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MIT Open Access Articles
Mostrando recursos 1 - 20 de 12,935
Multiplexed Protease Activity Assay for Low-Volume Clinical Samples Using Droplet-Based Microfluidics and Its Application to Endometriosis - Chen, Chia-Hung; Sarkar, Aniruddh; Beste, Michael T.; Isaacson, Keith B.; Lauffenburger, Douglas A.; Griffith, Linda G.; Han, Jongyoon; Miller, Miles Aaron
As principal degrading enzymes of the extracellular matrix, metalloproteinases (MPs) contribute to various pathologies and represent a family of promising drug targets and biomarker candidates. However, multiple proteases and endogenous inhibitors interact to govern MP activity, often leading to highly context-dependent protease function that unfortunately has impeded associated clinical utility. We present a method for rapidly assessing the activity of multiple specific proteases in small volumes (<20 μL) of complex biological fluids such as clinical samples that are available only in very limited amounts. It uses a droplet-based microfluidic platform that injects the sample into thousands of picoliter-scale droplets from...
Helix versus coil polypeptide macromers: gel networks with decoupled stiffness and permeability - Oelker, Abigail M.; Morey, Shannon M.; Griffith, Linda G.; Hammond, Paula T.
As a platform for investigating the individual effects of substrate stiffness, permeability, and ligand density on cellular behavior, we developed a set of hydrogels with stiffness tuned by polymer backbone rigidity, independent of cross-link density and concentration. Previous studies report that poly(propargyl-L-glutamate) (PPLG), synthesized by ring-opening polymerization of the N-carboxy anhydride of γ-propargyl-L-glutamate (γpLglu), adopts a rigid a-helix conformation: we hypothesized that a random copolymer (PPDLG) with equal amounts of γpLglu and γ-propargyl-D-glutamate (γpDglu) monomers would exhibit a more flexible random coil conformation. The resulting macromers exhibited narrow molecular weight distributions (PDI = 1.15) and were grafted with ethylene glycol...
The small molecule, genistein, increases hepcidin expression in human hepatocytes - Zhen, Aileen W.; Nguyen, Nancy H.; Gibert, Yann; Motola, Shmulik; Buckett, Peter; Wessling-Resnick, Marianne; Fraenkel, Ernest; Fraenkel, Paula G.
Hepcidin, a peptide hormone that decreases intestinal iron absorption and macrophage iron release, is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. Endogenous stimulants of Hepcidin transcription include bone morphogenic protein 6 (BMP6) and interleukin-6 (IL-6) by effects on mothers against decapentaplegic homolog (Smad)4 or signal transducer and activator of transcription (Stat)3, respectively. We conducted a small-scale chemical screen in zebrafish embryos to identify small molecules that modulate hepcidin expression. We found that treatment with the isoflavone, genistein, from 28-52 hours postfertilization in zebrafish embryos enhanced Hepcidin transcript levels,...
Polyglutamine Expanded Huntingtin Dramatically Alters the Genome-Wide Binding of HSF1 - Riva, Laura; Koeva, Martina I.; Yildirim, Ferah; Pirhaji, Leila; Dinesh, Deepika; Mazor, Tali; Duennwald, Martin L.; Fraenkel, Ernest
In Huntington's disease (HD), polyglutamine expansions in the huntingtin (Htt) protein cause subtle changes in cellular functions that, over-time, lead to neurodegeneration and death. Studies have indicated that activation of the heat shock response can reduce many of the effects of mutant Htt in disease models, suggesting that the heat shock response is impaired in the disease. To understand the basis for this impairment, we have used genome-wide chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) to examine the effects of mutant Htt on the master regulator of the heat shock response, HSF1. We find that, under normal conditions, HSF1...
Precision [bar over v][subscript e]-electron scattering measurements with IsoDAR to search for new physics - Shaevitz, M. H.; Shimizu, I.; Winslow, L.; Conrad, Janet; Spitz, Joshua B.; Toups, Matthew
IsoDAR provides a pure and intense [bar over v][subscript e] source with an average energy of 6.5 MeV produced through [superscript 8]Li β decay. This source can be paired with a large scintillator detector, such as KamLAND, to produce a sample of [bar over v][subscript e]-electron scatters that is more than 5 times larger than what has been collected before. Such a sample would allow for a 3.2% measurement of sin[superscript 2]θ[subscript W] and a sensitive search for nonstandard interactions.
Nuclear σ terms and scalar-isoscalar WIMP-nucleus interactions from lattice QCD - Beane, S. R.; Cohen, S. D.; Lin, H.-W.; Savage, M. J.; Detmold, William
It has been argued that the leading scalar-isoscalar weakly interacting massive particle (WIMP) -nucleus interactions receive parametrically enhanced contributions in the context of nuclear effective field theories . These contributions arise from meson-exchange currents (MECs) and potentially modify the impulse approximation estimates of these interactions by 10%–60%. We point out that these MECs also contribute to the quark mass dependence of nuclear binding energies, that is, nuclear σ terms. In this work, we use recent lattice QCD calculations of the binding energies of the deuteron, [superscript 3]He and [superscript 4]He at pion masses near 500 and 800 MeV, combined with...
Combination of measurements of the top-quark pair production cross section from the Tevatron Collider - Gomez-Ceballos, Guillelmo; Goncharov, Maxim; Paus, Christoph M. E.
We combine six measurements of the inclusive top-quark pair (t[bar over t]) production cross section (σ[subscript tt]-) from data collected with the CDF and D0 detectors at the Fermilab Tevatron with proton-antiproton collisions at √s = 1.96 TeV. The data correspond to integrated luminosities of up to 8.8 fb[superscript −1]. We obtain a value of σ[subscript t[bar over t]] = 7.60 ± 0.41 pb for a top-quark mass of m[subscript t] = 172.5 GeV. The contributions to the uncertainty are 0.20 pb from statistical sources, 0.29 pb from systematic sources, and 0.21 pb from the uncertainty on the integrated luminosity. The result is in...
Protocol design contests - Winstein, Keith; Das, Somak; Ma, Joshua; Balakrishnan, Hari; Sivaraman Kaushalram, Anirudh; Varley, Pauline P.; Batalha, Joao; Goyal, Ameesh K.
In fields like data mining and natural language processing, design contests have been successfully used to advance the state of the art. Such contests offer an opportunity to bring the excitement and challenges of protocol design---one of the core intellectual elements of research and practice in networked systems---to a broader group of potential contributors, whose ideas may prove important. Moreover, it may lead to an increase in the number of students, especially undergraduates or those learning via online courses, interested in pursuing a career in the field.
We describe the creation of the infrastructure and our experience with a protocol design...
Measurement of the [bar over B][0 over s] → D[− over s]D[+ over s] and [bar over B][0 over s] → D[superscript −]D[+ over s] Effective Lifetimes - Ilten, Philip James; Williams, Michael
The first measurement of the effective lifetime of the [bar over B][0 over s] meson in the decay[bar over B][0 over s] → D[− over s]D[+ over s] is reported using a proton-proton collision data set, corresponding to an integrated luminosity of 3 fb[superscript −1], collected by the LHCb experiment. The measured value of the [bar over B][0 over s] → D[− over s]D[+ over s] effective lifetime is 1.379 ± 0.026 ± 0.017 ps, where the uncertainties are statistical and systematic, respectively. This lifetime translates into a measurement of the decay width of the light [bar over B][0 over s] mass...
Serologic Evidence that Ascaris and Toxoplasma Infections Impact Inflammatory Responses to Helicobacter pylori in Colombians - Ek, Courtney; Whary, Mark T.; Ihrig, Melanie; Bravo, Luis E.; Correa, Pelayo; Fox, James G.
Background: Helicobacter pylori-infected children from coastal Tumaco, Colombia, have more parasitism, and adults have lower gastric cancer risk compared with high-altitude Pasto/Tuquerres residents. Because helminth and Toxoplasma gondii infections alter helicobacter gastritis in rodent models, we determined whether seropositivity to Ascaris lumbricoides or T. gondii was associated with Th2-IgG1 or Th1-IgG2 responses to H. pylori.
Methods: Sera (240) from the two populations were evaluated for A. lumbricoides and T. gondii seropositivity and results correlated with IgE and IgG isotype responses to H. pylori.
Results: Most Tumaco children and adults were seropositive for A. lumbricoides (89%, 66%), T. gondii (59%, 98%), or both (45%,...
An Experimental Study of the Learnability of Congestion Control - Sivaraman Kaushalram, Anirudh; Winstein, Keith; Thaker, Pratiksha R.; Balakrishnan, Hari
When designing a distributed network protocol, typically it is infeasible to fully define the target network where the protocol is intended to be used. It is therefore natural to ask: How faithfully do protocol designers really need to understand the networks they design for? What are the important signals that endpoints should listen to? How can researchers gain confidence that systems that work well on well-characterized test networks during development will also perform adequately on real networks that are inevitably more complex, or future networks yet to be developed? Is there a tradeoff between the performance of a protocol and...
Convergent synthesis of a steroidal antiestrogen-mitomycin C hybrid using “click” chemistry - Hanson, Robert N.; Hua, Edward; Labaree, David; Hochberg, Richard B.; Proffitt, Kyle; Essigmann, John M.; Croy, Robert G.
A convergent synthesis of a novel estrogen receptor-targeted drug hybrid was developed based on structures of the potent anti-proliferative mitomycin C and the steroidal anti-estrogen RU 39411. The steroidal antiestrogen was prepared with an azido-triethylene glycoloxy linker while the mitomycin C derivative (porfirimycin) incorporated a complementary 7-N-terminal alkyne. The two components were ligated using the Huisgen [3 + 2] cycloaddition (“click”) reaction. Preliminary biological assays demonstrated that the final hybrid compound retained both potent anti-estrogenic and anti-proliferative activities.
Study of heavy-flavor quarks produced in association with top-quark pairs at √s = 7 TeV using the ATLAS detector - Taylor, Frank E.
Using a sample of dilepton top-quark pair (t[bar over t]) candidate events, a study is performed of the production of top-quark pairs together with heavy-flavor (HF) quarks, the sum of t[bar over t] + b + X and t[bar over t] + c + X, collectively referred to as t[bar over t] + HF. The data set used corresponds to an integrated luminosity of 4.7 fb[superscript −1] of proton-proton collisions at a center-of-mass energy of 7 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. The presence of additional HF (b or c) quarks in the t[bar over t] sample...
Measurement of the inclusive isolated prompt photons cross section in pp collisions at √s = 7 TeV with the ATLAS detector using 4.6 fb[superscript -1] - Taylor, Frank E.
A measurement of the cross section for the production of isolated prompt photons in pp collisions at a center-of-mass energy √s = 7 TeV is presented. The results are based on an integrated luminosity of 4.6 fb[superscript −1] collected with the ATLAS detector at the LHC. The cross section is measured as a function of photon pseudorapidity η[superscript γ] and transverse energy E[γ over T] in the kinematic range 100 ≤ E[γ over T] < 1000 GeV and in the regions |η[superscript γ]| < 1.37 and 1.52 ≤ |η[superscript γ]| < 2.37. The results are compared to leading-order parton-shower Monte Carlo models and...
Phase-space dependence of particle-ratio fluctuations in Pb + Pb collisions from 20A to 158A GeV beam energy - Roland, Christof E.; RolandG, unther M.; Roland, Gunther M.
A novel approach, the identity method, was used for particle identification and the study of fluctuations of particle yield ratios in Pb + Pb collisions at the CERN Super Proton Synchrotron (SPS). This procedure allows one to measure the moments of the multiplicity distributions of protons (p), kaons (K), pions (π), and electrons (e) in case of incomplete particle identification. Using these moments the excitation function of the fluctuation measure ν[subscript dyn] [A,B] was measured, with A and B denoting different particle types. The obtained energy dependence of ν[subscript dyn] agrees with previously published NA49 results on the related measure...
Single spin asymmetries of inclusive hadrons produced in electron scattering from a transversely polarized [superscript 3]He target - Allada, Kalyan C.; Bertozzi, William; Gilad, Shalev; Huang, J.; Moffit, B.; Puckett, A. J. R.; Sulkosky, V.; Zhan, X.
We report the first measurement of target single spin asymmetries (A[subscript N]) in the inclusive hadron production reaction, e + [superscript 3]He[superscript ↑] → h + X, using a transversely polarized [superscript 3]He target. The experiment was conducted at Jefferson Lab in Hall A using a 5.9-GeV electron beam. Three types of hadrons (π[superscript ±], K[superscript ±], and proton) were detected in the transverse hadron momentum range 0.54 < p[subscript T] < 0.74 GeV/c. The range of x[subscript F] for pions was −0.29 < x[subscript F] < −0.23 and for kaons was −0.25 < x[subscript F] < −0.18. The observed...
Proposal to use neutron scattering to access scalar spin chirality fluctuations in kagome lattices - Nagaosa, Naoto; Lee, Patrick A.
In the theory of quantum spin liquid, gauge fluctuation is an emergent excitation at low energy. The gauge magnetic field is proportional to the scalar spin chirality S[subscript 1] ⋅ S[subscript 2] × S[subscript 3]. It is therefore highly desirable to measure the fluctuation spectrum of the scalar spin chirality. We show that in the Kagome lattice with a Dzyaloshinskii-Moriya term, the fluctuation in S[subscript z], which is readily measured by neutron scattering, contains a piece which is proportional to the chirality fluctuation.
Projective construction of two-dimensional symmetry-protected topological phases with U(1), SO(3), or SU(2) symmetries - Ye, Peng; Wen, Xiao-Gang
We propose a general approach to construct symmetry protected topological (SPT) states (i.e., the short-range entangled states with symmetry) in 2D spin/boson systems on lattice. In our approach, we fractionalize spins/bosons into different fermions, which occupy nontrivial Chern bands. After the Gutzwiller projection of the free fermion state obtained by filling the Chern bands, we can obtain SPT states on lattice. In particular, we constructed a U(1) SPT state of a spin-1 model, a SO(3) SPT state of a boson system with spin-1 bosons and spinless bosons, and a SU(2) SPT state of a spin-1/2 boson system. By applying the...
Gapped symmetry preserving surface state for the electron topological insulator - Wang, Chong; Potter, Andrew C.; Todadri, Senthil
It is well known that the three-dimensional (3D) electronic topological insulator (TI) with charge-conservation and time-reversal symmetry cannot have a trivial insulating surface that preserves symmetry. It is often implicitly assumed that if the TI surface preserves both symmetries then it must be gapless. Here we show that it is possible for the TI surface to be both gapped and symmetry preserving, at the expense of having surface-topological order. In contrast to analogous bosonic topological insulators, this symmetric surface topological order is intrinsically non-Abelian. We show that the surface-topological order provides a complete nonperturbative definition of the electron TI that...
Superconductivity with intrinsic topological order induced by pure Coulomb interaction and time-reversal symmetry breaking - Wen, Xiao-Gang; Tang, Evelyn May Yin
Recently, in certain flat band lattice systems at commensurate fillings, fractional quantum Hall states have been found, which have anyonic excitations. We study such systems away from commensuration, i.e., the ground state of an anyon gas in such a system. The presence of the underlying lattice allows access to an entirely new regime where the anyon kinetic energy can be larger than their interaction energy. Within the flux-attachment approach, using a mean field and then adding fluctuations, we find several possible superfluid states. Two have intrinsic topological order: fractionalized quasiparticles with a fusion structure of (Z[subscript 2])[superscript 4] and (Z[subscript...