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
LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. ...Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4 × 10−48 cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5 σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3 × 10−43 cm2 (7.1 × 10−42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020.
The optical design and performance of the recently opened 13A biological small‐angle X‐ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation ...Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high‐flux X‐rays in the energy range 4.0–23.0 keV. MoB4C double‐multilayer and Si(111) double‐crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high‐flux beam of ∼4 × 1014 photons s−1 to a high‐energy‐resolution beam of ΔE/E ≃ 1.5 × 10−4; both modes share a constant beam exit. With a set of Kirkpatrick–Baez (KB) mirrors, the X‐ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four‐bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra‐SAXS with a minimum scattering vector q down to 0.0004 Å−1, which allows resolving ordered d‐spacing up to 1 µm. A microbeam, of 10–50 µm beam size, is tailored by a combined set of high‐heat‐load slits followed by micrometre‐precision slits situated at the front‐end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in‐vacuum X‐ray pixel detectors is installed to perform synchronized small‐ and wide‐angle X‐ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra‐SAXS in one beamline.
The optical design and performance of the BioSAXS beamline at the Taiwan Photon Source are reported
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.
Atomic layer deposition (ALD)-based TiN electrode on ferroelectric HfZrO 2 metal/ferroelectric/metal (MFM) capacitor and ferroelectric field-effect transistor (FeFET) is demonstrated experimentally ...with weight transfer, that is, <inline-formula> <tex-math notation="LaTeX">\Delta {P} </tex-math></inline-formula>, per pulse analysis through consecutive alternating potentiation/depression (Pot./Dep.) training pulses. The weight training pulse schemes are studied to have symmetric and linear synapse weight transfer to increase the accuracy and accelerate the deep neural network (DNN) training. With ALD TiN inserted, <inline-formula> <tex-math notation="LaTeX">\alpha _{p} / \alpha _{d} = -0.63 </tex-math></inline-formula> / −0.84, asymmetry <inline-formula> <tex-math notation="LaTeX">\vert \alpha _{p} - \alpha _{d}\vert =0.21 </tex-math></inline-formula>, and polarization modulation ratio (Pot./Dep.) = 97%/98% are achieved for MFM capacitor, and <inline-formula> <tex-math notation="LaTeX">\alpha _{p} / \alpha _{d} = -1.32 </tex-math></inline-formula> / −1.88, asymmetry <inline-formula> <tex-math notation="LaTeX">\vert \alpha _{p} - \alpha _{d}\vert =0.56 </tex-math></inline-formula>, and <inline-formula> <tex-math notation="LaTeX">G_{\text {max}} / G_{\text {min}} > 10\times </tex-math></inline-formula> are delivered for FeFET.
The 3D vertical ferroelectric tunneling junction (FTJ) of bilayer antiferroelectric (AFE) Hf 1-x Zr x O 2 (HZO) and Al 2 O 3 has been demonstrated for NAND-compatible feasibility. A bilayer-type FTJ ...is explored for the designs of the dielectric interlayer Al 2 O 3 0 nm to 4 nm and the ferroelectric type, while the current mechanism is revealed. The multilevel AFE-FTJ is exhibited for both the Program and Erase operations and realizes a synaptic device. High-density emerging memory and computing-in-memory (CiM) are in high demanded for the future era and can be feasible by the proposed vertical FTJ.
Primary intraosseous carcinoma (PIOC) is a rare but aggressive type of odontogenic tumour arising within the jawbone. Diagnosis criteria and treatment strategy remain difficult and controversial. The ...present study aimed to clarify the clinicopathological features and determine prognostic factors in management of PIOC. A retrospective study of 30 patients with PIOC, treated at the Hospital of Stomatology of Sun Yat-sen University between 2009 and 2017, was conducted. Clinical, histopathological and treatment modality data were collected. Follow-up data were recorded to determine prognostic factors. There were 19 males and 11 females with a mean age of 52.3 years. The most common location of the tumour was the mandible (90%). Having a history of tooth extraction or tooth mobility was the major characteristic symptom (63.3%), jaw swelling coming in second (53.3%). Half of the patients underwent surgery alone. The estimated 2-year overall survival rate (OS) and recurrence-free survival rate (RFS) were 61.3% and 40.1%, respectively. Higher histological grade was an independent risk factor for poor OS (hazard ratio (HR) 0.233 0.059–0.915, P=0.037), while at pN+ stage for RFS, HR=5.627 1.199–26.409, P=0.029. Because of its rarity and intrabony site, the classification, staging and treatment guidelines for PIOC should be further studied and established.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death, reflecting the need for better understanding the oncogenesis, and developing new diagnostic and therapeutic targets for the ...malignancy. Emerging evidence suggests that small nucleolar RNAs (snoRNAs) have malfunctioning roles in tumorigenesis. Our recent study demonstrated that small nucleolar RNA 42 (SNORA42) was overexpressed in lung tumors. Here, we investigate the role of SNORA42 in tumorigenesis of NSCLC. We simultaneously assess genomic dosages and expression levels of SNORA42 and its host gene, KIAA0907, in 10 NSCLC cell lines and a human bronchial epithelial cell line. We then determine in vitro functional significance of SNORA42 in lung cancer cell lines through gain- and loss-of-function analyses. We also inoculate cancer cells with SNORA42-siRNA into mice through either tail vein or subcutaneous injection. We finally evaluate expression level of SNORA42 on frozen surgically resected lung tumor tissues of 64 patients with stage I NSCLC by using quantitative reverse transcriptase PCR assay. Genomic amplification and associated high expression of SNORA42 rather than KIAA0907 are frequently observed in lung cancer cells, suggesting that SNORA42 overexpression is activated by its genomic amplification. SNORA42 knockdown in NSCLC cells inhibits in vitro and in vivo tumorigenicity, whereas enforced SNORA42 expression in bronchial epitheliums increases cell growth and colony formation. Such pleiotropy of SNORA42 suppression could be achieved at least partially through increased apoptosis of NSCLC cells in a p53-dependent manner. SNORA42 expression in lung tumor tissue specimens is inversely correlated with survival of NSCLC patients. Therefore, SNORA42 activation could have an oncogenic role in lung tumorigenesis and provide potential diagnostic and therapeutic targets for the malignancy.
The ferroelectric HfZrO2 (HZO) is focused on coercive voltage for onset of negative capacitance (NC) with sub-2.3kbT/q subthreshold swing (SS). The Fe-FETs with ultra-thin HZO (<10 nm) is ...experimentally obtained gradual transition on SS and VT shift on annealing temperatures and sweep ranges. The polarization hysteresis of metal/ferroelectric/metal (MFM) is employed to match FET load line and balances the charge from positive capacitance (PC) to NC with increasing applied bias. The adjustment for charge of FET load line to reduce NC onset voltage is discussed. The feasible concept of coupling the ferroelectric Hf-based oxide is practicable to following current CMOS architectures.
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•FE-HZO is focused on coercive voltage for onset of NC with sub-2.3kbT/q SS.•The intersection of FET load line and the spread hysteresis loop with ferroelectric voltage drop for the charge balance is employed to determine PC to NC.•The adjustment for charge of FET load line to reduce NC onset voltage is discussed as a feasible choice.
We report on broadly based systematic investigations of the modeling components for open heavy-flavor diffusion and energy loss in strongly interacting matter in their application to heavy-flavor ...observables in high-energy heavy–ion collisions, conducted within an EMMI Rapid Reaction Task Force framework. Initial spectra including cold-nuclear-matter effects, a wide variety of space-time evolution models, heavy-flavor transport coefficients, and hadronization mechanisms are scrutinized in an effort to quantify pertinent uncertainties in the calculations of nuclear modification factors and elliptic flow of open heavy-flavor particles in nuclear collisions. We develop procedures for error assessments and criteria for common model components to improve quantitative estimates for the (low-momentum) heavy-flavor diffusion coefficient as a long-wavelength characteristic of QCD matter as a function of temperature, and for energy loss coefficients of high-momentum heavy-flavor particles.
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