Dysregulation of the corticotropin-releasing factor (CRF)-urocortin (UCN) system has been implicated in stress-related psychopathologies such as depression and anxiety. It has been proposed that ...CRF-CRF receptor type 1 (CRFR1) signalling promotes the stress response and anxiety-like behaviour, whereas UCNs and CRFR2 activation mediate stress recovery and the restoration of homeostasis. Recent findings, however, provide clear evidence that this view is overly simplistic. Instead, a more complex picture has emerged that suggests that there are brain region- and cell type-specific effects of CRFR signalling that are influenced by the individual's prior experience and that shape molecular, cellular and ultimately behavioural responses to stressful challenges.
Cancer/testis (CT) antigens, of which more than 40 have now been identified, are encoded by genes that are normally expressed only in the human germ line, but are also expressed in various tumour ...types, including melanoma, and carcinomas of the bladder, lung and liver. These immunogenic proteins are being vigorously pursued as targets for therapeutic cancer vaccines. CT antigens are also being evaluated for their role in oncogenesis--recapitulation of portions of the germline gene-expression programme might contribute characteristic features to the neoplastic phenotype, including immortality, invasiveness, immune evasion, hypomethylation and metastatic capacity.
We present our current best estimate of the plausible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next several years, with the intention ...of providing information to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals for the third (O3), fourth (O4) and fifth observing (O5) runs, including the planned upgrades of the Advanced LIGO and Advanced Virgo detectors. We study the capability of the network to determine the sky location of the source for gravitational-wave signals from the inspiral of binary systems of compact objects, that is binary neutron star, neutron star–black hole, and binary black hole systems. The ability to localize the sources is given as a sky-area probability, luminosity distance, and comoving volume. The median sky localization area (90% credible region) is expected to be a few hundreds of square degrees for all types of binary systems during O3 with the Advanced LIGO and Virgo (HLV) network. The median sky localization area will improve to a few tens of square degrees during O4 with the Advanced LIGO, Virgo, and KAGRA (HLVK) network. During O3, the median localization volume (90% credible region) is expected to be on the order of
10
5
,
10
6
,
10
7
Mpc
3
for binary neutron star, neutron star–black hole, and binary black hole systems, respectively. The localization volume in O4 is expected to be about a factor two smaller than in O3. We predict a detection count of
1
-
1
+
12
(
10
-
10
+
52
) for binary neutron star mergers, of
0
-
0
+
19
(
1
-
1
+
91
) for neutron star–black hole mergers, and
17
-
11
+
22
(
79
-
44
+
89
) for binary black hole mergers in a one-calendar-year observing run of the HLV network during O3 (HLVK network during O4). We evaluate sensitivity and localization expectations for unmodeled signal searches, including the search for intermediate mass black hole binary mergers.
The liquid metal and solid ceramic pebble breeder blankets have become the most promising blankets for ITER-TBMs or DEMO reactors in China and the world due to their potential advantages. In recent ...years the corresponding research work on fusion reactor materials mainly focuses on structural materials, plasma facing materials and the functional materials for the blanket such as breeder, coating and flow channel insert etc. for the successful application of fusion energy in the near future. The R&D on those materials in the two kinds of blankets is being carried out widely in China, including fabrication and manufacturing techniques, physical/mechanical properties assessment before and after irradiation, joining techniques for structural materials, compatibility evaluation, and the development and verification of the criteria for fusion material designs. The progress on main R&D activities of fusion reactor materials in China is introduced and prospected in the paper.
A thermal/optical carbon analyzer equipped with seven-wavelength light source/detector (405–980 nm) for monitoring spectral reflectance (R) and transmittance (T) of filter samples allowed "thermal ...spectral analysis (TSA)" and wavelength (λ)-dependent organic-carbon (OC)–elemental-carbon (EC) measurements. Optical sensing was calibrated with transfer standards traceable to absolute R and T measurements, adjusted for loading effects to report spectral light absorption (as absorption optical depth (τa, λ)), and verified using diesel exhaust samples. Tests on ambient and source samples show OC and EC concentrations equivalent to those from conventional carbon analysis when based on the same wavelength (~ 635 nm) for pyrolysis adjustment. TSA provides additional information that evaluates black-carbon (BC) and brown-carbon (BrC) contributions and their optical properties in the near infrared to the near ultraviolet parts of the solar spectrum. The enhanced carbon analyzer can add value to current aerosol monitoring programs and provide insight into more accurate OC and EC measurements for climate, visibility, or health studies.
Human mutations that truncate the massive sarcomere protein titin TTN-truncating variants (TTNtvs) are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure ...and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtvs, diminish contractile performance and are pathogenic. By combining functional analyses with RNA sequencing, we explain why truncations in the A-band domain of TTN cause DCM, whereas truncations in the I band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS cell–derived cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and β-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodeling.
Degenerative changes are commonly found in spine imaging but often occur in pain-free individuals as well as those with back pain. We sought to estimate the prevalence, by age, of common degenerative ...spine conditions by performing a systematic review studying the prevalence of spine degeneration on imaging in asymptomatic individuals.
We performed a systematic review of articles reporting the prevalence of imaging findings (CT or MR imaging) in asymptomatic individuals from published English literature through April 2014. Two reviewers evaluated each manuscript. We selected age groupings by decade (20, 30, 40, 50, 60, 70, 80 years), determining age-specific prevalence estimates. For each imaging finding, we fit a generalized linear mixed-effects model for the age-specific prevalence estimate clustering in the study, adjusting for the midpoint of the reported age interval.
Thirty-three articles reporting imaging findings for 3110 asymptomatic individuals met our study inclusion criteria. The prevalence of disk degeneration in asymptomatic individuals increased from 37% of 20-year-old individuals to 96% of 80-year-old individuals. Disk bulge prevalence increased from 30% of those 20 years of age to 84% of those 80 years of age. Disk protrusion prevalence increased from 29% of those 20 years of age to 43% of those 80 years of age. The prevalence of annular fissure increased from 19% of those 20 years of age to 29% of those 80 years of age.
Imaging findings of spine degeneration are present in high proportions of asymptomatic individuals, increasing with age. Many imaging-based degenerative features are likely part of normal aging and unassociated with pain. These imaging findings must be interpreted in the context of the patient's clinical condition.
Ni–carbon nanotube (CNTs) composite coatings were deposited on a carbon steel by electrodeposition. The effect of incorporation of CNTs into the nickel coating on the morphology of the coating ...surface and corrosion properties was investigated. Scanning electron microscopy (SEM) showed that the CNTs appear well dispersed in the nickel layer. Corrosion tests were performed in aqueous NaCl (3.5 wt.%) using a weight loss method and electrochemical measurements for bare, pure nickel coated and CNTs–nickel coated samples. The results showed that addition of CNTs in the deposition process of nickel significantly increased the resistance to corrosion. The anti-corrosion mechanism of the composite coating is also discussed.
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