HLA-F*01:01 presents peptides with N-terminal flexibility and a preferred length of 16 residues.

HLA-F belongs to the non-classical HLA-Ib molecules with a marginal polymorphic nature and tissue-restricted distribution. HLA-F is a ligand of the NK cell receptor KIR3DS1, whose activation initiates an antiviral downstream immune response and lead to delayed disease progression of HIV-1. During the time course of HIV infection, the expression of HLA-F is upregulated while its interaction with KIR3DS1 is diminished. Understanding HLA-F peptide selection and presentation is essential to a comprehensive understanding of this dynamic immune response and the molecules function. In this study, we were able to recover stable pHLA-F*01:01 complexes and analyze the characteristics of peptides naturally presented by HLA-F. These HLA-F-restricted peptides exhibit a non-canonical length without a defined N-terminal anchor. The peptide characteristics lead to a unique presentation profile and influence the stability of the protein. Furthermore, we demonstrate that almost all source proteins of HLA-F-restricted peptides are described to interact with HIV proteins. Understanding the balance switch between HLA-Ia and HLA-F expression and peptide selection will support to understand the role of HLA-F in viral pathogenesis

CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence

The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A–HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a “lock and key” interaction is typical of innate receptor–ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors

Attitude control for satellites flying in VLEO using aerodynamic surfaces

This paper analyses the use of aerodynamic control surfaces, whether passive or active, in order to carry out very low Earth orbit (VLEO) attitude maneuver operations. Flying a satellite in a very low Earth orbit with an altitude of less than 450 km, namely VLEO, is a technological challenge. It leads to several advantages, such as increasing the resolution of optical payloads or increase signal to noise ratio, among others. The atmospheric density in VLEO is much higher than in typical low earth orbit altitudes, but still free molecular flow. This has serious consequences for the maneuverability of a satellite because significant aerodynamic torques and forces are produced. In order to guarantee the controllability of the spacecraft they have to be analyzed in depth. Moreover, at VLEO the density of atomic oxygen increases, which enables the use of air-breathing electric propulsion (ABEP). Scientists are researching in this field to use ABEP as a drag compensation system, and consequently an attitude control based on aerodynamic control could make sense. This combination of technologies may represent an opportunity to open new markets. In this work, several satellite geometric configurations were considered to analyze aerodynamic control: 3-axis control with feather configuration and 2-axis control with shuttlecock configuration. The analysis was performed by simulating the attitude of the satellite as well as the disturbances affecting the spacecraft. The models implemented to simulate the disturbances were the following: Gravitational gradient torque disturbance, magnetic dipole torque disturbance (magnetic field model IGRF12), and aerodynamic torque disturbances (aerodynamic model DTM2013 and wind model HWM14).The maneuvers analyzed were the following: detumbling or attitude stabilization, pointing and demisability. Different VLEO parameters were analyzed for every geometric configuration and spacecraft maneuver. The results determined which of the analyzed geometric configurations suits better for every maneuver

The benefits of very low earth orbit for earth observation missions

Very low Earth orbits (VLEO), typically classified as orbits below approximately 450 km in altitude, have the potential to provide significant benefits to spacecraft over those that operate in higher altitude orbits. This paper provides a comprehensive review and analysis of these benefits to spacecraft operations in VLEO, with parametric investigation of those which apply specifically to Earth observation missions. The most significant benefit for optical imaging systems is that a reduction in orbital altitude improves spatial resolution for a similar payload specification. Alternatively mass and volume savings can be made whilst maintaining a given performance. Similarly, for radar and lidar systems, the signal-to-noise ratio can be improved. Additional benefits include improved geospatial position accuracy, improvements in communications link-budgets, and greater launch vehicle insertion capability. The collision risk with orbital debris and radiation environment can be shown to be improved in lower altitude orbits, whilst compliance with IADC guidelines for spacecraft post-mission lifetime and deorbit is also assisted. Finally, VLEO offers opportunities to exploit novel atmosphere-breathing electric propulsion systems and aerodynamic attitude and orbit control methods. However, key challenges associated with our understanding of the lower thermosphere, aerodynamic drag, the requirement to provide a meaningful orbital lifetime whilst minimising spacecraft mass and complexity, and atomic oxygen erosion still require further research. Given the scope for significant commercial, societal, and environmental impact which can be realised with higher performing Earth observation platforms, renewed research efforts to address the challenges associated with VLEO operations are required

A review of gas-surface interaction models for orbital aerodynamics applications

Renewed interest in Very Low Earth Orbits (VLEO) - i.e. altitudes below 450 km - has led to an increased demand for accurate environment characterisation and aerodynamic force prediction. While the former requires knowledge of the mechanisms that drive density variations in the thermosphere, the latter also depends on the interactions between the gas-particles in the residual atmosphere and the surfaces exposed to the flow. The determination of the aerodynamic coefficients is hindered by the numerous uncertainties that characterise the physical processes occurring at the exposed surfaces. Several models have been produced over the last 60 years with the intent of combining accuracy with relatively simple implementations. In this paper the most popular models have been selected and reviewed using as discriminating factors relevance with regards to orbital aerodynamics applications and theoretical agreement with gas-beam experimental data. More sophisticated models were neglected, since their increased accuracy is generally accompanied by a substantial increase in computation times which is likely to be unsuitable for most space engineering applications. For the sake of clarity, a distinction was introduced between physical and scattering kernel theory based gas-surface interaction models. The physical model category comprises the Hard Cube model, the Soft Cube model and the Washboard model, while the scattering kernel family consists of the Maxwell model, the Nocilla-Hurlbut-Sherman model and the Cercignani-Lampis-Lord model. Limits and assets of each model have been discussed with regards to the context of this paper. Wherever possible, comments have been provided to help the reader to identify possible future challenges for gas-surface interaction science with regards to orbital aerodynamic applications

Inductive Plasma Thruster (IPT) design for an Atmosphere-Breathing Electric Propulsion System (ABEP)

Challenging space missions include those at very low altitudes, where the atmosphere is source of aerodynamic drag on the spacecraft, therefore an efficient propulsion system is required to extend the mission lifetime. One solution is Atmosphere-Breathing Electric Propulsion (ABEP). It collects atmospheric particles to use as propellant for an electric thruster. This would minimize the requirement of limited propellant availability. The system could be applied to any planet with atmosphere, enabling new mission at these altitude ranges for continuous orbiting. Challenging is also the presence of reactive chemical species, such as atomic oxygen in Earth orbit. Such components are erosion source of (not only) propulsion system components, i.e. acceleration grids, electrodes, and discharge channels of conventional EP systems (RIT and HET). IRS is developing within the DISCOVERER project an intake and a thruster for an ABEP system. This paper deals with the design and first operation of the inductive plasma thruster (IPT) developed at IRS. The paper describes its design aided by numerical tools such as HELIC and ADAMANT. Such a device is based on RF electrodeless discharge aided by externally applied static magnetic field. The IPT is composed by a movable injector, to variate the discharge channel length, and a movable electromagnet to variate position and intensity of the magnetic field. By changing these parameters along with a novel antenna design for electric propulsion, the aim is to achieve the highest efficiency for the ionization stage by enabling the formation of helicon-based discharge. Finally, the designed IPT is presented and the feature of the birdcage antenna highlighted

Concepts and Applications of Aerodynamic Attitude and Orbital Control for Spacecraft in Very Low Earth Orbit

Spacecraft operations below 450km, namely Very Low Earth Orbit (VLEO), can offer significant advantages over traditional low Earth orbits, for example enhanced ground resolution for Earth observation, improved communications latency and link budget, or improved signal-to-noise ratio. Recently, these lower orbits have begun to be exploited as a result of technology development, particularly component miniaturisation and cost-reduction, and concerns over the increasing debris population in commercially exploited orbits. However, the high cost of orbital launch and challenges associated with atmospheric drag, causing orbital decay and eventually re-entry are still a key barrier to their wider use for large commercial and civil spacecraft. Efforts to address the impact of aerodynamic drag are being sought through the development of novel drag-compensation propulsion systems and identification of materials which can reduce aerodynamic drag by specularly reflecting the incident gas. However, the presence of aerodynamic forces can also be utilised to augment or improve spacecraft operations at these very low altitudes by providing the capability to perform coarse pointing control and trim or internal momentum management for example. This paper presents concepts for the advantageous use of spacecraft aerodynamics developed as part of DISCOVERER, a Horizon 2020 funded project with the aim to revolutionise Earth observation satellite operations in VLEO. The combination of novel spacecraft geometries and use of aerodynamic control methods are explored, demonstrating the potential for a new generation of Earth observation satellites operating at lower altitudes

Discoverer - Making commercial satellite operations in very low earth orbit a reality

DISCOVERER is a €5.7M European Commission funded Horizon 2020 project developing technologies to enable commercially-viable sustained-operation of satellites in very low Earth orbits. Why operate closer to the Earth? For communications applications latency is significantly reduced and link budgets improved, and for remote sensing improved link budgets allow higher resolution or smaller instruments, all providing cost benefits. In addition, all applications benefit from increased launch mass to lower altitudes, whilst end-of-life removal is ensured due to the increased atmospheric drag. However, this drag must also be minimised and compensated for. One of the key technologies being developed by DISCOVERER are materials that encourage specular reflection of the residual atmosphere at these altitudes. Combined with appropriate geometric designs these can significantly reduce drag, provide usable lift for aerodynamic attitude and orbit control, and improve the collection efficiency of aerodynamic intakes for atmosphere breathing electric propulsion systems, all of which are being developed as part of DISCOVERER. The paper provides highlights from the developments to date, and the potential for a new class of aerodynamic commercial satellites operating at altitudes below the International Space Station

Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways

A specific small-molecule inhibitor of p97 would provide an important tool to investigate diverse functions of this essential ATPase associated with diverse cellular activities (AAA) ATPase and to evaluate its potential to be a therapeutic target in human disease. We carried out a high-throughput screen to identify inhibitors of p97 ATPase activity. Dual-reporter cell lines that simultaneously express p97-dependent and p97-independent proteasome substrates were used to stratify inhibitors that emerged from the screen. N^2,N^4-dibenzylquinazoline-2,4-diamine (DBeQ) was identified as a selective, potent, reversible, and ATP-competitive p97 inhibitor. DBeQ blocks multiple processes that have been shown by RNAi to depend on p97, including degradation of ubiquitin fusion degradation and endoplasmic reticulum-associated degradation pathway reporters, as well as autophagosome maturation. DBeQ also potently inhibits cancer cell growth and is more rapid than a proteasome inhibitor at mobilizing the executioner caspases-3 and -7. Our results provide a rationale for targeting p97 in cancer therapy