Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature

Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy and targeting these features might enhance the efficacy of current treatment. A detailed study of the biological characteristics and behaviour of metastatic OS cells may provide a rational basis for innovative treatment strategies. The aim of this review is to give an overview of the biological changes in metastatic OS cells and the preclinical and clinical efforts targeting the different steps in OS metastases and how these contribute to designing a metastasis directed treatment for OS

Technological challenges in low-mass interstellar probe communication

Building on a preliminary paper design of a downlink from a swarm of low-mass interstellar probes for returning scientific data from the vicinity of Proxima Centauri, the most critical technology issues are summarized, and their significance is explained in the context of the overall system design. The primary goal is to identify major challenges or showstoppers if such a downlink were to be constructed using currently available off-the-shelf technology, and thereby provide direction and motivation to future research on the constituent design challenges and technologies. While there are not any fundamental physical limits that prevent such communication systems, currently available technologies fall significantly short in several areas and there are other major design challenges with uncertain solutions. The greatest identified challenges are in mass constraints, multiplexing simultaneous communication from multiple probes to the same target exoplanet, attitude control and pointing accuracy, and Doppler shifts due to uncertainty in probe velocity. The greatest technology challenges are electrical power, high power and wavelength-agile optical sources, very selective and wavelength-agile banks of optical bandpass filters, and single-photon detectors with extremely low dark-count rates. For a critical subset of these, we describe the nature of the difficulties we encounter and their origins in the overall system context. A receiver that limits reception to a single probe is also considered and compared to the swarm case

Challenges in Scientific Data Communication from Low-mass Interstellar Probes

An optical downlink for the return of scientific data from space probes at interstellar distances is studied. The context is probes moving at relativistic speed using a terrestrial directed-energy beam for propulsion, necessitating very low mass probes. Achieving simultaneous communication from a swarm of probes launched at regular intervals to a target at the distance of Proxima Centauri is addressed. The analysis focuses on fundamental physical and statistical communication limitations on downlink performance rather than a concrete implementation. Transmission time/distance and probe mass are chosen to achieve the best data latency versus volume trade-off. Challenges in targeting multiple probe trajectories with a single receiver are addressed, including multiplexing, parallax, and target-star proper motion. Constraints on transmit aperture size make a compelling argument in favor of free-space optical communications, and this is the assumed approach for our baseline analysis. Relevant sources of background radiation, including cosmic, atmospheric, and receiver dark count, are identified and estimated. Direct detection enables high photon efficiency and incoherent aperture combining. A novel burst pulse-position modulation (BPPM) beneficially expands the optical bandwidth and ameliorates receiver dark counts. A canonical receive optical collector combines minimum transmit power with constrained swarm-probe coverage. Theoretical limits on reliable data recovery and sensitivity to the various BPPM model parameters are applied, including a wide range of total collector areas. Significant near-term technological obstacles are identified. Enabling innovations include a high peak-to-average power ratio, a large source extinguishing factor, the shortest atmosphere-transparent wavelength to minimize target-star interference, adaptive optics for atmospheric turbulence, very selective bandpass filtering (possibly with multiple passbands), very low dark count single-photon superconducting detectors, and very accurate attitude control and pointing mechanisms