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Optics and the Brain, BRAIN 2022

作者： Ozana, Nisan Lue, Niyom Renna, Marco Robinson, mitchell Martin, Alyssa Blackwell, Megan Carp, Stefan A. Franceschini, Maria A. Massachusetts General Hospital and Harvard Medical School Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology BostonMA United States MIT Lincoln Laboratory LexingtonMA United States MIT Health Sciences and Technology Program CambridgeMA United States

In this paper, we present a continuous wave (CW) and time-domain (TD) diffuse correlation spectroscopy (DCS) for cerebral blood flow monitoring at 1064nm. Findings show high brain sensitivity and fast monitoring which... 详细信息

ISBN: (纸本)9781957171036

关键词： Neuroimaging

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Necrosis as a fundamental driver of loss of resilience and biological decline: what if we could intervene?

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Oncogene 2025年 1-12页

作者： Carina Kern Bill Davis Halime Karakoy Nikodem Grzesiak Joseph V. Bonventre Alexander W. Justin Kianoush Kashani Elizabeth Reynolds Keith Siew Damian Miles Bailey LinkGevity Babraham Research Campus Cambridge UK Division of Renal Medicine Brigham and Women’s Hospital Harvard Medical School Boston MA USA Harvard Stem Cell Institute Harvard Boston MA USA Harvard-MIT Health Sciences and Technology Cambridge MA USA MRC Laboratory of Molecular Biology Cambridge Biomedical Campus Cambridge UK Division of Nephrology and Hypertension Division of Pulmonary and Critical Care Medicine Department of Medicine Mayo Clinic Rochester MN USA Starburst Aerospace El Segundo CA USA NASA Human Research Program Microsoft and Translational Research Institute for Space Health Space-H Program Houston CA USA London Tubular Centre Royal Free Hospital London UK UCL Centre for Kidney and Bladder Health University College London London UK Bexorg Inc New Haven CT USA Neurovascular Research Laboratory Faculty of Life Sciences and Education University of South Wales Pontypridd UK Life Sciences Working Group European Space Agency Paris France

Necrosis is uncontrolled cell death that marks the irreversible threshold of biological degeneration. Rooted in the Greeknekros(death), it is a pivotal mechanism underlying numerous diseases, including cancer, as well as renal, cardiac, neuronal, and hepatic disorders, and more broadly, the aging process. Despite its profound impact on morbidity and mortality, necrosis remains untreatable and has long been viewed as a chaotic, unavoidable aspect of biology. This review examines the mechanisms of necrosis and outlines its far-reaching impact on health, as revealed by emerging evidence. Furthermore, we explore its potential as a game-changing therapeutic target. Inhibiting necrosis could revolutionize treatments for acute and chronic age-related conditions like cancer, kidney disease, cardiovascular disease (including heart attacks and strokes), and neurodegeneration, while also preserving resilience—and even slowing aging itself. Beyond Earth, where microgravity, cosmic radiation, and oxidative stress accelerate cellular decline, targeting necrosis may also hold the key to preserving astronaut resilience and health on long-duration space missions, offering insights that could reshape human longevity both on and off the planet.

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Interrogation of sample dynamics using interferometric diffuse correlation spectroscopy

Interrogation of sample dynamics using interferometric diffu...

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Optics and the Brain, BRAIN 2019 - Part of Biophotonics Congress: Optics in the Life sciences Congress 2019

作者： Robinson, mitchell B. Carp, Stefan A. Tamborini, Davide Boas, David A. Franceschini, Maria Angela A. Martinos Center for Biomedical Imaging Harvard Medical School Massachusetts General Hospital BostonMA United States Harvard-MIT Program in Health Sciences and Technology Massachusetts Institute of Technology CambridgeMA United States Department of Biomedical Engineering Neurophotonics Center Boston University BostonMA United States

Diffuse correlation spectroscopy (DCS) is a technique that has traditionally required low noise, single photo counting detectors. By utilizing an interferometric approach, we show that these hardware conditions can be... 详细信息

ISBN: (纸本)9781943580545

关键词： Light scattering Photodetectors Single mode fibers Single photon avalanche diodes Spectroscopy Visible light

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Preventable Errors in the Operating Room-Part 2: Retained Foreign Objects, Sharps Injuries, and Wrong Site Surgery

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Current Problems in Surgery 2007年第6期44卷 352-381页

作者： Dagi, T. Forcht Berguer, Ramon Moore, Stephen Reines, H. David The Harvard-MIT Program in Health Sciences and Technology The Uniformed Services University of the Health Sciences Boston MA United States University of California at Davis Contra Costa County Regional Medical Center Martinez CA United States Quality and Safety Inova Health System Falls Church VA United States Virginia Commonwealth University Inova Fairfax Hospital Falls Church VA United States

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HDAC5 Controls MEF2C‐Driven Sclerostin Expression in Osteocytes

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Journal of Bone and Mineral Research 2015年第3期30卷 400-411页

作者： Wein, Marc N. Spatz, Jordan Nishimori, Shigeki Doench, John Root, David Babij, Philip Nagano, Kenichi Baron, Roland Brooks, Daniel Bouxsein, Mary Pajevic, Paola Divieti Kronenberg, Henry M. Endocrine Unit Massachusetts General Hospital Boston MA United States Harvard–Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology (HST) Bioastronautics Program Cambridge MA United States Center for Advanced Orthopaedic Studies BIDMC Boston MA United States Broad Institute of MIT and Harvard Cambridge MA United States Amgen Inc Department of Metabolic Disorders Thousand Oaks CA United States Harvard School of Dental Medicine Boston MA United States

Osteocytes secrete paracrine factors that regulate the balance between bone formation and destruction. Among these molecules, sclerostin (encoded by the gene SOST) inhibits osteoblastic bone formation and is an osteoporosis drug target. The molecular mechanisms underlying SOST expression remain largely unexplored. Here, we report that histone deacetylase 5 (HDAC5) negatively regulates sclerostin levels in osteocytes in vitro and in vivo. HDAC5 shRNA increases, whereas HDAC5 overexpression decreases SOST expression in the novel murine Ocy454 osteocytic cell line. HDAC5 knockout mice show increased levels of SOST mRNA, more sclerostin‐positive osteocytes, decreased Wnt activity, low trabecular bone density, and reduced bone formation by osteoblasts. In osteocytes, HDAC5 binds and inhibits the function of MEF2C, a crucial transcription factor for SOST expression. Using chromatin immunoprecipitation, we have mapped endogenous MEF2C binding in the SOST gene to a distal intergenic enhancer 45 kB downstream from the transcription start site. HDAC5 deficiency increases SOST enhancer MEF2C chromatin association and H3K27 acetylation and decreases recruitment of corepressors NCoR and HDAC3. HDAC5 associates with and regulates the transcriptional activity of this enhancer, suggesting direct regulation of SOST gene expression by HDAC5 in osteocytes. Finally, increased sclerostin production achieved by HDAC5 shRNA is abrogated by simultaneous knockdown of MEF2C, indicating that MEF2C is a major target of HDAC5 in osteocytes. © 2014 American Society for Bone and Mineral Research. © 2014 American Society for Bone and Mineral Research.

关键词： EPIGENETICS OSTEOCYTES OSTEOPOROSIS WNT/ß‐CATENIN/LRPS

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The expanding world of tissue engineering: The building blocks and new applications of tissue engineered constructs

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IEEE Reviews in Biomedical Engineering 2013年 6卷 47-62页

作者： Zorlutuna, Pinar Vrana, Nihal Engin Khademhosseini, Ali Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge MA United States Biomedical Engineering Program Mechanical Engineering Department University of Connecticut 191 Auditorium Rd. Storrs CT 06269-3139 United States Protip SAS 8 Place de l' Hopital 67000 Strasbourg France Department of Medicine Harvard Medical School Brigham and Women's Hospital Cambridge MA United States Wyss Institute for Biologically Inspired Engineering Harvard University Cambridge Cambridge MA 02139 United States

The field of tissue engineering has been growing in the recent years as more products have made it to the market and as new uses for the engineered tissues have emerged, motivating many researchers to engage in this multidisciplinary field of research. Engineered tissues are now not only considered as end products for regenerative medicine, but also have emerged as enabling technologies for other fields of research ranging from drug discovery to biorobotics. This widespread use necessitates a variety of methodologies for production of tissue engineered constructs. In this review, these methods together with their non-clinical applications will be described. First, we will focus on novel materials used in tissue engineering scaffolds;such as recombinant proteins and synthetic, self assembling polypeptides. The recent advances in the modular tissue engineering area will be discussed. Then scaffold-free production methods, based on either cell sheets or cell aggregates will be described. Cell sources used in tissue engineering and new methods that provide improved control over cell behavior such as pathway engineering and biomimetic microenvironments for directing cell differentiation will be discussed. Finally, we will summarize the emerging uses of engineered constructs such as model tissues for drug discovery, cancer research and biorobotics applications. © 2008-2011 IEEE.

关键词： Recombinant proteins

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Biodegradable, multireservoir microdevice for drug delivery

Biodegradable, multireservoir microdevice for drug delivery

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2003 MRS Fall Meeting

作者： Kim, Grace Y. Richards Grayson, Amy C. Cima, Michael J. Langer, Robert Department of Materials Science and Engineering Massachusetts Institute of Technology Cambridge MA Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge MA School of Chemical and Biomolecular Engineering Biomedical Engineering Program Cornell University Ithaca NY Department of Chemical Engineering Massachusetts Institute of Technology Cambridge MA

Drugs have been released from an array of reservoirs in a biodegradable, polymeric microdevice. The reservoirs are formed in a polylactic acid (PLA) substrate and covered with a thin polymer membrane of a faster degrading polymer such as poly(lactic-co-glycolic) acid (PLGA) or a polyanhydride (PA). It is hypothesized that the release characteristics are a result of the drug-membrane interaction, chemical degradation of the membrane, and mechanical rupture of the membrane. This drug delivery platform features an entirely passive mechanism, the ability to simultaneously deliver multiple drugs with different release profiles, and independent drug formulation of the various drug payloads, which is not possible with other drug delivery technologies such as hydrogels or microspheres. The polymer microdevice is now being developed to deliver interleukin-2, followed by the chemotherapeutic carmustine (BCNU) for in vivo experiments. The combination of these two agents has been show to have a synergistic effect in prolonging survival after an intercranial 9L gliosarcoma challenge in a rat model. © 2004 Materials Research Society.

关键词： Drug dosage

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Astronaut bio-suit system to enable planetary exploration

Astronaut bio-suit system to enable planetary exploration

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International Astronautical Federation - 55th International Astronautical Congress 2004

作者： Newman, Dava J. Bethke, Kristen Carr, Christopher Hoffman, Jeffrey Trotti, Guillermo Department of Aeronautics and Astronautics Technology and Policy Program Massachusetts Institute of Technology Department of Aeronautics and Astronautics 77 Massachusetts Avenue Cambridge MA 02139 United States Harvard-MIT Division of Health Sciences and Technology Trotti and Associates Inc. 28 Waldron Court Marblehead MA 01945 United States

The Bio-Suit System concept is designed to revolutionize human space exploration by providing enhanced astronaut extravehicular activity (EVA) locomotion and performance, based on the idea of a 'second skin' capability and of biomechanically and cybernetically augmented human performance capacity. The novel Bio-Suit concept provides an overall exploration system realized through symbiotic relationships between a suite of advanced technologies, creative design, and human modeling and analysis. By working at the intersection of engineering, design, and operations, new emergent capabilities and interrelationships could help realize the new Vision for Space Exploration. The second skin envisioned is capable of augmenting our biological skin by providing mechanical counter pressure. Perhaps the 'epidermis' of such a second skin will be a 'spray-on' polymer providing natural locomotion for explorers. Several concepts for a mechanical counter pressure suit have been developed, and subsequently, initial prototypes have been tested. To determine engineering requirements for future prototypes, the three-dimensional anthropometry of the moving human body has been studied.

关键词： Space probes

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Velocity gradients in spatially resolved laser Doppler flowmetry and dynamic light scattering with confocal and coherence gating

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Physical Review E 2016年第2期94卷 022604-022604页

作者： Néstor Uribe-Patarroyo Brett E. Bouma Wellman Center for Photomedicine Harvard Medical School and Massachusetts General Hospital 40 Blossom Street Boston Massachusetts 02114 USA and Harvard-MIT Program in Health Sciences and Technology Cambridge Massachusetts 02139 USA

Dynamic light scattering (DLS) is widely used to characterize diffusive motion to obtain precise information on colloidal suspensions by calculating the autocorrelation function of the signal from a heterodyne optical system. DLS can also be used to determine the flow velocity field in systems that exhibit mass transport by incorporating the effects of the deterministic motion of scatterers on the autocorrelation function, a technique commonly known as laser Doppler flowmetry. DLS measurements can be localized with confocal and coherence gating techniques such as confocal microscopy and optical coherence tomography, thereby enabling the determination of the spatially resolved velocity field in three dimensions. It has been thought that spatially resolved DLS can determine the axial velocity as well as the lateral speed in a single measurement. We demonstrate, however, that gradients in the axial velocity of scatterers exert a fundamental influence on the autocorrelation function even in well-behaved, nonturbulent flow. By obtaining the explicit functional relation between axial-velocity gradients and the autocorrelation function, we show that the velocity field and its derivatives are intimately related and their contributions cannot be separated. Therefore, a single DLS measurement cannot univocally determine the velocity field. Our extended theoretical model was found to be in good agreement with experimental measurements.

关键词： Light scattering Optical techniques Photon correlation spectroscopy

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Sequential Multi-Dimensional Self-Supervised Learning for Clinical Time Series

arXiv

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arXiv 2023年

作者： Raghu, Aniruddh Chandak, Payal Alam, Ridwan Guttag, John Stultz, Collin M. Massachusetts Institute of Technology CambridgeMA United States Harvard-MIT Program in Health Sciences and Technology CambridgeMA United States

Self-supervised learning (SSL) for clinical time series data has received significant attention in recent literature, since these data are highly rich and provide important information about a patient’s physiological state. However, most existing SSL methods for clinical time series are limited in that they are designed for unimodal time series, such as a sequence of structured features (e.g., lab values and vitals signs) or an individual high-dimensional physiological signal (e.g., an electrocardiogram). These existing methods cannot be readily extended to model time series that exhibit multimodality, with structured features and high-dimensional data being recorded at each timestep in the sequence. In this work, we address this gap and propose a new SSL method — Sequential Multi-Dimensional SSL — where a SSL loss is applied both at the level of the entire sequence and at the level of the individual high-dimensional data points in the sequence in order to better capture information at both scales. Our strategy is agnostic to the specific form of loss function used at each level – it can be contrastive, as in SimCLR, or non-contrastive, as in VICReg. We evaluate our method on two real-world clinical datasets, where the time series contains sequences of (1) high-frequency electrocardiograms and (2) structured data from lab values and vitals signs. Our experimental results indicate that pre-training with our method and then fine-tuning on downstream tasks improves performance over baselines on both datasets, and in several settings, can lead to improvements across different self-supervised loss functions. Copyright © 2023, The Authors. All rights reserved.

关键词： Supervised learning

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