595 research outputs found
Comblike, Monodisperse Polypeptoid Drag-Tags for DNA Separations by End-Labeled Free-Solution Electrophoresis (ELFSE)
The development of innovative technologies designed to reduce the cost and increase the throughput of DNA separations continues to be important for large-scale sequencing and genotyping efforts. We report research aimed at the further development of a free-solution bioconjugate method of DNA size separation by capillary electrophoresis (CE), in particular, the determination of an optimal molecular architecture for polyamide-based "drag-tags". We synthesized several branched poly(N-methoxyethyl glycine)s (poly(NMEG)s, a class of polypeptoids) as novel friction-generating entities for end-on attachment to DNA molecules. A 30-mer poly(NMEG) "backbone," comprising five evenly spaced reactive -amino groups, was synthesized on solid phase, cleaved, and purified to monodispersity by RP-HPLC. Three different comblike derivatives of this backbone molecule were created by (1) acetylating the -amino groups or (2) appending small, monodisperse NMEG oligomers (a tetramer and an octamer). Grafting of the oligo(NMEG)s was done using solution-phase amide bond formation chemistry. Once purified to total monodispersity, the three different drag-tags were studied by freesolution electrophoresis to observe the effect of branching on their hydrodynamic drag or "R" and hence their ability to separate DNA. Drag was found to scale linearly with total molecular weight, regardless of branch length. The octamer-branched drag-tag-DNA conjugate was used to separate ssDNA products of 50, 75, 100, and 150 bases in length by free-solution CE in less than 10 min. Hence, the use of branched or comblike drag-tags is both a feasible and an effective way to achieve high frictional drag, allowing the high-resolution separation of relatively large DNA molecules by free-solution CE without the need to synthesize very long polymers
Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis
Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base
Going home after infant cardiac surgery: a UK qualitative study
National Institute for Health Research Health Services and Delivery Research programme (Project No: 10/2002/29)
Search for astrophysical sources of neutrinos using cascade events in IceCube
The IceCube neutrino observatory has established the existence of a flux of
high-energy astrophysical neutrinos inconsistent with the expectation from
atmospheric backgrounds at a significance greater than . This flux has
been observed in analyses of both track events from muon neutrino interactions
and cascade events from interactions of all neutrino flavors. Searches for
astrophysical neutrino sources have focused on track events due to the
significantly better angular resolution of track reconstructions. To date, no
such sources have been confirmed. Here we present the first search for
astrophysical neutrino sources using cascades interacting in IceCube with
deposited energies as small as 1 TeV. No significant clustering was observed in
a selection of 263 cascades collected from May 2010 to May 2012. We show that
compared to the classic approach using tracks, this statistically-independent
search offers improved sensitivity to sources in the southern sky, especially
if the emission is spatially extended or follows a soft energy spectrum. This
enhancement is due to the low background from atmospheric neutrinos forming
cascade events and the additional veto of atmospheric neutrinos at declinations
.Comment: 14 pages, 9 figures, 1 tabl
Book Reviews
With the observation of high-energy astrophysical neutrinos by the IceCube Neutrino Observatory, interest has risen in models of PeV-mass decaying dark matter particles to explain the observed flux. We present two dedicated experimental analyses to test this hypothesis. One analysis uses 6 years of IceCube data focusing on muon neutrino âtrackâ events from the Northern Hemisphere, while the second analysis uses 2 years of âcascadeâ events from the full sky. Known background components and the hypothetical flux from unstable dark matter are fitted to the experimental data. Since no significant excess is observed in either analysis, lower limits on the lifetime of dark matter particles are derived: we obtain the strongest constraint to date, excluding lifetimes shorter than s at 90% CL for dark matter masses above 10 TeV
Measurement of the multi-TeV neutrino cross section with IceCube using Earth absorption
Neutrinos interact only very weakly, so they are extremely penetrating.
However, the theoretical neutrino-nucleon interaction cross section rises with
energy such that, at energies above 40 TeV, neutrinos are expected to be
absorbed as they pass through the Earth. Experimentally, the cross section has
been measured only at the relatively low energies (below 400 GeV) available at
neutrino beams from accelerators \cite{Agashe:2014kda, Formaggio:2013kya}. Here
we report the first measurement of neutrino absorption in the Earth, using a
sample of 10,784 energetic upward-going neutrino-induced muons observed with
the IceCube Neutrino Observatory. The flux of high-energy neutrinos transiting
long paths through the Earth is attenuated compared to a reference sample that
follows shorter trajectories through the Earth. Using a fit to the
two-dimensional distribution of muon energy and zenith angle, we determine the
cross section for neutrino energies between 6.3 TeV and 980 TeV, more than an
order of magnitude higher in energy than previous measurements. The measured
cross section is (stat.) (syst.)
times the prediction of the Standard Model \cite{CooperSarkar:2011pa},
consistent with the expectation for charged and neutral current interactions.
We do not observe a dramatic increase in the cross section, expected in some
speculative models, including those invoking new compact dimensions
\cite{AlvarezMuniz:2002ga} or the production of leptoquarks
\cite{Romero:2009vu}.Comment: Preprint version of Nature paper 10.1038/nature2445
Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
We report a quasi-differential upper limit on the extremely-high-energy (EHE)
neutrino flux above GeV based on an analysis of nine years of
IceCube data. The astrophysical neutrino flux measured by IceCube extends to
PeV energies, and it is a background flux when searching for an independent
signal flux at higher energies, such as the cosmogenic neutrino signal. We have
developed a new method to place robust limits on the EHE neutrino flux in the
presence of an astrophysical background, whose spectrum has yet to be
understood with high precision at PeV energies. A distinct event with a
deposited energy above GeV was found in the new two-year sample, in
addition to the one event previously found in the seven-year EHE neutrino
search. These two events represent a neutrino flux that is incompatible with
predictions for a cosmogenic neutrino flux and are considered to be an
astrophysical background in the current study. The obtained limit is the most
stringent to date in the energy range between and GeV. This result constrains neutrino models predicting a three-flavor
neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\
{\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}10^9\ {\rm GeV}$. A significant part
of the parameter-space for EHE neutrino production scenarios assuming a
proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review
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