OLED Encapsulation by Room Temperature Plasma-Assisted ALD Al2O3 Films

Organic light emitting diodes (OLEDs, both small molecule and polymer LEDs) require excellent gas and moisture permeation barrier layers to increase their lifetime. The quality of the barrier layer is ultimately controlled by the presence of defects in the layer. Although a barrier layer may be intrinsically excellent (water vapor transmission rate, WVTR = 10-6 g·m-2·day-1) the protected device may fail in the presence of defects that lead to preferential diffusion pathways for H2O (e.g., defects caused by particles from the environment and/or production process). The state-of-the-art barrier coatings are micrometer-thick multi-layer structure, in which organic interlayers are alternated with inorganic barrier layers with the purpose of decoupling the above-mentioned defects. Recently, atomic layer deposition (ALD) has been successfully tested for the deposition of very thin (<50 nm) single layer permeation barriers on pristine polymer substrates [1,2], showing the potential of this highly uniform and conformal deposition technique in the field of moisture permeation barriers. In this contribution the encapsulation of OLEDs by plasma-assisted ALD of thin (20-40 nm) Al2O3 layers is addressed. The layers are synthesized at room temperature by sequentially exposing the substrate to Al(CH3)3 vapor and a remote inductively coupled O2 plasma in Oxford Instruments FlexALTM and OpALTM reactors. The intrinsic quality of the deposited ALD layers was determined by monitoring the oxidation of a Ca film encapsulated by the Al2O3 film: WVTR values as low as 2·10-6 g·m-2·day-1 have been measured. The potential of ALD layers in encapsulating OLEDs, and therefore in successfully covering the defects present on the device, has been investigated by means of electroluminescence measurements of polymer-LEDs (effective emitting area of 5.8 cm2). The black spot density and area growth were followed as a function of the time under standard conditions of 20°C and 50% relative humidity. Within a 500 h test ALD-encapsulated OLEDs show approximately half the black spot density compared to devices encapsulated by plasma deposited a-SiNx:H (300 nm thick). The black spot density is further reduced by combining the a-SiNx:H and ALD Al2O3 layers. These results point towards a very promising application of ALD Al2O3 layers in the field of OLED encapsulation and will be interpreted in terms of possible mechanisms related to film growth in multi-layer structures

The UFM1 Pathway Impacts HCMV US2-Mediated Degradation of HLA Class I

To prevent accumulation of misfolded proteins in the endoplasmic reticulum, chaperones perform quality control on newly translated proteins and redirect misfolded proteins to the cytosol for degradation by the ubiquitin-proteasome system. This pathway is called ER-associated protein degradation (ERAD). The human cytomegalovirus protein US2 induces accelerated ERAD of HLA class I molecules to prevent immune recognition of infected cells by CD8(+) T cells. Using US2-mediated HLA-I degradation as a model for ERAD, we performed a genome-wide CRISPR/Cas9 library screen to identify novel cellular factors associated with ERAD. Besides the identification of known players such as TRC8, p97, and UBE2G2, the ubiquitin-fold modifier1 (UFM1) pathway was found to affect degradation of HLA-I. UFMylation is a post-translational modification resembling ubiquitination. Whereas we observe ubiquitination of HLA-I, no UFMylation was detected on HLA-I or several other proteins involved in degradation of HLA-I, suggesting that the UFM1 pathway impacts ERAD in a different manner than ubiquitin. Interference with the UFM1 pathway seems to specifically inhibit the ER-to-cytosol dislocation of HLA-I. In the absence of detectable UFMylation of HLA-I, UFM1 may contribute to US2-mediated HLA-I degradation by misdirecting protein sorting indirectly. Mass spectrometry analysis of US2-expressing cells showed that ribosomal proteins are a major class of proteins undergoing extensive UFMylation; the role of these changes in protein degradation may be indirect and remains to be established.This article belongs to the Special Issue Ubiquitin and Ubiquitin-Like Proteins: From Basic Mechanisms to Human Disorder

Reduced incorporation of Fatty acids into triacylglycerol in myotubes from obese individuals with type 2 diabetes.

Altered skeletal muscle lipid metabolism is a hallmark feature of type 2 (T2D). Here we investigated muscle lipid turnover in T2D versus BMI- controls and examined if putative in vivo differences would be preserved myotubes.Male obese T2D individuals (T2D) (n=6) and their BMI-matched (C) (n=6) underwent a hyperinsulinemic-euglycemic clamp, VO2max test, underwater weighing and muscle biopsy of v. lateralis. 14C-palmitate and 14C-oleate oxidation rates and incorporation into lipids were measured tissue, as well as in primary myotubes.Palmitate oxidation (C: 0.99 +/- T2D: 0.53 +/- 0.07nmol/mg protein; P=0.03) and incorporation of fatty into triacylglycerol (TAG) (C: 0.45 +/- 0.13, T2D: 0.11 +/- 0.02nmol/mg P=0.047) were significantly reduced in muscle homogenates of T2D. These reductions were not retained for palmitate oxidation in primary myotubes (P=0.38); however, incorporation of FAs into TAG was lower in T2D oleate and P=0.11 for palmitate), with a strong correlation of TAG between muscle tissue and primary myotubes (r=0.848, P=0.008).Our data that the ability to incorporate FAs into TAG is an intrinsic feature of muscle cells that is reduced in individuals with T2D

Introducing the DizzyQuest: an app-based diary for vestibular disorders

BACKGROUND Most questionnaires currently used for assessing symptomatology of vestibular disorders are retrospective, inducing recall bias and lowering ecological validity. An app-based diary, administered multiple times in daily life, could increase the accuracy and ecological validity of symptom measurement. The objective of this study was to introduce a new experience sampling method (ESM) based vestibular diary app (DizzyQuest), evaluate response rates, and to provide examples of DizzyQuest outcome measures which can be used in future research. METHODS Sixty-three patients diagnosed with a vestibular disorder were included. The DizzyQuest consisted of four questionnaires. The morning- and evening-questionnaires were administered once each day, the within-day-questionnaire 10 times a day using a semi-random time schedule, and the attack questionnaire could be completed after the occurrence of a vertigo or dizziness attack. Data were collected for 4~weeks. Response rates and loss-to-follow-up were determined. Reported symptoms in the within-day-questionnaire were compared within and between patients and subgroups of patients with different vestibular disorders. RESULTS Fifty-one patients completed the study period. Average response rates were significantly higher than the desired response rate of \textgreater 50% (p \textless 0.001). The attack-questionnaire was used 159 times. A variety of neuro-otological symptoms and different disease profiles were demonstrated between patients and subgroups of patients with different vestibular disorders. CONCLUSION The DizzyQuest is able to capture vestibular symptoms within their psychosocial context in daily life, with little recall bias and high ecological validity. The DizzyQuest reached the desired response rates and showed different disease profiles between subgroups of patients with different vestibular disorders. This is the first time ESM was used to assess daily symptoms and quality of life in vestibular disorders, showing that it might be a useful tool in this population

The UFM1 Pathway Impacts HCMV US2-Mediated Degradation of HLA Class I

To prevent accumulation of misfolded proteins in the endoplasmic reticulum, chaperones perform quality control on newly translated proteins and redirect misfolded proteins to the cytosol for degradation by the ubiquitin-proteasome system. This pathway is called ER-associated protein degradation (ERAD). The human cytomegalovirus protein US2 induces accelerated ERAD of HLA class I molecules to prevent immune recognition of infected cells by CD8(+) T cells. Using US2-mediated HLA-I degradation as a model for ERAD, we performed a genome-wide CRISPR/Cas9 library screen to identify novel cellular factors associated with ERAD. Besides the identification of known players such as TRC8, p97, and UBE2G2, the ubiquitin-fold modifier1 (UFM1) pathway was found to affect degradation of HLA-I. UFMylation is a post-translational modification resembling ubiquitination. Whereas we observe ubiquitination of HLA-I, no UFMylation was detected on HLA-I or several other proteins involved in degradation of HLA-I, suggesting that the UFM1 pathway impacts ERAD in a different manner than ubiquitin. Interference with the UFM1 pathway seems to specifically inhibit the ER-to-cytosol dislocation of HLA-I. In the absence of detectable UFMylation of HLA-I, UFM1 may contribute to US2-mediated HLA-I degradation by misdirecting protein sorting indirectly. Mass spectrometry analysis of US2-expressing cells showed that ribosomal proteins are a major class of proteins undergoing extensive UFMylation; the role of these changes in protein degradation may be indirect and remains to be established

Exercise-induced modulation of cardiac lipid content in healthy lean young men

Cardiac lipid accumulation is associated with decreased cardiac function and energy status (PCr/ATP). It has been suggested that elevated plasma fatty acid (FA) concentrations are responsible for the cardiac lipid accumulation. Therefore, the aim of the present study was to investigate if elevating plasma FA concentrations by exercise results in an increased cardiac lipid content, and if this influences cardiac function and energy status. Eleven male subjects (age 25.4 ± 1.1 years, BMI 23.6 ± 0.8 kg/m2) performed a 2-h cycling protocol, once while staying fasted and once while ingesting glucose, to create a state of high versus low plasma FA concentrations, respectively. Cardiac lipid content was measured by proton magnetic resonance spectroscopy (1H-MRS) at baseline, directly after exercise and again 4 h post-exercise, together with systolic function (by multi-slice cine-MRI) and cardiac energy status (by 31P-MRS). Plasma FA concentrations were increased threefold during exercise and ninefold during recovery in the fasted state compared with the glucose-fed state (p < 0.01). Cardiac lipid content was elevated at the end of the fasted test day (from 0.26 ± 0.04 to 0.44 ± 0.04%, p = 0.003), while it did not change with glucose supplementation (from 0.32 ± 0.03 to 0.26 ± 0.05%, p = 0.272). Furthermore, PCr/ATP was decreased by 32% in the high plasma FA state compared with the low FA state (n = 6, p = 0.014). However, in the high FA state, the ejection fraction 4 h post-exercise was higher compared with the low FA state (63 ± 2 vs. 59 ± 2%, p = 0.018). Elevated plasma FA concentrations, induced by exercise in the fasted state, lead to increased cardiac lipid content, but do not acutely hamper systolic function. Although the lower cardiac energy status is in line with a lipotoxic action of cardiac lipid content, a causal relationship cannot be proven

Sensitivity of the Atlantic meridional overturning circulation to South Atlantic freshwater anomalies

The sensitivity of the Atlantic Meridional Overturning Circulation (AMOC) to changes in basin integrated net evaporation is highly dependent on the zonal salinity contrast at the southern border of the Atlantic. Biases in the freshwater budget strongly affect the stability of the AMOC in numerical models. The impact of these biases is investigated, by adding local anomaly patterns in the South Atlantic to the freshwater fluxes at the surface. These anomalies impact the freshwater and salt transport by the different components of the ocean circulation, in particular the basin-scale salt-advection feedback, completely changing the response of the AMOC to arbitrary perturbations. It is found that an appropriate dipole anomaly pattern at the southern border of the Atlantic Ocean can collapse the AMOC entirely even without a further hosing. The results suggest a new view on the stability of the AMOC, controlled by processes in the South Atlantic. <br/

Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans

Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol in a randomized double-blind cross-over study for 30 days. Resveratrol significantly reduced sleeping- and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1α protein levels, increased citrate synthase activity without change in mitochondrial content, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels, and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction