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
The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of the mammalian brain, is photoentrained by light signals from the eyes through the retinohypothalamic tract. Retinal rod and ...cone cells are not required for photoentrainment. Recent evidence suggests that the entraining photoreceptors are retinal ganglion cells (RGCs) that project to the SCN. The visual pigment for this photoreceptor may be melanopsin, an opsin-like protein whose coding messenger RNA is found in a subset of mammalian RGCs. By cloning rat melanopsin and generating specific antibodies, we show that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of a subset of rat RGCs. In mice heterozygous for tau-lacZ targeted to the melanopsin gene locus, β-galactosidase-positive RGC axons projected to the SCN and other brain nuclei involved in circadian photoentrainment or the pupillary light reflex. Rat RGCs that exhibited intrinsic photosensitivity invariably expressed melanopsin. Hence, melanopsin is most likely the visual pigment of phototransducing RGCs that set the circadian clock and initiate other non-image-forming visual functions.
FeFETs with 5-nm-thick Hf 0.5 Zr 0.5 O 2 (HZO) have been demonstrated in memory operations for the ON/OFF current ratio >10 4 at zero gate voltage and a memory window (MW) of 0.6-0.7 V. A gradual ...transition of the ferroelectricity with an increasing crystallization temperature for the gate-last process was presented. The excellent data retention are the <inline-formula> <tex-math notation="LaTeX">{\sim }\textsf {2}\times \textsf {10}^{\textsf {4}} </tex-math></inline-formula> ON/OFF ratio and 0.67 V extrapolated to ten years with V P/E = ±4.8 V. The MW remains >0.2 V after 10 6 cycles for read and vanishes with cycles of 10 3 −10 4 for write, which is the bottleneck for ferroelectric (FE)-type memories. The mechanism of retention and endurance is discussed. The characteristic of this letter is an unaffected coercive-field (~1 MV/cm) with scaling FE-HZO down to 5-nm thickness, which is beneficial for reducing the operation voltage. A comparable performance with thick HZO (>5 nm) on high data retention and endurance with low voltage for read is achieved. The ultrathin FE layer proposes a realistic emerging memory for 1T architecture.
The defining problem in frustrated quantum magnetism, the ground state of the nearest-neighbor S=1/2 antiferromagnetic Heisenberg model on the kagome lattice, has defied all theoretical and numerical ...methods employed to date. We apply the formalism of tensor-network states, specifically the method of projected entangled simplex states, which combines infinite system size with a correct accounting for multipartite entanglement. By studying the ground-state energy, the finite magnetic order appearing at finite tensor bond dimensions, and the effects of a next-nearest-neighbor coupling, we demonstrate that the ground state is a gapless spin liquid. We discuss the comparison with other numerical studies and the physical interpretation of this result.
Summary
Ectomycorrhizal (EM) fungi form symbiotic associations with plant roots that regulate nutrient exchange between forest plants and soil. Environmental metagenomics approaches that employ ...next‐generation sequencing show great promise for studying EM symbioses; however, metatranscriptomic studies have been constrained by the inherent difficulties associated with isolation and sequencing of RNA from mycorrhizae. Here we apply an optimized method for combined DNA/RNA extraction using field‐collected EM fungal–pine root clusters, together with protocols for taxonomic identification of expressed ribosomal RNA, and inference of EM function based on plant and fungal metatranscriptomics. We used transcribed portions of ribosomal RNA genes to identify several transcriptionally dominant fungal taxa associated with loblolly pine including Amphinema, Russula and Piloderma spp. One taxon, Piloderma croceum, has a publically available genome that allowed us to identify patterns of gene content and transcript abundance. Over 1500 abundantly expressed Piloderma genes were detected from mycorrhizal roots, including genes for protein metabolism, cell signalling, electron transport, terpene synthesis and other extracellular activities. In contrast, Piloderma gene encoding an ammonia transporter showed highest transcript abundance in soil samples. Our methodology highlights the potential of metatranscriptomics to identify genes associated with symbiosis and ecosystem function using field‐collected samples.
This paper reports the current potentials of cold gas dynamic spraying (CGDS). CGDS has been significantly developed to produce several functional solutions categorized as follows: deposits with a ...single powder nature, composites-based deposits, nanotechnological deposits and hybrid coating/substrate assemblies. CGDS process has improved in proficiency and is still gaining attention from scientists and industry. Covering a wide range of materials, both standard and advanced, this additive manufacturing process offers substantial applications for surface functionalization, structural or dimensional restoration, bulk production providing specific material properties, and art/decoration. Progress in terms of material processing capabilities and applications are ongoing. CGDS brings opportunities of better materials and innovative solutions. This review also indicates some recent challenges of cold spraying. Those represent future research directions to increase the enactment of CGDS as a proven viable innovative additive manufacturing method.
Display omitted
•CGDS has been significantly developed to produce several functional solutions.•CGDS offers substantial applications for surface functionalization, restoration, bulk production, and art/decoration.•CGDS enables producing various deposits possibilities and hybrid coating/substrate assemblies.•Current challenges of cold gas dynamic spraying are reported.
We apply a global three-dimensional Goddard Earth Observing System (GEOS) chemical transport model (GEOS-Chem) driven by the NASA/GEOS-4 assimilated meteorological fields to quantify the impacts of ...the East Asian summer monsoon (EASM) on interannual variations of June-July-August (JJA) surface-layer O3 concentrations over China. With anthropogenic emissions fixed at year 2005 levels, the model simulation for years 1986–2006 shows that the changes in meteorological parameters alone lead to interannual variations in JJA surface-layer O3 concentrations by 2–5% over central eastern China, 1–3% in northwestern China, and 5–10% over the Tibetan Plateau as well as the border and coastal areas of southern China, as the interannual variations are relative to the average O3 concentrations over the 21 yr period. Over the years 1986–2006, the O3 concentration averaged over all of China is found to correlate positively with the EASM index with a large correlation coefficient of +0.75, indicating that JJA O3 concentrations are lower (or higher) in weaker (or stronger) EASM years. Relative to JJA surface-layer O3 concentrations in the strongest EASM years (1990, 1994, 1997, 2002, and 2006), O3 levels in the weakest EASM years (1988, 1989, 1996, 1998, and 2003) are lower over almost all of China with a national mean lower O3 concentration by 2.0 ppbv (parts per billion by volume; or 4%). Regionally, the largest percentage differences in O3 concentration between the weakest and strongest EASM years are found to exceed 6% in northeastern China, southwestern China, and over the Tibetan Plateau. Sensitivity studies show that the difference in transboundary transport of O3 is the most dominant factor that leads to lower-O3 concentrations in the weakest EASM years than in the strongest EASM years, which, together with the enhanced vertical convections in the weakest EASM years, explain about 80% of the differences in surface-layer O3 concentrations between the weakest and strongest EASM years. We also find that the impacts the EASM strength on JJA surface-layer O3 can be particularly strong (comparable in magnitude to the impacts on O3 by changes in anthropogenic emissions over years 1986–2006) for certain years. The largest increases in O3 by anthropogenic emissions are simulated over southeastern China, whereas the largest impacts of the EASM on O3 are found over central and western China.
We used the nested grid version of the global three-dimensional Goddard Earth Observing System chemical transport model (GEOS-Chem) to examine the interannual variations (IAVs) of aerosols over ...heavily polluted regions in China for years 2004–2012. The role of variations in meteorological parameters was quantified by a simulation with fixed anthropogenic emissions at year 2006 levels and changes in meteorological parameters over 2004–2012. Simulated PM2.5 (particles with a diameter of 2.5 μm or less) aerosol concentrations exhibited large IAVs in North China (NC; 32–42° N, 110–120° E), with regionally averaged absolute percent departure from the mean (APDM) values of 17, 14, 14, and 11% in December-January-February (DJF), March-April-May (MAM), June-July-August (JJA), and September-October-November (SON), respectively. Over South China (SC; 22–32° N, 110–120° E), the IAVs in PM2.5 were found to be the largest in JJA, with the regional mean APDM values of 14% in JJA and of about 9% in other seasons. The concentrations of PM2.5 over the Sichuan Basin (SCB; 27–33° N, 102–110° E) were simulated to have the smallest IAVs among the polluted regions examined in this work, with APDM values of 8–9% in all seasons. All aerosol species (sulfate, nitrate, ammonium, black carbon, and organic carbon) were simulated to have the largest IAVs over NC in DJF, corresponding to the large variations in meteorological parameters over NC in this season. Process analyses were performed to identify the key meteorological parameters that determined the IAVs of different aerosol species in different regions. While the variations in temperature and specific humidity, which influenced the gas-phase formation of sulfate, jointly determined the IAVs of sulfate over NC in both DJF and JJA, wind (or convergence of wind) in DJF and precipitation in JJA were the dominant meteorological factors to influence IAVs of sulfate over SC and the SCB. The IAVs in temperature and specific humidity influenced gas-to-aerosol partitioning, which were the major factors that led to the IAVs of nitrate aerosol in China. The IAVs in wind and precipitation were found to drive the IAVs of organic carbon aerosol. We also compared the IAVs of aerosols simulated with variations in meteorological parameters alone with those simulated with variations in anthropogenic emissions alone; the variations in meteorological fields were found to dominate the IAVs of aerosols in northern and southern China over 2004–2012. Considering that the IAVs in meteorological fields are mainly associated with natural variability in the climate system, the IAVs in aerosol concentrations driven by meteorological parameters have important implications for the effectiveness of short-term air quality control strategies in China.
The aim of this study is to promote significant bond strength with laser surface texturing tools for different coating deposited by spray processes. Pulsed nanosecond laser has been used to improve ...the ultimate adhesion strength of thermal spray coating designed for specific applications, and the full potential of this technology must be further explored. This technology proposes several benefits such as free of grit-particle inclusions, limited affected zone and the interface contact quality. The most important improvement is the coating anchoring in the substrate by laser patterned surface. Adhesion bond strength has been improved and evaluated with the contact area. Fracture mechanic analysis has been studied and it showed that the pattern morphology has an impact on crack propagation. A mixed-mode failure has been defined and chosen to explain adhesion strength improvements for the different applications. Laser surface texturing was performed on light metal alloys substrates before cold spraying of light metal alloys powder, wire-arc metallization and atmospheric plasma spraying of thermal barrier coating without bond coat. This study has highlighted laser potential to enhance adhesion bond strength in the dry deposition field.
•Our study covers surface laser texturing to enhance coating adhesion strength•This paper focuses on anchoring mechanisms induced by prior surface treatments•Adhesion strength and deposition efficiency were increased for different thermal spray processes with laser surface texturing•A short pulsed laser is used with a low power (20W), a high frequency (varying between 10 and 100kHz) and an adapted wavelength (λ=1064μm)•Bonding mechanisms and failures mode are described for conventional and laser treated samples