Summary
Background
Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral ...cutaneous melanoma (NAM) in Asians are not well understood.
Objectives
To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma.
Methods
We performed comprehensive genomic profiling of 409 cancer‐associated genes, using next‐generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs.
Results
Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild‐type (triple‐WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell‐cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell‐cycle aberrations were independent prognostic factors of melanoma‐specific survival.
Conclusions
This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians.
What's already known about this topic?
Mutation frequencies of driver genes vary between melanoma subtypes.
Acral melanoma is the most common subtype of melanoma in Asians.
KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype
What does this study add?
NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment.
Melanomas with cell‐cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration.
What is the translational message?
Cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival.
These observations should be explored further for future drug development.
Linked Comment: Johansson. Br J Dermatol 2020; 182:1085.
Plain language summary available online
This paper studies dynamic mechanical responses and damage mechanisms of plastic fiber-reinforced polymer matrix composite laminate under low velocity impact. First, the plastic damage model is ...introduced for intralaminar damage, where Puck’s failure criteria and strain based damage evolution laws for fiber and matrix are used, and the bilinear cohesive model is adopted for delamination. Second, an uncoupled numerical scheme for dealing with the intralaminar plastic deformation and damage evolution by finite element analysis (FEA) is originally proposed based on the strain equivalence hypothesis, in which the effective stresses and strains are first solved using the backward Euler algorithm and then the nominal stresses and damage variables are updated independently. Finally, the proposed algorithm is implemented using ABAQUS-VUMAT by the time stepping algorithm. For two composite specimens under transverse impact, the impact force-time curve, the impact displacement-time curve and the dissipated energy at different impact energies are studied by comparing the results using experiments and FEA. Numerical results show the plastic damage model leads to higher precision than the elastic damage model as the impact energy becomes relatively large.
Ultrafast electron microscopy (UEM) has been demonstrated as an effective table-top technique for imaging the temporally evolving dynamics of matter with a subparticle spatial resolution on the ...timescale of atomic motion. However, imaging the faster motion of electron dynamics in real time has remained beyond reach. Here we demonstrate more than an order of magnitude (16 times) enhancement in the typical temporal resolution of UEM by generating isolated ∼30 fs electron pulses, accelerated at 200 keV, via the optical-gating approach, with sufficient intensity to probe efficiently the electronic dynamics of matter. Moreover, we investigate the feasibility of attosecond optical gating to generate isolated subfemtosecond electron pulses and attain the desired temporal resolution in electron microscopy to establish 'attomicroscopy' to allow the imaging of electron motion in the act.
The effect of COD:N ratio on sludge properties and their role in membrane fouling were examined using a well-controlled aerobic membrane bioreactor receiving a synthetic high strength wastewater ...containing glucose. Membrane performance was improved with an increase in the COD/N ratio (100:5–100:1.8) (i.e. reduced N dosage). Surface analysis of sludge by X-ray photoelectron spectroscopy (XPS) indicates significant differences in surface concentrations of elements C, O and N that were observed under different COD/N ratios, implying changes in the composition of extracellular polymeric substances (EPS). Fourier transform-infrared spectroscopy (FTIR) revealed a unique characteristic peak (CO bonds) at 1735 cm−1 under nitrogen limitation conditions. Total EPS decreased with an increase in COD/N ratio, corresponding to a decrease in the proteins (PN) to carbohydrates (CH) ratio in EPS. There were no significant differences in the total soluble microbial products (SMPs) but the ratio of PN/CH in SMPs decreased with an increase in COD/N ratios. The results suggest that EPS and SMP composition and the presence of a small quantity of filamentous microorganisms played an important role in controlling membrane fouling.
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•An increase in COD:N ratio led to improved membrane performance.•Surface concentrations of elements O and N and C bonds are different under different COD:N ratios.•Bound EPS/SMP composition is more important than the quantity in controlling membrane fouling.•The presence of a small quantity of filamentous microorganisms led to improved membrane performance.•A characteristic peak of FTIR at 1735 cm−1 was observed for sludge under N deficiency.
With the usage of gas ferrocene Fe(C 5 H 5 ) 2 as a reactant, which is different from the traditional thin Fe film, to grow the high-quality carbon nanotubes (CNTs) in the high aspect ratio (AR) ...trench structure, it has many advantages to be the through-silicon vias (TSVs) material for the three-dimensional (3-D) stacking technology. In this work, we successfully demonstrate the full process flow, including CNT growing, chemical-mechanical planarization (CMP), and wafer temporary bonding for CNTs as TSVs in the 3-D stacking connection. The flexibility for this demonstrated process flow makes the integration of real high dense devices and CNTs as TSVs for the 3-D connection more easily.
The purpose of this paper is to explore the effects of different failure criteria including Puck, Hashin and Chang–Chang criteria on the dynamic progressive failure properties of carbon fiber ...composite laminates. First, a unified theoretical framework on the intralaminar damage and interlaminar delamination of composites based on the variational form of the initial value problem with an interface discontinuity is presented. Second, a parametric modeling plug-in for impact analysis of laminates is established using ABAQUS–PYTHON scripting language. Third, the intralaminar damage models using three failure criteria are implemented by the explicit finite element subroutine ABAQUS–VUMAT and the delamination is simulated by the bilinear cohesive model in ABAQUS. Finally, numerical analysis is performed on carbon fiber composite specimens with different materials, layups and impact energies to study the impact force–time/displacement curves and the dissipated energy as well as the damage evolution behaviors of the matrix and delamination interface. Results show that the impact responses and energy dissipation using three criteria are basically consistent except some difference in damage features for matrix cracking and delamination. This research provides a fundamental support for appropriate selection and use of different failure criteria in order to achieve high-efficiency and high-fidelity simulation in the impact analysis.
Post-traumatic stress disorder (PTSD) is usually considered a psychiatric disorder upon emotional trauma. However, with the rising number of conflicts and traffic accidents around the world, the ...incidence of PTSD has skyrocketed along with traumatic brain injury (TBI), a complex neuropathological disease due to external physical force and is also the most common concurrent disease of PTSD. Recently, the overlap between PTSD and TBI is increasingly attracting attention, as it has the potential to stimulate the emergence of novel treatments for both conditions. Of note, treatments exploiting the microRNAs (miRNAs), a well-known class of small non-coding RNAs (ncRNAs), have rapidly gained momentum in many nervous system disorders, given the miRNAs' multitudinous and key regulatory role in various biological processes, including neural development and normal functioning of the nervous system. Currently, a wealth of studies has elucidated the similarities of PTSD and TBI in pathophysiology and symptoms; however, there is a dearth of discussion with respect to miRNAs in both PTSD and TBI. In this review, we summarize the recent available studies of miRNAs in PTSD and TBI and discuss and highlight promising miRNAs therapeutics for both conditions in the future.
Background
The expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS ...using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes.
Methods
A total of 28 clinical variables and 39 mucosal cellular and molecular variables were analyzed using principal component analysis. Cluster analysis was performed on 246 prospectively recruited Chinese CRS patients with at least 1‐year postoperative follow‐up. Difficult‐to‐treat CRS was characterized in each generated cluster.
Results
Seven subject clusters were identified. Cluster 1 (13.01%) was comparable to the classic well‐defined eosinophilic CRS with polyps, having severe disease and the highest proportion of difficult‐to‐treat CRS. Patients in cluster 2 (16.26%) and cluster 4 (13.82%) had relatively lower proportions of presence of polyps and presented mild inflammation with moderate proportions of difficult‐to‐treat cases. Subjects in cluster 2 were highly atopic. Cluster 3 (7.31%) and cluster 6 (21.14%) were characterized by severe or moderate neutrophilic inflammation, respectively, and with elevated levels of IL‐8 and high proportions of difficult‐to‐treat CRS. Cluster 5 (4.07%) was a unique group characterized by the highest levels of IL‐10 and lacked difficult‐to‐treat cases. Cluster 7 (24.39%) demonstrated the lowest symptom severity, a low proportion of difficult‐to‐treat CRS, and low inflammation load. Finally, we found that difficult‐to‐treat CRS was associated with distinct clinical features and biomarkers in the different clusters.
Conclusions
Distinct clinicopathobiologic clusters of CRS display differences in clinical response to treatments and characteristics of difficult‐to‐treat CRS.
Two submerged anaerobic membrane bioreactors (SAnMBRs) (thermophilic vs. mesophilic) were operated for a period of 3.5 months with kraft evaporator condensate at a feed chemical oxygen demand of ...10,000
mg/L. The results show that the filtration behavior of the two systems was significantly different. The filtration resistance in the thermophilic SAnMBR was about 5–10 times higher than that of the mesophilic system when operated under similar hydrodynamic conditions. Comparison of sludge properties and cake layer structure from the two systems was made to elucidate major factors governing the different filtration characteristics. There were more soluble microbial products (SMP) and biopolymer clusters (BPC) produced and a larger portion of fine flocs (<15
μm) in the thermophilic SAnMBR. Analysis of bound extracellular polymeric substances (EPS) showed that the thermophilic sludge had a higher protein/polysaccharide ratio in EPS, as compared to that in the mesophilic sludge. A series of analyses, including Fourier transform infrared (FTIR) spectroscopy, energy dispersive X-ray spectroscopy (EDX), confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), atomic force microscopy (AFM) and particle size analyzer showed that the cake layer formed in the thermophilic SAnMBR contained higher levels of both organic and inorganic foulants, smaller particle sizes, and especially, a denser and more compact sludge cake structure. These results indicate that floc size, SMP, BPC, bound EPS as well as cake layer structure are the major factors governing membrane fouling in SAnMBR systems.
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