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Mukherji S.,Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology | Ebert M.S.,Massachusetts Institute of Technology | Ebert M.S.,Howard Hughes Medical Institute | Zheng G.X.Y.,Massachusetts Institute of Technology | And 6 more authors.
Nature Genetics | Year: 2011

MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression. © 2011 Nature America, Inc. All rights reserved. Source


Rapoport B.I.,Harvard University | Rapoport B.I.,Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology
PLoS Computational Biology | Year: 2010

Each year in the past three decades has seen hundreds of thousands of runners register to run a major marathon. Of those who attempt to race over the marathon distance of 26 miles and 385 yards (42.195 kilometers), more than two-fifths experience severe and performance-limiting depletion of physiologic carbohydrate reserves (a phenomenon known as 'hitting the wall'), and thousands drop out before reaching the finish lines (approximately 1-2% of those who start). Analyses of endurance physiology have often either used coarse approximations to suggest that human glycogen reserves are insufficient to fuel a marathon (making 'hitting the wall' seem inevitable), or implied that maximal glycogen loading is required in order to complete a marathon without 'hitting the wall.' The present computational study demonstrates that the energetic constraints on endurance runners are more subtle, and depend on several physiologic variables including the muscle mass distribution, liver and muscle glycogen densities, and running speed (exercise intensity as a fraction of aerobic capacity) of individual runners, in personalized but nevertheless quantifiable and predictable ways. The analytic approach presented here is used to estimate the distance at which runners will exhaust their glycogen stores as a function of running intensity. In so doing it also provides a basis for guidelines ensuring the safety and optimizing the performance of endurance runners, both by setting personally appropriate paces and by prescribing midrace fueling requirements for avoiding 'the wall.' The present analysis also sheds physiologically principled light on important standards in marathon running that until now have remained empirically defined: The qualifying times for the Boston Marathon. © 2010 Benjamin I. Rapoport. Source


Zeisberg E.M.,Beth Israel Deaconess Medical Center | Kalluri R.,Beth Israel Deaconess Medical Center | Kalluri R.,Harvard University | Kalluri R.,Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology
Circulation Research | Year: 2010

Cardiac fibroblasts play a critical role in maintenance of normal cardiac function. They are indispensable for damage control and tissue remodeling on myocardial injury and principal mediators of pathological cardiac remodeling and fibrosis. Despite their manyfold functions, cardiac fibroblasts remain poorly characterized in molecular terms. Evidence is evolving that cardiac fibroblasts are a heterogeneous population and likely derive from various distinct tissue niches in health and disease. Here, we review our emerging understanding of where cardiac fibroblasts come from, as well as how we can possibly use this knowledge to develop novel therapies for cardiac fibrosis. © 2010 American Heart Association, Inc. Source


Villiger M.,Harvard University | Bouma B.E.,Harvard University | Bouma B.E.,Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology
Optics Letters | Year: 2014

The differential Mueller matrix expresses the local action of an optical medium on the evolution of a propagating electromagnetic field, including partially coherent and partially polarized waves. Here, we present a derivation of the differential Mueller matrix from the canonical form of Type I Mueller matrices without making use of the exponential generators of uniform media. We demonstrate how to practically obtain this parameterization numerically using an eigenvalue decomposition and find validity criteria to ensure that the matrix satisfies the constraints of a physical system. This provides a convenient tool-set to investigate depolarization effects and extends previous treatments of the differential Mueller matrix formalism. © 2014 Optical Society of America. Source


Wang L.,Nanjing Southeast University | Asghar W.,Harvard University | Demirci U.,Harvard University | Demirci U.,Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology | And 2 more authors.
Nano Today | Year: 2013

Circulating tumor cells (CTCs) originate from the primary tumor mass and enter into the peripheral bloodstream. CTCs hold the key to understanding the biology of metastasis and also play a vital role in cancer diagnosis, prognosis, disease monitoring, and personalized therapy. However, CTCs are rare in blood and hard to isolate. Additionally, the viability of CTCs can easily be compromised under high shear stress while releasing them from a surface. The heterogeneity of CTCs in biomarker expression makes their isolation quite challenging; the isolation efficiency and specificity of current approaches need to be improved. Nanostructured substrates have emerged as a promising biosensing platform since they provide better isolation sensitivity at the cost of specificity for CTC isolation. This review discusses major challenges faced by CTC isolation techniques and focuses on nanostructured substrates as a platform for CTC isolation. © 2013 Elsevier Ltd. All rights reserved. Source

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