Fibroblasts co-expressing tyrosinase and the b-protein synthesise both eumelanin and phaeomelanin

AbstractMelanin synthesis in the mouse involves the interaction of many pigmentation loci. Tyrosinase, the product of the albino (c) locus, catalyses the first step of the pathway. The brown (b) locus protein has significant homology to tyrosinase and controls black/brown coat coloration, but its function is controversial. To investigate the function of the b-protein and its interaction with tyrosinase, we established cell lines expressing both tyrosinase and the b-protein by transfecting tyrosinase-expressing fibroblasts with a b-protein expression vector. The tyrosinase-expressing parent line does not have l-dopachrome tautomerase activity, but this enzyme is detectable in double transfectants as well as in fibroblasts expressing the b-protein alone. Cells expressing both proteins have a higher steady-state level of tyrosinase than fibroblasts expressing tyrosinase alone, and contain elevated levels of melanin intermediates. This is thought to result from interaction of tyrosinase with the b-protein. Only phaeomelanin is detectable in fibroblasts expressing tyrosinase alone, whereas double transfectants synthesise significantly more phaeomelanin and detectable eumelanin

Evaluation of Thermal Versus Plasma-Assisted ALD Al2O3 as Passivation for InAlN/AlN/GaN HEMTs

Al2O3 films deposited by thermal and plasma-assisted atomic layer deposition (ALD) were evaluated as passivation layers for InAlN/AlN/GaN HEMTs. As a reference, a comparison was made with the more conventional plasma enhanced chemical vapor deposition deposited SiNx passivation. The difference in sheet charge density, threshold voltage, f(T) and f(max) was moderate for the three samples. The gate leakage current differed by several orders of magnitude, in favor of Al2O3 passivation, regardless of the deposition method. Severe current slump was measured for the HEMT passivated by thermal ALD, whereas near-dispersion free operation was observed for the HEMT passivated by plasma-assisted ALD. This had a direct impact on the microwave output power. Large-signal measurements at 3 GHz revealed that HEMTs with Al2O3 passivation exhibited 77% higher output power using plasma-assisted ALD compared with thermal ALD

Tuning composition in graded AlGaN channel HEMTs toward improved linearity for low-noise radio-frequency amplifiers

Compositionally graded channel AlGaN/GaN high electron mobility transistors (HEMTs) offer a promising route to improve device linearity, which is necessary for low-noise radio-frequency amplifiers. In this work, we demonstrate different grading profiles of a 10-nm-thick AlxGa1-xN channel from x = 0 to x = 0.1 using hot-wall metal-organic chemical vapor deposition (MOCVD). The growth process is developed by optimizing the channel grading and the channel-to-barrier transition. For this purpose, the Al-profiles and the interface sharpness, as determined from scanning transmission electron microscopy combined with energy-dispersive x-ray spectroscopy, are correlated with specific MOCVD process parameters. The results are linked to the channel properties (electron density, electron mobility, and sheet resistance) obtained by contactless Hall and terahertz optical Hall effect measurements coupled with simulations from solving self-consistently Poisson and Schr\uf6dinger equations. The impact of incorporating a thin AlN interlayer between the graded channel and the barrier layer on the HEMT properties is investigated and discussed. The optimized graded channel HEMT structure is found to have similarly high electron density (∼9 7 10 12 cm-2) as the non-graded conventional structure, though the mobility drops from ∼ 2360 cm2/V s in the conventional to ∼ 960 cm2/V s in the graded structure. The transconductance gm of the linearly graded channel HEMTs is shown to be flatter with smaller g m ′ and g m ″ as compared to the conventional non-graded channel HEMT implying improved device linearity

Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study:idarubicin dose selection, tissue response and survival

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance. METHODS AND ANALYSIS: The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival. ETHICS AND DISSEMINATION: Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden. TRIAL REGISTRATION NUMBER: EudraCT number: 2021-001257-31

Characterization of Electro-Thermal Effects in GaN Based HEMTs

This paper presents a new method for characterizing electro-thermal effects in GaN based HEMTs. The proposed method characterizes the thermal and bias dependence of the current through the 2-DEG individually. The temperature dependence is characterized by TLM measurements versus ambient temperature, showing an increasing sheet resistivity with temperature. The thermal impedance is determined from low frequency impedance measurements, indicating thermal response up to at least 100 MHz. The isothermal bias dependence is measured above the thermal cut-off with a LSNA, showing a nonlinear current versus voltage characteristic

Extraction of an Electrothermal Mobility Model for AlGaN/GaN Heterostructures

An electron mobility model for AlGaN/GaN heterostructures taking both the lattice temperature and electric field into account is proposed. Numerical device simulation of an ungated Al0.25Ga0.75N/GaN HEMT structure on 4H-SiC substrate is compared to measured electrical characteristics. Mobility model parameters are extracted by comparing iso-thermal numerical simulations with microwave (6 GHz) large signal measurements. The extracted model was used in static simulations, showing good agreement with measurements

Characterization of Electro-Thermal Effects in GaN Based HEMTs

This paper presents a new method for characterizing electro-thermal effects in GaN based HEMTs. The proposed method characterizes the thermal and bias dependence of the current through the 2-DEG individually. The temperature dependence is characterized by TLM measurements versus ambient temperature, showing an increasing sheet resistivity with temperature. The thermal impedance is determined from low frequency impedance measurements, indicating thermal response up to at least 100 MHz. The isothermal bias dependence is measured above the thermal cut-off with a LSNA, showing a nonlinear current versus voltage characteristic