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arXiv 2022年

作者： Rajagopal, Abhejit Leynes, Andrew P. Dwork, Nicholas Scholey, Jessica E. Hope, Thomas A. Larson, Peder E.Z. Department of Radiology and Biomedical Imaging University of California San Francisco94158 United States Uc Berkeley-UCSF Joint Graduate Program in Bioengineering University of California San Francisco United States University of California BerkeleyCA United States Department of Radiation Oncology University of California San Francisco94158 United States Departments of Pediatrics and Radiology University of Colorado Anschutz 80045 United States

In this paper, we review physics- and data-driven reconstruction techniques for simultaneous positron emission tomography (PET) / magnetic resonance imaging (MRI) systems, which have significant advantages for clinical imaging of cancer, neurological disorders, and heart disease. These reconstruction approaches utilize priors, either structural or statistical, together with a physics-based description of the PET system response. However, due to the nested representation of the forward problem, direct PET/MRI reconstruction is a nonlinear problem. We elucidate how a multi-faceted approach accommodates hybrid data- and physics-driven machine learning for reconstruction of 3D PET/MRI, summarizing important deep learning developments made in the last 5 years to address attenuation correction, scattering, low photon counts, and data consistency. We also describe how applications of these multi-modality approaches extend beyond PET/MRI to improving accuracy in radiation therapy planning. We conclude by discussing opportunities for extending the current state-of-the-art following the latest trends in physics- and deep learning-based computational imaging and next-generation detector hardware. Copyright © 2022, The Authors. All rights reserved.

关键词： Magnetic resonance imaging

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Clinical anthropometrics and body composition from 3D whole-body surface scans (vol 70, pg 1265, 2016)

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EUROPEAN JOURNAL OF CLINICAL NUTRITION 2021年第3期75卷 574-574页

作者： Ng, B. K. Hinton, B. J. Fan, B. Kanaya, A. M. Shepherd, J. A. Department of Radiology and Biomedical Imaging University of California San Francisco San Francisco USA The UC Berkeley—UCSF Graduate Program in Bioengineering San Francisco USA Department of Medicine University of California San Francisco San Francisco USA

A Correction to this paper has been published: https://***/10.1038/s41430-020-00808-y

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Linking physical phenotype to drug resistance: Single-cell mechanical measurements of acute promyelocytic Leukemia 23

Linking physical phenotype to drug resistance: Single-cell m...

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23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019

作者： Li, Brian L. Maslan, Annie M. Streets, Aaron M. Sohn, Lydia L. UC Berkeley UCSF Graduate Program in Bioengineering Berkeley and San Francisco United States UC Berkeley Center for Computational Biology Berkeley United States UC Berkeley Biophysics Graduate Group Berkeley United States UC Berkeley Department of Mechanical Engineering Berkeley United States

ISBN: (纸本)9781733419000

Mechanical testing of cancer cells has established that certain pathophysiological phenotypes are strongly associated with abnormal cell mechanics. We used a microfluidic platform previously developed in our laboratory to perform rapid mechanical phenotyping of acute promyelocytic leukemia (APL) cells. These measurements revealed that drug-resistant APL cells exhibit more solid-like viscoelastic behavior compared to drug-responsive cells and that this mechanical difference could be due to chromatin condensation. Our work demonstrates that single-cell mechanical phenotyping could serve to predict drug-resistance in APL. © 2019 CBMS-0001.

关键词： Mechanical testing

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De novo protein fold families expand the designable ligand binding site space

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PLoS Computational Biology 2021年第11期17卷 e1009620-e1009620页

作者： Pan, Xingjie Kortemme, Tanja Department of Bioengineering and Therapeutic Sciences University of California San Francisco San FranciscoCA United States UC Berkeley-UCSF Graduate Program in Bioengineering University of California San Francisco San FranciscoCA United States University of California San Francisco San FranciscoCA United States Chan Zuckerberg Biohub San FranciscoCA United States

A major challenge in designing proteins de novo to bind user-defined ligands with high affinity is finding backbones structures into which a new binding site geometry can be engineered with high precision. Recent advances in methods to generate protein fold families de novo have expanded the space of accessible protein structures, but it is not clear to what extend de novo proteins with diverse geometries also expand the space of designable ligand binding functions. We constructed a library of 25,806 high-quality ligand binding sites and developed a fast protocol to place ("match") these binding sites into both naturally occurring and de novo protein families with two fold topologies: Rossman and NTF2. Each matching step involves engineering new binding site residues into each protein "scaffold", which is distinct from the problem of comparing already existing binding pockets. 5,896 and 7,475 binding sites could be matched to the Rossmann and NTF2 fold families, respectively. De novo designed Rossman and NTF2 protein families can support 1,791 and 678 binding sites that cannot be matched to naturally existing structures with the same topologies, respectively. While the number of protein residues in ligand binding sites is the major determinant of matching success, ligand size and primary sequence separation of binding site residues also play important roles. The number of matched binding sites are power law functions of the number of members in a fold family. Our results suggest that de novo sampling of geometric variations on diverse fold topologies can significantly expand the space of designable ligand binding sites for a wealth of possible new protein functions. © 2021 Pan, Kortemme. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

关键词： Topology

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The type 1 diabetes immune niche: Immunomodulatory biomaterial design considerations for beta cell transplant therapies

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Journal of Immunology and Regenerative Medicine 2022年 17卷

作者： Claire E. Hilburger Matthew J. Rosenwasser Derfogail Delcassian Department of Bioengineering University of California Berkeley CA 94720 USA UC Berkeley-UC San Francisco Graduate Program in Bioengineering University of California Berkeley CA 94720 USA

Islet transplantation is a promising therapy for a subset of people with Type 1 diabetes (T1D). However, beta cell transplant clinical trials have largely failed to maintain long-term normal glycemia in transplant recipients. This is broadly due to immune rejection of the transplanted islets themselves or the devices in which these cells are encapsulated. As an autoimmune condition, the T1D host presents a uniquely challenging immunological niche for the transplant of additional beta cells. An understanding of the autoimmune environment is crucial for the development of successful beta cell transplant therapies. Here, we provide an overview of the immune cell pathways leading to autoimmune T1D, and the resulting immune niche. Next, we examine biomaterial platforms that can be used for cell transplantation, and describe those that seek to modulate the immune environment to mitigate immune rejection. These approaches include delivery of localized immune cues, co-transplantation with immunomodulatory cells, strategies to engineer islets ex-vivo, and antigen-specific immunomodulation to generate operational tolerance. Finally, we describe therapies which seek to prevent T1D progression which could be repurposed to support beta cell transplantation and future immunoengineering design considerations for successful islet transplantation therapies.

关键词： Immunomodulation Islet transplantation Operational tolerance Biomaterials T1D Diabetes

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A complete allosteric map of a GTPase switch in its native cellular network

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Cell Systems 2023年第3期14卷 237-246.e7页

作者： Mathy, Christopher J.P. Mishra, Parul Flynn, Julia M. Perica, Tina Mavor, David Bolon, Daniel N.A. Kortemme, Tanja Department of Bioengineering and Therapeutic Sciences University of California San Francisco San Francisco 94158 CA United States Quantitative Biosciences Institute University of California San Francisco San Francisco 94158 CA United States The UC Berkeley-UCSF Graduate Program in Bioengineering University of California San Francisco San Francisco 94158 CA United States Department of Biochemistry and Molecular Biotechnology University of Massachusetts Medical School Worcester 01605 MA United States Chan Zuckerberg Biohub San Francisco 94158 CA United States School of Life Sciences University of Hyderabad Telangana Hyderabad India

Allosteric regulation is central to protein function in cellular networks. A fundamental open question is whether cellular regulation of allosteric proteins occurs only at a few defined positions or at many sites distributed throughout the structure. Here, we probe the regulation of GTPases—protein switches that control signaling through regulated conformational cycling—at residue-level resolution by deep mutagenesis in the native biological network. For the GTPase Gsp1/Ran, we find that 28% of the 4,315 assayed mutations show pronounced gain-of-function responses. Twenty of the sixty positions enriched for gain-of-function mutations are outside the canonical GTPase active site switch regions. Kinetic analysis shows that these distal sites are allosterically coupled to the active site. We conclude that the GTPase switch mechanism is broadly sensitive to cellular allosteric regulation. Our systematic discovery of new regulatory sites provides a functional map to interrogate and target GTPases controlling many essential biological processes. © 2023 The Authors

关键词： allostery cellular regulation Gsp1 GTPases mutational scanning protein networks Ran

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A compact planar triple-nuclear coil for small animal 1H, 13C, and 31P Metabolic MR Imaging at 14.1 T

arXiv

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arXiv 2021年

作者： Leynes, A.P. Chen, Y. Sukumar, S. Xu, D. Zhang, X. Department of Radiology and Biomedical Imaging University of California San Francisco Byers Hall 102D 1700 4th Street San FranciscoCA94158 United States UC Berkeley and UCSF Joint Graduate Group in Bioengineering San Francisco BerkeleyCA United States

Multi-nuclear radio-frequency (RF) coils at ultrahigh field strengths are challenging to develop due to the high operating frequency, increased electromagnetic interaction among the coil elements, and increased electromagnetic interaction between the coils and the subject. In this work, a triple-nuclear surface coil for 1H, 13C, and 31P for small animal metabolic imaging at 14.1 T is built by nesting three surface coil geometries: a lumped-element L-C loop coil, a butterfly coil, and a microstrip transmission line (MTL) resonator. The loop coil, butterfly coil, and MTL are tuned to 31P, 13C, and 1H, respectively. The successful bench tests and phantom imaging with this novel triple-nuclear coil demonstrates the feasibility of the design for triple-nuclear MR imaging and spectroscopy studies at the ultrahigh field of 14.1 T. In particular, the microstrip transmission line resonator demonstrates excellent coil performance for proton imaging at 600 MHz, where conventional lumped-element design is limited. © 2021, CC BY.

关键词： Resonators

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Author Correction: Miniscope3D: optimized single-shot miniature 3D fluorescence microscopy

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Light, science & applications 2023年第1期12卷 93页

作者： Kyrollos Yanny Nick Antipa William Liberti Sam Dehaeck Kristina Monakhova Fanglin Linda Liu Konlin Shen Ren Ng Laura Waller UCB/UCSF Joint Graduate Program in Bioengineering University of California Berkeley CA 94720 USA. kyrollosyanny@***. Department of Electrical Engineering & Computer Sciences University of California Berkeley CA 94720 USA. naantipa@***. Department of Electrical Engineering & Computer Sciences University of California Berkeley CA 94720 USA. TIPs Department Université libre de Bruxelles (ULB) 1050 Brussels Belgium. UCB/UCSF Joint Graduate Program in Bioengineering University of California Berkeley CA 94720 USA.

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Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis

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Bone Research 2019年第4期7卷 354-370页

作者： Courtney MMazur Jonathon JWoo Cristal SYee Aaron JFields Claire Acevedo Karsyn NBailey Serra Kaya Tristan WFowler Jeffrey CLotz Alexis Dang Alfred CKuo Thomas PVail Tamara Alliston Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC Berkeley-UCSF Graduate Program in Bioengineering San FranciscoCA 94143USA Department of Mechanical Engineering University of UtahSalt Lake CityUT 84112USA San Francisco Veterans Affairs Medical Center San FranciscoCA 94121USA

Osteoarthritis(OA),long considered a primary disorder of articular cartilage,is commonly associated with subchondral bone ***,the cellular mechanisms responsible for changes to subchondral bone in OA,and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration,remain *** knee joints from human patients with end-stage OA,we found evidence of profound defects in osteocyte *** of osteocyte perilacunar/canalicular remodeling(PLR)was most severe in the medial compartment of OA subchondral bone,with lower protease expression,diminished canalicular networks,and disorganized and hypermineralized extracellular *** a step toward evaluating the causality of PLR suppression in OA,we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact,using Cre recombinase driven by the 9.6-kb DMP1 *** only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone,but it also compromised *** in the absence of injury,osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content,change chondrocyte production of collagen II,aggrecan,and MMP13,and increase the incidence of cartilage lesions,consistent with early ***,in humans and mice,defects in PLR coincide with cartilage ***-derived MMP13 emerges as a critical regulator of cartilage homeostasis,likely via its effects on ***,these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis.

关键词： MMP13 homeostasis likely

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Fourier diffuserscope: Single-shot 3d fourier light field microscopy with a diffuser

arXiv

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arXiv 2020年

作者： Liu, Fanglin Linda Grace, K.U.O. Antipa, Nick Yanny, Kyrollos Waller, Laura Electrical Engineering and Computer Sciences University of California Berkeley94709 United States UCB/UCSF Joint Graduate Program in Bioengineering University of California BerkeleyCA94709 United States

Light field microscopy (LFM) uses a microlens array (MLA) near the sensor plane of a microscope to achieve single-shot 3D imaging of a sample, without any moving parts. Unfortunately, the 3D capability of LFM comes with a significant loss of lateral resolution at the focal plane, which is highly undesirable in microscopy. Placing the MLA near the pupil plane of the microscope, rather than the image plane, can mitigate the artifacts near focus and provide an efficient shift-invariant model at the expense of field-of-view. Here, we show that our Fourier DiffuserScope achieves significantly better performance than Fourier LFM. Fourier DiffuserScope uses a diffuser in the pupil plane to encode depth information, then reconstructs volumetric information computationally by solving a sparsity-constrained inverse problem. Our diffuser consists of randomly placed microlenses with varying focal lengths. We show that by randomizing the microlens positions, a larger lateral field-of-view can be achieved compared to a conventional MLA;furthermore, by adding diversity to the focal lengths, the axial depth range is increased. To predict system performance based on diffuser parameters, we for the first time establish a theoretical framework as a design guideline, followed by numerical simulations to verify. Under both theoretical and numerical analysis, we demonstrate that our diffuser design provides more uniform resolution over a larger volume, both laterally and axially, outperforming the MLA used in LFM. We build an experiment system with an optimized lens set and achieve 3 volume. Copyright © 2020, The Authors. All rights reserved.

关键词： Microlenses

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