2,512 research outputs found
Two experiments for the price of one? -- The role of the second oscillation maximum in long baseline neutrino experiments
We investigate the quantitative impact that data from the second oscillation
maximum has on the performance of wide band beam neutrino oscillation
experiments. We present results for the physics sensitivities to standard three
flavor oscillation, as well as results for the sensitivity to non-standard
interactions. The quantitative study is performed using an experimental setup
similar to the Fermilab to DUSEL Long Baseline Neutrino Experiment (LBNE). We
find that, with the single exception of sensitivity to the mass hierarchy, the
second maximum plays only a marginal role due to the experimental difficulties
to obtain a statistically significant and sufficiently background-free event
sample at low energies. This conclusion is valid for both water Cherenkov and
liquid argon detectors. Moreover, we confirm that non-standard neutrino
interactions are very hard to distinguish experimentally from standard
three-flavor effects and can lead to a considerable loss of sensitivity to
\theta_{13}, the mass hierarchy and CP violation.Comment: RevTex 4.1, 23 pages, 10 figures; v2: Typos corrected, very minor
clarifications; matches published version; v3: Fixed a typo in the first
equation in sec. III
Grape Seed Proanthocyanidins Inhibit Melanoma Cell Invasiveness by Reduction of PGE2 Synthesis and Reversal of Epithelial-to-Mesenchymal Transition
Melanoma is the leading cause of death from skin disease due, in large part, to its propensity to metastasize. We have examined the effect of grape seed proanthocyanidins (GSPs) on melanoma cancer cell migration and the molecular mechanisms underlying these effects using highly metastasis-specific human melanoma cell lines, A375 and Hs294t. Using in vitro cell invasion assays, we observed that treatment of A375 and Hs294t cells with GSPs resulted in a concentration-dependent inhibition of invasion or cell migration of these cells, which was associated with a reduction in the levels of cyclooxygenase (COX)-2 expression and prostaglandin (PG) E2 production. Treatment of cells with celecoxib, a COX-2 inhibitor, or transient transfection of melanoma cells with COX-2 small interfering RNA, also inhibited melanoma cell migration. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate, an inducer of COX-2, enhanced the phosphorylation of ERK1/2, a protein of mitogen-activated protein kinase family, and subsequently cell migration whereas both GSPs and celecoxib significantly inhibited 12-O-tetradecanoylphorbol-13-acetate -promoted cell migration as well as phosphorylation of ERK1/2. Treatment of cells with UO126, an inhibitor of MEK, also inhibited the migration of melanoma cells. Further, GSPs inhibited the activation of NF-κB/p65, an upstream regulator of COX-2, in melanoma cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-κB, also inhibited cell migration. Additionally, inhibition of melanoma cell migration by GSPs was associated with reversal of epithelial-mesenchymal transition process, which resulted in an increase in the levels of epithelial biomarkers (E-cadherin and cytokeratins) while loss of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in melanoma cells. Together, these results indicate that GSPs have the ability to inhibit melanoma cell invasion/migration by targeting the endogenous expression of COX-2 and reversing the process of epithelial-to-mesenchymal transition
A novel planar optical sensor for simultaneous monitoring of oxygen, carbon dioxide, pH and temperature
The first quadruple luminescent sensor is presented which enables simultaneous detection of three chemical parameters and temperature. A multi-layer material is realized and combines two spectrally independent dually sensing systems. The first layer employs ethylcellulose containing the carbon dioxide sensing chemistry (fluorescent pH indicator 8-hydroxy-pyrene-1,3,6-trisulfonate (HPTS) and a lipophilic tetraalkylammonium base). The cross-linked polymeric beads stained with a phosphorescent iridium(III) complex are also dispersed in ethylcellulose and serve both for oxygen sensing and as a reference for HPTS. The second (pH/temperature) dually sensing system relies on the use of a pH-sensitive lipophilic seminaphthorhodafluor derivative and luminescent chromium(III)-activated yttrium aluminum borate particles (simultaneously acting as a temperature probe and as a reference for the pH indicator) which are embedded in polyurethane hydrogel layer. A silicone layer is used to spatially separate both dually sensing systems and to insure permeation selectivity for the CO2/O2 layer. The CO2/O2 and the pH/temperature layers are excitable with a blue and a red LED, respectively, and the emissions are isolated with help of optical filters. The measurements are performed at two modulation frequencies for each sensing system and the modified Dual Lifetime Referencing method is used to access the analytical information. The feasibility of the simultaneous four-parameter sensing is demonstrated. However, the practical applicability of the material may be compromised by its high complexity and by the performance of individual indicators
Non-standard interactions versus non-unitary lepton flavor mixing at a neutrino factory
The impact of heavy mediators on neutrino oscillations is typically described
by non-standard four-fermion interactions (NSIs) or non-unitarity (NU). We
focus on leptonic dimension-six effective operators which do not produce
charged lepton flavor violation. These operators lead to particular
correlations among neutrino production, propagation, and detection non-standard
effects. We point out that these NSIs and NU phenomenologically lead, in fact,
to very similar effects for a neutrino factory, for completely different
fundamental reasons. We discuss how the parameters and probabilities are
related in this case, and compare the sensitivities. We demonstrate that the
NSIs and NU can, in principle, be distinguished for large enough effects at the
example of non-standard effects in the --sector, which basically
corresponds to differentiating between scalars and fermions as heavy mediators
as leading order effect. However, we find that a near detector at superbeams
could provide very synergistic information, since the correlation between
source and matter NSIs is broken for hadronic neutrino production, while NU is
a fundamental effect present at any experiment.Comment: 32 pages, 5 figures. Final version published in JHEP. v3: Typo in Eq.
(27) correcte
Electroweak Baryogenesis and Dark Matter with an approximate R-symmetry
It is well known that R-symmetric models dramatically alleviate the SUSY
flavor and CP problems. We study particular modifications of existing
R-symmetric models which share the solution to the above problems, and have
interesting consequences for electroweak baryogenesis and the Dark Matter (DM)
content of the universe. In particular, we find that it is naturally possible
to have a strongly first-order electroweak phase transition while
simultaneously relaxing the tension with EDM experiments. The R-symmetry (and
its small breaking) implies that the gauginos (and the neutralino LSP) are
pseudo-Dirac fermions, which is relevant for both baryogenesis and DM. The
singlet superpartner of the U(1)_Y pseudo-Dirac gaugino plays a prominent role
in making the electroweak phase transition strongly first-order. The
pseudo-Dirac nature of the LSP allows it to behave similarly to a Dirac
particle during freeze-out, but like a Majorana particle for annihilation today
and in scattering against nuclei, thus being consistent with current
constraints. Assuming a standard cosmology, it is possible to simultaneously
have a strongly first-order phase transition conducive to baryogenesis and have
the LSP provide the full DM relic abundance, in part of the allowed parameter
space. However, other possibilities for DM also exist, which are discussed. It
is expected that upcoming direct DM searches as well as neutrino signals from
DM annihilation in the Sun will be sensitive to this class of models.
Interesting collider and Gravity-wave signals are also briefly discussed.Comment: 50 pages, 10 figure
Charming CP Violation and Dipole Operators from RS Flavor Anarchy
Recently the LHCb collaboration reported evidence for direct CP violation in
charm decays. The value is sufficiently large that either substantially
enhanced Standard Model contributions or non-Standard Model physics is required
to explain it. In the latter case only a limited number of possibilities would
be consistent with other existing flavor-changing constraints. We show that
warped extra dimensional models that explain the quark spectrum through flavor
anarchy can naturally give rise to contributions of the size required to
explain the the LHCb result. The D meson asymmetry arises through a sizable
CP-violating contribution to a chromomagnetic dipole operator. This happens
naturally without introducing inconsistencies with existing constraints in the
up quark sector. We discuss some subtleties in the loop calculation that are
similar to those in Higgs to \gamma\gamma. Loop-induced dipole operators in
warped scenarios and their composite analogs exhibit non-trivial dependence on
the Higgs profile, with the contributions monotonically decreasing when the
Higgs is pushed away from the IR brane. We show that the size of the dipole
operator quickly saturates as the Higgs profile approaches the IR brane,
implying small dependence on the precise details of the Higgs profile when it
is quasi IR localized. We also explain why the calculation of the coefficient
of the lowest dimension 5D operator is guaranteed to be finite. This is true
not only in the charm sector but also with other radiative processes such as
electric dipole moments, b to s\gamma, \epsilon'/\epsilon_K and \mu\ to
e\gamma. We furthermore discuss the interpretation of this contribution within
the framework of partial compositeness in four dimensions and highlight some
qualitative differences between the generic result of composite models and that
obtained for dynamics that reproduces the warped scenario.Comment: 14 page
Subcellular fractionation method to study endosomal trafficking of Kaposi’s sarcoma-associated herpesvirus
Background
Virus entry involves multiple steps and is a highly orchestrated process on which successful infection collectively depends. Entry processes are commonly analyzed by monitoring internalized virus particles via Western blotting, polymerase chain reaction, and imaging techniques that allow scientist to track the intracellular location of the pathogen. Such studies have provided abundant direct evidence on how viruses interact with receptor molecules on the cell surface, induce cell signaling at the point of initial contact with the cell to facilitate internalization, and exploit existing endocytic mechanisms of the cell for their ultimate infectious agenda. However, there is dearth of knowledge in regards to trafficking of a virus via endosomes. Herein, we describe an optimized laboratory procedure to isolate individual organelles during different stages of endocytosis by performing subcellular fractionation. This methodology is established using Kaposi’s sarcoma-associated herpesvirus (KSHV) infection of human foreskin fibroblast (HFF) cells as a model. With KSHV and other herpesviruses alike, envelope glycoproteins have been widely reported to physically engage target cell surface receptors, such as integrins, in interactions leading to entry and subsequent infection.
Results
Subcellular fractionation was used to isolate early and late endosomes (EEs and LEs) by performing a series of centrifugations steps. Specifically, a centrifugation step post-homogenization was utilized to obtain the post-nuclear supernatant containing intact intracellular organelles in suspension. Successive fractionation via sucrose density gradient centrifugation was performed to isolate specific organelles including EEs and LEs. Intracellular KSHV trafficking was directly traced in the isolated endosomal fractions. Additionally, the subcellular fractionation approach demonstrates a key role for integrins in the endosomal trafficking of KSHV. The results obtained from fractionation studies corroborated those obtained by traditional imaging studies.
Conclusions
This study is the first of its kind to employ a sucrose flotation gradient assay to map intracellular KSHV trafficking in HFF cells. We are confident that such an approach will serve as a powerful tool to directly study intracellular trafficking of a virus, signaling events occurring on endosomal membranes, and dynamics of molecular events within endosomes that are crucial for uncoating and virus escape into the cytosol
Testing matter effects in propagation of atmospheric and long-baseline neutrinos
We quantify our current knowledge of the size and flavor structure of the
matter effects in the evolution of atmospheric and long-baseline neutrinos
based solely on the analysis of the corresponding neutrino data. To this aim we
generalize the matter potential of the Standard Model by rescaling its
strength, rotating it away from the e-e sector, and rephasing it with respect
to the vacuum term. This phenomenological parametrization can be easily
translated in terms of non-standard neutrino interactions in matter. We show
that in the most general case, the strength of the potential cannot be
determined solely by atmospheric and long-baseline data. However its flavor
composition is very much constrained and the present determination of the
neutrino masses and mixing is robust under its presence. We also present an
update of the constraints arising from this analysis in the particular case in
which no potential is present in the e-mu and e-tau sectors. Finally we
quantify to what degree in this scenario it is possible to alleviate the
tension between the oscillation results for neutrinos and antineutrinos in the
MINOS experiment and show the relevance of the high energy part of the spectrum
measured at MINOS.Comment: PDFLaTeX file using JHEP3 class, 25 pages, 7 figures included.
Accepted for publication in JHE
Neurofilament Light Regulates Axon Caliber, Synaptic Activity, and Organelle Trafficking in Cultured Human Motor Neurons
Neurofilament light (NFL) is one of the proteins forming multimeric neuron-specific intermediate filaments, neurofilaments, which fill the axonal cytoplasm, establish caliber growth, and provide structural support. Dominant missense mutations and recessive nonsense mutations in the neurofilament light gene (NEFL) are among the causes of Charcot–Marie–Tooth (CMT) neuropathy, which affects the peripheral nerves with the longest axons. We previously demonstrated that a neuropathy-causing homozygous nonsense mutation in NEFL led to the absence of NFL in patient-specific neurons. To understand the disease-causing mechanisms, we investigate here the functional effects of NFL loss in human motor neurons differentiated from induced pluripotent stem cells (iPSC). We used genome editing to generate NEFL knockouts and compared them to patient-specific nonsense mutants and isogenic controls. iPSC lacking NFL differentiated efficiently into motor neurons with normal axon growth and regrowth after mechanical axotomy and contained neurofilaments. Electrophysiological analysis revealed that motor neurons without NFL fired spontaneous and evoked action potentials with similar characteristics as controls. However, we found that, in the absence of NFL, human motor neurons 1) had reduced axonal caliber, 2) the amplitude of miniature excitatory postsynaptic currents (mEPSC) was decreased, 3) neurofilament heavy (NFH) levels were reduced and no compensatory increases in other filament subunits were observed, and 4) the movement of mitochondria and to a lesser extent lysosomes was increased. Our findings elaborate the functional roles of NFL in human motor neurons. NFL is not only a structural protein forming neurofilaments and filling the axonal cytoplasm, but our study supports the role of NFL in the regulation of synaptic transmission and organelle trafficking. To rescue the NFL deficiency in the patient-specific nonsense mutant motor neurons, we used three drugs, amlexanox, ataluren (PTC-124), and gentamicin to induce translational read-through or inhibit nonsense-mediated decay. However, the drugs failed to increase the amount of NFL protein to detectable levels and were toxic to iPSC-derived motor neurons
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