872 research outputs found
Examples of M5-Brane Elliptic Genera
We determine the modified elliptic genus of an M5-brane wrapped on various
one modulus Calabi-Yau spaces, using modular invariance together with some
known Gopakumar-Vafa invariants of small degrees. As a bonus, we find
nontrivial relations among Gopakumar-Vafa invariants of different degrees and
genera from modular invariance.Comment: 13 page
Measurement of Trace I-129 Concentrations in CsI Powder and Organic Liquid Scintillator with Accelerator Mass Spectrometry
Levels of trace radiopurity in active detector materials is a subject of
major concern in low-background experiments. Procedures were devised to measure
trace concentrations of I-129 in the inorganic salt CsI as well as in organic
liquid scintillator with Accelerator Mass Spectrometry (AMS) which leads to
improvement in sensitivities by several orders of magnitude over other methods.
No evidence of their existence in these materials were observed. Limits of < 6
X 10^{-13} g/g and < 2.6 X 10^{-17} g/g on the contaminations of I-129 in CsI
and liquid scintillator, respectively, were derived.These are the first results
in a research program whose goals are to develop techniques to measure trace
radioactivity in detector materials by AMS.Comment: Proceedings of 10th International Conference on Accelerator Mass
Spectrometr
Solidification of Al alloys under electromagnetic pulses and characterization of the 3D microstructures under synchrotron x-ray tomography
A novel programmable electromagnetic pulse device was developed and used to study the solidification of Al-15 pct Cu and Al-35 pct Cu alloys. The pulsed magnetic fluxes and Lorentz forces generated inside the solidifying melts were simulated using finite element methods, and their effects on the solidification microstructures were characterized using electron microscopy and synchrotron X-ray tomography. Using a discharging voltage of 120 V, a pulsed magnetic field with the peak Lorentz force of ~1.6 N was generated inside the solidifying Al-Cu melts which were showed sufficiently enough to disrupt the growth of the primary Al dendrites and the Al2Cu intermetallic phases. The microstructures exhibit a strong correlation to the characteristics of the applied pulse, forming a periodical pattern that resonates the frequency of the applied electromagnetic field
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A multilevel neo-institutional analysis of infection prevention and control in English hospitals: coerced safety culture change?
Despite committed policy, regulative and professional efforts on healthcare safety, little is known about how such macro-interventions permeate organisations and shape culture over time. Informed by neo-institutional theory, we examined how inter-organisational influences shaped safety practices and inter-subjective meanings following efforts for coerced culture change. We traced macro-influences from 2000 to 2015 in infection prevention and control (IPC). Safety perceptions and meanings were inductively analysed from 130 in-depth qualitative interviews with senior- and middle-level managers from 30 English hospitals. A total of 869 institutional interventions were identified; 69% had a regulative component. In this context of forced implementation of safety practices, staff experienced inherent tensions concerning the scope of safety, their ability to be open and prioritisation of external mandates over local need. These tensions stemmed from conflicts among three co-existing institutional logics prevalent in the NHS. In response to requests for change, staff flexibly drew from a repertoire of cognitive, material and symbolic resources within and outside their organisations. They crafted 'strategies of action', guided by a situated assessment of first-hand practice experiences complementing collective evaluations of interventions such as 'pragmatic', 'sensible' and also 'legitimate'. Macro-institutional forces exerted influence either directly on individuals or indirectly by enriching the organisational cultural repertoire
Suppression of pyrimidine biosynthesis by targeting DHODH enzyme robustly inhibits rotavirus replication
Rotavirus infection remains a great health burden worldwide especially in some developing countries. It causes severe dehydrating diarrhea in infants, young
children, as well as immunocompromised and organ transplanted patients. Viral replication heavily relies on the host to supply nucleosides. Thus, host enzymes
involved in nucleotide biosynthesis represent potential targets for antiviral development. Dihydroorotate dehydrogenase (DHODH) is the rate-limiting enzyme in the
de novo biosynthesis pathway of pyrimidines. In this study, we demonstrated that two specific DHODH enzyme inhibitors, brequinar (BQR) and leflunomide (LFM)
robustly inhibited rotavirus replication in conven
Hormone therapy and fractures in postmenopausal women
Background:Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV- women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures.Methods:A prospective study of 1765 (1350 WLWH and 415 HIV-) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist).Results:At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV- women [49.8 (46.4-53) vs. 50.7 (47.5-54), P = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17% vs. 26%, P < 0.0001). A greater proportion of WLWH than HIV- women reported hormone therapy use (8% vs. 4%, P = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy (P = 0.69) and HIV status (P = 0.53) were not.Conclusion:Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes
Dynamics of a close-loop controlled MEMS resonator
The dynamics of a close-loop electrostatic MEMS resonator, proposed as a platform for ultra sensitive mass sensors, is investigated. The parameter space of the resonator actuation voltage is investigated to determine the optimal operating regions. Bifurcation diagrams of the resonator response are obtained at five different actuation voltage levels. The resonator exhibits bi-stability with two coexisting stable equilibrium points located inside a lower and an upper potential wells. Steady-state chaotic attractors develop inside each of the potential wells and around both wells. The optimal region in the parameter space for mass sensing purposes is determined. In that region, steady-state chaotic attractors develop and spend most of the time in the safe lower well while occasionally visiting the upper well. The robustness of the chaotic attractors in that region is demonstrated by studying their basins of attraction. Further, regions of large dynamic amplification are also identified in the parameter space. In these regions, the resonator can be used as an efficient long-stroke actuator
Macrophage fumarate hydratase restrains mtRNA-mediated interferon production
Metabolic rewiring underlies the effector functions of macrophages1-3, but the mechanisms involved remain incompletely defined. Here, using unbiased metabolomics and stable isotope-assisted tracing, we show that an inflammatory aspartate-argininosuccinate shunt is induced following lipopolysaccharide stimulation. The shunt, supported by increased argininosuccinate synthase (ASS1) expression, also leads to increased cytosolic fumarate levels and fumarate-mediated protein succination. Pharmacological inhibition and genetic ablation of the tricarboxylic acid cycle enzyme fumarate hydratase (FH) further increases intracellular fumarate levels. Mitochondrial respiration is also suppressed and mitochondrial membrane potential increased. RNA sequencing and proteomics analyses demonstrate that there are strong inflammatory effects resulting from FH inhibition. Notably, acute FH inhibition suppresses interleukin-10 expression, which leads to increased tumour necrosis factor secretion, an effect recapitulated by fumarate esters. Moreover, FH inhibition, but not fumarate esters, increases interferon-β production through mechanisms that are driven by mitochondrial RNA (mtRNA) release and activation of the RNA sensors TLR7, RIG-I and MDA5. This effect is recapitulated endogenously when FH is suppressed following prolonged lipopolysaccharide stimulation. Furthermore, cells from patients with systemic lupus erythematosus also exhibit FH suppression, which indicates a potential pathogenic role for this process in human disease. We therefore identify a protective role for FH in maintaining appropriate macrophage cytokine and interferon responses
Highly Efficient Gene Editing of Cystic Fibrosis Patient-Derived Airway Basal Cells Results in Functional CFTR Correction
There is a strong rationale to consider future cell therapeutic approaches for cystic fibrosis (CF) in which autologous proximal airway basal stem cells, corrected for CFTR mutations, are transplanted into the patient's lungs. We assessed the possibility of editing the CFTR locus in these cells using zinc-finger nucleases and have pursued two approaches. The first, mutation-specific correction, is a footprint-free method replacing the CFTR mutation with corrected sequences. We have applied this approach for correction of ΔF508, demonstrating restoration of mature CFTR protein and function in air-liquid interface cultures established from bulk edited basal cells. The second is targeting integration of a partial CFTR cDNA within an intron of the endogenous CFTR gene, providing correction for all CFTR mutations downstream of the integration and exploiting the native CFTR promoter and chromatin architecture for physiologically relevant expression. Without selection, we observed highly efficient, site-specific targeted integration in basal cells carrying various CFTR mutations and demonstrated restored CFTR function at therapeutically relevant levels. Significantly, Omni-ATAC-seq analysis revealed minimal impact on the positions of open chromatin within the native CFTR locus. These results demonstrate efficient functional correction of CFTR and provide a platform for further ex vivo and in vivo editing. © 2020 The American Society of Gene and Cell TherapySuzuki et al. report correction of the CFTR defect in cystic fibrosis airway basal stem cells. They utilized gene-editing strategies either specific for the ΔF508 CFTR mutation or applicable to most CFTR mutations. Both approaches yielded highly efficient correction without selection, restoring CFTR function to therapeutically relevant levels
Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at TeV
The elliptic, , triangular, , and quadrangular, , azimuthal
anisotropic flow coefficients are measured for unidentified charged particles,
pions and (anti-)protons in Pb-Pb collisions at TeV
with the ALICE detector at the Large Hadron Collider. Results obtained with the
event plane and four-particle cumulant methods are reported for the
pseudo-rapidity range at different collision centralities and as a
function of transverse momentum, , out to GeV/.
The observed non-zero elliptic and triangular flow depends only weakly on
transverse momentum for GeV/. The small dependence
of the difference between elliptic flow results obtained from the event plane
and four-particle cumulant methods suggests a common origin of flow
fluctuations up to GeV/. The magnitude of the (anti-)proton
elliptic and triangular flow is larger than that of pions out to at least
GeV/ indicating that the particle type dependence persists out
to high .Comment: 16 pages, 5 captioned figures, authors from page 11, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186
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