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In this work, we design and experimentally demonstrate the first, to the best of our knowledge, integrated polarization splitters and rotators at blue wavelengths. We develop compact and efficient designs for both a polarization splitter and rotator at a 422-nm wavelength, an important laser-cooling transition for 88Sr+ ions. These devices are fabricated in a 200-mm wafer-scale process and experimentally demonstrated, resulting in a measured polarization-splitter transverse-electric thru-port coupling of 98.0% and transverse-magnetic tap-port coupling of 77.6% for a compact 16-µm-long device and a polarization-rotator conversion efficiency of 92.2% for a separate compact 111-µm-long device. This work paves the way for more sophisticated integrated control of trapped-ion and neutral-atom quantum systems.
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INTRODUCTION: Associations of cerebellar atrophy with specific neuropathologies in Alzheimer's disease and related dementias (ADRD) have not been systematically analyzed. This study examined cerebellar gray matter volume across major pathological subtypes of ADRD. METHODS: Cerebellar gray matter volume was examined using voxel-based morphometry in 309 autopsy-proven ADRD cases and 80 healthy controls. ADRD subtypes included AD, mixed Lewy body disease and AD (LBD-AD), and frontotemporal lobar degeneration (FTLD). Clinical function was assessed using the Clinical Dementia Rating (CDR) scale. RESULTS: Distinct patterns of cerebellar atrophy were observed in all ADRD subtypes. Significant cerebellar gray matter changes appeared in the early stages of most subtypes and the very early stages of AD, LBD-AD, FTLD-TDP type A, and progressive supranuclear palsy. Cortical atrophy positively predicted cerebellar atrophy across all subtypes. DISCUSSION: Our findings establish pathology-specific profiles of cerebellar atrophy in ADRD and propose cerebellar neuroimaging as a non-invasive biomarker for differential diagnosis and disease monitoring. HIGHLIGHTS: Cerebellar atrophy was examined in 309 patients with autopsy-proven neurodegeneration. Distinct patterns of cerebellar atrophy are found in all pathological subtypes of Alzheimer's disease and related dementias (ADRD). Cerebellar atrophy is seen in early-stage (Clinical Dementia Rating [CDR] ≤1) AD, Lewy body dementia (LBD), frontotemporal lobar degeneration with tau-positive inclusion (FTLD-tau), and FTLD-transactive response DNA binding protein (FTLD-TDP). Cortical atrophy positively predicts cerebellar atrophy across all neuropathologies.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Degeneración Lobar Frontotemporal , Enfermedad por Cuerpos de Lewy , Enfermedades Neurodegenerativas , Humanos , Enfermedad de Alzheimer/patología , Degeneración Lobar Frontotemporal/genética , Enfermedad por Cuerpos de Lewy/diagnóstico , Atrofia , Proteínas tau/metabolismoRESUMEN
This paper proposes a quadrilateral approach to advance biopharmaceutical manufacturing by fostering collaboration among biopharma, lab informatics, healthcare systems, and academia. Through a retrospection based on Gary Pisano's analysis and real-world examples like insitro and Spark Therapeutics, we highlight the imperative of continuous process innovation and regulatory collaboration. We emphasize leveraging technological advancements, particularly in machine learning and artificial intelligence (AI), to catalyze a paradigm shift in drug manufacturing and delivery. The discussion extends to fostering academic and business partnerships, akin to Silicon Valley's ecosystem, and engaging healthcare systems in a more integrated role, exemplified by the advent of point-of-care manufacturing. The paper underscores the unique potential of the State of Delaware to propel forward the biopharma manufacturing space, advocating for a coordinated effort to translate scientific advancements into real healthcare benefits.