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William L. Hwang

Bio: William L. Hwang is an academic researcher from Harvard University. The author has contributed to research in topics: Pancreatic cancer & Medicine. The author has an hindex of 20, co-authored 52 publications receiving 2413 citations. Previous affiliations of William L. Hwang include Broad Institute & Duke University.


Papers
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Journal ArticleDOI
TL;DR: Droplet interface bilayers provide a superior platform for the biophysical analysis of membrane proteins and can also form networks, with features that include built-in batteries and sensors.
Abstract: Droplet interface bilayers (DIBs) provide a superior platform for the biophysical analysis of membrane proteins. The versatile DIBs can also form networks, with features that include built-in batteries and sensors.

429 citations

Proceedings ArticleDOI
06 Mar 2006
TL;DR: This work develops the first systematic droplet routing method that can be integrated with biochip synthesis, which minimizes the number of cells used fordroplet routing, while satisfying constraints imposed by throughput considerations and fluidic properties.
Abstract: Recent advances in microfluidics are expected to lead to sensor systems for high-throughput biochemical analysis. CAD tools are needed to handle increased design complexity for such systems. Analogous to classical VLSI synthesis, a top-down design automation approach can shorten the design cycle and reduce human effort. We focus here on the droplet routing problem, which is a key issue in biochip physical design automation. We develop the first systematic droplet routing method that can be integrated with biochip synthesis. The proposed approach minimizes the number of cells used for droplet routing, while satisfying constraints imposed by throughput considerations and fluidic properties. A real-life biochemical application is used to evaluate the proposed method.

228 citations

Journal ArticleDOI
TL;DR: An engineered protein pore with diode-like properties is developed that can be incorporated into droplet interface bilayers in droplet networks to form devices with electrical properties including those of a current limiter, a half-wave rectifier and a full- wave rectifier.
Abstract: Recently, we demonstrated that submicrolitre aqueous droplets submerged in an apolar liquid containing lipid can be tightly connected by means of lipid bilayers1,2,3,4,5 to form networks4,5,6. Droplet interface bilayers have been used for rapid screening of membrane proteins7,8 and to form asymmetric bilayers with which to examine the fundamental properties of channels and pores9. Networks, meanwhile, have been used to form microscale batteries and to detect light4. Here, we develop an engineered protein pore with diode-like properties that can be incorporated into droplet interface bilayers in droplet networks to form devices with electrical properties including those of a current limiter, a half-wave rectifier and a full-wave rectifier. The droplet approach, which uses unsophisticated components (oil, lipid, salt water and a simple pore), can therefore be used to create multidroplet networks with collective properties that cannot be produced by droplet pairs. Aqueous droplets connected by single lipid bilayers have been used to examine the properties of protein channels and pores, and networks of droplets can form microscale batteries and detect light. Now, by inserting an engineered pore with diode-like properties into the interface bilayers, droplet networks that mimic simple electronic devices have been produced.

212 citations

Journal ArticleDOI
TL;DR: The droplet interface bilayer (DIB), which is formed by connecting lipid monolayer-encased aqueous droplets submerged in an oil-lipid mixture, provides a general platform for studying the effects of bilayer leaflet composition on the behavior of ion channels and pores.
Abstract: In cell membranes, the lipid compositions of the inner and outer leaflets differ. Therefore, a robust model system that enables single-channel electrical recording with asymmetric bilayers would be very useful. We and others recently developed the droplet interface bilayer (DIB), which is formed by connecting lipid monolayer-encased aqueous droplets submerged in an oil−lipid mixture. Here, we incorporate lipid vesicles of different compositions into aqueous droplets and immerse them in an oil bath to form asymmetric DIBs (a-DIBs). Both α-helical and β-barrel membrane proteins insert readily into a-DIBs, and their activity can be measured by single-channel electrical recording. We show that the gating behavior of outer membrane protein G (OmpG) from Escherichia coli differs depending on the side of insertion in an asymmetric DIB with a positively charged leaflet opposing a negatively charged leaflet. The a-DIB system provides a general platform for studying the effects of bilayer leaflet composition on the...

201 citations

Journal ArticleDOI
TL;DR: Data from numerous retrospective series and a handful of prospective studies provide burgeoning evidence that the combination of palliative radiotherapy and ICI is safe overall without a substantial site-specific increase in adverse events.
Abstract: Immune-checkpoint inhibitors targeting cytotoxic T- lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death 1 ligand 1 (PD-L1) have transformed the care of patients with a wide range of advanced-stage malignancies. More than half of these patients will also have an indication for treatment with radiotherapy. The effects of both radiotherapy and immune-checkpoint inhibition (ICI) involve a complex interplay with the innate and adaptive immune systems, and accumulating evidence suggests that, under certain circumstances, the effects of radiotherapy synergize with those of ICI to augment the antitumour responses typically observed with either modality alone and thus improve clinical outcomes. However, the mechanisms by which radiotherapy and immune-checkpoint inhibitors synergistically modulate the immune response might also affect both the type and severity of treatment-related toxicities. Moreover, in patients receiving immune-checkpoint inhibitors, the development of immune-related adverse events has been linked with superior treatment responses and patient survival durations, suggesting a relationship between the antitumour and adverse autoimmune effects of these agents. In this Review, we discuss the emerging data on toxicity profiles related to immune-checkpoint inhibitors and radiotherapy, both separately and in combination, their potential mechanisms, and the approaches to managing these toxicities.

196 citations


Cited by
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Journal ArticleDOI
TL;DR: Recommendations for specific organ system-based toxicity diagnosis and management are presented and, in general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, with the exception of endocrinopathies that have been controlled by hormone replacement.
Abstract: PurposeTo increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapyMethodsA multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline Guideline development involved a systematic review of the literature and an informal consensus process The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017ResultsThe systematic review identified 204 eligible publications Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports Due to the paucity of high-quality evidence on management

2,386 citations

Journal ArticleDOI
TL;DR: In nanopore analytics, individual molecules pass through a single nanopore giving rise to detectable temporary blockades in ionic pore current, which ranges from nucleic acids, peptides, proteins, and biomolecular complexes to organic polymers and small molecules.
Abstract: In nanopore analytics, individual molecules pass through a single nanopore giving rise to detectable temporary blockades in ionic pore current. Reflecting its simplicity, nanopore analytics has gained popularity and can be conducted with natural protein as well as man-made polymeric and inorganic pores. The spectrum of detectable analytes ranges from nucleic acids, peptides, proteins, and biomolecular complexes to organic polymers and small molecules. Apart from being an analytical tool, nanopores have developed into a general platform technology to investigate the biophysics, physicochemistry, and chemistry of individual molecules (critical review, 310 references).

1,022 citations

Journal ArticleDOI
TL;DR: Some of the exciting developments so far in miniaturized optofluidic platforms bring fluid and light together and exploit their microscale interaction for a large variety of applications are overviewed.
Abstract: The realization of miniaturized optofluidic platforms offers potential for achieving more functional and more compact devices. Such integrated systems bring fluid and light together and exploit their microscale interaction for a large variety of applications. The high sensitivity of compact microphotonic devices can generate effective microfluidic sensors, with integration capabilities. By turning the technology around, the exploitation of fluid properties holds the promise of highly flexible, tunable or reconfigurable microphotonic devices. We overview some of the exciting developments so far.

946 citations

Journal ArticleDOI
TL;DR: This paper will review available drop generation and manipulation techniques in droplet based microfluidics to identify and shed light on similarities and underlying physical principles.
Abstract: Droplet based microfluidics is a rapidly growing interdisciplinary field of research combining soft matter physics, biochemistry and microsystems engineering. Its applications range from fast analytical systems or the synthesis of advanced materials to protein crystallization and biological assays for living cells. Precise control of droplet volumes and reliable manipulation of individual droplets such as coalescence, mixing of their contents, and sorting in combination with fast analysis tools allow us to perform chemical reactions inside the droplets under defined conditions. In this paper, we will review available drop generation and manipulation techniques. The main focus of this review is not to be comprehensive and explain all techniques in great detail but to identify and shed light on similarities and underlying physical principles. Since geometry and wetting properties of the microfluidic channels are crucial factors for droplet generation, we also briefly describe typical device fabrication methods in droplet based microfluidics. Examples of applications and reaction schemes which rely on the discussed manipulation techniques are also presented, such as the fabrication of special materials and biophysical experiments.

938 citations