561975 research outputs found
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Conceptions of data protection and privacy: legal and philosophical perspectives
No full textThis open access book offers a clear and concise overview of leading conceptions of data protection and privacy, exploring their social value through philosophical theorisations and European and US-American legal perspectives.Featuring prominent experts and emerging scholars, the book presents diverse understandings to showcase the multifaceted interests and values embedded in the concepts of data protection and privacy. It links philosophical and legal perspectives on privacy to historical and contemporary rights struggles. The book also addresses privacy challenges posed by the digital revolution, including advances in AI, and recent efforts to safeguard privacy.Aimed at scholars, researchers, and students in law and philosophy, the book covers key theoretical and legal positions on privacy and data protection. Legal practitioners will find insights into landmark EU and US constitutional decisions, such as the German Constitutional Court's Census Decision and Carpenter v United States. Additionally, it is valuable for anyone seeking to understand the legal and philosophical foundations of globally influential regulations like the GDPR and the AI Act
<monospace>robostrategy</monospace>: Field and Target Assignment Optimization in the Sloan Digital Sky Survey V
No full textWe present an algorithmic method for efficiently planning a long-term, large-scale multiobject spectroscopy program. The Sloan Digital Sky Survey V (SDSS-V) Focal Plane System performs multiobject spectroscopy using 500 robotic positioners to place fibers feeding optical and infrared spectrographs across a wide field. SDSS-V uses this system to observe targets throughout the year at two observatories in support of the science goals of its Milky Way Mapper and Black Hole Mapper programs. These science goals require observations of objects over time with preferred temporal spacings (referred to as "cadences"), which can differ from object to object even in the same area of sky. robostrategy is the software we use to construct our planned observations so that they can best achieve the desired goals given the time available as a function of sky brightness and local sidereal time, and to assign fibers to targets during specific observations. We use linear programming techniques to seek optimal allocations of time under the constraints given. We present the methods and example results obtained with this software
International expert consensus on gene therapy for hereditary hearing loss: Based on clinical trials
No full textBackground:Hereditary hearing loss is one of the most common disabling disorders in children and lacks effective pharmacological treatments. Recent breakthroughs in OTOF gene therapy clinical trials necessitate standardized frameworks to guide emerging therapies. This study aims to establish the first international consensus on the clinical application of gene therapy for hereditary hearing loss.Methods:A modified Delphi process was conducted from March 2024 to March 2025, involving 46 multidisciplinary experts from several countries across otology, genetics, audiology, gene therapy, and hearing rehabilitation. After a systematic literature review, as well as integration of research and clinical expertise and experience, three iterative voting rounds (two anonymous surveys and one online consensus meeting) were performed. Statements required ≥75% agreement for inclusion.Findings:From 9,093 publications, 69 were used to draft and support the consensus statements. A total of 30 statements relevant to six domains achieved consensus on gene therapy for hereditary hearing loss, including ethical review (1 statement), patient selection criteria (12 statements), diagnosis and preoperative evaluation (9 statements), gene therapy drug delivery (4 statements), follow-up (3 statements), and post-treatment auditory and speech rehabilitation (1 statement).Conclusions:This consensus provides the first globally endorsed framework for gene therapy in hereditary hearing loss. It standardizes clinical trial design and patient management, accelerating translation from research to practice while ensuring safety. The guidelines are immediately applicable to OTOF-related hearing loss and adaptable to other genetic forms
On the Range of Existence of the Intermetallic Compounds FeSi and PtSi
No full textIntermetallic compounds play a key role as catalysts in numerous important chemical reactions. Iron- and platinum-based intermetallic compounds have gained a lot of attention because of their advantageous properties in industrial processes and their widespread application. To understand the atomic and electronic structure as well as the catalytic properties of the compounds, it is crucial to analyze the phases and determine the parameter range (i.e., composition and temperature) over which these compounds remain stable as even minor deviations in the composition can substantially alter a compound's chemical and physical properties. This makes the exact determination of homogeneity ranges particularly critical. The range of existence of FeSi and PtSi is revisited, and for FeSi, no measurable homogeneity range is observed at 800 degrees C, while PtSi demonstrates a narrow phase width at 825 degrees C. Phase boundaries of the neighboring phases (Fe3Si, FeSi2, Pt6Si5, and (Si, Pt)) and their corresponding lattice parameters are reported in addition
X-ray contrast-adjustable 3D printing for multimodal fusion of microCT and histology
No full textIntroduction: Phantoms and reference structures are essential tools for calibration and correlative imaging in pre-clinical and research applications of X-ray-based imaging. They serve as reference standards, ensuring consistency and accuracy in imaging results. However, generating individual phantoms often involves a complex creation process, high production costs, and significant time investment.Material and methods: Conic reference structures were 3D printed using a mixture of UV-curable resin and X-ray contrast agents. These structures were then embedded together with lung specimens of SARS-CoV-2-infected rhesus macaques in a methyl methacrylate-based solution. The polymerized blocks were scanned using propagation-based phase-contrast microCT, a method chosen for its superior ability to enhance contrast, especially in low-absorbing biological samples. Utilizing the conic reference structures, subsequently performed histological sections were co-registered into the 3D context of the microCT datasets.Results: The produced 3D printed models were highly visible in terms of contrast and detail in both imaging methods, allowing for a precise co-registration of microCT and histological imaging.Conclusions: The novel methodology of using contrast agents and resin in 3D printing enables the generation of customizable, contrast-specific phantoms and reference structures. These can be straightforwardly segmented from the embedding material, significantly simplifying and enhancing the workflow of multimodal imaging processes. In this study, 3D printed conic reference structures were effectively used to automate and streamline the precise multimodal fusion of microCT and histological imaging
New mitochondrial K<sub>V</sub>1.3 conjugates are potent and specific inducers of apoptosis in cancer models
No full textMitochondrial KV1.3 channels (mitoKV1.3) have emerged as promising targets for cancer therapy due to their role in regulating apoptosis, independent of upstream signalling pathways and Bcl-2 family protein levels. Here, we present a new non-psoralene Kv1.3 mitochondria-targeted conjugates. These conjugates, particularly cis-8 and cis-9, exhibit nanomolar affinity and high selectivity for KV1.3 while effectively inducing apoptosis in tumor cells. Unlike their parent KV1.3 inhibitors, which lack cytotoxicity, the mitoKV1.3 conjugates induce rapid mitochondrial depolarization, and caspase-3/7 activation, culminating in dose-dependent tumor cell death in both 2D and 3D models. Mechanistically, cis-8 and cis-9 disrupt mitochondrial membrane potential and selectively target cancer cells, sparing normal cells at lower concentrations. Notably, KV1.3 knockout models confirmed the dependence of cytotoxicity on mitoKV1.3 inhibition. The conjugates demonstrated robust antitumor activity in murine pancreatic intraepithelial neoplasia (PanIN)-derived organoids, with preferential action over normal pancreatic organoids, highlighting their tumor selectivity. Importantly, safety assessments showed no significant DNA damage or chromosomal aberrations at non-cytotoxic doses. This study introduces a new structural class of mitochondria-targeted KV1.3 inhibitors with enhanced solubility compared to psoralen-based analogues. The unique mechanism of action, characterized by rapid depolarization and moderate ROS dependence, underscores their potential as selective anticancer agents. These findings warrant further investigation into in vivo efficacy and potential synergy with existing therapies
