Heterostructures of atomically thin van der Waals bonded monolayers have opened a unique platform to engineer Coulomb correlations, shaping excitonic
, Mott insulating
or superconducting phases
. In ...transition metal dichalcogenide heterostructures
, electrons and holes residing in different monolayers can bind into spatially indirect excitons
with a strong potential for optoelectronics
, valleytronics
, Bose condensation
, superfluidity
and moiré-induced nanodot lattices
. Yet these ideas require a microscopic understanding of the formation, dissociation and thermalization dynamics of correlations including ultrafast phase transitions. Here we introduce a direct ultrafast access to Coulomb correlations between monolayers, where phase-locked mid-infrared pulses allow us to measure the binding energy of interlayer excitons in WSe
/WS
hetero-bilayers by revealing a novel 1s-2p resonance, explained by a fully quantum mechanical model. Furthermore, we trace, with subcycle time resolution, the transformation of an exciton gas photogenerated in the WSe
layer directly into interlayer excitons. Depending on the stacking angle, intra- and interlayer species coexist on picosecond scales and the 1s-2p resonance becomes renormalized. Our work provides a direct measurement of the binding energy of interlayer excitons and opens the possibility to trace and control correlations in novel artificial materials.
Virtual photons can mediate interaction between atoms, resulting in an energy shift known as a collective Lamb shift. Observing the collective Lamb shift is challenging, since it can be obscured by ...radiative decay and direct atom-atom interactions. Here, we place two superconducting qubits in a transmission line terminated by a mirror, which suppresses decay. We measure a collective Lamb shift reaching 0.8% of the qubit transition frequency and twice the transition linewidth. We also show that the qubits can interact via the transmission line even if one of them does not decay into it.
A significant consequence of Typhoon Morakot in August 2009 was the production of vast volumes of driftwood in Pacific Asia. We have quantified the flux of this coarse woody debris (CWD) to the ...oceans from typhoon-triggered landslides in Taiwan, where Morakot made landfall, by combining remote sensing (using FORMOSAT-2 imagery and aerial photography), analysis of forest biomass, and field observations. A total of 3.8–8.4 TgCWD was transported to the oceans, carrying 1.8–4.0 Tg of organic carbon. In addition to the local effects on the marine and coastal environment from such a highly concentrated flux of carbon and nutrients, storm-driven mobilization of CWD may represent a significant, if infrequent, transfer of terrestrial biomass to the oceans. If the frequency of relatively rare, extreme storms such as Morakot increases in a changing climate, this transport mechanism may play an important role in feedbacks between global climate, storm intensity, and carbon cycling.
The standard core accretion model for planetesimal formation in protoplanetary discs (PPDs) is subject to a number of challenges. One is related to the vertical settling of dust to the disc mid-plane ...against turbulent stirring. This is particularly relevant in the presence of the vertical shear instability (VSI), a purely hydrodynamic instability applicable to the outer parts of PPDs, which drives moderate turbulence characterized by large-scale vertical motions. We investigate the evolution of dust and gas in the vicinity of local pressure enhancements (pressure bumps) in a PPD with turbulence sustained by the VSI. Our goal is to determine the morphology of dust concentrations and if dust can concentrate sufficiently to reach conditions that can trigger the streaming instability (SI). We performed a suite of global 2D axisymmetric and 3D simulations of dust and gas for a range of values for Σ
d
∕Σ
g
(ratio of dust-to-gas surface mass densities or metallicity), particle Stokes numbers,
τ
, and pressure bump amplitude,
A
. Dust feedback onto the gas is included. For the first time, we use global 3D simulations to demonstrate the collection of dust in long-lived vortices induced by the VSI. These vortices, which undergo a slow radial inward drift, are the dusty analogs of large long-lived vortices found in previous dust-free simulations of the VSI. Without a pressure bump and for solar metallicity
Z
≈ 0.01 and Stokes numbers
τ
~ 10
−2
, we find that such vortices can reach dust-to-gas density ratios slightly below unity in the discs’ mid-plane, while for
Z
≳ 0.05, long-lived vortices are largely absent. In the presence of a pressure bump, for
Z
≈ 0.01 and
τ
~ 10
−2
, a dusty vortex forms that reaches dust-to-gas ratios of a few times unity, such that the SI is expected to develop, before it eventually shears out into a turbulent dust ring. At intermediate metallicities,
Z
~ 0.03, this occurs for
τ
~ 5 × 10
−3
, but with a weaker and more short-lived vortex, while for larger
τ
, only a turbulent dust ring forms. For
Z
≳ 0.03, we find that the dust ring becomes increasingly axisymmetric for increasing
τ
and dust-to-gas ratios reach order unity for
τ
≳ 5 × 10
−3
. Furthermore, the vertical mass flow profile of the disc is strongly affected by dust for
Z
≳ 0.03, such that gas is transported inward near the mid-plane and outward at larger heights, which is the reversed situation compared to simulations with zero or small amounts of dust. We find viscous
α
-values to drop moderately as ~10
−3
–10
−4
for metallicities increasing as
Z
= 0–0.05. Our results suggest that the VSI can play an active role in the formation of planetesimals through the formation of vortices for plausible values of metallicity and particle size. Also, it may provide a natural explanation for the presence or absence of asymmetries of observed dust rings in PPDs, depending on the background metallicity.
Although post-traumatic stress disorder (PTSD) and depression are commonly observed following injury, few studies have focused on the effect of psychiatric symptoms on return to work (RTW) following ...occupational injury.
To determine the impact of psychiatric symptoms on RTW after occupational injury.
PubMed (1980-2014), MEDLINE (1980-2014) and PsycINFO (1980-2014) databases were examined with linked fields of research in February 2015. Reference lists of eligible articles were also searched. Cohort, case-control, cross-sectional studies and intervention studies were selected according to predefined criteria. Evidence was synthesized qualitatively according to the Downs and Black and Crombie checklist. The standard checklist was used to assess the methodological quality of each study by two reviewers.
Five of the 56 records met the inclusion and exclusion criteria. After occupational injury, the rates of RTW after the injuries varied widely, ranging from 31 to 63%. PTSD symptoms and depressive symptoms appeared to be negatively associated with RTW.
Currently, the evidence is insufficient to draw conclusions about the effects of psychiatric symptoms on RTW after occupational injury and more studies are needed. Future studies with large sample sizes are warranted to determine the prevalence of RTW and to detect the psychiatric factors.
Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx) has critical role in the induction of ...carcinogenesis. Several studies have shown that thyroid hormone (TH) suppresses HCC development and protects hepatocytes from HBx-induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species (ROS) inflicted DNA damage. We further found that TH induced biogenesis of mitochondria (MITO) and autophagy of HBx-targeted MITO simultaneously, consequently leading to suppression of HBx-promoted ROS and carcinogenesis. Using microarray data analysis, this protective effect of TH was found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx protein and trigger selective mitophagy. The pathological significance of the TH/PINK1 pathway in liver protection was confirmed by the concomitant decrease in expression of both TR and PINK1 in matched HCC tumor tissues and negatively correlated with aggressive progression of cancer and poor prognosis. Our data indicate that TH/PINK1/Parkin pathway has a critical role in protecting hepatocytes from HBx-induced carcinogenesis. Notably, several liver-targeting therapeutic derivatives of TH facilitating prevention or therapy of steatosis have been identified. Furthermore, our proof-of-concept experiments suggest that application of T
constitutes an effective novel therapeutic or preventive option for HCC. Thus, the utilization of the agonists of TRs could be the meaningful strategy in liver relative diseases, ranging from simple hepatic steatosis to HCC.
Sirtuin deacetylases and FOXO (Forkhead box, class O) transcription factors have important roles in many biological pathways, including cancer development. SIRT1 and SIRT2 deacetylate FOXO factors to ...regulate FOXO function. Because acetylation and ubiquitination both modify the ɛ-amino group of lysine residues, we investigated whether FOXO3 deacetylation by SIRT1 or SIRT2 facilitates FOXO3 ubiquitination and subsequent proteasomal degradation. We found that SIRT1 and SIRT2 promote FOXO3 poly-ubiquitination and degradation. Proteasome-inhibitor treatment prevented sirtuin-induced FOXO3 degradation, indicating that this process is proteasome dependent. In addition, we demonstrated that E3 ubiquitin ligase subunit Skp2 binds preferentially to deacetylated FOXO3. Overexpression of Skp2 caused poly-ubiquitination of FOXO3 and degradation, whereas knockdown of Skp2 increased the amount of FOXO3 protein. We also present evidence that SCF-Skp2 ubiquitinates FOXO3 directly in vitro. Furthermore, mutating four known acetylated lysine residues (K242, K259, K290 and K569) of FOXO3 into arginines to mimic deacetylated FOXO3 resulted in enhanced Skp2 binding but with inhibition of FOXO3 ubiquitination; this suggests that some or all of these four lysine residues are likely the sites for ubiquitination. In the livers of mice deficient in SIRT1, we detected increased expression of FOXO3, indicating SIRT1 regulates FOXO3 protein levels in vivo. Furthermore, we found that the elevation of SIRT1 and Skp2 expression in malignant PC3 and DU145 prostate cells is responsible for the downregulation of FOXO3 protein levels in these cells. Taken together, our data support the notion that deacetylation of FOXO3 by SIRT1 or SIRT2 facilitates Skp2-mediated FOXO3 poly-ubiquitination and proteasomal degradation.
Summary
Background
Aspirin increases the risk of gastrointestinal bleeding.
Aim
To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users.
Methods
Low‐dose (75‐325 mg daily) ...aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti‐inflammatory drugs (NSAIDs), cyclooxygenase‐2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine‐2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers.
Results
A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio HR: 2.75, 95% confidence interval CI: 2.06‐3.65), NSAIDs (HR: 8.61, 95% CI: 3.28‐22.58), steroids (HR: 10.50, 95% CI: 1.98‐55.57), SSRIs (HR: 11.71, 95% CI: 1.40‐97.94), PPIs (HR: 8.47, 95% CI: 2.26‐31.71), and H2RAs (HR: 10.83, 95% CI: 2.98‐39.33) were significantly associated with LGIB.
Conclusions
The risk of LGIB was higher in low‐dose aspirin users than in aspirin nonusers in this nationwide cohort. Low‐dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.
Linked ContentThis article is linked to Taha and Chen et al papers. To view these articles visit https://doi.org/10.1111/apt.14114 and https://doi.org/10.1111/apt.14138.
CHEK1 encodes the serine/threonine kinase CHK1, a central component of the DNA damage response. CHK1 regulates cell cycle checkpoints following genotoxic stress to prevent the entry of cells with ...damaged DNA into mitosis and coordinates various aspects of DNA repair. Accordingly, CHK1 has become a target of considerable interest in oncology. CHK1 inhibitors potentiate the efficacy of DNA-damaging chemotherapeutics by abrogating CHK1-mediated cell cycle arrest and preventing repair of damaged DNA. In addition, CHK1 inhibitors interfere with the biological role of CHK1 as a principal regulator of the cell cycle that controls the initiation of DNA replication, stabilizes replication forks, and coordinates mitosis. Since these functions of CHK1 facilitate progression through an unperturbed cell cycle, CHK1 inhibitors are being developed not only as chemopotentiators, but also as single-agent therapies. This review is intended to provide information on the current progress of CHK1 inhibitors in pre-clinical and clinical development and will focus on mechanisms of single-agent activity and potential strategies for patient tailoring and combinations with non-genotoxic agents.
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