236 research outputs found
Quantum Gates and Memory using Microwave Dressed States
Trapped atomic ions have been successfully used for demonstrating basic
elements of universal quantum information processing (QIP). Nevertheless,
scaling up of these methods and techniques to achieve large scale universal
QIP, or more specialized quantum simulations remains challenging. The use of
easily controllable and stable microwave sources instead of complex laser
systems on the other hand promises to remove obstacles to scalability.
Important remaining drawbacks in this approach are the use of magnetic field
sensitive states, which shorten coherence times considerably, and the
requirement to create large stable magnetic field gradients. Here, we present
theoretically a novel approach based on dressing magnetic field sensitive
states with microwave fields which addresses both issues and permits fast
quantum logic. We experimentally demonstrate basic building blocks of this
scheme to show that these dressed states are long-lived and coherence times are
increased by more than two orders of magnitude compared to bare magnetic field
sensitive states. This changes decisively the prospect of microwave-driven ion
trap QIP and offers a new route to extend coherence times for all systems that
suffer from magnetic noise such as neutral atoms, NV-centres, quantum dots, or
circuit-QED systems.Comment: 9 pages, 4 figure
Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells
Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients
Dark Force Detection in Low Energy e-p Collisions
We study the prospects for detecting a light boson X with mass m_X < 100 MeV
at a low energy electron-proton collider. We focus on the case where X
dominantly decays to e+ e- as motivated by recent "dark force" models. In order
to evade direct and indirect constraints, X must have small couplings to the
standard model (alpha_X 10 MeV).
By comparing the signal and background cross sections for the e- p e+ e- final
state, we conclude that dark force detection requires an integrated luminosity
of around 1 inverse attobarn, achievable with a forthcoming JLab proposal.Comment: 38 pages, 19 figures; v2, references adde
Exploiting inflammation for therapeutic gain in pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with <5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC
Molecular Analysis of Precursor Lesions in Familial Pancreatic Cancer
PMCID: PMC3553106This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Direct Bacterial Killing In Vitro by Recombinant Nod2 Is Compromised by Crohn's Disease-Associated Mutations
Background: A homeostatic relationship with the intestinal microflora is increasingly appreciated as essential for human health and wellbeing. Mutations in the leucine-rich repeat (LRR) domain of Nod2, a bacterial recognition protein, are associated with development of the inflammatory bowel disorder, Crohn’s disease. We investigated the molecular mechanisms underlying disruption of intestinal symbiosis in patients carrying Nod2 mutations. Methodology/Principal Findings: In this study, using purified recombinant LRR domains, we demonstrate that Nod2 is a direct antimicrobial agent and this activity is generally deficient in proteins carrying Crohn’s-associated mutations. Wildtype, but not Crohn’s-associated, Nod2 LRR domains directly interacted with bacteria in vitro, altered their metabolism and disrupted the integrity of the plasma membrane. Antibiotic activity was also expressed by the LRR domains of Nod1 and other pattern recognition receptors suggesting that the LRR domain is a conserved anti-microbial motif supporting innate cellular immunity. Conclusions/Significance: The lack of anti-bacterial activity demonstrated with Crohn’s-associated Nod2 mutations in vitro, supports the hypothesis that a deficiency in direct bacterial killing contributes to the association of Nod2 polymorphism
Gene Transcription and Splicing of T-Type Channels Are Evolutionarily-Conserved Strategies for Regulating Channel Expression and Gating
T-type calcium channels operate within tightly regulated biophysical constraints for supporting rhythmic firing in the brain, heart and secretory organs of invertebrates and vertebrates. The snail T-type gene, LCav3 from Lymnaea stagnalis, possesses alternative, tandem donor splice sites enabling a choice of a large exon 8b (201 aa) or a short exon 25c (9 aa) in cytoplasmic linkers, similar to mammalian homologs. Inclusion of optional 25c exons in the III–IV linker of T-type channels speeds up kinetics and causes hyperpolarizing shifts in both activation and steady-state inactivation of macroscopic currents. The abundant variant lacking exon 25c is the workhorse of embryonic Cav3 channels, whose high density and right-shifted activation and availability curves are expected to increase pace-making and allow the channels to contribute more significantly to cellular excitation in prenatal tissue. Presence of brain-enriched, optional exon 8b conserved with mammalian Cav3.1 and encompassing the proximal half of the I–II linker, imparts a ∼50% reduction in total and surface-expressed LCav3 channel protein, which accounts for reduced whole-cell calcium currents of +8b variants in HEK cells. Evolutionarily conserved optional exons in cytoplasmic linkers of Cav3 channels regulate expression (exon 8b) and a battery of biophysical properties (exon 25c) for tuning specialized firing patterns in different tissues and throughout development
Crohn's Disease and Early Exposure to Domestic Refrigeration
Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood.Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD.This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood
Secluded Dark Matter Coupled to a Hidden CFT
Models of secluded dark matter offer a variant on the standard WIMP picture
and can modify our expectations for hidden sector phenomenology and detection.
In this work we extend a minimal model of secluded dark matter, comprised of a
U(1)'-charged dark matter candidate, to include a confining hidden-sector CFT.
This provides a technically natural explanation for the hierarchically small
mediator-scale, with hidden-sector confinement generating m_{gamma'}>0.
Furthermore, the thermal history of the universe can differ markedly from the
WIMP picture due to (i) new annihilation channels, (ii) a (potentially) large
number of hidden-sector degrees of freedom, and (iii) a hidden-sector phase
transition at temperatures T << M_{dm} after freeze out. The mediator allows
both the dark matter and the Standard Model to communicate with the CFT, thus
modifying the low-energy phenomenology and cosmic-ray signals from the secluded
sector.Comment: ~50p, 8 figs; v2 JHEP versio
Single-Scale Natural SUSY
We consider the prospects for natural SUSY models consistent with current
data. Recent constraints make the standard paradigm unnatural so we consider
what could be a minimal extension consistent with what we now know. The most
promising such scenarios extend the MSSM with new tree-level Higgs interactions
that can lift its mass to at least 125 GeV and also allow for flavor-dependent
soft terms so that the third generation squarks are lighter than current bounds
on the first and second generation squarks. We argue that a common feature of
almost all such models is the need for a new scale near 10 TeV, such as a scale
of Higgsing or confinement of a new gauge group. We consider the question
whether such a model can naturally derive from a single mass scale associated
with supersymmetry breaking. Most such models simply postulate new scales,
leaving their proximity to the scale of MSSM soft terms a mystery. This
coincidence problem may be thought of as a mild tuning, analogous to the usual
mu problem. We find that a single mass scale origin is challenging, but suggest
that a more natural origin for such a new dynamical scale is the gravitino
mass, m_{3/2}, in theories where the MSSM soft terms are a loop factor below
m_{3/2}. As an example, we build a variant of the NMSSM where the singlet S is
composite, and the strong dynamics leading to compositeness is triggered by
masses of order m_{3/2} for some fields. Our focus is the Higgs sector, but our
model is compatible with a light stop (with the other generation squarks heavy,
or with R-parity violation or another mechanism to hide them from current
searches). All the interesting low-energy mass scales, including linear terms
for S playing a key role in EWSB, arise dynamically from the single scale
m_{3/2}. However, numerical coefficients from RG effects and wavefunction
factors in an extra dimension complicate the otherwise simple story.Comment: 32 pages, 3 figures; version accepted by JHE
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