Cs Draper Laboratory

Cambridge, MA, United States

Cs Draper Laboratory

Cambridge, MA, United States
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Erb T.M.,University of Pittsburgh | Schneider C.,Magee Womens Research Institute | Mucko S.E.,Magee Womens Research Institute | Sanfilippo J.S.,University of Pittsburgh | And 4 more authors.
Stem Cells and Development | Year: 2011

Our understanding of paracrine and epigenetic control of trophectoderm (TE) differentiation is limited by available models of preimplantation human development. Simple, defined media for selective TE differentiation of human embryonic stem cells (hESCs) were developed, enabling mechanistic studies of early placental development. Paracrine requirements of preimplantation human development were evaluated with hESCs by measuring lineage-specific transcription factor expression levels in single cells and morphological transformation in response to selected paracrine and epigenetic modulators. Bone morphogenic protein 4 (BMP4) addition to feeder-free pluripotent stem cells on matrigel frequently formed CDX2-positive TE. However, BMP4 or activin A inhibition alone also produced a mix of mesoderm and extraembryonic endoderm under these conditions. Further, BMP4 failed to form TE from adherent hESC maintained in standard feeder-dependent monolayers. Given that the efficiency and selectivity of BMP4-induced TE depended on medium components, we developed a basal medium containing insulin and heparin. In this medium, BMP4 induction of TE was dose dependent and with activin A inhibition by SB431542 (SB), approached 100% of cells. This paracrine stimulation of pluripotent cells transformed colony morphology from a cuboidal to squamous epithelium quantitatively on day 3, and produced significant multinucleated syncytiotrophoblasts by day 8. Addition of trichostatin A, a histone deacetylase (HDAC) inhibitor, reduced HDAC3, histone H3K9 methylation, and slowed differentiation in a dose-dependent manner. Modulators of BMP4- or HDAC-dependent signaling might adversely influence the timing and viability of early blastocyst developed in vitro. Since blastocyst development is synchronized to uterine receptivity, epigenetic regulators of TE differentiation might adversely affect implantation in vivo. © Copyright 2011, Mary Ann Liebert, Inc.

Pararas E.E.L.,Cs Draper Laboratory | Pararas E.E.L.,Massachusetts Eye and Ear Infirmary | Chen Z.,Massachusetts Eye and Ear Infirmary | Fiering J.,Cs Draper Laboratory | And 7 more authors.
Journal of Controlled Release | Year: 2011

Reciprocating drug delivery is a means of delivering soluble drugs directly to closed fluid spaces in the body via a single cannula without an accompanying fluid volume change. It is ideally suited for drug delivery into small, sensitive and unique fluid spaces such as the cochlea. We characterized the pharmacokinetics of reciprocating drug delivery to the scala tympani within the cochlea by measuring the effects of changes in flow parameters on the distribution of drug throughout the length of the cochlea. Distribution was assessed by monitoring the effects of DNQX, a reversible glutamate receptor blocker, delivered directly to the inner ear of guinea pigs using reciprocating flow profiles. We then modeled the effects of those parameters on distribution using both an iterative curve-fitting approach and a computational fluid dynamic model. Our findings are consistent with the hypothesis that reciprocating delivery distributes the drug into a volume in the base of the cochlea, and suggest that the primary determinant of distribution throughout more distal regions of the cochlea is diffusion. Increases in flow rate distributed the drug into a larger volume that extended more apically. Over short time courses (less than 2 h), the apical extension, though small, significantly enhanced apically directed delivery of drug. Over longer time courses (> 5 h) or greater distances (> 3 mm), maintenance of drug concentration in the basal scala tympani may prove more advantageous for extending apical delivery than increases in flow rate. These observations demonstrate that this reciprocating technology is capable of providing controlled delivery kinetics to the closed fluid space in the cochlea, and may be suitable for other applications such as localized brain and retinal delivery. © 2011 Elsevier B.V. All rights reserved.

Smith S.P.,Cs Draper Laboratory | Johnson D.M.S.,Cs Draper Laboratory
AIAA Guidance, Navigation, and Control (GNC) Conference | Year: 2013

Improvements in aerospace guidance, navigation and control are driven by advances in the basic science and technology underpinning PN&T. Today, quantum sensing has the potential to enable very high performance inertial measurement units with greatly reduced resource demands. However, even these instruments still produce long-term drifts which are incompatible with modern long-duration missions and position and attitude requirements. These limitations have driven the satellite navigation revolution (e.g., GPS, GLONASS, and Galileo), and low resource demand receivers have clearly demonstrated the power of precision positioning information on many platforms. These systems, however, depend on delicate signals that can be prone to either unintentional corruption, for example reflected signals in an urban environment or intentional jamming or spoofing. Combining information from multiple sources can enable very accurate position and attitude determination over long durations. Modern consumer technology development is providing the ubiquitous low resource imaging systems, multi-band RF receivers, magnetometers and other sensors, which are required for a robust, multi-sensor approach for external aided navigation. Future systems will blend signals from a variety of sources, including new inertial sensors, to provide the most robust, jam-proof, stable navigation solution possible.

Dibiasio C.M.,Cs Draper Laboratory | Culpepper M.L.,Massachusetts Institute of Technology
Precision Engineering | Year: 2012

Early stage design of precision flexure systems that utilize strain-based displacement sensing is difficult due to the strong coupling between the mechanical and sensing subsystems. Traditional tools for flexure system and compliant mechanism synthesis are not capable of simultaneously optimizing the mechanical and sensing subsystems. The building block synthesis approach developed in this work is the only tool capable of designing compliant mechanisms with integrated strain based sensing. Building block modeling allows for rapid synthesis and vetting of concepts. This approach also allows the designer to determine concept feasibility, identify performance limits and tradeoffs, and obtain 1st order estimates of flexure geometry. In short, this method enables one to find an optimal design and set first order design parameters. The utility of the building block approach is detailed in a case study detailing the synthesis and modeling of three different one degree-of-freedom translational stages that are all derived from the series and parallel addition of fixed-guided cantilever beam building blocks. © 2012 Elsevier Inc. All rights reserved.

Cipolloni J.J.,Cs Draper Laboratory | Looft F.J.,Worcester Polytechnic Institute | Virani S.,Worcester Polytechnic Institute
Procedia Computer Science | Year: 2015

The successful application of most modern complex systems depends on human components as part of their system architectures. While the complexity of these systems is further complicated due to those human elements, most of these complex system designs may still be well-engineered using traditional systems engineering approaches and methodologies. Reference architectures (RA) are applied in this paper to demonstrate their use for defining systems that are human centered. That is, systems where the human is not the proverbial cog in the architecture rather where the human is the core emphasis of the design. This paper proposes a construct for Equipped-Human Reference Architecture (EHRA) as a useful systems engineering tool for addressing the complexity inherent in developing human centric systems. We assert that well conceived and constructed EHRA could provide a reusable and evolving set of architecture guidelines and constraints that define the complete equipped-human design space. Additionally, well-structured EHRA should be extensible to provide usable systems engineering design tools in order to aid equipped-human systems (EHS) developers when they are designing and evolving specific EHS solution architectures. © 2015 Published by Elsevier B.V.

Lowry N.,Massachusetts Institute of Technology | Mangoubi R.,Cs Draper Laboratory | Desai M.,Cs Draper Laboratory | Sammak P.,University of Pittsburgh
2010 7th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2010 - Proceedings | Year: 2010

We present nonparametric methods for segmenting and classifying stem cell nuclei so as to enable the automatic monitoring of stem cell growth and development. The approach is based on combining level set methods, multiresolutionwavelet analysis, and non-parametric estimation of the density functions of the wavelet coefficients from the decomposition. Additionally, to deal with small size textureswhere the largest inscribed rectangular windowmay not contain a sufficient number of pixels for multiresolution analysis, we propose an adjustable windowing method that enables the multiresolution analysis of elongated and irregularly shaped nuclei. We illustrate cases where the adjustable windowing approach combinedwith non-parametric density models yields better classification for cases where parametric densitymodeling of wavelet coefficients may not applicable. ©2010 IEEE.

Cullinan M.A.,Massachusetts Institute of Technology | Cullinan M.A.,Intelligent Systems Technology, Inc. | Panas R.M.,Massachusetts Institute of Technology | Dibiasio C.M.,Massachusetts Institute of Technology | And 2 more authors.
Sensors and Actuators, A: Physical | Year: 2012

Traditional MEMS sensing systems do not scale down well to the nanoscale due to resolution and fabrication limitations. Therefore, new sensing systems need to be developed in order to meet the range and resolution requirements of nanoscale mechanical systems. Several nanoscale mechanical sensing systems have emerged that take advantage of nanoscale phenomena to improve the quality of nanoscale sensors. In this paper, we will discuss some of the fundamental limitations in scaling mechanical sensors down to the nanoscale and some of the emerging technologies for nanoscale sensing. © 2012 Elsevier B.V. All rights reserved.

Chiel B.S.,Boston University | Dever C.,Cs Draper Laboratory
Aerodynamic Decelerator Systems Technology Conferences | Year: 2015

Guided airdrop systems lacking propulsion can be adversely affected by high winds, especially if their guidance algorithms fail to take full advantage of vehicle maneuverability. In real-world flight tests of U.S. Army parafoils, both strong tail winds and unanticipated wind shifts prevented several lightweight systems from landing accurately. These systems’ guidance algorithms did not account for the high winds’ restricting effect on the range of obtainable ground track directions. This paper introduces two new guidance strategies, one simple and one advanced, that address high wind scenarios directly. First, they take into account estimated wind field behavior between the current vehicle altitude and ground level, whether the estimates come from simple forward predictions, sharing of wind field estimates between systems, or ground-level weather station wind sensing. Second, their planned trajectories more fully exploit vehicle maneuverability, including the possibility of facing into high winds while flying backwards or even planning trajectories that first fly away from the target in anticipation of being blown to their intended destination later. Compared to reasonable baseline methods, the presented algorithms significantly improve miss performance in real-world high wind conditions without degrading performance in light and moderate winds. In addition, simulation tests show a marked performance improvement whether the wind field estimate is a simple forward-prediction or a high-quality estimate obtained via wind estimate sharing or ground-level sensing. © 2015, AIAA American Institute of Aeronautics and Astronautics. All rights reserved.

Hammett R.,Cs Draper Laboratory
IEEE Aerospace Conference Proceedings | Year: 2011

An approach that uses rapid start-up computers to provide fault-tolerance and transient upset recovery while minimizing Size, Weight and Power (SWaP) is described. This paper provides a status report on a research project conducted by Draper Laboratory aimed at developing avionics suitable for both manned and unmanned space vehicles. They are intended to provide extremely high levels of reliability but with reduced SWaP as compared to current systems. The key to this is the ability to very rapidly power-up back-up hardware and to start up or restart software. A handoff of uncorrupted state data from the failing computer to the start-up or restart computer is also required. © 2011 IEEE.

Desai M.,Cs Draper Laboratory | Mangoubi R.,Cs Draper Laboratory
European Signal Processing Conference | Year: 2015

We address the problem of matched subspace detection in the presence of arbitrary noise and interferents, or interfering signals that may lie in a possibly unknown subspace, but that nevertheless corrupt the measurements. A hypothesis test that is robust to interferents yet sensitive to the signal of interest is formulated. The test is applicable to a large class of noise density functions. In addition, specific expressions for the generalized likelihood ratio (GLR) detectors are derived for the class of Generalized Gaussian noise. The detectors are generalizations of the χ2, t, and F statistics used with Gaussian noise. For matched filter detection, these expressions are simpler and computationally efficient. ROC performance results based on simulation demonstrate the superior performance obtained with detectors based on the correct noise model. The results also demonstrate the improved performance robust detectors offer when interferents are present. © 2002 EUSIPCO.

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