Summary
Background
In recent years, increasing attention has been focused on the skin hypopigmentation that develops after the initiation of imatinib mesylate therapy in patients with chronic myeloid ...leukaemia (CML).
Aim
To understand the underlying mechanism of this hypopigmentation effect, and to explore the possibility of using imatinib in the treatment of pigmentation disorders.
Methods
We examined the effects of imatinib on the proliferation, apoptosis, melanin content and melanogenic activity of human primary epidermal melanocytes. The responsible molecular events were also investigated in a mechanism study.
Results
We found that imatinib led to a dramatic decrease in total melanin content in cultured melanocytes, by affecting melanocyte number and/or melanogenesis in a dose‐dependent manner. This inhibition of melanogenesis was due to suppressed expression of tyrosinase and microphthalmia‐associated transcription factor (MiTF). Furthermore, stem cell factor (SCF)‐stimulated c‐Kit activation and melanocyte proliferation were completely abrogated by imatinib.
Conclusions
Inactivation of c‐Kit signalling by imatinib has inhibitory effects on melanocyte survival, proliferation and melanogenesis, which explains the clinical hypopigmentation seen in patients with CML. These results also support using imatinib as a clinical depigmentation agent when dosage being carefully determined.
The spatial scales of land‐atmosphere interactions over heterogeneous, realistic soil moisture patterns are critical to improve our understanding of land‐atmosphere interactions. However, these ...scales are poorly quantified. We use high‐resolution numerical experiments to quantify the spatial scales for a selected day during the Holistic Interactions of Shallow Clouds, Aerosols, and Land‐Ecosystems (HI‐SCALE) campaign in Oklahoma. A semi‐idealized approach (removing background winds and surface topography while retaining the real‐world data for other boundary conditions) enables examination of the local influence from the surface. Simulations that apply uniform surface, variable land cover with uniform soil moisture, and variable land cover with variable soil moisture are then compared. Land cover variations, especially water and urban surfaces, create two variance peaks in the surface sensible heat flux in the scales >10 km (meso‐β) and <6 km (meso‐γ). Both peaks are enhanced by the observation‐based soil moisture distribution that has most of its variance in the meso‐β scale. Atmospheric response in the meso‐β scale is hydrostatic with weak vertical motion. The land cover variations induce secondary circulations in the scales of 2.5–6 km. The additional soil moisture variability intensifies extreme circulations over dry soil patches and sharp sensible heat flux gradients, slightly extending the characteristic scales to 2.5–9 km. While their areal coverage is small, soil moisture variations on such “hotspots” lead to substantially larger convective cloud structure and domain‐mean rainfall, calling for a consideration of their non‐linear effect in large‐scale models.
Key Points
Soil moisture and land cover heterogeneities create sensible heat flux variabilities for both large (>10 km) and small (<6 km) scales
Land cover heterogeneities alone can induce secondary circulations in 2.5–6 km scales
Soil moisture heterogeneity strengthens the secondary circulations and extends their scale to 2.5–9 km
Scurs is a horn phenotype that exhibits as small corneous structures on the skull due to the deformed development of horn tissues. Previous genome-wide association analysis of scurs in Soay sheep ...showed a significant association to the polled locus, relaxin-like receptor 2 (RXFP2). However, the molecular mechanism underlying the development of scurs remains largely unknown. In the present study, we performed an iTRAQ-based quantitative proteomic analysis of horn tissues from both scurs and normal two-horned and four-horned individuals among Altay sheep to identify the differentially expressed proteins (DEPs) responsible for the scurs phenotype. In total, 232 proteins showed significant differential expression,and the most significant Gene ontology categories were the adhesion processes (biological adhesion (P=4.07×10–17) and cell adhesion (P=3.7×10–16)), multicellular organismal process (single-multicellular organism process (P=2.06×10–11) and multicellular organismal process (P=2.29×10–11)) and extracellular processes (extracellular matrix organization (P=4.77×10–16) and extracellular structure organization (P=4.93×10–16)). Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that extracellular matrix (ECM)-receptor interactions and focal adhesion pathways were the most significant pathways. This finding is consistent with the reduced formation of extracellular matrix in scurs and the development of deformed horn tissues. Our study helps to elucidate the inheritance pattern of sheep horn traits from the perspectives of downstream expressed proteins.
•Successful coupling of high-order, academic LES code with flexible RANS code.•Hybrid LES/RANS framework with dual meshes and physical consistency.•Coupling of LES and RANS with non-conforming ...computational domains.•Minimally intrusive coupling strategy: attractive for industrial CFD applications.
In a recently proposed dual-mesh hybrid framework (Xiao and Jenny, J. Comput. Phys. 231 (4) (2012)), LES and RANS simulations are conducted simultaneously on the same domain, but on different meshes. In the current work, this framework is further extended to allow for non-conforming computational domains for the LES and the RANS simulations. With this extension we developed a hybrid solver coupling a high-order LES code based on Cartesian meshes with a general-purpose RANS solver based on body-fitting meshes. A relaxation approach is used to enforce the solid boundary conditions in the LES. Plane channel flow at Reτ=590 and flows over periodic hills at two Reynolds numbers (Re=2800 and 10,595) are investigated with the new solver. The adequacy of the boundary representation and forcing strategy is shown. The numerical studies also demonstrate the flexibility of the extended solver and the predictive capability of the new hybrid framework, which consists of two solvers operating on the same physical domain, but with non-conforming computational domains (i.e., a Cartesian mesh based LES solver combined with a body-fitting mesh based RANS solver). The extensions explored in this study are of practical importance for industrial CFD applications as they successfully demonstrate how academic, very accurate, massively parallel LES solvers can be coupled with flexible RANS solvers. Since the coupling strategy is minimally intrusive, it is attractive for industrial purposes. With the current framework, the potential of many existing academic codes for practical flow simulations, where complex geometries and wall resolution requirements represent major hurdles, can be explored.
Characterized by low leakage current and low voltage stress of the power device, a neutral point clamped three-level inverter (NPCTLI) is suitable for a transformerless photovoltaic (PV) ...grid-connected system. Unfortunately, the shoot-through problem of bridge legs still exists in an NPCTLI, so its operation reliability is degraded. An improved three-level grid-connected inverter is proposed based on the NPCTLI and the dual-buck half-bridge inverter (DBHBI), and which avoids the shoot-through problem. The proposed topology guarantees no switching-frequency common-mode voltage and no shoot-through risk. Furthermore, the freewheeling diode of bridge legs of the DBHBI can be removed taking into consideration the unity power factor of grid current, and a straightforward topology is thus derived. The new topology is referred to as split-inductor NPCTLI (SI-NPCTLI). The operation mode, common-mode characteristic, and control strategy are analyzed. Finally, both the simulation and the experimental results of a 1-kW SI-NPCTLI prototype verify the analysis.
Abstract The puparial case is one of the most common ‘stages’ of necrophagous flies encountered in crime investigations of highly decomposed corpses. If methods for determining the weathering time of ...these puparial cases are developed, it is possible that the postmortem interval (PMI) could be estimated accordingly. Gas chromatography coupled with mass spectrometry (GC–MS) was used to determine the changes with the weathering time in cuticular hydrocarbons of the puparial cases of Chrysomya megacephala in the laboratory. The results have shown that cuticular hydrocarbons of the puparial cases were a mixture of n -alkanes, methyl-branched alkanes, and dimethyl-branched alkanes. The carbon chain length ranged from C21 to C35, and the hydrocarbon composition showed significant regular changes with the weathering time. For the even numbered n -alkanes with low molecular weight, namely n -C22, n -C24 and n -C26, the abundance increased significantly with the weathering time. For n -C26, in particular, a linear increase in abundance with the weathering time was observed. In addition, for most of the other low molecular weight hydrocarbons ( n -C26 or below), the abundance decreased significantly with the weathering time. It is concluded that, cuticular hydrocarbon is a potential indicator of the weathering time in C. megacephala , and possibly in other necrophagous flies, and might further be used to determine the PMI.
Oil monitoring is referred to as wear particle debris analysis and physical analysis of lubricants' properties. Information technology, such as database technology, image processing, expert system, ...data fusion and multi-agent system theories, etc. makes oil-monitoring procedures more intelligent. This paper introduces the development of some information systems such as management database, computer-aided wear particle analysis software used in oil monitoring. The basic principles and models of information technologies used in this field are presented. The development of IT as an integral element of an oil analysis-based condition monitoring system has been carried out in the authors' laboratory since 1986. Initially, the principal application of IT was to improve the data management and processing procedures. The second use of IT was in the development of a wear particle image processing system. The third aspect of utilizing IT is artificial intelligence. Finally, the application of IT-based network techniques is implemented. The progress in the application of IT in the authors' laboratory shows that the combination of information technology and oil monitoring can increase the speed of oil analysis, manage the information conveniently and obtain analysis conclusion more precisely in relation to practical application.
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•Rat toxicity varies around a constant for homologues or classified compounds.•Baseline toxicants share same modes of toxic action between rats and fish.•Difference in exposure routes ...results in the difference of toxicity to rats and fish.•Threshold of excess toxicity is too high in the toxic classification for fish.•Classification of excess toxicity should be based on critical lethal concentration.
The aim of this paper was to investigate baseline toxicity to rats and effect of exposure routes on toxicity in rats and fish. In this paper, 1588 industrial chemicals were selected to investigate baseline toxicity to rats. The results showed that rat toxicity varies around a constant for classified compounds or homologues. The toxic contributions of substituted functional groups have been calculated and alkanes were used as baseline toxicity. The toxic contributions, equal to toxic ratios (TR), show that small changes in chemical structure can result in different toxic effect in rat toxicity. However, this situation has not been observed in fish toxicity because the threshold of excess toxicity (e.g. log TR=1) was too high to distinguish differences in toxicity. Very close critical body residues (CBRs) calculated from percentage of absorption and bioconcentration factors indicate that most of aliphatic chemicals may share the same modes of toxic action between rat and fish species. The high estimation error of bioconcentration factor calculated from computer programs for some compounds suggests that classification of excess toxicity should be based on the CBRs, rather than the TR because the TR is closely related to the exposure routes.
Purpose
This study aims to study the effect of micro-groove texture geometric parameters on the lubrication characteristics of the tripod universal coupling.
Design/methodology/approach
The ...Navier–Stokes equation was used to analyse the influence of micro-groove geometric parameters on the coupling’s lubrication performance. Further, Kriging approximate model and neighborhood cultivation genetic algorithm (NCGA) were used to optimise the micro-groove geometric parameters and improve the coupling’s lubrication performance.
Findings
The results show that as the micro-groove depth and width increase, respectively, the oil film-bearing capacity first increases and then decreases; on the contrary, the friction coefficient first decreases and then increases. With the increase of the micro-groove inclination angle, the bearing capacity of the oil film first increases and then remains unchanged. At the same time, the friction coefficient first decreases and then increases slightly. The lubricating performance of the optimised coupling is significantly improved: the optimised oil film-bearing capacity increases by 12.5%, the friction coefficient reduces by 14% and the maximum oil film pressure increases by 4.3%.
Originality/value
At present, the grease lubrication performance of the micro-groove textured tripod universal coupling has not been studied. The micro-groove parameters are optimised, and the coupling’s lubrication performance is improved greatly by the Kriging model and NCGA algorithm. It is of great significance to extend the coupling’s fatigue life.
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