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Several starshade concepts for imaging exo-Earths would operate at the second Earth–Sun Lagrange point (L2) and consist of a starshade flying in formation tens to hundreds of thousands of kilometers from a telescope. The starshade would need to maintain meter-level lateral alignment with the line of sight from telescope to target star. A companion paper describes an optical sensing scheme using a pupil imaging camera in the telescope that can sense the relative lateral position to a few centimeters. A full flight-traceable formation flying framework that leverages this sensor is presented. In particular, a two-dimensional “disk deadbanding” algorithm is introduced for lateral control. The framework also maximizes the drift time between thruster burns to reduce interruption to scientific observations. The main sources of uncertainty affecting the control performance are compared, and it is found that spacecraft mass uncertainty is a driving factor. The formation flying environment is also analyzed to identify conditions that lead to worst-case differential gravity and solar radiation pressure disturbances. Finally, for a representative observation scenario with the Wide Field Infrared Space Telescope, this control system is tested through Monte Carlo simulations. The results show robust meter-level control with essentially optimal drift time between thruster burns.

Polymersomes are vesicles formed by self-assembly from block copolymers. A widely studied biodegradable diblock copolymer that forms polymersomes is poly(ethylene-glycol)-block-poly(ε-caprolactone) (PEG-b-PCL). Polymersomes from this copolymer have been prepared by various methods. Major drawbacks are either the use of organic solvents, the need for post-preparation steps or low polymer concentration in resulting dispersions. Here, we studied the use of dual asymmetric centrifugation (DAC) as alternative and innovative preparation method by which these disadvantages can be overcome. We investigated the influence of process parameters on the size of resulting particles and their morphology. Additionally, the ability of this method to encapsulate both hydrophilic and hydrophobic drugs into polymersomes was assessed to evaluate its usefulness in the manufacture of nano-therapeutics. We found, that depending on process parameters, formation of nanosized vesicles with considerable drug encapsulation is achievable. Interestingly, with DAC polymersomes could also be prepared from a high molecular weight copolymer that was not able to generate vesicles by conventional methods. In addition, no organic solvents are used, no postprocessing is necessary and preparation is done quickly in a single vessel, minimizing product loss. DAC leads to highly concentrated, drug-loaded polymersome dispersions and therefore represents a major step towards their applicability in nanomedicine.

Background Use of enzyme replacement therapy (ERT) to treat Fabry disease, caused by deficient lysosomal α -galactosidase A activity, can lead to formation of neutralizing antidrug antibodies (ADAs). These antibodies are associated with increased accumulation of plasma globotriaosylceramide (Gb3) and disease progression. Because agalsidase ERT can saturate ADA-binding sites during infusions (achieving agalsidase/antibody equilibrium), we investigated in this open cohort study whether saturated patients (who have excess agalsidase after infusions) experience better clinical outcomes compared with not saturated patients (who have excess ADAs after infusions). Methods We isolated ADAs from sera of 26 men with Fabry disease receiving ERT (for a median of 94 months) and determined the amount of agalsidase necessary for antibody saturation. Clinical and biochemical outcomes included measurements of eGFR, interventricular septum thickness, and lyso-Gb3. Results ADA titers decreased significantly in all patients during infusion. Agalsidase- α and agalsidase- β had similar ADA-binding capacity and comparable ADA saturation frequency. Fourteen patients with saturated ADAs presented with mild (but significant) loss of eGFR, stable septum thickness, and significantly decreased lyso-Gb3 levels. The 12 not saturated patients had a more pronounced and significant loss of eGFR, increased septum thickness, and a smaller, nonsignificant reduction in lyso-Gb3, over time. In three patients, dose escalation resulted in partially elevated ADA titers, but importantly, also in reduced lyso-Gb3 levels. Conclusions A not saturated ADA status during infusion is associated with progressive loss of eGFR and ongoing cardiac hypertrophy. Dose escalation can result in saturation of ADAs and decreasing lyso-Gb3 levels, but may lead to increased ADA titers.

The HabEx (Habitable Exoplanet) space telescope mission concept carries two complementary optical systems as part of its baseline design, a coronagraph and a starshade, that are designed to detect and characterize planetary systems around nearby stars. The starshade is an external occulter which would be 72 m in diameter and fly some 124,000 km ahead of the telescope. A starshade instrument on board the telescope enables formation flying to maintain the starshade within 1 m of the line of sight to the star. The starshade instrument has various modes, including imaging from the near UV through to the near infrared and integral field spectroscopy in the visible band. The coronagraph would provide imaging and integral field spectroscopy in the visible band and would reach out to 1800 nm for low resolution spectroscopy in the near infrared. To provide the necessary stability for the coronagraph, the telescope would be equipped with a laser metrology system allowing measurement and control of the relative positions of the principal mirrors. In addition, a fine guidance sensor is needed for precision attitude control. The requirements for telescope stability for coronagraphy are discussed. The design and requirements on the starshade will also be discussed.

The Habitable Exoplanet Imaging Mission (HabEx) Study is one of four studies sponsored by NASA for consideration by the 2020 Decadal Survey Committee as a potential flagship astrophysics mission. A primary science directive of HabEx would be to image and characterize potential habitable exoplanets around nearby stars. As such, the baseline design of the HabEx observatory includes two complimentary starlight suppression systems that reveal the reflected light from the exoplanet – an internal coronagraph instrument, and an external, formation-flying starshade occulter. In addition, two general astrophysics instruments are baselined: a high-resolution ultraviolet spectrograph, and an ultraviolet, visible, and near-infrared (UV/Vis/NIR), multi-purpose, wide-field imaging camera and spectrograph. In this paper, we present the baseline architecture concept for a 4m HabEx telescope, including key requirements and a description of the mission and payload designs.

The HabEx (Habitable Exoplanet) concept study is defining a future space telescope with the primary mission of detecting and characterizing planetary systems around nearby stars. The telescope baseline design includes a high-contrast coronagraph and a starshade to enable the direct optical detection of exoplanets as close as 70 mas to their star. In addition to the study of exoplanets, HabEx carries two dedicated instruments for general astrophysics. The first instrument is a camera enabling imaging on a 3 arc minute field of view in two bands stretching from the UV at 150 nm to the near infrared at 1800 nm. The same instrument can also be operated as a multi-object spectrograph, with resolution of 2000. The second instrument is a high-resolution UV spectrograph operating from 300 nm down to 115 nm with up to 60,0000 resolution. HabEx would provide the highest resolution UV/optical images ever obtained. Diffraction limited at 0.4 μm, it would outperform all current and approved facilities, including the 30 m class ground-based extremely large telescopes (ELTs), which will achieve ~0.01 arcsecond resolution at near-infrared (IR) wavelengths with adaptive optics, but will be seeing-limited at optical wavelengths. HabEx would observe wavelengths inaccessible from the ground, including the UV and in optical/near-IR atmospheric absorption bands. Operating at L2, far above the Earth’s atmosphere and free from the large thermal swings inherent to HST’s low-Earth orbit, HabEx would provide an ultra-stable platform that will enable science ranging from precision astrometry to the most sensitive weak lensing maps ever obtained. Here we discuss the design concepts of the general astrophysics optical instruments for the proposed observatory.

The Habitable Exoplanet Imaging Mission (HabEx) concept has been designed to enable an extensive suite of science, broadly put under the rubric of General Astrophysics, in addition to its exoplanet direct imaging science. General astrophysics directly addresses multiple NASA programmatic branches, and HabEx will enable investigations ranging from cosmology, to galaxy evolution, to stellar population studies, to exoplanet transit spectroscopy, to Solar System studies. This poster briefly describes one of the two primary HabEx General Astrophysics instruments, the HabEx Workhorse Camera (HWC). HWC will be a dual-detector UV-to-near-IR imager and multi-object grism spectrometer with a microshutter array and a moderate (3' x 3') field-of-view. We detail some of the key science we expect HWC to undertake, emphasizing unique capabilities enabled by a large-aperture, highly stable space-borne platform at these wavelengths.

Starshades, combined with future space telescopes, provide the ability to detect Earth-like exoplanets in the habitable zone by producing high contrast ratios at small inner working angles. The primary function of a starshade is to suppress light from a target star such that its orbiting planets are revealed. In order to do so, the optical edges of the starshade must maintain their precise in-plane profile to produce the necessary apodization function. However, an equally important consideration is the interaction of these edges with light emanating from our own Sun as scattered and/or diffracted sunlight can significantly degrade the achievable contrast. This paper describes the technical efforts performed to obtain precision, low-scatter optical edges for future starshades. Trades between edge radius (i.e. sharpness) and surface reflectivity have been made and small-scale coupons have been produced using scalable manufacturing processes. A custom scattered light testbed has been developed to quantify the magnitude of scattered light over all sun angles. Models have also been developed to make predictions on the level of reflected and/or diffracted light for various edge architectures. The results of these studies have established a current baseline approach which implements photochemical etching techniques on thin metal foils.

We present an update to our paper from last year on the design and capabilities of the Ultraviolet Spectrograph (UVS) instrument on the Habitable Exoplanet Observatory (HabEx) concept. The design has been matured to be both more compact and serviceable while delivering all the required capabilities that the original Science Traceability Matrix (STM) demanded. Since last year the project has begun design considerations for a second Architecture for the overall mission, and we present design changes that optimize the performance of the instrument when combined with that Optical Telescope Assembly (OTA). Results of a start at a community driven Design Reference Mission (DRM) are also included to illustrate the anticipated performance of the instrument.

The HabEx mission concept is intended to directly image planetary systems around nearby stars, and to perform a wide range of general astrophysics and solar system observations. Its main goal is the discovery and characterization of Earthlike exoplanets through high-contrast imaging and spectroscopy. The baseline HabEx concept would use both a coronagraph and a starshade for exoplanet science. We describe an alternative, “HabEx Lite” concept, which would use a starshade (only) for exoplanet science. The benefit is lower cost: by deleting the complex coronagraph instrument; by lowering observatory mass; by relaxing tolerances and stability requirements; by permitting use of a compact on-axis telescope design; by use of a smaller launch vehicle. The scientific penalty of this lower cost option is a smaller number of detected exoplanets of all types, including exoEarth candidates, and a smaller fraction of exoplanets with measured orbits. Our approach uses a non-deployed segmented primary mirror, whose manufacture is within current capabilities.

Aim: MicroRNA-222 (miR-222) and miR-29c have been identified as important modulators of cardiac growth and may protect against pathological cardiac remodeling. miR-222 and -29c may thus serve as functional biomarkers for exercise-induced cardiac adaptations. This investigation compared the effect of two workload-matched high-intensity interval training (HIIT) protocols with different recovery periods on miR-222 and -29c levels.Methods: Sixty-three moderately trained females and males (22.0 ± 1.7 years) fulfilled the eligibility criteria and were randomized into two HIIT groups using sex and exercise capacity. During a controlled 4-week intervention (two sessions/week) a 4 × 30 HIIT group performed 4 × 30 s runs (all-out, 30 s active recovery) and a 8 × 15 HIIT group performed 8 × 15 s runs (all-out, 15 s active recovery). miR-222 and -29c as well as transforming growth factor-beta1 (TGF-beta1) mRNA levels were determined during high-intensity running as well as aerobic exercise using capillary blood from earlobes. Performance parameters were assessed using an incremental continuous running test (ICRT) protocol with blood lactate diagnostic and heart rate (HR) monitoring to determine HR recovery and power output at individual anaerobic threshold (IAT).Results: At baseline, acute exercise miR-222 and -29c levels were increased only in the 4 × 30 HIIT group (both p < 0.01, pre- vs. post-exercise). After the intervention, acute exercise miR-222 levels were still increased in the 4 × 30 HIIT group (p < 0.01, pre- vs. post-exercise) while in the 8 × 15 HIIT group again no acute effect was observed. However, both HIIT interventions resulted in elevated resting miR-222 and -29c levels (all p < 0.001, pre- vs. post-intervention). Neither of the two miRNAs were elevated at any ICRT speed level at baseline nor follow-up. While HR recovery was improved by >24% in both HIIT groups (both p ≤ 0.0002) speed at IAT was improved by 3.6% only in the 4 × 30 HIIT group (p < 0.0132). Correlation analysis suggested an association between both miRNAs and TGF-beta1 mRNA (all p ≤ 0.006, r ≥ 0.74) as well as change in speed at IAT and change in miR-222 levels (p = 0.024, r = 0.46).Conclusions: HIIT can induce increased circulating levels of cardiac growth-associated miR-222 and -29c. miR-222 and miR-29c could be useful markers to monitor HIIT response in general and to identify optimal work/rest combinations.

Binary Zintl anions of the tetrel and pentel elements have been synthesized. The work's focus is on the synthesis and derivatization of Zintl anions and multi-metallic clusters of the elemental combinations of germanium/phosphorus and germanium/arsenic. Novel binary Zintl anions and multi-metallic clusters with the elements vanadium, niobium, tantalum, and cadmium are presented., Binäre Zintl-Anionen der Tetrele und Pentele wurden synthetisiert. Die Arbeit konzentriert sich auf die Synthese und Derivatisierung von Zintl-Anionen und multimetallischer Cluster der Elementkombinationen Germanium/Phosphor und Germanium/Arsen. Neue binäre Zintl-Anionen sowie multimetallische Cluster, die die Elemente Vanadium, Niob, Tantal und Cadmium enthalten werden vorgestellt.

Case T-569/18, Kordes' Rose Monique, General Court of the European Union, decision of 18 June 2019, EU:T:2019:421

Most members of the taxon Heteroptera, which includes 42,300 described species (12), display mutualistic relationships with diverse symbiotic bacteria (6, 30). While some stinkbug species of the families Lygaeidae, Artheneidae, Blissidae, and Cimicidae harbor their endosymbionts intracellularly in specific organs, called bacteriomes or mycetomes (16, 36–38, 43, 57), most phytophagus stinkbugs, particularly members of the infraorder Pentatomomorpha, extracellularly accommodate their symbiotic bacteria either in the lumen of the swollen part of the midgut (26, 60) or in the lumen of the separated sac-like tissues of the posterior midgut, called crypts or ceca (6, 54, 68). In plant-sucking stinkbugs of the superfamily Pentatomoidea (Heteroptera: Pentatomomorpha), species of the families Acanthosomatidae, Cydnidae, Parastrachiidae, Pentatomidae, Plataspidae, Scutelleridae, and Urostylididae harbor specific bacterial symbionts, which belong to distinct lineages in Gammaproteobacteria, indicating multiple evolutionary origins of symbiotic associations (2, 3, 13, 15, 17, 19, 23–25, 31, 34, 35, 44, 51–53). The gut symbionts of the Pentatomoidea are typically transmitted vertically by specific, postnatal transmission mechanisms, such as the bacterial contamination of the egg surface during egg deposition (1, 31, 53, 55), the excretion of a bacteria-containing mucus or jelly onto the egg mass (18, 25), and the deposition of bacteria-containing capsules together with the eggs (9, 14, 15, 47). In contrast, most representatives of the superfamilies Lygaeoidea and Coreoidea are associated with the betaproteobacterial symbionts of a specific clade in the genus Burkholderia, called the “stinkbug-associated beneficial and environmental (SBE)” group (4, 10, 22, 28, 29, 32, 33, 50). Based on a series of comprehensive studies on the coreoid species, Riptortus pedestris (Coreoidea: Alydidae), it has been reported that Burkholderia symbionts are not transmitted vertically, but are acquired anew by nymphal insects from the environment every generation (29), whereas partial vertical transmission of the Burkholderia symbiont has been reported in chinch bugs (4, 22). Due to the transmission mechanism, the phylogeny of the Burkholderia symbiont does not mirror the phylogeny of the host insects, but symbionts form a coherent group with soil-isolated strains in an intermixed manner (28, 29, 32), indicating an alternating host–symbiont relationship. In addition, a recent study revealed that representatives of the family Largidae of the superfamily Pyrrhocoroidea, a monophyletic sister taxon of Coreoidea and Lygaeoidea (67), are also associated with Burkholderia symbionts (61). However, these largid species are, in contrast to lygaeoid/coreoid species, consistently associated with Burkholderia strains of the so-called “plant-associated beneficial and environmental (PBE)” group, which are phylogenetically distinct from the SBE strains (63). In the PBE-group, stinkbug-associated strains do not form a monophyletic cluster, but are intermixed with soil-isolated and plant-associated strains, also indicating a promiscuous host–symbiont association in pyrrhocorid stinkbugs. The family Stenocephalidae of the superfamily Coreoidea is a small stinkbug group, all members of which live and feed on various species of the Euphorbiaceae, commonly known as spurges (58). Landsbury (39, 40) identified two genera (Dicranocephalus and Psotilnus) and 36 species, whereas Moulet (45, 46) considered only one genus (Dicranocephalus) and 16 valid species. Although the group is widely distributed, most are known from the tropics and subtropics of the Eastern Hemisphere, including Australia. This small family is of special taxonomic interest because it shows characteristics that are transitional between Coreoidea (e.g., numerous hemelytral veins and a four-lobed salivary gland) and Lygaeoidea (e.g., laciniate ovipositor and an XY chromosome) (11, 12, 58). Therefore, the phylogenetic position of Stenocephalidae was controversial for a long time (11). In addition to the taxonomical importance of this family, its gut symbiotic association has not yet been characterized. The objective of this study was to analyze and compare the bacterial populations of midgut crypts in the stenocephalid species Dicranocephalus albipes, D. agilis, and D. medius (Fig. 1A) from Europe, and D. lateralis from Japan (Heteroptera: Stenocephalidae). The phylogenetic position of the bacterial gut symbiont was elucidated by analyses of 16S rRNA and gyrB gene sequences. The localization as well as morphological characteristics of the gut symbiont of D. medius was investigated in detail by fluorescence in situ hybridization (FISH) and transmission electron microscopy (TEM), respectively. The results obtained revealed that a novel clade of Burkholderia is associated with the stenocephalid species. Fig. 1 A representative of the family Stenocephalidae associated with Burkholderia symbionts in their midgut crypts. (A) An adult female of Dicranocephalus medius sitting on its Euphorbia host plant. (B) Dissected midgut of the fourth section (m4) with two rows ...

The evolution of microstructure defects under compression, their mutual interactions at high defect densities and the effect of these phenomena on the hardening were studied in metastable austenitic steel containing 16 wt% Cr, 6 wt% Mn and 9 wt% Ni. At this chemical composition, the estimated martensite start temperature and the stacking fault energy of austenite are about −240 °C and 26 mJ/m2, respectively. Consequently, the metastable austenite should be thermodynamically stable far below the room temperature and the formation of stacking faults should be retarded. The microstructure analysis, which was performed by means of XRD, ECCI, EBSD and TEM, revealed that the dislocation slip is the dominant deformation mechanism in the initial stages of the deformation process (e≤0.05). After a critical stress level was reached, stacking faults started to form and widen. In regions with high local stacking fault densities, twinning and the formation of e-martensite were detected simultaneously. The local deformation mechanism and the related microstructure changes were found to depend on the orientation of the respective grain. In favorably oriented grains, deformation bands consisting of e-martensite and twins were predominantly formed in the primary slip system. In other grains, the dislocation slip remained the dominant deformation mechanism. The coexistence of faulting, twinning and dislocation slip and the interaction between the dislocations and stacking faults are discussed as the main reasons for the high observed density of microstructure defects and high hardening.

Covering up to January 2016Cannabis sativa L. is a prolific, but not exclusive, producer of a diverse group of isoprenylated resorcinyl polyketides collectively known as phytocannabinoids. The modular nature of the pathways that merge into the phytocannabinoid chemotype translates in differences in the nature of the resorcinyl side-chain and the degree of oligomerization of the isoprenyl residue, making the definition of phytocannabinoid elusive from a structural standpoint. A biogenetic definition is therefore proposed, splitting the phytocannabinoid chemotype into an alkyl- and a β-aralklyl version, and discussing the relationships between phytocannabinoids from different sources (higher plants, liverworts, fungi). The startling diversity of cannabis phytocannabinoids might be, at least in part, the result of non-enzymatic transformations induced by heat, light, and atmospheric oxygen on a limited set of major constituents (CBG, CBD, Δ9-THC and CBC and their corresponding acidic versions), whose degradation is detailed to emphasize this possibility. The diversity of metabotropic (cannabinoid receptors), ionotropic (thermos-TRPs), and transcription factors (PPARs) targeted by phytocannabinoids is discussed. The integrated inventory of these compounds and their biological macromolecular end-points highlights the opportunities that phytocannabinoids offer to access desirable drug-like space beyond the one associated to the narcotic target CB1.

We directly show how impurity atoms induce the condensation of a representative electronic phase, the charge density wave (CDW) phase, in atomic scale with scanning tunneling microscopy. Oxygen impurity atoms on the self-assembled metallic atomic wire array on a silicon crystal condense the CDW locally above the pristine transition temperature. More interestingly, the CDW along the wires is induced not by a single atomic impurity but by the cooperation of multiple impurities. First-principles calculations disclose the mechanism of the cooperation as the coherent superposition of the local lattice strain induced by impurities, stressing the coupled electronic and lattice degrees of freedom for the CDW. This opens the possibility of the strain engineering over electronic phases of atomic-scale systems.

Recently, the nanomechanical properties (i.e. stiffness) of endothelial cells have been identified as crucial for appropriate endothelial function. One major determinant of endothelial stiffness is the endothelial sodium channel (EnNaC). EnNaC-dependent stiffening leads to reduced nitric oxide release, which is a hallmark for endothelial dysfunction. In the current study, we hypothesized that endothelial function is directly linked to the overall function of the arterial system.Sixty-four human ex-vivo arterial samples were collected from femoral bypass or vein-stripping procedures. Nanomechanical characteristics of ex-vivo endothelium from isolated arterial side branches were determined using atomic force microscopy. The endothelium's potential to respond to EnNaC inhibition by amiloride was defined as endothelial amiloride index. In addition, patients' arterial stiffness was determined by pulse wave velocity (PWV).Fifty-three percentage of the ex-vivo samples responded 'classically' to amiloride with endothelial softening, whereas 47% of the patients' samples did not. Interestingly, a lack of endothelial softening in the presence of amiloride in vitro was observed with higher frequency among samples obtained from individuals with elevated PWV. Further, an increased PWV was associated with impaired renal function and endothelial dysfunction (higher levels of von Willebrand factor).Here, we report differential responses of human ex-vivo vessels to amiloride. Although the mechanism of differential amiloride response is still unknown, the data indicate that drug action on endothelial function could differ strongly among patients, especially in those with a vascular end-organ damage determined by PWV.

The activation of different deformation mechanisms in high-alloy austenitic steels depends strongly on the concentration of the alloying elements, as they change the driving force for the martensitic phase transformation and the stacking fault energy in the austenite. Consequently, local chemical gradients alter the local deformation behaviour tremendously. In this contribution, the correlations between the local chemical composition, the corresponding difference between the Gibbs energies of austenite and α ′ - martensite , martensite start temperature, stacking fault energy, observed stacking fault density and the prevailing deformation mechanism are illustrated.

In this study, the formation of deformation bands during plastic deformation in austenite is analysed. The movement of (partial) dislocations on neighboring lattice planes formed pronounced deformation bands, which were identified as ϵ-martensite if the stacking faults are predominantly aligned on every second {111} lattice plane. In these deformation bands, α′-martensite nuclei are formed, severely fragmenting the mean free path of dislocations. The strain hardening is found to depend directly on the nucleation rate of α′-martensite. The α′-martensite nuclei represented effective barriers for (partial) dislocation movement in the deformation bands. On the basis of three different grain sizes, the strain-hardening capability of the martensitic γ ϵ α′ phase transformation is analysed. Although the triggering stress for nucleation of α′-martensite is influenced by grain size, the absolute value of the strain hardening due to α′-martensite formation is the same. This is related to the fact that the continuous fragmentation of the dislocation mean free path is in the same order of magnitude for all grain sizes. Using a basic approach that treated the continuous reduction of the dislocation mean free path as a Hall–Petch-like effect, comparable with strain hardening in TWIP steels, the contribution of the effect to the increasing strength in austenitic TRIP steels is estimated.