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Influence of denatured and intermediate states of folding on protein aggregation (vol 14, pg 993, 2005)

PROTEIN SCIENCE 2005年第5期14卷 1380-1380页

作者： Fawzi, NL Chubukov, V Clark, LA Brown, S Head-Gordon, T UCSF/UCB Joint Graduate Group in Bioengineering Department of Bioengineering Donner 272 University of California at Berkeley Berkeley CA 94720 USA.

We simulate the aggregation thermodynamics and kinetics of proteins L and G,each of which self-assembles to the same alpha/beta [corrected] topology through distinct foldingmechanisms. We find that the aggregation kinetics of both proteins at an experimentally relevantconcentration exhibit both fast and slow aggregation pathways, although a greater proportion ofprotein G aggregation events are slow relative to those of found for protein L. These kineticdifferences are correlated with the amount and distribution of intrachain contacts formed in thedenatured state ensemble (DSE), or an intermediate state ensemble (ISE) if it exists, as well as thefolding timescales of the two proteins. Protein G aggregates more slowly than protein L due to itsrapidly formed folding intermediate, which exhibits native intrachain contacts spread across theprotein, suggesting that certain early folding intermediates may be selected for by evolution due totheir protective role against unwanted aggregation. Protein L shows only localized native structurein the DSE with timescales of folding that are commensurate with the aggregation timescale, leavingit vulnerable to domain swapping or nonnative interactions with other chains that increase theaggregation rate. Folding experiments that characterize the structural signatures of the DSE, ISE,or the transition state ensemble (TSE) under nonaggregating conditions should be able to predictregions where interchain contacts will be made in the aggregate, and to predict slower aggregationrates for proteins with contacts that are dispersed across the fold. Since proteins L and G can bothform amyloid fibrils, this work also provides mechanistic and structural insight into the formationof prefibrillar species.

关键词： Protein Folding Proteins

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The disassembly of a core-satellite nanoassembled substrate for colorimetric biomolecular detection

The disassembly of a core-satellite nanoassembled substrate ...

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14th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2010, MicroTAS 2010

作者： Waldeisen, J.R. Wang, T. Ross, B.M. Lee, L.P. UCSF/UCB Joint Graduate Group in Bioengineering University of California Berkeley United States

ISBN: (纸本)9781618390622

We present the fabrication of gold nanoassemblies constructed on a two-dimensional substrate, demonstrate colorimetric biomolecular sensing functionality via protease-mediate disassembly, and systematically analyze the "naked eye" detection properties by calculating a figure of merit. Optimization of the scattering spectra of the core-satellite nanoassemblies maximizes the signal-to-noise ratio during biosensing and enables the large colorimetric shift of this assay from orange (>630 nm) to green (∼560 nm) via the observation of scattered light in dark field (DF). Nanoconstructs with 50 nm cores and 30 nm or 50 nm satellites were found to be ideal for colorimetric readout.

关键词： Plasmonics

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Miniscope3D:optimized single-shot miniature 3D fluorescence microscopy

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Light(Science & Applications) 2020年第1期9卷 367-379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 CaliforniaBerkeleyCA 94720USA Department of Electrical Engineering&Computer Sciences University of CaliforniaBerkeleyCA 94720USA TIPs Department Universite libre de Bruxelles(ULB)1050 BrusselsBelgium

Miniature fluorescence microscopes are a standard tool in systems ***,widefield miniature microscopes capture only 2D information,and modifications that enable 3D capabilities increase the size and weight and have poor resolution outside a narrow depth ***,we achieve the 3D capability by replacing the tube lens of a conventional 2D Miniscope with an optimized multifocal phase mask at the objective’s aperture *** the phase mask at the aperture stop significantly reduces the size of the device,and varying the focal lengths enables a uniform resolution across a wide depth *** phase mask encodes the 3D fluorescence intensity into a single 2D measurement,and the 3D volume is recovered by solving a sparsity-constrained inverse *** provide methods for designing and fabricating the phase mask and an efficient forward model that accounts for the fieldvarying aberrations in miniature *** demonstrate a prototype that is 17mm tall and weighs 2.5 grams,achieving 2.76μm lateral,and 15μm axial resolution across most of the 900×700×390μm^(3) volume at 40 volumes per *** performance is validated experimentally on resolution targets,dynamic biological samples,and mouse brain *** with existing miniature single-shot volume-capture implementations,our system is smaller and lighter and achieves a more than 2×better lateral and axial resolution throughout a 10×larger usable depth *** microscope design provides single-shot 3D imaging for applications where a compact platform matters,such as volumetric neural imaging in freely moving animals and 3D motion studies of dynamic samples in incubators and lab-on-a-chip devices.

关键词： enable resolution narrow

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High-density spheroid arrays for 3-D liver cell culture and secretion analysis

High-density spheroid arrays for 3-D liver cell culture and ...

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10th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2006

作者： Zhang, Mimi Y. Di Carlo, Dino Wu, Liz Y. Lee, Luke P. Berkeley Sensor and Actuator Center UCSF/UCB Joint Program in Bioengineering University of California Berkeley CA United States

To effectively coalesce otherwise monolayer liver cells (hepatocytes) seeded into microfluidic channels, we present a high-density cell-trapping array chip for rapid three-dimensional hepatocyte spheroid self-assembly. Moreover, by modifying trap geometries, spheroids of varying sizes can be formed in order to optimize the spatial microenvironment for improving cell viability and function. Preliminary sensitivity analysis of albumin secretion detection demonstrates the feasibility of using an optimized chemiluminescent immunoassay to determine the albumin concentrations in the range of 1 ng/mL to 500 ng/mL. © 2006 Society for Chemistry and Micro-Nano Systems.

关键词： Cell culture

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Research: Association of low-amplitude QRSs with false-positive asystole alarms

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Biomedical Instrumentation and Technology 2016年第5期50卷 329-335页

作者： Pelter, Michele M. Fidler, Richard Hu, Xiao Department of Physiological Nursing United States United States UCSF School of Nursing United States Healthcare Simulation Programs United States Institute for Computational Health Sciences UCB/UCSF Joint Bio-Engineering Graduate Program at UCSF United States

Background: Although electrocardiographic monitoring is valuable for continuous surveillance of intensive care unit (ICU) patients, false alarms are common and have been cited as a cause of alarm fatigue. ANSI/ AAMI EC12:2002 states that electrocardiograms (ECGs) should not detect a QRS if the waveform is less than 0.15 mV (1.5 mm) for adult patients, in order to avoid mislabeling P waves or baseline noise as QRSs during complete heart block or asystole. However, ECG software algorithms often use more conservative QRS thresholds, which may result in false-positive asystole alarms in patients with low-amplitude QRS complexes. Objectives: To 1) assess the frequency of low QRS amplitude in a group of ICU patients with one or more false-positive asystole alarms and 2) determine whether low-amplitude QRSs are associated with false-positive asystole alarms during continuous ECG monitoring. Methods: Hospital-acquired standard 12-lead ECGs were examined in a group of 82 ICU patients who had one or more falsepositive asystole alarms. Low QRS amplitude was deined as a unidirectional (only positive or negative) QRS of less than 5 mm in two of four leads (I, II, III, and V1). Results: Low-amplitude QRSs were present in 45 of 82 (55%) patients. The presence of low-amplitude QRSs did not difer according to age, sex, or race. Patients treated in the cardiac ICU had the highest proportion of low-amplitude QRSs. An equivalent proportion of patients had false-positive asystole alarms by group (no low-amplitude QRSs 95% vs. low-amplitude QRSs 87%;P = 0.229). Eight patients (10%) had both true- and false-positive asystole alarms (two [5%] with no low-amplitude QRSs and six [13%] with low-amplitude QRSs;P = 0.229). Conclusion: Low-amplitude QRS, as assessed from hospital 12-lead ECGs, occurs frequently and is more common in cardiac ICU patients. However, this ECG feature did not identify patients with false-positive asystole alarms during continuous ECG monitoring. © Copyright AAMI 2016

关键词： Electrocardiograms

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MultiWienerNet: Deep learning for fast shift-varying deconvolution

MultiWienerNet: Deep learning for fast shift-varying deconvo...

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Computational Optical Sensing and Imaging, COSI 2021 - Part of OSA Imaging and Applied Optics Congress 2021

作者： Shuai, Richard W. Yanny, Kyrollos Monakhova, Kristina Waller, Laura Department of Electrical Engineering and Computer Sciences University of California Berkeley United States UCB/UCSF Joint Graduate Program in Bioengineering University of California Berkeley United States

We present a deep-learning method based on Wiener filters and U-Nets that performs image reconstruction in systems with spatially-varying aberrations. We train on simulated microscopy measurements and test on experime... 详细信息

ISBN: (纸本)9781557528209

关键词： Image reconstruction

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Information-Theoretic Design for High-Dimensional Computational Imaging

Information-Theoretic Design for High-Dimensional Computatio...

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Computational Optical Sensing and Imaging, COSI 2024 - Part of Optica Imaging Congress

作者： Markley, Eric Kabuli, Leyla Chien, Tiffany Pinkard, Henry Waller, Laura UCB/UCSF Joint Graduate Program in Bioengineering University of California Berkeley United States Department of Electrical Engineering and Computer Sciences University of California Berkeley United States

We present a technique for information-theoretic optimization of computational imaging systems demonstrated in snapshot 3D microscopy. By directly evaluating measurement quality and decoupling optimization from downst... 详细信息

关键词： Decoding

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Spectral DefocusCam: hyperspectral imaging using defocus and a spectral filter array

Spectral DefocusCam: hyperspectral imaging using defocus and...

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Computational Optical Sensing and Imaging, COSI 2022

作者： Foley, Christian Monakhova, Kristina Yanny, Kyrollos Waller, Laura Department of Electrical Engineering and Computer Sciences University of California Berkeley United States UCB/UCSF Joint Graduate Program in Bioengineering University of California Berkeley United States

We propose a compact hyperspectral camera based on a focus-tunable lens and spectral filter array. The camera captures then fuses multiple defocused measurements to obtain a high-resolution hyperspectral volume. ©... 详细信息

ISBN: (纸本)9781557528209

关键词： Hyperspectral imaging

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Snapshot hyperspectral imaging using a random phase mask and spectral filter array

Snapshot hyperspectral imaging using a random phase mask and...

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Computational Optical Sensing and Imaging, COSI 2020 - Part of Imaging and Applied Optics Congress 2020

作者： Monakhova, Kristina Yanny, Kyrollos Waller, Laura Department of Electrical Engineering and Computer Sciences University of California Berkeley United States UCB/UCSF Joint Graduate Program in Bioengineering University of California Berkeley United States

We introduce a snapshot hyperspectral imager that uses a random phase mask, repeated spectral filter array, and compressive recovery to achieve high spatial and spectral resolution in a small form factor. © 2020 ... 详细信息

ISBN: (纸本)9781557528209

关键词： Hyperspectral imaging

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Microfluidic cell analysis platform: Cell culture and electrochemical lysis 11

Microfluidic cell analysis platform: Cell culture and electr...

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11th International Conference on Miniaturized Systems for Chemistry and Life Sciences, uTAS 2007

作者： Tanner Nevill, J. Cooper, Ryan Dueck, Megan Di Carlo, Dino Lee, Luke P. UCSF UCB Joint Graduate Group in Bioengineering Biomolecular Nanotechnology Center Berkeley Sensor and Actuator Center University of California Berkeley United States

ISBN: (纸本)9780979806407

We present an integrated microfluidic platform developed for automated cell culture and lysate analysis. Through the combination of previous technologies developed in our lab - on-chip cell culture and electrochemical lysis - we have designed, fabricated and characterized a platform that cultures cells for extended periods and lyses them on demand without the need for the addition of lysing or washing reagents. We have accomplished the successful culture and lysis of four cell lines: HeLa, MCF7, Jurkat, and CHO. Cells were cultured successfully for greater than five days, and complete on-demand lysis was demonstrated by local electrochemical generation of hydroxide. Lysate was shown to contain both nucleic acids and proteins. Additionally, the biological activity of the lysate was investigated by studying the effects of electrochemical lysis on the enzymatic activity of a model enzyme. © 2007 CBMS.

关键词： Cell culture

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