In this paper, based on LS-Dyna code, a new finite element (FE) simulation of the ballistic perforation of the ceramic/composite targets, which impacted by cylindrical tungsten projectiles, has been ...presented. Research on this method has been conducted by a few research groups in recent years. The ceramic material, which is the front plate, has been made of Alumina 99.5% and composite back-up plate composed of Twaron fibers. The 2-dimensional (2D), axi-symmetric, dynamic-explicit, Lagrangian model has been considered in this simulation. The Johnson–Cook, Johnson–Holmquist and Composite-Damage materials behaviors have been used for projectile, ceramic and composite materials respectively. The brittle fracture and fragmentation of ceramic conoid, the failure criteria based on fracture of fibers or matrixes of composite materials and erosion or flattening of projectile during perforation have been considered. The residual velocity and perforation time has been obtained and compared with the available analytical models. The results show that when the ceramic is impacted by a projectile, a fragmented ceramic conoid breaks from ceramic tile and the semi-angle of ceramic conoid with increasing initial velocity decreases. Furthermore, the dishing of composite layers at high impact velocities and the delamination of layers near the ballistic limit velocity decrease.
In this paper we further develop a model for the heating of coronal loops by Alfvén wave turbulence (AWT). The Alfvén waves are assumed to be launched from a collection of kilogauss flux tubes in the ...photosphere at the two ends of the loop. Using a three-dimensional magnetohydrodynamic model for an active-region loop, we investigate how the waves from neighboring flux tubes interact in the chromosphere and corona. For a particular combination of model parameters we find that AWT can produce enough heat to maintain a peak temperature of about 2.5 MK, somewhat lower than the temperatures of 3-4 MK observed in the cores of active regions. The heating rates vary strongly in space and time, but the simulated heating events have durations less than 1 minute and are unlikely to reproduce the observed broad differential emission measure distributions of active regions. The simulated spectral line nonthermal widths are predicted to be about 27 km s−1, which is high compared to the observed values. Therefore, the present AWT model does not satisfy the observational constraints. An alternative "magnetic braiding" model is considered in which the coronal field lines are subject to slow random footpoint motions, but we find that such long-period motions produce much less heating than the shorter-period waves launched within the flux tubes. We discuss several possibilities for resolving the problem of producing sufficiently hot loops in active regions.
ABSTRACT Alfvén waves are believed to play an important role in the heating and acceleration of the fast solar wind emanating from coronal holes. Nonlinear interactions between the dominant waves and ...minority waves have the potential to transfer wave energy either to smaller perpendicular scales ("direct cascade") or to larger scales ("inverse cascade"). In this paper we use reduced magnetohydrodynamic (RMHD) simulations to investigate how the cascade rates depend on perpendicular wavenumber and radial distance from the Sun center. For models with a smooth background atmosphere, we find that an inverse cascade ( ) occurs for the dominant waves at radii between 1.4 and and dimensionless wavenumbers in the inertial range ( ), and a direct cascade ( ) occurs elsewhere. For a model with density fluctuations, there are multiple regions with an inverse cascade. In both cases, the cascade rate varies significantly with perpendicular wavenumber, indicating that the cacsade is a highly nonlocal process. As a result of the inverse cascades, the energy dissipation rates are much lower than expected from a phenomenological model and are insufficient to maintain the temperature of the background atmosphere. We conclude that RMHD models are unable to reproduce the observed properties of the fast solar wind.
Cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) are keratinocyte carcinomas, the most frequently diagnosed cancers in fair-skinned populations. Ultraviolet radiation (UVR) is ...the main driving carcinogen for these tumors, but immunosuppression, pigmentary factors, and aging are also risk factors. Scientific discoveries have improved the understanding of the role of human papillomaviruses (HPV) in cSCC as well as the skin microbiome and a compromised immune system in the development of both cSCC and BCC. Genomic analyses have uncovered genetic risk variants, high-risk susceptibility genes, and somatic events that underlie common pathways important in keratinocyte carcinoma tumorigenesis and tumor characteristics that have enabled development of prediction models for early identification of high-risk individuals. Advances in chemoprevention in high-risk individuals and progress in targeted and immune-based treatment approaches have the potential to decrease the morbidity and mortality associated with these tumors. As the incidence and prevalence of keratinocyte carcinoma continue to increase, strategies for prevention, including effective sun-protective behavior, educational interventions, and reduction of tanning bed access and usage, are essential. Gaps in our knowledge requiring additional research to reduce the high morbidity and costs associated with keratinocyte carcinoma include better understanding of factors leading to more aggressive tumors, the roles of microbiome and HPV infection, prediction of response to therapies including immune checkpoint blockade, and how to tailor both prevention and treatment to individual risk factors and needs.
We present a combined tomographic weak gravitational lensing analysis of the Kilo Degree Survey (KV450) and the Dark Energy Survey (DES-Y1). We homogenize the analysis of these two public cosmic ...shear datasets by adopting consistent priors and modeling of nonlinear scales, and determine new redshift distributions for DES-Y1 based on deep public spectroscopic surveys. Adopting these revised redshifts results in a 0.8
σ
reduction in the DES-inferred value for
S
8
, which decreases to a 0.5
σ
reduction when including a systematic redshift calibration error model from mock DES data based on the MICE2 simulation. The combined KV450+DES-Y1 constraint on
S
8
= 0.762
−0.024
+0.025
is in tension with the
Planck
2018 constraint from the cosmic microwave background at the level of 2.5
σ
. This result highlights the importance of developing methods to provide accurate redshift calibration for current and future weak-lensing surveys.
We present a tomographic cosmic shear analysis of the Kilo-Degree Survey (KiDS) combined with the VISTA Kilo-Degree Infrared Galaxy Survey. This is the first time that a full optical to near-infrared ...data set has been used for a wide-field cosmological weak lensing experiment. This unprecedented data, spanning 450 deg
2
, allows us to significantly improve the estimation of photometric redshifts, such that we are able to include robustly higher-redshift sources for the lensing measurement, and – most importantly – to solidify our knowledge of the redshift distributions of the sources. Based on a flat ΛCDM model we find
S
8
≡ σ
8
Ω
m
/0.3 = 0.737
+0.040
−0.036
in a blind analysis from cosmic shear alone. The tension between KiDS cosmic shear and the Planck-Legacy CMB measurements remains in this systematically more robust analysis, with
S
8
differing by 2.3
σ
. This result is insensitive to changes in the priors on nuisance parameters for intrinsic alignment, baryon feedback, and neutrino mass. KiDS shear measurements are calibrated with a new, more realistic set of image simulations and no significant B-modes are detected in the survey, indicating that systematic errors are under control. When calibrating our redshift distributions by assuming the 30-band COSMOS-2015 photometric redshifts are correct (following the Dark Energy Survey and the Hyper Suprime-Cam Survey), we find the tension with
Planck
is alleviated. The robust determination of source redshift distributions remains one of the most challenging aspects for future cosmic shear surveys.
Targeted Genomic Profiling of Acral Melanoma Yeh, Iwei; Jorgenson, Eric; Shen, Ling ...
JNCI : Journal of the National Cancer Institute,
10/2019, Letnik:
111, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Abstract
Background
Acral melanoma is a rare type of melanoma that affects world populations irrespective of skin color and has worse survival than other cutaneous melanomas. It has relatively few ...single nucleotide mutations without the UV signature of cutaneous melanomas, but instead has a genetic landscape characterized by structural rearrangements and amplifications. BRAF mutations are less common than in other cutaneous melanomas, and knowledge about alternative therapeutic targets is incomplete.
Methods
To identify alternative therapeutic targets, we performed targeted deep-sequencing on 122 acral melanomas. We confirmed the loss of the tumor suppressors p16 and NF1 by immunohistochemistry in select cases.
Results
In addition to BRAF (21.3%), NRAS (27.9%), and KIT (11.5%) mutations, we identified a broad array of MAPK pathway activating alterations, including fusions of BRAF (2.5%), NTRK3 (2.5%), ALK (0.8%), and PRKCA (0.8%), which can be targeted by available inhibitors. Inactivation of NF1 occurred in 18 cases (14.8%). Inactivation of the NF1 cooperating factor SPRED1 occurred in eight cases (6.6%) as an alternative mechanism of disrupting the negative regulation of RAS. Amplifications recurrently affected narrow loci containing PAK1 and GAB2 (n = 27, 22.1%), CDK4 (n = 27, 22.1%), CCND1 (n = 24, 19.7%), EP300 (n = 20, 16.4%), YAP1 (n = 15, 12.3%), MDM2 (n = 13, 10.7%), and TERT (n = 13, 10.7%) providing additional and possibly complementary therapeutic targets. Acral melanomas with BRAFV600E mutations harbored fewer genomic amplifications and were more common in patients with European ancestry.
Conclusion
Our findings support a new, molecularly based subclassification of acral melanoma with potential therapeutic implications: BRAFV600E mutant acral melanomas with characteristics similar to nonacral melanomas that could benefit from BRAF inhibitor therapy, and non-BRAFV600E mutant acral melanomas. Acral melanomas without BRAFV600E mutations harbor a broad array of therapeutically relevant alterations. Expanded molecular profiling would increase the detection of potentially targetable alterations for this subtype of acral melanoma.
A three-dimensional magnetohydrodynamic (MHD) model for the propagation and dissipation of Alfven waves in a coronal loop is developed. The model includes the lower atmospheres at the two ends of the ...loop. The waves originate on small spatial scales (less than 100 km) inside the kilogauss flux elements in the photosphere. The model describes the nonlinear interactions between Alfven waves using the reduced MHD approximation. The increase of Alfven speed with height in the chromosphere and transition region (TR) causes strong wave reflection, which leads to counter-propagating waves and turbulence in the photospheric and chromospheric parts of the flux tube. Part of the wave energy is transmitted through the TR and produces turbulence in the corona. We find that the hot coronal loops typically found in active regions can be explained in terms of Alfven wave turbulence, provided that the small-scale footpoint motions have velocities of 1-2 km s--1 and timescales of 60-200 s. The heating rate per unit volume in the chromosphere is two to three orders of magnitude larger than that in the corona. We construct a series of models with different values of the model parameters, and find that the coronal heating rate increases with coronal field strength and decreases with loop length. We conclude that coronal loops and the underlying chromosphere may both be heated by Alfvenic turbulence.
Summary
Background
Acral lentiginous melanoma (ALM) is a rare melanoma subtype that disproportionately afflicts people of colour. ALMs have a worse prognosis than other melanoma subtypes; this has ...been attributed to aggressive biological behaviour, more advanced stage at presentation and possible disparities in access to health care.
Objectives
To examine, using comprehensive patient data and long‐term follow‐up information in a well‐characterized cohort, how patient, tumour and clinical management variables impact overall and melanoma‐specific survival.
Methods
We characterized a consecutive cohort of 123 ALMs diagnosed from 1987 to 2013 and analysed predictors of overall and melanoma‐specific survival for their association with survival.
Results
Univariate hazard ratios and 95% confidence intervals using Cox regression models showed that increased Breslow depth, presence of ulceration, receipt of radiation, chemo‐ and vaccine therapy were associated with worse melanoma‐specific survival. Notably, nonwhite race/ethnicity was not associated with worse overall or melanoma‐specific survival. Multivariate modelling adjusting for patient, tumour and management variables revealed Breslow depth > 2 mm and disease extent as significantly associated with poor melanoma‐specific survival.
Conclusions
Melanoma‐specific mortality among patients with ALM is associated with increased tumour thickness and more advanced stage at presentation, but not with race/ethnicity. Advanced tumour features at presentation and access to care may account for less favourable survival outcomes reported among nonwhite patients.
What's already known about this topic?
Acral lentiginous melanoma (ALM) is a rare histological variant of cutaneous melanoma (CM), arising on the palms, soles and nail beds.
ALM accounts for a greater proportion of CMs among Hispanics, Asians and African Americans.
ALMs have a distinct epidemiology and, unlike other CM subtypes, are not associated with personal history of atypical naevi, or sun exposure.
Additionally, ALMs have a worse prognosis compared with other CMs.
What does this study add?
Comprehensive evaluation of clinical variables that impact outcomes, including melanoma‐specific survival, in a community‐based study setting with equal access to care, has been undertaken.
Melanoma‐specific mortality among patients with ALM is associated with increased tumour thickness and more advanced stage at presentation, but not with race/ethnicity.
Advanced tumour features at presentation and access to care may account for less favourable survival outcomes reported among nonwhite patients.
Respond to this article
Linked Comment: Berk‐Krauss and Stein. Br J Dermatol 2017; 177:341–342
Plain language summary available online
Summary
Background
Genome‐wide association studies (GWAS) have identified thousands of susceptibility variants, although most have been associated with small individual risk estimates that offer ...little predictive value. However, combining multiple variants into polygenic risk scores (PRS) may be more informative. Multiple studies have developed PRS composed of GWAS‐identified variants for cutaneous cancers. This review highlights data from these studies.
Objectives
To review published GWAS and PRS studies for melanoma, cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), and discuss their potential clinical utility.
Methods
We searched PubMed and the National Human Genome Research Institute–European Bioinformatics Institute GWAS catalogue to identify relevant studies.
Results
Results from 21 GWAS (11 melanoma, 3 cSCC, 7 BCC) and 11 PRS studies are summarized. Six loci in pigmentation genes overlap between these three cancers (ASIP/RALY, IRF4, MC1R, OCA2, SLC45A2 and TYR). Additional loci overlap for cSCC/BCC and BCC/melanoma, but no other loci are shared between cSCC and melanoma. PRS for melanoma show roughly two‐to‐threefold increases in risk and modest improvements in risk prediction (2–7% increases). PRS are associated with twofold and threefold increases in risk of cSCC and BCC, respectively, with small improvements (2% increase) in predictive ability.
Conclusions
Existing data indicate that PRS may offer small, but potentially meaningful, improvements to risk prediction. Additional research is needed to clarify the potential utility of PRS in cutaneous carcinomas. Clinical translation will require well‐powered validation studies incorporating known risk factors to evaluate PRS as tools for screening.
What's already known about this topic?
Over 50 susceptibility loci for melanoma, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) have been identified in genome‐wide association studies (GWAS).
Polygenic risk scores (PRS) using variants identified from GWAS have also been developed for melanoma, BCC and cSCC, and investigated with respect to clinical risk prediction.
What does this study add?
This review provides an overview of GWAS findings and the potential clinical utility of PRS for melanoma, BCC and cSCC.
Linked Comment: Soura and Stratigos. Br J Dermatol 2019; 181:1117–1118.
Plain language summary available online
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