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MIT Open Access Articles
Mostrando recursos 1 - 20 de 13,889
Development of siRNA-probes for studying intracellular trafficking of siRNA nanoparticles - Alabi, Christopher A.; Sahay, Gaurav; Langer, Robert; Anderson, Daniel Griffith
One important barrier facing the delivery of short interfering RNAs (siRNAs) via synthetic nanoparticles is the rate of nanoparticle disassembly. However, our ability to optimize the release kinetics of siRNAs from nanoparticles for maximum efficacy is limited by the lack of methods to track their intracellular disassembly. Towards this end, we describe the design of two different siRNA-based fluorescent probes whose fluorescence emission changes in response to the assembly state of the nanoparticle. The first probe design involves a redox-sensitive fluorescence-quenched probe that fluoresces only when the nanoparticle is disassembled in a reductive environment. The second probe design is based...
Modelling human embryoid body cell adhesion to a combinatorial library of polymer surfaces - Epa, V. Chandana; Yang, Jing; Mei, Ying; Hook, Andrew L.; Langer, Robert; Davies, Martyn C.; Alexander, Morgan R.; Winkler, David A.; Anderson, Daniel Griffith
Designing materials to control biology is an intense focus of biomaterials and regenerative medicine research. Discovering and designing materials with appropriate biological compatibility or active control of cells and tissues is being increasingly undertaken using high throughput synthesis and assessment methods. We report a relatively simple but powerful machine-learning method of generating models that link microscopic or molecular properties of polymers or other materials to their biological effects. We illustrate the potential of these methods by developing the first robust, predictive, quantitative, and purely computational models of adhesion of human embryonic stem cell embryoid bodies (hEB) to the surfaces of...
Combinatorial discovery of polymers resistant to bacterial attachment - Hook, Andrew L; Chang, Chien-Yi; Yang, Jing; Luckett, Jeni; Cockayne, Alan; Atkinson, Steve; Mei, Ying; Bayston, Roger; Irvine, Derek J; Langer, Robert; Williams, Paul; Davies, Martyn C; Alexander, Morgan R; Anderson, Daniel Griffith
Bacterial attachment and subsequent biofilm formation pose key challenges to the optimal performance of medical devices. In this study, we determined the attachment of selected bacterial species to hundreds of polymeric materials in a high-throughput microarray format. Using this method, we identified a group of structurally related materials comprising ester and cyclic hydrocarbon moieties that substantially reduced the attachment of pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli). Coating silicone with these 'hit' materials achieved up to a 30-fold (96.7%) reduction in the surface area covered by bacteria compared with a commercial silver hydrogel coating in vitro, and the...
One-Step Multipurpose Surface Functionalization by Adhesive Catecholamine - Kang, Sung Min; Hwang, Nathaniel S.; Yeom, Jihyeon; Park, Sung Young; Messersmith, Phillip B.; Choi, Insung S.; Langer, Robert; Lee, Haeshin; Anderson, Daniel Griffith
Surface modification is one of the most important techniques in modern science and engineering. The facile introduction of a wide variety of desired properties onto virtually any material surface is an ultimate goal in surface chemistry. To achieve this goal, the incorporation of structurally diverse molecules onto any material surface is an essential capability for ideal surface modification. Here, a general strategy for surface modification is presented in which many diverse surfaces can be functionalized by immobilizing a wide variety of molecules. This strategy functionalizes surfaces by a one-step immersion of substrates in a one-pot mixture of a molecule and...
In Vitro-In Vivo Translation of Lipid Nanoparticles for Hepatocellular siRNA Delivery - Matthews, Jonathan; Chang, Philip H.; Niroui, Farnaz; Severgnini, Mariano; Whitehead, Kathryn Ann; Dorkin, Joseph Robert; Anderson, Daniel Griffith
A significant challenge in the development of clinically viable siRNA delivery systems is a lack of in vitro–in vivo translatability: many delivery vehicles that are initially promising in cell culture do not retain efficacy in animals. Despite its importance, little information exists on the predictive nature of in vitro methodologies, most likely due to the cost and time associated with generating in vitro–in vivo data sets. Recently, high-throughput techniques have been developed that have allowed the examination of hundreds of lipid nanoparticle formulations for transfection efficiency in multiple experimental systems. The large resulting data set has allowed the development of...
Remotely Activated Protein-Producing Nanoparticles - Schroeder, Avi; Goldberg, Michael S.; Kastrup, Christian; Wang, Yingxia; Jiang, Shan; Joseph, Brian J.; Levins, Christopher G.; Kannan, Sneha T.; Langer, Robert; Anderson, Daniel Griffith
The development of responsive nanomaterials, nanoscale systems that actively respond to stimuli, is one general goal of nanotechnology. Here we develop nanoparticles that can be controllably triggered to synthesize proteins. The nanoparticles consist of lipid vesicles filled with the cellular machinery responsible for transcription and translation, including amino acids, ribosomes, and DNA caged with a photolabile protecting group. These particles served as nanofactories capable of producing proteins including green fluorescent protein (GFP) and enzymatically active luciferase. In vitro and in vivo, protein synthesis was spatially and temporally controllable, and could be initiated by irradiating micrometer-scale regions on the time scale...
Origins of tumor-associated macrophages and neutrophils - Cortez-Retamozo, Virna; Etzrodt, Martin; Newton, Andita; Rauch, Philipp J.; Chudnovskiy, Aleksey; Berger, Cedric; Ryan, Russell J. H.; Iwamoto, Yoshiko; Marinelli, Brett; Gorbatov, Rostic; Forghani, Reza; Novobrantseva, Tatiana I.; Koteliansky, Victor; Figueiredo, Jose-Luiz; Chen, John W.; Anderson, Daniel Griffith; Nahrendorf, Matthias; Swirski, Filip K.; Weissleder, Ralph; Pittet, Mikael J.
Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) can control cancer growth and exist in almost all solid neoplasms. The cells are known to descend from immature monocytic and granulocytic cells, respectively, which are produced in the bone marrow. However, the spleen is also a recently identified reservoir of monocytes, which can play a significant role in the inflammatory response that follows acute injury. Here, we evaluated the role of the splenic reservoir in a genetic mouse model of lung adenocarcinoma driven by activation of oncogenic Kras and inactivation of p53. We found that high numbers of TAM and TAN precursors...
Lipid-derived nanoparticles for immunostimulatory RNA adjuvant delivery - Nguyen, David N.; Mahon, Kerry P.; Chikh, Ghania; Kim, Phillip; Chung, Hattie; Vicari, Alain P.; Love, Kevin T.; Goldberg, Michael; Chen, Steve; Krieg, Arthur M.; Chen, Jianzhu; Langer, Robert; Anderson, Daniel Griffith
The specific activation of Toll-like receptors (TLRs) has potential utility for a variety of therapeutic indications including antiviral immunotherapy and as vaccine adjuvants. TLR7 and TLR 8 may be activated by their native ligands, single-stranded RNA, or by small molecules of the imidazoquinoline family. However the use of TLR7/8 agonists for in vivo therapy is limited by instability, in the case of RNA, or systemic biodistribution and toxicity in the case of small molecule agonists. We hypothesized that unique lipid-like materials, termed “lipidoids,” could be designed to efficiently deliver immunostimulatory RNA (isRNA) to TLR-expressing cells to drive innate and adaptive...
Achievability of nonlinear degrees of freedom in correlatively changing fading channels - Karzand, Mina; Zheng, Lizhong
A new approach toward the noncoherent communications over the time varying fading channels is presented. In this approach, the relationship between the input signal space and the output signal space of a correlatively changing fading channel is shown to be a nonlinear mapping between manifolds of different dimensions. Studying this mapping, it is shown that using nonlinear decoding algorithms for single input-multiple output (SIMO) and multiple input multiple output (MIMO) systems, extra numbers of degrees of freedom (DOF) are available. We call them the nonlinear degrees of freedom.
Bit-Wise Unequal Error Protection for Variable-Length Block Codes With Feedback - Gorantla, Siva K.; Zheng, Lizhong; Coleman, Todd P.; Nakiboglu, Baris
The bit-wise unequal error protection problem, for the case when the number of groups of bits l is fixed, is considered for variable-length block codes with feedback. An encoding scheme based on fixed-length block codes with erasures is used to establish inner bounds to the achievable performance for finite expected decoding time. A new technique for bounding the performance of variable-length block codes is used to establish outer bounds to the performance for a given expected decoding time. The inner and the outer bounds match one another asymptotically and characterize the achievable region of rate-exponent vectors, completely. The single-message message-wise...
Linear information coupling problems - Huang, Shao-Lun; Zheng, Lizhong
Many network information theory problems face the similar difficulty of single letterization. We argue that this is due to the lack of a geometric structure on the space of probability distribution. In this paper, we develop such a structure by assuming that the distributions of interest are close to each other. Under this assumption, the K-L divergence is reduced to the squared Euclidean metric in an Euclidean space. Moreover, we construct the notion of coordinate and inner product, which will facilitate solving communication problems. We will also present the application of this approach to the point-to-point channel and the general...
Adjoint-consistent formulations of slip models for coupled electroosmotic flow systems - Prudhomme, Serge; van der Zee, Kris G; Carey, Graham F; Garg, Vikram V.
Models based on the Helmholtz 'slip' approximation are often used for the simulation of electroosmotic flows. The objectives of this paper are to construct adjoint-consistent formulations of such models, and to develop adjoint-based numerical tools for adaptive mesh refinement and parameter sensitivity analysis.
We show that the direct formulation of the 'slip' model is adjoint inconsistent, and leads to an ill-posed adjoint problem. We propose a modified formulation of the coupled 'slip' model, which is shown to be well-posed, and therefore automatically adjoint-consistent.
Numerical examples are presented to illustrate the computation and use of the adjoint solution in two-dimensional microfluidics problems.
Nucleon electromagnetic form factors from lattice QCD using a nearly physical pion mass - Green, J. R.; Syritsyn, S. N.; Engelhardt, M.; Krieg, S.; Negele, John W.; Pochinsky, Andrew
We present lattice QCD calculations of nucleon electromagnetic form factors using pion masses m[subscript π] = 149, 202, and 254 MeV and an action with clover-improved Wilson quarks coupled to smeared gauge fields, as used by the Budapest-Marseille-Wuppertal Collaboration. Particular attention is given to the removal of the effects of excited-state contamination by calculations at three source-sink separations and the use of the summation and generalized pencil-of-function methods. The combination of a calculation at the nearly physical mass m[subscript π] = 149 MeV in a large spatial volume (m[subscript π]L[subscript s] = 4.2) and the removal of excited-state effects yields agreement with...
Ultra-rapid laser protein micropatterning: screening for directed polarization of single neurons - Scott, Mark A.; Wissner-Gross, Zachary D.; Yanik, Mehmet Fatih
Protein micropatterning is a powerful tool for studying the effects of extracellular signals on cell development and regeneration. Laser micropatterning of proteins is the most flexible method for patterning many different geometries, protein densities, and concentration gradients. Despite these advantages, laser micropatterning remains prohibitively slow for most applications. Here, we take advantage of the rapid multi-photon induced photobleaching of fluorophores to generate sub-micron resolution patterns of full-length proteins on polymer monolayers, with sub-microsecond exposure times, i.e. one to five orders of magnitude faster than all previous laser micropatterning methods. We screened a range of different PEG monolayer coupling chemistries, chain-lengths...
Fully automated cellular-resolution vertebrate screening platform with parallel animal processing - Chang, Tsung-Yao; Pardo-Martin, Carlos; Allalou, Amin; Yanik, Mehmet Fatih; Wahlby, Carolina
The zebrafish larva is an optically-transparent vertebrate model with complex organs that is widely used to study genetics, developmental biology, and to model various human diseases. In this article, we present a set of novel technologies that significantly increase the throughput and capabilities of our previously described vertebrate automated screening technology (VAST). We developed a robust multi-thread system that can simultaneously process multiple animals. System throughput is limited only by the image acquisition speed rather than by the fluidic or mechanical processes. We developed image recognition algorithms that fully automate manipulation of animals, including orienting and positioning regions of interest...
A simple class of efficient compression schemes supporting local access and editing - Zhou, Hongchao; Wang, Da; Wornell, Gregory W.
In this paper, we study the problem of compressing a collection of sequences of variable length that allows us to efficiently add, read, or edit an arbitrary sequence without decompressing the whole data. This problem has important applications in data servers, file-editing systems, and bioinformatics. We propose a novel and practical compression scheme, which shows that, by paying a small price in storage space (3% extra storage space in our examples), we can retrieve or edit a sequence (a few hundred bits) by accessing compressed bits close to the entropy of the sequence.
Scalar quantization with noisy partitions and its application to Flash ADC design - Wang, Da; Polyanskiy, Yury; Wornell, Gregory W.
Motivated by recent circuit designs for Flash ADCs with imperfect comparators, we investigate the problem of scalar quantization with noisy partition points, where the partition point locations are perturbed from the designated values by noise during the placement process. For this problem setting, we derive a high resolution approximation for mean square error, and analyze the optimal partition point density accordingly. Our results indicate that it is necessary to take the effect of noise into account in the design process. In particular, we derive the optimal partition point density when the input distribution is Gaussian or uniform, and show when...
Lossy compression of permutations - Wang, Da; Mazumdar, Arya; Wornell, Gregory W.
We investigate the lossy compression of permutations by analyzing the trade-off between the size of a source code and the distortion with respect to Kendall tau distance, Spearman's footrule, Chebyshev distance and ℓ[subscript 1] distance of inversion vectors. We show that given two permutations, Kendall tau distance upper bounds the ℓ[subscript 1] distance of inversion vectors and a scaled version of Kendall tau distance lower bounds the ℓ[subscript 1] distance of inversion vectors with high probability, which indicates an equivalence of the source code designs under these two distortion measures. Similar equivalence is established for all the above distortion measures,...
Toward Photon-Efficient Key Distribution Over Optical Channels - Kochman, Yuval; Wang, Ligong; Wornell, Gregory W.
This paper considers the distribution of a secret key over an optical (bosonic) channel in the regime of high photon efficiency, i.e., when the number of secret key bits generated per detected photon is high. While, in principle, the photon efficiency is unbounded, there is an inherent tradeoff between this efficiency and the key generation rate (with respect to the channel bandwidth). We derive asymptotic expressions for the optimal generation rates in the photon-efficient limit, and propose schemes that approach these limits up to certain approximations. The schemes are practical, in the sense that they use coherent or temporally entangled...
The effect of block-wise feedback on the throughput-delay trade-off in streaming - Joshi, Gauri; Kochman, Yuval; Wornell, Gregory W.
Unlike traditional file transfer where only total delay matters, streaming applications impose delay constraints on each packet and require them to be in order. To achieve fast in-order packet decoding, we have to compromise on the throughput. We study this trade-off between throughput and in-order decoding delay, and in particular how it is affected by the frequency of block-wise feedback, whereby the source receives full channel state feedback at periodic intervals. Our analysis shows that for the same throughput, having more frequent feedback significantly reduces the in-order decoding delay. For any given block-wise feedback delay, we present a spectrum of...