β-Ga 2 O 3 Schottky barrier diodes were fabricated in a vertical geometry structure consisting of Ni/Au rectifying contacts without edge termination on Si-doped epitaxial layers (10 μm, n~4×10 15 cm ...-3 ) on Sn-doped bulk Ga 2 O 3 substrates with full-area Ti/Au back Ohmic contacts. The reverse breakdown voltage, VBR, was a function of rectifying contact area, ranging from 1600 Vat 3.1×10 -6 cm 2 (20-μm diameter) to ~250 Vat 2.2×10 -3 cm -2 (0.53-mm diameter). The current density near breakdown was not strongly dependent on contact circumference but did scale with contact area, indicating that the bulk current contribution was dominant. The lowest ON-state resistance, Ron, was 1.6 mQ· cm 2 for the largest diode and 25 mQ·cm 2 for the 1600-V rectifier, leading to a Baliga figure-of-merit (V2BR/Ron) for the latter of approximately 102.4 MW·cm -2 . The ON-OFF ratio was measured at a forward voltage of 1.3 V and ranged from 3×10 7 to 2.5×10 6 for reverse biases from -5 to -40 V and showed only a small dependence on temperature in the range from 25 °C to 100 °C.
Extracellular Matrix Protein 1 (ECM1) is a marker for tumorigenesis and is correlated with invasiveness and poor prognosis in various types of cancer. However, the functional role of ECM1 in cancer ...metastasis is unclear. Here, we detected high ECM1 level in breast cancer patient sera that was associated with recurrence of tumor. The modulation of ECM1 expression affected not only cell migration and invasion, but also sphere-forming ability and drug resistance in breast cancer cell lines. In addition, ECM1 regulated the gene expression associated with the epithelial to mesenchymal transition (EMT) progression and cancer stem cell (CSC) maintenance. Interestingly, ECM1 increased β-catenin expression at the post-translational level through induction of MUC1, which was physically associated with β-catenin. Indeed, the association between β-catenin and the MUC1 cytoplasmic tail was increased by ECM1. Furthermore, forced expression of β-catenin altered the gene expression that potentiated EMT progression and CSC phenotype maintenance in the cells. These data provide evidence that ECM1 has an important role in cancer metastasis through β-catenin stabilization.
The continuous growth of atmospheric nitrous oxide (N2O) is of concern for its potential role in global warming and future stratospheric ozone destruction. Climate feedbacks that enhance N2O ...emissions in response to global warming are not well understood, and past records of N2O from ice cores are not sufficiently well resolved to examine the underlying climate‐N2O feedbacks on societally relevant time scales. Here, we present a new high‐resolution and high‐precision N2O reconstruction obtained from the Greenland NEEM (North Greenland Eemian Ice Drilling) and the Antarctic Styx Glacier ice cores. Covering the N2O history of the past two millennia, our reconstruction shows a centennial‐scale variability of ~10 ppb. A pronounced minimum at ~600 CE coincides with the reorganizations of tropical hydroclimate and ocean productivity changes. Comparisons with proxy records suggest association of centennial‐ to millennial‐scale variations in N2O with changes in tropical and subtropical land hydrology and marine productivity.
Plain Language Summary
Nitrous oxide (N2O) is a greenhouse and ozone‐depleting gas. The growing level of N2O in the atmosphere is of global concern, and records of past N2O variations can provide an important context for understanding the links between N2O and climate change. In this study, we report new, high‐quality N2O records covering the last two millennia using ice cores obtained from Greenland and Antarctica. Our N2O records show rapid centennial‐scale changes in atmospheric N2O and confirm a pronounced minimum near 600 CE. Comparison with climate records suggests that hydroclimate change on land and changes in marine productivity contribute to centennial‐ to millennial‐scale N2O variations.
Key Points
We report records of N2O concentration for the last 2,000 yr from the Styx ice core in Antarctca and NEEM ice core in Greenland
The data accurately reveal the timing and magnitude of N2O variations on centennial time scales
Variations in N2O are associated with changes in tropical and subtropical land hydrology and marine productivity
The genetics behind the progression of myelodysplasia to secondary acute myeloid leukemia (sAML) is poorly understood. In this study, we profiled somatic mutations and their dynamics using next ...generation sequencing on serial samples from a total of 124 patients, consisting of a 31 patient discovery cohort and 93 patients from two validation cohorts. Whole-exome analysis on the discovery cohort revealed that 29 of 31 patients carry mutations related to at least one of eight commonly mutated pathways in AML. Mutations in genes related to DNA methylation and splicing machinery were found in T-cell samples, which expand at the initial diagnosis of the myelodysplasia, suggesting their importance as early disease events. On the other hand, somatic variants associated with signaling pathways arise or their allelic burdens expand significantly during progression. Our results indicate a strong association between mutations in activated signaling pathways and sAML progression. Overall, we demonstrate that distinct categories of genetic lesions play roles at different stages of sAML in a generally fixed order.
Aim
Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely ...insufficient. The aim of this study was to elucidate the microbiota‐driven mechanisms involved in the development of nonalcoholic hepatic steatosis.
Methods and Results
Ob/ob mice and their wild‐type lean control mice were fed an AIN‐93G diet for 12 weeks. Faecal microbiota composition, faecal bile acid (BA) profile and intestinal and hepatic markers of BA metabolism were analysed. Ob/ob mice had significantly less faecal taurine‐conjugated BAs compared to their lean controls. The proportions of butyrate‐producing bacteria were lower in ob/ob mice compared to those in lean mice. Intestinal expression of farnesoid X receptor (FXR) mRNA was significantly higher, whereas hepatic expression of cholesterol‐7α‐hydroxylase 1 (CYP7A1) and small heterodimer partner (SHP) were significantly lower in ob/ob mice compared to those in control mice.
Conclusion
Microbiota‐associated BAs deconjugation may induce nonalcoholic fatty liver disease (NAFLD) by activating intestinal FXR signalling and blocking hepatic FXR‐SHP pathway, thereby accelerating fat synthesis.
Significance and Impact of the Study
We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD.
ABSTRACT
Objective
To evaluate cervical stiffness during pregnancy using ultrasound‐derived elastography, a method used to estimate the average tissue displacement (strain) within a defined region of ...interest when oscillatory compression is applied.
Methods
Strain was calculated in two regions of interest, the endocervical canal and the entire cervix, from three anatomical planes of the cervix: mid‐sagittal in the plane used for cervical length measurement and in cross‐sectional planes located at the internal and external cervical os. Associations between strain values, method of ascertainment and patient characteristics were assessed using linear mixed models to account for within‐subject correlation. Inter‐rater agreement in defining the degree of cervical stiffness was evaluated in 120 regions of interest acquired by two operators in 20 patients.
Results
A total of 1557 strain estimations were performed in 262 patients at 8–40 weeks of gestation. Adjusting for other sources of variation, (1) cervical tissue strain estimates obtained in the endocervical canal were on average 33% greater than those obtained in the entire cervix; (2) measurements obtained in the cross‐sectional plane of the external cervical os and sagittal plane were 45% and 13% greater than those measured in the cross‐sectional plane of the internal cervical os, respectively; (3) mean strain rates were 14% and 5% greater among parous women with and without a history of preterm delivery compared with those of nulliparous women, respectively, and were on average 13% greater among women with a cervical length of between 25 and 30 mm compared to those with a cervical length of > 30 mm; and (4) cervical tissue strain was more strongly associated with cervical length than with gestational age.
Conclusion
Semiquantitative elastography can be employed to evaluate changes in cervical stiffness during pregnancy.
Despite the high prevalence of tuberculosis (TB) and the disease burden of osteoporosis and osteoporotic fractures, there is still a lack of well-designed, large-scale studies demonstrating ...associations among them. We aimed to investigate the effect of TB on the incidence of osteoporosis and osteoporotic fractures.
This was a nationwide population–based cohort study.
This study was conducted using the National Health Insurance Service Database of South Korea. We included patients with newly diagnosed TB aged >40 years from January 2006 to December 2017. An uninfected control for each TB patient was randomly extracted by frequency matching for sex, age, income level, residence, and registration date at a 2:1 ratio. The primary outcome was the incidence of osteoporosis and osteoporotic fractures between the two groups, adjusted for sex, age, income level, residence, comorbidities, body mass index, blood pressure, laboratory tests, alcohol drinking, and smoking. The risk factors associated with osteoporosis or osteoporotic fractures were also investigated.
A total of 164,389 patients with TB and 328,778 matched controls were included (71.9% males). The mean duration of follow-up was 7.00 ± 3.49 years. The incidence of osteoporosis in patients with TB was 6.1 cases per 1000 person-years, which was significantly higher than that in matched controls (adjusted hazard ratio aHR 1.349, 95% confidence interval CI 1.302–1.398, P < 0.001). The incidence of osteoporotic fractures was also higher in patients with TB than in controls (aHR 1.392, 95% CI 1.357–1.428, P < 0.001). Among fractures, the risk of hip fracture was the highest (aHR 1.703, 95% CI 1.612–1.798, P < 0.001).
TB independently contributes to the incidence of osteoporosis and osteoporotic fractures, particularly hip fractures.
To study the relationship of echocardiographic epicardial adipose tissue (EAT) with coronary artery disease (CAD) risk factors and the extent of coronary atherosclerosis.
EAT thickness was measured ...in 527 patients undergoing their first coronary angiography. EAT was defined as an echo-lucent area on the free wall of the right ventricle on the still image of the two-dimensional echocardiogram at end diastole in the parasternal long-axis and parasternal short-axis views. A CT scan at the umbilicus was acquired to measure abdominal visceral adipose tissue (VAT) from a random sample of 30 patients. The extent of coronary atherosclerosis was assessed using a coronary atherosclerosis score based on the quantitative coronary angiography results.
EAT thickness was correlated with abdominal VAT (r(s) = 0.626, p<0.001), age (r(s) = 0.480, p<0.001), waist circumference (r(s) = 0.309, p<0.001), body mass index (r(s) = 0.233, p<0.001), C reactive protein (r(s) = 0.224, p<0.001), and the homoeostasis model assessment score (r(s) = 0.249, p<0.001). EAT was thicker in subjects with CAD than in those without CAD (4.0 vs 1.5 mm, p<0.001). Patients with unstable angina had thicker EAT than those with stable angina or atypical chest pain (4.0, 3.0, and 1.5 mm, respectively, p<0.001). EAT (> or =3.0 mm) was an independent factor of CAD on multiple logistic analysis (odds ratio = 3.357; 95% CI 2.177 to 5.175, p<0.001).
These results suggest that EAT may reflect the amount of visceral fat, which is associated with insulin resistance and inflammation. The echocardiographic measurement of EAT may provide additional information for assessing CAD risk and predicting the extent and activity of CAD.
The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been ...discussed as a novel and effective method for decolonizing MDRO.
To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage.
This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube.
A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P = 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P = 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio = 6.810, P = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT.
Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.
Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To ...constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42<L<117 MeV. This value is slightly lower but consistent with the L values deduced from a recent measurement of the neutron skin thickness of ^{208}Pb.
PDF
