In recent years, instrumentation enabling pulsar observations with unprecedentedly high fractional bandwidth has been under development which can be used to substantially improve the precision of ...pulsar timing experiments. The traditional template-matching method used to calculate pulse times of arrival (ToAs) may not function effectively on these broad-band data due to a variety of effects such as diffractive scintillation in the interstellar medium, profile variation as a function of frequency, dispersion measure (DM) evolution, and so forth. In this paper, we describe the channelized discrete Fourier transform method that can greatly mitigate the influence of the aforementioned effects when measuring ToAs from broad-band timing data. The method is tested on simulated data, and its potential in improving timing precision is shown. We further apply the method to PSR J1909−3744 data collected at the Nançay Radio Telescope with the Nançay Ultimate Pulsar Processing Instrument. We demonstrate removal of systematics due to the scintillation effect as well as improvement on ToA measurement uncertainties. Our method also determines temporal variations in DM, which are consistent with multichannel timing approaches used earlier.
Organisms that protect their germ-cell lineages from damage often do so at considerable cost: limited metabolic resources become partitioned away from maintenance of the soma, leaving the ageing ...somatic tissues to navigate survival amid an environment containing damaged and poorly functioning proteins. Historically, experimental paradigms that limit reproductive investment result in lifespan extension. We proposed that germline-deficient animals might exhibit heightened protection from proteotoxic stressors in somatic tissues. We find that the forced re-investment of resources from the germ line to the soma in Caenorhabditis elegans results in elevated somatic proteasome activity, clearance of damaged proteins and increased longevity. This activity is associated with increased expression of rpn-6, a subunit of the 19S proteasome, by the FOXO transcription factor DAF-16. Ectopic expression of rpn-6 is sufficient to confer proteotoxic stress resistance and extend lifespan, indicating that rpn-6 is a candidate to correct deficiencies in age-related protein homeostasis disorders.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The spread of coronavirus disease 2019 (COVID-19) has affected both physical health and mental well-being around the world. Stress-related reactions, if prolonged, may result in mental health ...problems. We examined the consequences of the COVID-19 pandemic on mental health in a multinational study and explored the effects of government responses to the outbreak. We sampled 18,171 community adults from 35 countries/societies, stratified by age, gender, and region of residence. Across the 35 societies, 26.6% of participants reported moderate to extremely severe depression symptoms, 28.2% moderate to extremely severe anxiety symptoms, and 18.3% moderate to extremely severe stress symptoms. Coronavirus anxiety comprises two factors, namely Perceived Vulnerability and Threat Response. After controlling for age, gender, and education level, perceived vulnerability predicted higher levels of negative emotional symptoms and psychological distress, whereas threat response predicted higher levels of self-rated health and subjective well-being. People in societies with more stringent control policies had more threat response and reported better subjective health. Coronavirus anxiety exerts detrimental effects on subjective health and well-being, but also has the adaptive function in mobilizing safety behaviors, providing support for an evolutionary perspective on psychological adaptation.
Aims/hypothesis
FTO
harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for
FTO
in obesity risk in Asians, its association with type 2 ...diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the
FTO
locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.
Methods
All studies published on the association between
FTO
-rs9939609 (or proxy
r
2
> 0.98) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.
Results
The
FTO
-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (
p
= 9.0 × 10
−19
), overweight by 1.13-fold/allele (
p
= 1.0 × 10
−11
) and type 2 diabetes by 1.15-fold/allele (
p
= 5.5 × 10
−8
). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele,
p
= 6.6 × 10
−5
). The
FTO
-rs9939609 minor allele increased BMI by 0.26 kg/m
2
per allele (
p
= 2.8 × 10
−17
), WHR by 0.003/allele (
p
= 1.2 × 10
−6
), and body fat percentage by 0.31%/allele (
p
= 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of
FTO
variation on obesity-related traits and type 2 diabetes was similar in the two populations.
Conclusions/interpretation
FTO
is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore,
FTO
is also associated with type 2 diabetes independently of BMI.
Abstract
HESS J1843–033 is a very high energy gamma-ray source whose origin remains unidentified. This work presents, for the first time, the energy spectrum of gamma rays beyond 100 TeV from the ...HESS J1843–033 region using the data recorded by the Tibet air shower array and its underground muon detector array. A gamma-ray source with an extension of 0.°34 ± 0.°12 is successfully detected above 25 TeV at (
α
,
δ
) = (281.°09 ± 0.°10, −3.°76 ± 0.°09) near HESS J1843–033 with a statistical significance of 6.2
σ
, and the source is named TASG J1844–038. The position of TASG J1844–038 is consistent with those of HESS J1843–033, eHWC J1842–035, and LHAASO J1843–0338. The measured gamma-ray energy spectrum in 25 TeV <
E
< 130 TeV is described with
dN
/
dE
=
(
9.70
±
1.89
)
×
10
−
16
(
E
/40 TeV)
−3.26±0.30
TeV
−1
cm
−2
s
−1
, and the spectral fit to the combined spectra of HESS J1843–033, LHAASO J1843–0338, and TASG J1844–038 implies the existence of a cutoff at 49.5 ± 9.0 TeV. Associations of TASG J1844–038 with SNR G28.6–0.1 and PSR J1844–0346 are also discussed in detail for the first time.
Cervical dystonia is a neurological disorder characterized by sustained, involuntary movements of the head and neck. Most cases of cervical dystonia are idiopathic, with no obvious cause, yet some ...cases are acquired, secondary to focal brain lesions. These latter cases are valuable as they establish a causal link between neuroanatomy and resultant symptoms, lending insight into the brain regions causing cervical dystonia and possible treatment targets. However, lesions causing cervical dystonia can occur in multiple different brain locations, leaving localization unclear. Here, we use a technique termed 'lesion network mapping', which uses connectome data from a large cohort of healthy subjects (resting state functional MRI, n = 1000) to test whether lesion locations causing cervical dystonia map to a common brain network. We then test whether this network, derived from brain lesions, is abnormal in patients with idiopathic cervical dystonia (n = 39) versus matched controls (n = 37). A systematic literature search identified 25 cases of lesion-induced cervical dystonia. Lesion locations were heterogeneous, with lesions scattered throughout the cerebellum, brainstem, and basal ganglia. However, these heterogeneous lesion locations were all part of a single functionally connected brain network. Positive connectivity to the cerebellum and negative connectivity to the somatosensory cortex were specific markers for cervical dystonia compared to lesions causing other neurological symptoms. Connectivity with these two regions defined a single brain network that encompassed the heterogeneous lesion locations causing cervical dystonia. These cerebellar and somatosensory regions also showed abnormal connectivity in patients with idiopathic cervical dystonia. Finally, the most effective deep brain stimulation sites for treating dystonia were connected to these same cerebellar and somatosensory regions identified using lesion network mapping. These results lend insight into the causal neuroanatomical substrate of cervical dystonia, demonstrate convergence across idiopathic and acquired dystonia, and identify a network target for dystonia treatment.
High-energy X-rays and
γ
-rays from solar flares were discovered just over fifty years ago. Since that time, the standard for the interpretation of spatially integrated flare X-ray spectra at ...energies above several tens of keV has been the collisional thick-target model. After the launch of the
Reuven Ramaty High Energy Solar Spectroscopic Imager
(
RHESSI
) in early 2002, X-ray spectra and images have been of sufficient quality to allow a greater focus on the energetic electrons responsible for the X-ray emission, including their origin and their interactions with the flare plasma and magnetic field. The result has been new insights into the flaring process, as well as more quantitative models for both electron acceleration and propagation, and for the flare environment with which the electrons interact. In this article we review our current understanding of electron acceleration, energy loss, and propagation in flares. Implications of these new results for the collisional thick-target model, for general flare models, and for future flare studies are discussed.
CD73 is a cell surface 5'-nucleotidase that converts AMP to adenosine, an immune suppressive molecule. CD73 may promote immune escape in cancer by contributing to the degradation of extracellular ATP ...released by dying cancer cells in hypoxic tumors or following chemotherapy. However, whether CD73 exerts a critical oncogenic function during tumorigenesis is unknown. In this study, we used genetically deficient mice to investigate its contribution to autochthonous tumor formation. CD73 deficiency suppressed the development of 3-methylcholanthrene (MCA)-induced fibrosarcomas through a mechanism relying upon IFN-γ, natural killer (NK) cells, and CD8(+) T cells. Similarly, CD73 deficiency also suppressed prostate tumorigenesis in TRAMP transgenic mice. Importantly, treatment with an anti-CD73 monoclonal antibody effectively suppressed growth of established MCA-induced tumors or TRAMP-C1 prostate tumors and inhibited the development of TRAMP-C1 lung metastases. The therapeutic activity of anti-CD73 monoclonal antibody against primary tumors was dependent on CD8(+) T cells, whereas its antimetastatic activity was dependent on host CD73 expression independent of T cells or NK cells. Taken together, our findings indicate that CD73 is a critical factor in tumorigenesis and that anti-CD73 antibodies may offer a novel generalized strategy to blunt immune escape and treat cancer.
Next-generation xenon detectors with multiton-year exposure are powerful direct probes of dark matter candidates, in particular the favorite weakly interacting massive particles. Coupled with the ...features of low thresholds and backgrounds, they are also excellent telescopes of solar neutrinos. In this paper, we study the discovery potential of ton-scale xenon detectors in electromagnetic moments of solar neutrinos. Relevant neutrino-atom scattering processes are calculated by applying a state-of-the-art atomic many-body method-relativistic random phase approximation. Limits on these moments are derived from existing data and estimated with future experiment specifications. With one ton-year exposure, XENON-1T can improve the effective millicharge constraint by a factor of 2. With LZ and DARWIN, the projected improvement on the solar neutrino effective millicharge (magnetic moment) is around 7 (2) times smaller than the current bound. If LZ can keep the same background level and push the electron recoil threshold to 0.5 keV, the projected improvement on the millicharge (magnetic moment) is about 10 (3) times smaller than the current bound. An unconventional setup of placing a strong 51Cr neutrino source by a ton-scale xenon detector is also considered.
This study investigated the in vitro susceptibilities of methicillin-resistant
Staphylococcus aureus
(MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 ...hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7 % were susceptible; however, 30.0 % (
n
= 517) exhibited MICs of 2 μg/ml and 0.3 % (
n
= 6) demonstrated intermediate susceptibility (MICs of 4 μg/ml). Nearly all isolates (≥99.9 %) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC
90
values were 2 μg/ml for ceftobiprole and 1 μg/ml for nemonoxacin. The MIC
90
values of mupirocin and tyrothricin were 0.12 and 4 μg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 μg/ml, the MIC
90
values were 2 μg/ml for teicoplanin, 0.5 μg/ml for daptomycin, and 0.5 μg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 μg/ml (2, 0.06, and 0.12 μg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (
n
= 6), teicoplanin (
n
= 1), daptomycin (
n
= 2), or tigecycline (
n
= 1), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 μg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.
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