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MIT Open Access Articles
Mostrando recursos 41 - 60 de 14,222
Effect of Small-Molecule-Binding Affinity on Tumor Uptake In Vivo: A Systematic Study Using a Pretargeted Bispecific Antibody - Rhoden, John J.; Ruiz-Yi, Benjamin; Wittrup, Karl Dane; Frangioni, John V.; Orcutt, Kelly Davis
Small-molecule ligands specific for tumor-associated surface receptors have wide applications in cancer diagnosis and therapy. Achieving high-affinity binding to the desired target is important for improving detection limits and for increasing therapeutic efficacy. However, the affinity required for maximal binding and retention remains unknown. Here, we present a systematic study of the effect of small-molecule affinity on tumor uptake in vivo with affinities spanning a range of three orders of magnitude. A pretargeted bispecific antibody with different binding affinities to different DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based small molecules is used as a receptor proxy. In this particular system targeting carcinoembryonic antigen, a...
Optogenetically Induced Behavioral and Functional Network Changes in Primates - Gerits, Annelies; Farivar, Reza; Rosen, Bruce R.; Wald, Lawrence L.; Vanduffel, Wim; Boyden, Edward Stuart
Optogenetics is currently the state-of-the-art method for causal-oriented brain research. Despite an increasingly large number of invertebrate and rodent studies showing profound electrophysiological and behavioral effects induced by optogenetics, only two primate studies have reported modulation of local single-cell activity but with no behavioral effects. Here, we show that optogenetic stimulation of cortical neurons within rhesus monkey arcuate sulcus, during the execution of a visually guided saccade task, evoked significant and reproducible changes in saccade latencies as a function of target position. Moreover, using concurrent optogenetic stimulation and opto-fMRI), we observed optogenetically induced changes in fMRI activity in specific functional...
Cell-Type-Specific Synchronization of Neural Activity in FEF with V4 during Attention - Gregoriou, Georgia G.; Gotts, Stephen J.; Desimone, Robert
Shifts of gaze and shifts of attention are closely linked and it is debated whether they result from the same neural mechanisms. Both processes involve the frontal eye fields (FEF), an area which is also a source of top-down feedback to area V4 during covert attention. To test the relative contributions of oculomotor and attention-related FEF signals to such feedback, we recorded simultaneously from both areas in a covert attention task and in a saccade task. In the attention task, only visual and visuomovement FEF neurons showed enhanced responses, whereas movement cells were unchanged. Importantly, visual, but not movement or...
Slug and Sox9 Cooperatively Determine the Mammary Stem Cell State - Guo, Wenjun; Keckesova, Zuzana; Donaher, Joana Liu; Shibue, Tsukasa; Tischler, Verena; Reinhardt, Ferenc; Itzkovitz, Shalev; Noske, Aurelia; Bell, George; Tam, Wai Leong; Mani, Sendurai A.; van Oudenaarden, Alexander; Weinberg, Robert A.; Zurrer-Hardi, Ursina; van Oudenaarden, Alexander; Weinberg, Robert A.
Regulatory networks orchestrated by key transcription factors (TFs) have been proposed to play a central role in the determination of stem cell states. However, the master transcriptional regulators of adult stem cells are poorly understood. We have identified two TFs, Slug and Sox9, that act cooperatively to determine the mammary stem cell (MaSC) state. Inhibition of either Slug or Sox9 blocks MaSC activity in primary mammary epithelial cells. Conversely, transient coexpression of exogenous Slug and Sox9 suffices to convert differentiated luminal cells into MaSCs with long-term mammary gland-reconstituting ability. Slug and Sox9 induce MaSCs by activating distinct autoregulatory gene expression...
Building biomedical materials layer-by-layer - Hammond, Paula T.
In this materials perspective, the promise of water based layer-by-layer (LbL) assembly as a means of generating drug-releasing surfaces for biomedical applications, from small molecule therapeutics to biologic drugs and nucleic acids, is examined. Specific advantages of the use of LbL assembly versus traditional polymeric blend encapsulation are discussed. Examples are provided to present potential new directions. Translational opportunities are discussed to examine the impact and potential for true biomedical translation using rapid assembly methods, and applications are discussed with high need and medical return.
A Demonstration of Light Guides for Light Detection in Liquid Argon TPCs - Ignarra, C.M.
Liquid Argon (LAr) Time Projection Chambers (TPCs) are a developing technology that is becoming a popular choice for neutrino and dark matter experiments due to the low cost of the LAr as a target material and the high signal efficiency and background rejection that these detectors can achieve. When excited by a passing charged particle created in a neutrino interaction, argon produces scintillation light at 128 nm. Several types of systems exist for detecting this light. Most involve shifting the wavelength of the light using Tetraphenyl Butadiene (TPB), resulting in visible light which is detected by a PMT.I will discuss...
Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing - Lander, Eric S.; Hodis, Eran
Lung adenocarcinoma, the most common subtype of non-small cell lung cancer, is responsible for more than 500,000 deaths per year worldwide. Here, we report exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. These analyses revealed a mean exonic somatic mutation rate of 12.0 events/megabase and identified the majority of genes previously reported as significantly mutated in lung adenocarcinoma. In addition, we identified statistically recurrent somatic mutations in the splicing factor gene U2AF1 and truncating mutations affecting RBM10 and ARID1A. Analysis of nucleotide context-specific mutation signatures grouped the sample set into distinct clusters that correlated with smoking history...
Solid-Cryogen Cooling Technique for Superconducting Magnets of NMR and MRI - Iwasa, Yukikazu; Hahn, Seungyong; Park, Dong Keun; Bascunan, Juan
This paper describes a solid-cryogen cooling technique currently being developed at the M.I.T. Francis Bitter Magnet Laboratory for application to superconducting magnets of NMR and MRI. The technique is particularly appropriate for “dry” magnets that do not rely on liquid cryogen, e.g., liquid helium (LHe), as their primary cooling sources. In addition, the advantages of a cryocirculator (a combination of a cryocooler and a working fluid circulator) over a cryocooler as the primary cooling source for dry magnets are described. The four magnets described here, all incorporating this cooling technique described and currently being developed at the FBML, are: 1)...
Effect of spatial variability on the bearing capacity of cement-treated ground - Kasama, Kiyonobu; Zen, Kouki; Whittle, Andrew
This paper presents a reliability assessment for the undrained bearing capacity of a surface strip foundation based on the results of a probabilistic study in which the shear strength and unit weight of cement-treated ground are represented as random fields in Monte Carlo simulations of undrained stability using numerical limit analyses. The results show how the bearing capacity is related to the coefficient of variation and correlation length scale in both shear strength and unit weight. Based on the results, the authors propose an overdesign factor, tolerable percentage of defective core specimens, and resistance factors for LRFD ultimate limit state...
A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions - Khalil, Ahmad S.; Lu, Timothy K.; Bashor, Caleb J.; Ramirez, Cherie L.; Pyenson, Nora C.; Joung, J. Keith; Collins, James J.; Lu, Timothy K.
Eukaryotic transcription factors (TFs) perform complex and combinatorial functions within transcriptional networks. Here, we present a synthetic framework for systematically constructing eukaryotic transcription functions using artificial zinc fingers, modular DNA-binding domains found within many eukaryotic TFs. Utilizing this platform, we construct a library of orthogonal synthetic transcription factors (sTFs) and use these to wire synthetic transcriptional circuits in yeast. We engineer complex functions, such as tunable output strength and transcriptional cooperativity, by rationally adjusting a decomposed set of key component properties, e.g., DNA specificity, affinity, promoter design, protein-protein interactions. We show that subtle perturbations to these properties can transform an...
Friction Characteristics of Steel Pistons for Diesel Engines - Kim, Dallwoo; Ito, Akemi; Ishikawa, Yasuhiro; Osawa, Katsuyuki; Iwasaki, Yoshiyuki
The use of iron pistons is increasing due to the higher power requirements of diesel truck engines. Expansion of the iron piston is a common concern. The purpose of this study is to clarify the lubrication conditions of cast iron and steel pistons. Friction of steel and cast iron pistons were measured using the floating liner method. The friction of conventional aluminum pistons was also measured for comparison in this study. The measurement of the secondary motion of each piston was carried out to analyse piston friction, and the following findings were obtained. The cast iron piston showed boundary lubrication...
Adaptive Control of Scalar Plants in the Presence of Unmodeled Dynamics - Hussain, Heather Syeda; Matsutani, Megumi M.; Annaswamy, Anuradha M.; Lavretsky, Eugene
Robust adaptive control of scalar plants in the presence of unmodeled dynamics is established in this paper. It is shown that implementation of a projection algorithm with standard adaptive control of a scalar plant ensures global boundedness of the overall adaptive system for a class of unmodeled dynamics.
MIG-13 controls anteroposterior cell migration by interacting with UNC-71/ADM-1 and SRC-1 in Caenorhabditis elegans - Masuda, Hitomi; Nakamura, Kuniaki; Takata, Nozomu; Itoh, Bunsho; Hirose, Takashi; Moribe, Hiroki; Mekada, Eisuke; Okada, Masato
The transmembrane protein MIG-13 is a key regulator required for anterior migration of neural cells in Caenorhabditis elegans, but the signaling mechanisms involved remain unknown. Here, we isolated a suppressor mutation in the unc-71/adm-1 gene, which rescued the AVM neuron migration defect in mig-13 mutants. Genetic analyses revealed that UNC-71 at least partly acts downstream of MIG-13 and has an inhibitory effect on the anterior cell migration. The unc-71 mutation also rescued the anterior migration defect of AVM neuron in src-1 mutants. These findings suggest that MIG-13 controls anteroposterior cell migration by interacting with UNC-71 and SRC-1 in C. elegans.
Fixin' to Divide - Mohammad, Duaa H.; Yaffe, Michael B.; Yaffe, Michael B.
In this issue of Molecular Cell, Yata et al. (2012) show that the mitotic kinase and cell-cycle regulator Plk1 can directly stimulate the DNA repair process, providing a potential mechanism of crosstalk between DNA repair and cell-cycle signaling.
Label-Free Imaging of Membrane Potential Using Membrane Electromotility - Oh, Seungeun; Fang-Yen, Christopher; Choi, Wonshik; Yaqoob, Zahid; Fu, Dan; Park, YongKeun; Dassari, Ramachandra R.; Feld, Michael S.; Dassari, Ramachandra R.; Feld, Michael S.
Electrical activity may cause observable changes in a cell's structure in the absence of exogenous reporter molecules. In this work, we report a low-coherence interferometric microscopy technique that can detect an optical signal correlated with the membrane potential changes in individual mammalian cells without exogenous labels. By measuring milliradian-scale phase shifts in the transmitted light, we can detect changes in the cells' membrane potential. We find that the observed optical signals are due to membrane electromotility, which causes the cells to deform in response to the membrane potential changes. We demonstrate wide-field imaging of the propagation of electrical stimuli in...
An Analytical Approximation of the Joint Distribution of Aggregate Queue-Lengths in an Urban Network - Wang, Carter; Osorio Pizano, Carolina
Traditional queueing network models assume infinite queue capacities due to the complexity of capturing interactions between finite capacity queues. Accounting for this correlation can help explain how congestion propagates through a network. Joint queue-length distribution can be accurately estimated through simulation. Nonetheless, simulation is a computationally intensive technique, and its use for optimization purposes is challenging. By modeling the system analytically, we lose accuracy but gain efficiency and adaptability and can contribute novel information to a variety of congestion related problems, such as traffic signal optimization.
We formulate an analytical technique that combines queueing theory with aggregation-disaggregation techniques in order to...
Nanophotonic quantum phase switch with a single atom - Tiecke, T. G.; Thompson, J. D.; de Leon, N. P.; Liu, L. R.; Lukin, M. D.; Vuletic, Vladan
By analogy to transistors in classical electronic circuits, quantum optical switches are important elements of quantum circuits and quantum networks. Operated at the fundamental limit where a single quantum of light or matter controls another field or material system, such a switch may enable applications such as long-distance quantum communication, distributed quantum information processing and metrology, and the exploration of novel quantum states of matter. Here, by strongly coupling a photon to a single atom trapped in the near field of a nanoscale photonic crystal cavity, we realize a system in which a single atom switches the phase of a...
Relationships Between the Built Environment and Walking and Weight Status Among Older Women in Three U.S. States - Troped, Philip J.; Starnes, Heather A.; Puett, Robin C.; Tamura, Kosuke; Cromley, Ellen K.; James, Peter; Ben-Joseph, Eran; Melly, Steven J.; Laden, Francine
There are few studies of built environment associations with physical activity and weight status among older women in large geographic areas that use individual residential buffers to define environmental exposures. Among 23,434 women (70.0 ± 6.9 yr; range = 57–85) in 3 states, relationships between objective built environment variables and meeting physical activity recommendations via walking and weight status were examined. Differences in associations by population density and state were explored in stratified models. Population density (odds ratio [OR] = 1.04 [1.02, 1.07]), intersection density (ORs = 1.18–1.28), and facility density (ORs = 1.01–1.53) were positively associated with walking. Density...
Informal Land Markets--Perspectives for Policy - Sanyal, Bishwapriya
To propose a policy perspective, on any issue, one must begin with a historical awareness of how such issues have been addressed in the past. This is particularly important in prescribing policies for urban informal real estate markets because the characteristics of such markets are still not fully understood, even after fifty years of policy interventions to enhance their effectiveness. Lacking a clear definition of how informal markets operate and connect to the larger urban economy, past efforts to influence the functioning of such markets have been based primarily on “Learning by Doing,” the title of the World Bank’s first...
Toward Open Source Kenya: Creating and Sharing a GIS Database of Nairobi - Marcello, Elizabeth; Klopp, Jacqueline M.; Williams, Sarah E.
To make good decisions about the future direction of cities we need data to contextualize and make recommendations that are based on past results and potential models for the future. Yet access to information including geographic information systems (GIS) is challenging, particularly as data are often seen as a commodity or source of power by those who control it, a dynamic more severe in contexts like Kenya. By generating GIS data for our own transportation model and then sharing them with those interested in doing research on Nairobi, we experienced firsthand some of the power dynamics associated with accessing and...