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Targeted protein degradation (TPD) has emerged as a prominent and vital strategy for therapeutic intervention of cancers and other diseases. One such approach involves the exploration of proteolysis targeting chimeras (PROTACs) for the selective elimination of disease-causing proteins through the innate ubiquitin-proteasome pathway. Due to the unprecedented achievements of various PROTAC molecules in clinical trials, researchers have moved towards other physiological protein degradation approaches for the targeted degradation of abnormal proteins, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs), molecular glue degraders, and other derivatives for their precise mode of action. Despite numerous advantages, these molecules face challenges in solubility, permeability, bioavailability, and potential off-target or on-target off-tissue effects. Thus, an urgent need arises to direct the action of these degrader molecules specifically against cancer cells, leaving the proteins of non-cancerous cells intact. Recent advancements in TPD have led to innovative delivery methods that ensure the degraders are delivered in a cell- or tissue-specific manner to achieve cell/tissue-selective degradation of target proteins. Such receptor-specific active delivery or nano-based passive delivery of the PROTACs could be achieved by conjugating them with targeting ligands (antibodies, aptamers, peptides, or small molecule ligands) or nano-based carriers. These techniques help to achieve precise delivery of PROTAC payloads to the target sites. Notably, the successful entry of a Degrader Antibody Conjugate (DAC), ORM-5029, into a phase 1 clinical trial underscores the therapeutic potential of these conjugates, including LYTAC-antibody conjugates (LACs) and aptamer-based targeted protein degraders. Further, using bispecific antibody-based degraders (AbTACs) and delivering the PROTAC pre-fused with E3 ligases provides a solution for cell type-specific protein degradation. Here, we highlighted the current advancements and challenges associated with developing new tumour-specific protein degrader approaches and summarized their potential as single agents or combination therapeutics for cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Laser Ranging Interferometer (LRI) instrument on the Gravity Recovery and Climate Experiment (GRACE) Follow-On mission has provided the first laser interferometric range measurements between remote spacecraft, separated by approximately 220 km. Autonomous controls that lock the laser frequency to a cavity reference and establish the 5 degrees of freedom two-way laser link between remote spacecraft succeeded on the first attempt. Active beam pointing based on differential wave front sensing compensates spacecraft attitude fluctuations. The LRI has operated continuously without breaks in phase tracking for more than 50 days, and has shown biased range measurements similar to the primary ranging instrument based on microwaves, but with much less noise at a level of 1  nm/sqrt[Hz] at Fourier frequencies above 100 mHz.

Whether for identification and characterization of materials or for monitoring of the environment, space-based hyperspectral instruments are very useful. Hyperspectral instruments measure several dozens up to hundreds of spectral bands. These data help to reconstruct the spectral properties like reflectance or emission of Earth surface or the absorption of the atmosphere, and to identify constituents on land, water, and in the atmosphere. There are a lot of possible applications, from vegetation and water quality up to greenhouse gas monitoring. But the actual number of hyperspectral space-based missions or hyperspectral space-based data is limited. This will be changed in the next years by different missions. The German Aerospace Center (DLR) Earth Sensing Imaging Spectrometer (DESIS) is one of the new currently existing space-based hyperspectral instruments, launched in 2018 and ready to reduce the gap of space-born hyperspectral data. The instrument is operating onboard the International Space Station, using the Multi-User System for Earth Sensing (MUSES) platform. The instrument has 235 spectral bands in the wavelength range from visible (400 nm) to near-infrared (1000 nm), which results in a 2.5 nm spectral sampling distance and a ground sampling distance of 30 m from 400 km orbit of the International Space Station. In this article, the design of the instrument will be described.

A photoreceiver (PR) is required for the opto-electrical conversion of signals in intersatellite laser interferometers. Noise sources that originate or couple in the PR reduce the system carrier-to-noise-density, which is often represented by its phase noise density. In this work, we analyze the common noise sources in a PR used for space-based interferometry. Additionally, we present the results from the characterization of the PRs in GRACE-FO, a mission which will pioneer intersatellite laser interferometry. The estimated phase noise is shot-noise limited at 10 -4 rad/Hz 1/2 down to 10 -2 Hz, almost 4 orders of magnitude below the instrument top level requirement (0.5 rad/Hz 1/2 ). Below 10 -2 Hz, the PR finite phase response noise dominates but the levels still comply with the instrument requirement. The sub-mHz noise levels and the PR electronic noise have been identified as key design factors for the LISA PR.