The precise value of the mean neutron lifetime, τ
, plays an important role in nuclear and particle physics and cosmology. It is used to predict the ratio of protons to helium atoms in the primordial ...universe and to search for physics beyond the Standard Model of particle physics. We eliminated loss mechanisms present in previous trap experiments by levitating polarized ultracold neutrons above the surface of an asymmetric storage trap using a repulsive magnetic field gradient so that the stored neutrons do not interact with material trap walls. As a result of this approach and the use of an in situ neutron detector, the lifetime reported here 877.7 ± 0.7 (stat) +0.4/-0.2 (sys) seconds does not require corrections larger than the quoted uncertainties.
Activated STING in a vascular and pulmonary syndrome Liu, Y; Jesus, A A; Marrero, B ...
New England journal of medicine/The New England journal of medicine,
08/2014, Letnik:
371, Številka:
6
Journal Article
Recenzirano
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The study of autoinflammatory diseases has uncovered mechanisms underlying cytokine dysregulation and inflammation.
We analyzed the DNA of an index patient with early-onset systemic inflammation, ...cutaneous vasculopathy, and pulmonary inflammation. We sequenced a candidate gene, TMEM173, encoding the stimulator of interferon genes (STING), in this patient and in five unrelated children with similar clinical phenotypes. Four children were evaluated clinically and immunologically. With the STING ligand cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), we stimulated peripheral-blood mononuclear cells and fibroblasts from patients and controls, as well as commercially obtained endothelial cells, and then assayed transcription of IFNB1, the gene encoding interferon-β, in the stimulated cells. We analyzed IFNB1 reporter levels in HEK293T cells cotransfected with mutant or nonmutant STING constructs. Mutant STING leads to increased phosphorylation of signal transducer and activator of transcription 1 (STAT1), so we tested the effect of Janus kinase (JAK) inhibitors on STAT1 phosphorylation in lymphocytes from the affected children and controls.
We identified three mutations in exon 5 of TMEM173 in the six patients. Elevated transcription of IFNB1 and other gene targets of STING in peripheral-blood mononuclear cells from the patients indicated constitutive activation of the pathway that cannot be further up-regulated with stimulation. On stimulation with cGAMP, fibroblasts from the patients showed increased transcription of IFNB1 but not of the genes encoding interleukin-1 (IL1), interleukin-6 (IL6), or tumor necrosis factor (TNF). HEK293T cells transfected with mutant constructs show elevated IFNB1 reporter levels. STING is expressed in endothelial cells, and exposure of these cells to cGAMP resulted in endothelial activation and apoptosis. Constitutive up-regulation of phosphorylated STAT1 in patients' lymphocytes was reduced by JAK inhibitors.
STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in TMEM173. (Funded by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases; ClinicalTrials.gov number, NCT00059748.).
The cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations. Using bacterial artificial chromosome (BAC) transgenic mice that ...express EGFP-tagged ribosomal protein L10a in defined cell populations, we have developed a methodology for affinity purification of polysomal mRNAs from genetically defined cell populations in the brain. The utility of this approach is illustrated by the comparative analysis of four types of neurons, revealing hundreds of genes that distinguish these four cell populations. We find that even two morphologically indistinguishable, intermixed subclasses of medium spiny neurons display vastly different translational profiles and present examples of the physiological significance of such differences. This genetically targeted
translating
ribosome
affinity
purification (TRAP) methodology is a generalizable method useful for the identification of molecular changes in any genetically defined cell type in response to genetic alterations, disease, or pharmacological perturbations.
Neuroimaging (e.g. fMRI) data are increasingly used to attempt to identify not only brain regions of interest (ROIs) that are especially active during perception, cognition, and action, but also the ...qualitative causal relations among activity in these regions (known as effective connectivity; Friston, 1994). Previous investigations and anatomical and physiological knowledge may somewhat constrain the possible hypotheses, but there often remains a vast space of possible causal structures. To find actual effective connectivity relations, search methods must accommodate indirect measurements of nonlinear time series dependencies, feedback, multiple subjects possibly varying in identified regions of interest, and unknown possible location-dependent variations in BOLD response delays. We describe combinations of procedures that under these conditions find feed-forward sub-structure characteristic of a group of subjects. The method is illustrated with an empirical data set and confirmed with simulations of time series of non-linear, randomly generated, effective connectivities, with feedback, subject to random differences of BOLD delays, with regions of interest missing at random for some subjects, measured with noise approximating the signal to noise ratio of the empirical data.
The information industry has become a “new engine” driving the growth of the world economy. However, there are many controversies about whether digital technology can reduce the intensity of carbon ...emissions. Based on OECD data, KPWW method and multiple panel regression, this paper explores the impact and mechanism of digital technology innovation and technology spillover to the domestic carbon emission intensity. Through impulse response analysis and variance decomposition, the comprehensive impact of digital technology on carbon intensity is clarified. This paper concludes that technology innovation in the information industry will increase the intensity of carbon emissions, while cross-industry technology spillovers are persistent for reducing the intensity of domestic carbon emissions. Since the emission reduction effect of technology spillover is greater than the emission increase effect of technology innovation, the digital technology would empower domestic green development. Increasing the proportion of non-fossil energy use and optimizing the industrial structure are effective mechanisms for digital technology innovation to reduce carbon emission intensity.
•Technological innovation in the digital industry increase the intensity of CO2.•Cross-border and cross-industry technology spillovers reduce the intensity of CO2.•The combined impact of digital industry technology empowers green development.•Digital industry empowers green development through energy structure adjustment.•Non-OECD countries enjoy less emission reduction effects from digital empowerment.
To determine the frequency, accrual, attribution and outcome of neuropsychiatric (NP) events and impact on quality of life over 3 years in a large inception cohort of patients with systemic lupus ...erythematosus (SLE).
The study was conducted by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis. NP events were identified using the American College of Rheumatology case definitions, and decision rules were derived to determine the proportion of NP disease attributable to SLE. The outcome of NP events was recorded and patient-perceived impact determined by the SF-36.
1206 patients (89.6% female) with a mean (+/-SD) age of 34.5+/-13.2 years were included in the study. The mean disease duration at enrollment was 5.4+/-4.2 months. Over a mean follow-up of 1.9+/-1.2 years, 486/1206 (40.3%) patients had > or =1 NP events, which were attributed to SLE in 13.0-23.6% of patients using two a priori decision rules. The frequency of individual NP events varied from 47.1% (headache) to 0% (myasthenia gravis). The outcome was significantly better for those NP events attributed to SLE, especially if they occurred within 1.5 years of the diagnosis of SLE. Patients with NP events, regardless of attribution, had significantly lower summary scores for both mental and physical health over the study.
NP events in patients with SLE are of variable frequency, most commonly present early in the disease course and adversely impact patients' quality of life over time. Events attributed to non-SLE causes are more common than those due to SLE, although the latter have a more favourable outcome.
Rotational Velocities for M Dwarfs Jenkins, J. S; Ramsey, L. W; Jones, H. R. A ...
Astrophysical journal/The Astrophysical journal,
10/2009, Letnik:
704, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We present spectroscopic rotation velocities (v sin i) for 56 M dwarf stars using high-resolution Hobby-Eberly Telescope High Resolution Spectrograph red spectroscopy. In addition, we have also ...determined photometric effective temperatures, masses, and metallicities (Fe/H) for some stars observed here and in the literature where we could acquire accurate parallax measurements and relevant photometry. We have increased the number of known v sin i values for mid M stars by around 80% and can confirm a weakly increasing rotation velocity with decreasing effective temperature. Our sample of v sin is peak at low velocities (~3 km s-1). We find a change in the rotational velocity distribution between early M and late M stars, which is likely due to the changing field topology between partially and fully convective stars. There is also a possible further change in the rotational distribution toward the late M dwarfs where dust begins to play a role in the stellar atmospheres. We also link v sin i to age and show how it can be used to provide mid-M star age limits. When all literature velocities for M dwarfs are added to our sample, there are 198 with v sin i <= 10 km s-1 and 124 in the mid-to-late M star regime (M3.0-M9.5) where measuring precision optical radial velocities is difficult. In addition, we also search the spectra for any significant H Delta *a emission or absorption. Forty three percent were found to exhibit such emission and could represent young, active objects with high levels of radial-velocity noise. We acquired two epochs of spectra for the star GJ1253 spread by almost one month and the H Delta *a profile changed from showing no clear signs of emission, to exhibiting a clear emission peak. Four stars in our sample appear to be low-mass binaries (GJ1080, GJ3129, Gl802, and LHS3080), with both GJ3129 and Gl802 exhibiting double H Delta *a emission features. The tables presented here will aid any future M star planet search target selection to extract stars with low v sin i.