This introduction to quantum chromodynamics presents the basic concepts and calculations in a clear and didactic style accessible to those new to the field. Readers will find useful methods for ...obtaining numerical results, including pure gauge theory and quenched spectroscopy.
Despite development of new antiviral drugs, viral infections are still a major health problem. The most potent antiviral defense mechanism is the innate production of type I interferon (IFN-I), which ...not only limits virus replication but also promotes antiviral T cell immunity through mechanisms, which remain insufficiently studied. Using the murine lymphocytic choriomeningitis virus model system, we show here that IFN-I signaling on T cells prevented their rapid elimination in vivo. Microarray analyses uncovered that IFN-I triggered the expression of selected inhibitory NK-cell-receptor ligands. Consequently, T cell immunity of IFN-I receptor (IFNAR)-deficient T cells could be restored by NK cell depletion or in NK-cell-deficient hosts (Nfil3–/–). The elimination of Ifnar1–/– T cells was dependent on NK-cell-mediated perforin expression. In summary, we identified IFN-I as a key player regulating the protection of T cells against regulatory NK cell function.
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•Ifnar1–/– T cells proliferate in vitro, but not in vivo, suggesting cell interaction•Microarray analyses identify MHC molecules as being regulated by type I interferons•NK cell deficiency rescues expansion and function of IFN-I unresponsive T cells•NK-cell-mediated killing of activated Ifnar1–/– CD8+ T cells depends on perforin
Type I interferons (IFN-I) are important for promoting antiviral T cell immunity, but the mechanisms behind IFN-I action have been unclear. Xu et al. show that IFN-I protects antiviral T cells from regulatory cytotoxic effects of natural killer cells and promotes their expansion and antiviral effector functions.
Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes
. Their physical origin remains unknown, but dozens of possible models have been postulated
. Some FRB sources exhibit repeat ...bursts
. Although over a hundred FRB sources have been discovered
, only four have been localized and associated with a host galaxy
, and just one of these four is known to emit repeating FRBs
. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source
, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure
further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.
The Canadian Hydrogen Intensity Mapping Experiment (CHIME) is a novel transit radio telescope operating across the 400-800 MHz band. CHIME is composed of four 20 m × 100 m semicylindrical paraboloid ...reflectors, each of which has 256 dual-polarization feeds suspended along its axis, giving it a 200 deg2 field of view. This, combined with wide bandwidth, high sensitivity, and a powerful correlator, makes CHIME an excellent instrument for the detection of fast radio bursts (FRBs). The CHIME Fast Radio Burst Project (CHIME/FRB) will search beam-formed, high time and frequency resolution data in real time for FRBs in the CHIME field of view. Here we describe the CHIME/FRB back end, including the real-time FRB search and detection software pipeline, as well as the planned offline analyses. We estimate a CHIME/FRB detection rate of 2-42 FRBs sky-1 day-1 normalizing to the rate estimated at 1.4 GHz by Vander Wiel et al. Likely science outcomes of CHIME/FRB are also discussed. CHIME/FRB is currently operational in a commissioning phase, with science operations expected to commence in the latter half of 2018.
We report on the discovery of eight repeating fast radio burst (FRB) sources found using the Canadian Hydrogen Intensity Mapping Experiment (CHIME) telescope. These sources span a dispersion measure ...(DM) range of 103.5-1281 pc cm−3. They display varying degrees of activity: six sources were detected twice, another three times, and one 10 times. These eight repeating FRBs likely represent the bright and/or high-rate end of a distribution of infrequently repeating sources. For all sources, we determine sky coordinates with uncertainties of ∼10′. FRB 180916.J0158+65 has a burst-averaged DM = 349.2 0.3 pc cm−3 and a low DM excess over the modeled Galactic maximum (as low as ∼20 pc cm−3); this source also has a Faraday rotation measure (RM) of −114.6 0.6 rad m−2, which is much lower than the RM measured for FRB 121102. FRB 181030.J1054+73 has the lowest DM for a repeater, 103.5 0.3 pc cm−3, with a DM excess of ∼70 pc cm−3. Both sources are interesting targets for multi-wavelength follow-up due to their apparent proximity. The DM distribution of our repeater sample is statistically indistinguishable from that of the first 12 CHIME/FRB sources that have not yet repeated. We find, with 4 significance, that repeater bursts are generally wider than those of CHIME/FRB bursts that have not repeated, suggesting different emission mechanisms. Many of our repeater events show complex morphologies that are reminiscent of the first two discovered repeating FRBs. The repetitive behavior of these sources will enable interferometric localizations and subsequent host galaxy identifications.
We present a lattice QCD study of Nπ scattering in the positive-parity nucleon channel, where the puzzling Roper resonance N*(1440) resides in experiment. The study is based on the PACS-CS ensemble ...of gauge configurations with Nf=2+1 Wilson-clover dynamical fermions, mπ≃156 MeV and L≃2.9 fm. In addition to a number of qqq interpolating fields, we implement operators for Nπ in p-wave and Nσ in s-wave. In the center-of-momentum frame we find three eigenstates below 1.65 GeV. They are dominated by N(0), N(0)π(0)π(0) mixed with N(0)σ(0) and N(p)π(−p) with p≃2π/L, where momenta are given in parentheses. This is the first simulation where the expected multi-hadron states are found in this channel. The experimental Nπ phase shift would-in the approximation of purely elastic Nπ scattering-imply an additional eigenstate near the Roper mass mR≃1.43 GeV for our lattice size. We do not observe any such additional eigenstate, which indicates that Nπ elastic scattering alone does not render a low-lying Roper. Coupling with other channels, most notably with Nππ, seems to be important for generating the Roper resonance, reinforcing the notion that this state could be a dynamically generated resonance. Our results are in line with most of the previous lattice studies based just on qqq interpolators, which did not find a Roper eigenstate below 1.65 GeV. The study of the coupled-channel scattering including a three-particle decay Nππ remains a challenge.
Background
Cardiac rehabilitation improves health-related quality of life (HRQoL) and reduces hospitalizations in patients with heart failure, but international uptake of cardiac rehabilitation for ...heart failure remains low.
Design and methods
The aim of this multicentre randomized trial was to compare the REACH-HF (Rehabilitation EnAblement in CHronicHeart Failure) intervention, a facilitated self-care and home-based cardiac rehabilitation programme to usual care for adults with heart failure with reduced ejection fraction (HFrEF). The study primary hypothesis was that the addition of the REACH-HF intervention to usual care would improve disease-specific HRQoL (Minnesota Living with Heart Failure questionnaire (MLHFQ)) at 12 months compared with usual care alone.
Results
The study recruited 216 participants, predominantly men (78%), with an average age of 70 years and mean left ventricular ejection fraction of 34%. Overall, 185 (86%) participants provided data for the primary outcome. At 12 months, there was a significant and clinically meaningful between-group difference in the MLHFQ score of –5.7 points (95% confidence interval –10.6 to –0.7) in favour of the REACH-HF intervention group (p = 0.025). With the exception of patient self-care (p < 0.001) there was no significant difference in other secondary outcomes, including clinical events (p > 0.05) at follow-up compared with usual care. The mean cost of the REACH-HF intervention was £418 per participant.
Conclusions
The novel REACH-HF home-based facilitated intervention for HFrEF was clinically superior in disease-specific HRQoL at 12 months and offers an affordable alternative to traditional centre-based programmes to address current low cardiac rehabilitation uptake rates for heart failure.
Identification of germline mutation in patients with apparently sporadic pheochromocytomas and paragangliomas is crucial. Clinical indicators, which include young age, bilateral or multifocal, ...extra-adrenal, malignant, or recurrent tumors, predict the likelihood of harboring germline mutation in Caucasian subjects. However, data on the prevalence of germline mutation, as well as the applicability of these clinical indicators in Chinese, are lacking. We conducted a cross-sectional study at a single endocrine tertiary referral center in Hong Kong. Subjects with pheochromocytomas and paragangliomas were evaluated for the presence of germline mutations involving 10 susceptibility genes, which included NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, TMEM 127, MAX, and FH genes. Clinical indicators were assessed for their association with the presence of germline mutations. Germline mutations, 2 being novel, were found in 24.4% of the 41 Chinese subjects recruited and 11.4% among those with apparently sporadic presentation. The increasing number of the afore-mentioned clinical indicators significantly correlated with the likelihood of harboring germline mutation in one of the 10 susceptibility genes. (r=0.757, p=0.026). The presence of 2 or more clinical indicators should prompt genetic testing for germline mutations in Chinese subjects. In conclusion, our study confirmed that a significant proportion of Chinese subjects with apparently sporadic pheochromocytoma and paraganglioma harbored germline mutations and these clinical indicators identified from Caucasians series were also applicable in Chinese subjects. This information will be of clinical relevance in the design of appropriate genetic screening strategies in Chinese populations.
Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver‐damaging diseases, such as infection and alcohol intoxication. At ...least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca2+ influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels. Conclusion: Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease. (Hepatology 2015;61:275–284)
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