort of patients with Barth syndrome, where TAFAZZIN is mutated, and in a Tafazzin-deficient mouse model. Thus, the dynamic regulation of a single mitochondrial lipid is crucial for CD8+ T cell immunity., Graphical Abstract, Highlights • Cardiolipin is essential for in vivo and in vitro CD8+ T cell responses • Active cardiolipin synthesis and remodeling occurs during T cell differentiation • Cardiolipin synthesis supports CD8+ TM cell development, metabolism, and function • T cell defects are evident in TAZ KO mice and in Barth syndrome patients, Corrado et al. show that the mitochondrial membrane-specific lipid cardiolipin is required for the metabolic plasticity that is essential for effective CD8+ T cell function. Cardiolipin-deficient CD8+ T cells fail to respond to pathogens and are not able to adapt to nutrient stress.

Summary Regulatory T cells (Tregs) subdue immune responses. Central to Treg activation are changes in lipid metabolism that support their survival and function. Fatty acid binding proteins (FABPs) are a family of lipid chaperones required to facilitate uptake and intracellular lipid trafficking. One family member, FABP5, is expressed in T cells, but its function remains unclear. We show that in Tregs, genetic or pharmacologic inhibition of FABP5 function causes mitochondrial changes underscored by decreased OXPHOS, impaired lipid metabolism, and loss of cristae structure. FABP5 inhibition in Tregs triggers mtDNA release and consequent cGAS-STING-dependent type I IFN signaling, which induces heightened production of the regulatory cytokine IL-10 and promotes Treg suppressive activity. We find evidence of this pathway, along with correlative mitochondrial changes in tumor infiltrating Tregs, which may underlie enhanced immunosuppression in the tumor microenvironment. Together, our data reveal that FABP5 is a gatekeeper of mitochondrial integrity that modulates Treg function., Graphical Abstract, Highlights • FABP5 inhibition in Tregs alters mitochondria and enhances suppression • Disrupting FABP5 in Tregs results in mtDNA release and type I IFN signaling • cGAS/-STING-dependent type I IFN signals promote Treg IL-10 production • Tumor Tregs exhibit mitochondrial alterations and a type I IFN gene signature, Field et al. show that fatty acid binding protein 5 (FABP5) maintains mitochondrial integrity in regulatory T cells (Tregs). FABP5 inhibition results in mtDNA release, which triggers expression of IL-10 and promotes Treg suppressive capacity. These findings may have implications for therapeutically targeting Tregs in autoimmunity and cancer.

Although IL-4 is long associated with CD4 Th2 immune responses, its role in Th2 subset development in non-lymphoid tissues is less clear. We sought to better define IL-4's role in CD4 Th2 responses by using transgenic mice that express a dual IL-4 AmCyan/IL-13 DsRed (IL-4AC/IL-13DR) fluorescent reporter on an IL-4-sufficient or IL-4-deficient background. Using primary Th2 immune response models against house dust mite or Nippostrongylus brasiliensis (Nb) allergens, we examined the requirement for IL-4 by each of the defined Th2 subsets in the antigen draining lymph node, skin, and lung tissues. In the lymph node, a CXCR5+PD-1+ T follicular helper (Tfh) and a CXCR5loPD-1lo Th2 subset could be detected that expressed only IL-4AC but no IL-13DR. The number of IL-4AC+ Tfh cells was not affected by IL-4 deficiency whereas the number of IL-4AC+ Th2 cells was significantly reduced. In the non-lymphoid dermal or lung tissues of allergen primed or Nb-infected mice, three strikingly distinct T cell subsets could be detected that were IL-4AC, or IL-4AC/IL-13DR, or IL-13DR CD4. The IL-4- and IL-4/IL-13-expressing subsets were significantly reduced in IL-4-deficient mice, while the numbers of IL-13-expressing CD4 T cells were not affected by IL-4 deficiency indicating that other factors can play a role in directing the development of this Th2 subtype. Taken together, these data indicate that the appearance of IL-4-expressing Tfh cells in the lymph node is not dependent on IL-4 while the appearance of IL-4-expressing Th2 subsets in the lymph node and IL-4, IL-4/IL-13-expressing Th2 subsets in skin and lung tissues of antigen primed mice is significantly IL-4 dependent.

[ES] La integración de las tecnologías de energía renovable es un gran componente para alcanzar los serios objetivos medioambientales de diferentes gobiernos e instituciones a nivel mundial. Sin embargo, hay varios desafíos a lo largo de su camino para seguir aumentando en capacidad. La mayor penetración de estas tecnologías surge la necesidad de que proporcionen la misma fiabilidad y servicios que los generadores convencionales han hecho en la red eléctrica. El almacenamiento de energía proporciona una de las soluciones. La propuesta del trabajo fin de master era desarrollar una metodología que permita modelar y simular sistemas de almacenamiento de energía acoplado a campos fotovoltaicos, para optimizar su integración en las redes eléctricas. La metodología puede modelar cualquier ubicación y cualquier condición que requiera un proyecto de este tipo y calcular su dimensionamiento óptimo. Los parámetros que se puede variar son los siguientes: potencia, ratio DC/AC, ubicación, precios de la electricidad, mecanismos de fijación de precios de tarifas (existentes y propuestos), y finalmente costes de capital. En este modelo, además, se propuso una nueva configuración para beneficiarse de los excesos fotovoltaicos producidos a partir de un campo fotovoltaico sobredimensionado, mediante la conexión del sistema de baterías a un convertidor DC/DC de relativamente alta potencia. Se analizó diferentes casos de estudio, con el fin de mostrar como este tipo de sistema puede ayudar a reemplazar los generadores convencionales y asegurar la fiabilidad y calidad de la red eléctrica. Los casos que se estudia son: (i.) almacenamiento de excesos por “clipping”, (ii.) power-shifting, (iii.) regulación primaria y secundaria, y (iv.) acoplamiento de respuesta de demanda mediante vehículos eléctricos., [CA] La integració de les tecnologies d'energia renovable és un gran component per a aconseguir els seriosos objectius mediambientals de diferents governs i institucions a nivell mundial. No obstant això, hi ha diversos desafiaments al llarg del seu camí per a continuar augmentant en capacitat. La major penetració d'estes tecnologies sorgix la necessitat que proporcionen la mateixa fiabilitat i servicis que els generadors convencionals han fet en la xarxa elèctrica. L'emmagatzemament d'energia proporciona una de les solucions. La proposta del treball fi de màster era desenrotllar una metodologia que permeta modelar i simular sistemes d'emmagatzemament d'energia acoblat a camps fotovoltaics, per a optimitzar la seua integració en les xarxes elèctriques. La metodologia pot modelar qualsevol ubicació i qualsevol condició que requerisca un projecte d'este tipus i calcular el seu dimensionamiento òptim. Els paràmetres que es pot variar són els següents: potència, ràtio DC/AC, ubicació, preus de l'electricitat, mecanismes de fixació de preus de tarifes (existents i proposats) , i finalment costos de capital. En este model, a més, es va proposar una nova configuració per a beneficiar-se dels excessos fotovoltaics produïts a partir d'un camp fotovoltaic sobredimensionat, per mitjà de la connexió del sistema de bateries a un convertidor DC/DC de relativament alta potència. Es va analitzar diferents casos d'estudi, a fi de mostrar com este tipus de sistema pot ajudar a reemplaçar els generadors convencionals i assegurar la fiabilitat i qualitat de la xarxa elèctrica. Els casos que s'estudia són: (i.) emmagatzemament d'excessos per “clipping”, (ii.) power- shifting, (iii.) regulació primària i secundària, i (iv.) adaptament de resposta de demanda per mitjà de vehicles elèctrics., [EN] The integration of renewable energy technologies is an important component to achieve the serious environmental objectives of different governments and institutions worldwide. However, there are several challenges along the way to continue increasing in capacity. The greater penetration of these technologies arises the need to provide the same reliability and services that conventional generators have made in the electricity grid. Energy storage provides one of the solutions. The purpose of the master's project was to develop a methodology that allows modeling and simulating energy storage systems coupled to photovoltaic fields, to optimize their integration in electricity networks. The methodology can model any location and any condition that a project of this type requires and calculate its optimal sizing. The parameters that can be varied are the following: power, DC / AC ratio, location, electricity prices, tariff pricing mechanisms (existing and proposed), and finally capital costs. In this model, in addition, a new configuration was proposed to benefit from the photovoltaic excesses produced from an oversized photovoltaic field, by connecting the battery system to a DC/DC converter of relatively high power. Different cases studies were analyzed, in order to show how this type of system can help to replace conventional generators and ensure the reliability and quality of the electrical network. The cases studies were: (i.) Storage of excesses by "clipping", (ii.) Power-shifting, (iii.) Primary and secondary regulation, and (iv.) Demand response coupling by electric vehicles.

Type 2 immune responses in the skin cause a variety of pathologies, including urticaria and atopic dermatitis. Traditionally, CD4(+) helper T cells have been implicated in the pathogenesis of these conditions. However, recently a new player, the group 2 innate lymphoid (ILC2) cell, has emerged as an important contributor to skin allergies. In this review, we summarize our current knowledge of the role ILC2 cells play in the physiology and pathology of mouse and human skin.