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Tan H.T.,National University of Singapore | Lee Y.H.,Singapore MIT Alliance for Research and Technology | Chung M.C.M.,National University of Singapore
Mass Spectrometry Reviews | Year: 2012

Cancer presents high mortality and morbidity globally, largely due to its complex and heterogenous nature, and lack of biomarkers for early diagnosis. A proteomics study of cancer aims to identify and characterize functional proteins that drive the transformation of malignancy, and to discover biomarkers to detect early-stage cancer, predict prognosis, determine therapy efficacy, identify novel drug targets, and ultimately develop personalized medicine. The various sources of human samples such as cell lines, tissues, and plasma/serum are probed by a plethora of proteomics tools to discover novel biomarkers and elucidate mechanisms of tumorigenesis. Innovative proteomics technologies and strategies have been designed for protein identification, quantitation, fractionation, and enrichment to delve deeper into the oncoproteome. In addition, there is the need for high-throughput methods for biomarker validation, and integration of the various platforms of oncoproteome data to fully comprehend cancer biology. © 2012 Wiley Periodicals, Inc. Mass Spec Rev 31:583-605, 2012 Copyright © 2012 Wiley Periodicals, Inc.

Du N.,National University of Singapore | Du N.,Singapore MIT Alliance for Research and Technology | Yang Z.,National University of Singapore | Liu X.Y.,National University of Singapore | And 2 more authors.
Advanced Functional Materials | Year: 2011

Spider dragline silk, as a type of high-performance natural fiber, displays a unique combination of tensile strength and extensibility that gives rise to a greater toughness than any other natural or synthetic fiber. In contrast to silkworm silk, spider dragline silk displays a remarkable strain-hardening character for which the origin remains unknown. In this paper, the performance of silkworm silk and spider dragline fibers under stretching is compared based on a combined structural and mechanical analysis. The molecular origin of the strain-hardening of spider silk filaments is addressed in comparison to rubber and Kevlar. Unlike rubber, the occurrence of strain-hardening can be attributed to the unfolding of the intramolecular β-sheets in spider silk fibrils, which serve as "molecular spindles" to store lengthy molecular chains in space compactly. With the progressive unfolding and alignment of protein during fiber extension, protein backbones and nodes of the molecular network are stretched to support the load. Consequently the dragline filaments become gradually hardened, enabling efficient energy buffering when an abseiling spider escapes from a predator. As distinct from synthetic materials such as rubber (elastomers), this particular structural feature of spider draglines not only enables quick energy absorption, but also efficiently suppresses the drastic oscillation which occurs upon an impact. The mimicking of this strain-hardening character of spider silk will give rise to the design and fabrication of new advanced functional materials with applications in kinetic energy buffering and absorption. The structural response of spider dragline fiber to stretching is distinct from that of silkworm silk. The unfolding of the intramolecular β-sheets in spider silk fibrils gives rise to strain-hardening behavior, enabling efficient energy buffering and absorption when an abseiling spider escapes from a predator. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kurniawati H.,Queensland University of Technology | Bandyopadhyay T.,Singapore MIT Alliance for Research and Technology | Patrikalakis N.M.,Massachusetts Institute of Technology
Autonomous Robots | Year: 2012

Uncertainty in motion planning is often caused by three main sources: motion error, sensing error, and imperfect environment map. Despite the significant effect of all three sources of uncertainty to motion planning problems, most planners take into account only one or at most two of them. We propose a new motion planner, called Guided Cluster Sampling (GCS), that takes into account all three sources of uncertainty for robots with active sensing capabilities. GCS uses the Partially Observable Markov Decision Process (POMDP) framework and the point-based POMDP approach. Although point-based POMDPs have shown impressive progress over the past few years, it performs poorly when the environment map is imperfect. This poor performance is due to the extremely high dimensional state space, which translates to the extremely large belief space B. We alleviate this problem by constructing a more suitable sampling distribution based on the observations that when the robot has active sensing capability, B can be partitioned into a collection of much smaller sub-spaces, and an optimal policy can often be generated by sufficient sampling of a small subset of the collection. Utilizing these observations, GCS samples B in two-stages, a subspace is sampled from the collection and then a belief is sampled from the subspace. It uses information from the set of sampled sub-spaces and sampled beliefs to guide subsequent sampling. Simulation results on marine robotics scenarios suggest that GCS can generate reasonable policies for motion planning problems with uncertain motion, sensing, and environment map, that are unsolvable by the best point-based POMDPs today. Furthermore, GCS handles POMDPs with continuous state, action, and observation spaces. We show that for a class of POMDPs that often occur in robot motion planning, given enough time, GCS converges to the optimal policy. To the best of our knowledge, this is the first convergence result for point-based POMDPs with continuous action space. © 2012 Springer Science+Business Media, LLC.

Wongpiromsarn T.,Singapore MIT Alliance for Research and Technology | Topcu U.,California Institute of Technology | Murray R.M.,California Institute of Technology
IEEE Transactions on Automatic Control | Year: 2012

We present a methodology for automatic synthesis of embedded control software that incorporates a class of linear temporal logic (LTL) specifications sufficient to describe a wide range of properties including safety, stability, progress, obligation, response and guarantee. To alleviate the associated computational complexity of LTL synthesis, we propose a receding horizon framework that effectively reduces the synthesis problem into a set of smaller problems. The proposed control structure consists of a goal generator, a trajectory planner, and a continuous controller. The goal generator reduces the trajectory generation problem into a sequence of smaller problems of short horizon while preserving the desired system-level temporal properties. Subsequently, in each iteration, the trajectory planner solves the corresponding short-horizon problem with the currently observed state as the initial state and generates a feasible trajectory to be implemented by the continuous controller. Based on the simulation property, we show that the composition of the goal generator, trajectory planner and continuous controller and the corresponding receding horizon framework guarantee the correctness of the system with respect to its specification regardless of the environment in which the system operates. In addition, we present a response mechanism to handle failures that may occur due to a mismatch between the actual system and its model. The effectiveness of the proposed technique is demonstrated through an example of an autonomous vehicle navigating an urban environment. This example also illustrates that the system is not only robust with respect to exogenous disturbances but is also capable of properly handling violation of the environment assumption that is explicitly stated as part of the system specification. © 2012 IEEE.

Im E.-S.,Singapore MIT Alliance for Research and Technology | Gianotti R.L.,Massachusetts Institute of Technology | Eltahir E.A.B.,Massachusetts Institute of Technology
Journal of Climate | Year: 2014

This paper presents an evaluation of the performance of the Massachusetts Institute of Technology (MIT) regional climate model (MRCM) in simulating the West African monsoon. The MRCM is built on the Regional Climate Model, version 3 (RegCM3), but with several improvements, including coupling of Integrated Biosphere Simulator (IBIS) land surface scheme, a new surface albedo assignment method, new convective cloud and convective rainfall autoconversion schemes, and a modified scheme for simulating boundary layer height and boundary layer clouds. To investigate the impact of these more physically realistic representations when incorporated into MRCM, a series of experiments were carried out implementing two land surface schemes [IBIS with a new albedo assignment, and the Biosphere-Atmosphere Transfer Scheme (BATS)] and two convection schemes (Grell with the Fritsch-Chappell closure, and Emanuel in both the default form and modified with the new convective cloud cover and a rainfall autoconversion scheme). The analysis primarily focuses on comparing the rainfall characteristics, surface energy balance, and large-scale circulations against various observations. This work documents significant sensitivity in simulation of the West African monsoon to the choices of the land surface and convection schemes. Despite several deficiencies, the simulation with the combination of IBIS and the modified Emanuel scheme with the new convective cloud cover and a rainfall autoconversion scheme shows the best performance with respect to the spatial distribution of rainfall and the dynamics of the monsoon. The coupling of IBIS leads to representations of the surface energy balance and partitioning that show better agreement with observations compared to BATS. The IBIS simulations also reasonably reproduce the dynamical structures of the West African monsoon circulation. © 2014 American Meteorological Society.

Lee J.B.,Massachusetts Institute of Technology | Lee J.B.,University of Seoul | Hong J.,Massachusetts Institute of Technology | Bonner D.K.,Massachusetts Institute of Technology | And 3 more authors.
Nature Materials | Year: 2012

The encapsulation and delivery of short interfering RNA (siRNA) has been realized using lipid nanoparticles, cationic complexes, inorganic nanoparticles, RNA nanoparticles and dendrimers. Still, the instability of RNA and the relatively ineffectual encapsulation process of siRNA remain critical issues towards the clinical translation of RNA as a therapeutic. Here we report the synthesis of a delivery vehicle that combines carrier and cargo: RNA interference (RNAi) polymers that self-assemble into nanoscale pleated sheets of hairpin RNA, which in turn form sponge-like microspheres. The RNAi-microsponges consist entirely of cleavable RNA strands, and are processed by the cell's RNA machinery to convert the stable hairpin RNA to siRNA only after cellular uptake, thus inherently providing protection for siRNA during delivery and transport to the cytoplasm. More than half a million copies of siRNA can be delivered to a cell with the uptake of a single RNAi-microsponge. The approach could lead to novel therapeutic routes for siRNA delivery. © 2012 Macmillan Publishers Limited. All rights reserved.

Gianotti R.L.,Massachusetts Institute of Technology | Zhang D.,Singapore MIT Alliance for Research and Technology | Eltahir E.A.B.,Massachusetts Institute of Technology
Journal of Climate | Year: 2012

This paper describes an assessment of the Regional Climate Model, version 3 (RegCM3), coupled to two land surface schemes: the Biosphere-Atmosphere Transfer System, version 1e (BATS1e), and the Integrated Biosphere Simulator (IBIS). The model's performance in simulating precipitation over the Maritime Continent was evaluated against the 3-hourly Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis 3B42 product. It is found that the model suffers from three major errors in reproducing the observed rainfall histogram: underestimation of the frequency of dry periods, overestimation of the frequency of low-intensity rainfall, and underestimation of the frequency of high-intensity rainfall. Additionally, the model does not accurately reproduce the observed timing of the diurnal rainfall peak, particularly over land. These four errors persisted regardless of the choice of lateral boundary conditions, convective parameterization scheme, or land surface scheme. The magnitude of the wet-dry bias in the simulated volumes of rainfall was, however, strongly dependent on the choice of the convection scheme and lateral boundary conditions. The Grell convection scheme with Fritsch-Chappell closure was the best performing of the convection schemes, having the smallest error magnitudes in both the rainfall histogram and average diurnal cycle, and also having good representation of the land surface energy and evapotranspiration components. The 40-yr ECMWF Re-Analysis (ERA-40) was found to produce better simulations of observed rainfall when used as lateral boundary conditions than did the NCEP-NCAR reanalysis. Discussion of the nature of the major model errors is provided, along with some suggestions for improvement. © 2012 American Meteorological Society.

Grandey B.S.,University of Oxford | Grandey B.S.,Singapore MIT Alliance for Research and Technology | Stier P.,University of Oxford | Wagner T.M.,University of Oxford
Atmospheric Chemistry and Physics | Year: 2013

Strong positive relationships between cloud fraction (fc) and aerosol optical depth (τ) have been reported. Data retrieved from the MODerate resolution Imaging Spectroradiometer (MODIS) instrument show positive fc-τ relationships across most of the globe. A global mean f c increase of approximately 0.2 between low and high τ conditions is found for both ocean and land. However, these relationships are not necessarily due to cloud-aerosol interactions. Using state-of-the-art Monitoring Atmospheric Composition and Climate (MACC) reanalysis-forecast τ data, which should be less affected by retrieval artefacts, it is demonstrated that a large part of the observed fc-τ signal may be due to cloud contamination of satellite-retrieved τ. For longer MACC forecast time steps of 24 h, which likely contain less cloud contamination, some negative f c-τ relationships are found. The global mean fc increase between low and high τ conditions is reduced to 0.1, suggesting that cloud contamination may account for approximately one half of the satellite retrieved increase in fc. ECHAM5-HAM general circulation model (GCM) simulations further demonstrate that positive fc-τ relationships may arise due to covariation with relative humidity. Widespread negative simulated fc-τ relationships in the tropics are shown to arise due to scavenging of aerosol by convective precipitation. Wet scavenging events are likely poorly sampled in satellite-retrieved data, because the properties of aerosol below clouds cannot be retrieved. Quantifying the role of wet scavenging, and assessing GCM representations of this important process, remains a challenge for future observational studies of aerosol-cloud-precipitation interactions. © Author(s) 2013.

Li A.,Singapore MIT Alliance for Research and Technology
Methods in molecular biology (Clifton, N.J.) | Year: 2013

Atomic Force Microscopy (AFM) is a powerful tool for exploring the interaction between ligands and receptors, as well as their exact locations on the red cell surface. Here we discuss current and future applications for AFM based single-molecule force spectroscopy to study adhesion of Plasmodium-infected red blood cells. A protocol is provided for simultaneous topography and recognition imaging of the surface of Plasmodium falciparum-infected cells using CD36 functionalized tips.

Cottrill C.D.,Singapore MIT Alliance for Research and Technology
URISA Journal | Year: 2011

Interest in and concerns related to the issue of privacy in the location-aware environment have been growing as the availability and use of location-based services (LBS) and data have been expanding. Recent events such as "Locationgate" have brought this issue to the forefront of interest for lawmakers, application developers, agencies, and users; however, understanding the varying levels of responsibility for each has been lacking. This article attempts to provide a clear review of the methods by which privacy protection may take place at the levels of law, technology, and management so a better understanding of how a comprehensive approach to privacy protection may take place. While the majority of policy aspects reviewed are U.S.-based, an attempt has been made to provide an overall view of locational privacy policy environments on an international scale as well. It is hoped that this effort will result in a clearer understanding of the ways in which privacy protection efforts should address the related concepts of law, technology, and practice to effectively minimize the risk of privacy harm.

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