41 research outputs found

    SIRT3 deficiency exacerbates fatty liver by attenuating the HIF1α-LIPIN 1 pathway and increasing CD36 through Nrf2

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    Background: Deficiency of mitochondrial sirtuin 3 (SIRT3), a NAD+ -dependent protein deacetylase that maintains redox status and lipid homeostasis, contributes to hepatic steatosis. In this study, we investigated additional mechanisms that might play a role in aggravating hepatic steatosis in Sirt3-deficient mice fed a high-fat diet (HFD). Methods: Studies were conducted in wild-type (WT) and Sirt3−/− mice fed a standard diet or a HFD and in SIRT3- knockdown human Huh-7 hepatoma cells. Results: Sirt3−/− mice fed a HFD presented exacerbated hepatic steatosis that was accompanied by decreased expression and DNA-binding activity of peroxisome proliferator-activated receptor (PPAR) α and of several of its target genes involved in fatty acid oxidation, compared to WT mice fed the HFD. Interestingly, Sirt3 deficiency in liver and its knockdown in Huh-7 cells resulted in upregulation of the nuclear levels of LIPIN1, a PPARα co-activator, and of the protein that controls its levels and localization, hypoxia-inducible factor 1α (HIF-1α). These changes were prevented by lipid exposure through a mechanism that might involve a decrease in succinate levels. Finally, Sirt3−/− mice fed the HFD showed increased levels of some proteins involved in lipid uptake, such as CD36 and the VLDL receptor. The upregulation in CD36 was confirmed in Huh-7 cells treated with a SIRT3 inhibitor or transfected with SIRT3 siRNA and incubated with palmitate, an effect that was prevented by the Nrf2 inhibitor ML385. Conclusion: These findings demonstrate new mechanisms by which Sirt3 deficiency contributes to hepatic steatosi

    Reconfigurable multiplexed point of Care System for monitoring type 1 diabetes patients

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    At the point of care (POC), on-side clinical testing allows fast biomarkers determination even in resource-limited environments. Current POC systems rely on tests selective to a single analyte or complex multiplexed systems with important portability and performance limitations. Hence, there is a need for handheld POC devices enabling the detection of multiple analytes with accuracy and simplicity. Here we present a reconfigurable smartphone-interfaced electrochemical Lab-on-a-Chip (LoC)with two working electrodes for dual analyte determination enabling biomarkers' selection in situ and on-demand. Biomarkers selection was achieved by the use of electrodepositable alginate hydrogels. Alginate membranes containing either glucose oxidase (GOx)or lactate oxidase (LOx)were selectively electrodeposited on the surface of each working electrode in around 4 min, completing sample measurement in less than 1 min. Glucose and lactate determination was performed simultaneously and without cross-talk in buffer, fetal bovine serum (FBS)and whole blood samples, the latter being possible by the size-exclusion filtration capacity of the hydrogels. At optimal conditions, glucose and lactate were determined in a wide linear range (0–12 mM and 0–5 mM, respectively)and with high sensitivities (0.24 and 0.54 ÎŒA cm −2 mM −1 , respectively), which allowed monitoring of Type-1 diabetic patients with a simple dual analysis system. After the measurement, membranes were removed by disaggregation with the calcium-chelator phosphate buffer. At this point, new membranes could be electrodeposited, this time being selective to the same or another analyte. This conferred the system with on-demand biomarkers’ selection capacity. The versatility and flexibility of the current architecture is expected to impact in POC analysis in applications ranging from homecare to sanitary emergencies.Peer reviewe

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    Epitaxial strategies for defect reduction in GaN for vertical power devices

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    Group-III nitride materials, gallium nitride (GaN), aluminum nitride (AlN) and indium nitride (InN) have direct band gaps with band gap energies ranging from the infrared (InN) to the ultraviolet (GaN) and to the deep ultraviolet (AlN) wavelengths and covering the entire spectral range from 0.7 eV to 6.2 eV upon alloying. The invention of the GaN-based blue LEDs, for which the Nobel prize in Physics was awarded in 2014, has opened up avenues for exploration of IIINitride material and device technologies and has inspired generations of researchers in the semiconductor field. Group-III nitrides have also been demonstrated to be among the most promising semiconductors for next generation of efficient high-power, high-temperature and high-frequency electronic devices. The need to build a sustainable and efficient energy system motivates the development of vertical GaN transistors and diodes for applications with power ratings of 50-150 kW, e.g., in electric vehicles and industrial inverters. The key is to grow GaN layers with low concentration of defects (impurities and dislocations), which enables an expansion in both voltage and current ratings and reduction of cost. Despite intense investigations and impressive advances in the field, defects are still a major problem hindering exploiting the full potential of GaN in power electronics. This Licentiate thesis focuses on the development of two different epitaxial approaches in MOCVD for reducing dislocation densities in GaN with controlled doping for power device applications: i) growth of planar GaN layers trough NWs reformation, which can be further exploited as templates for a subsequent growth of thick drift layers and ii) homoepitaxial GaN growth. Special attention is put on understanding homoepitaxial growth under different nucleation schemes and thermal stability of GaN. We have established conditions in homoepitaxy to deliver state-of-the-art GaN material with low impurity levels combined with a reasonable growth rate suitable for growth of thick drift layers. The results are summarized in two papers: In Paper I we investigate GaN layers with different thicknesses on reformed GaN NW templates and highlight this approach as an alternative to the expensive GaN HVPE substrates. The sapphire used as a substrate limits to some extent the reduction of threading dislocations, however, the resulting GaN material presents smooth surfaces and thermal conductivity close to the bulk value, which suggests the potential of this approach to be integrated in GaN development as an active material for power devices on various substrates. In Paper II extensive study of homoepitaxial GaN growth by hot-wall MOCVD is presented together with results on the thermal stability of GaN under typical conditions used in our growth reactor. Understanding the evolution of GaN surface under different gas compositions and temperatures allows us to predict optimum homoepitaxial conditions. Analysis in the framework of Ga supersaturation of epilayers simultaneously grown on GaN templates and on GaN HVPE substrates reveals that residual strain and screw dislocation densities affect GaN nucleation and growth and lead to distinctively different morphologies on GaN templates and native substrates, respectively. The established comprehensive picture provides guidance for designing strategies for growth conditions optimization in homoepitaxy. We demonstrate homoepitaxial GaN-on-GaN grown under optimum growth conditions with state-of-the-art smooth surface with an rms value of 0.021 nm and an average TDD of 1.4·106 cm-2 which provide good basis for augmenting power device structures.Future work will be focused on GaN NWs reformation on different substrates, p- and n-type doping of homoepitaxial GaN with impurity control and the fabrication of pn power diode device structures for further processing and assessment by C3NiT partners.Funding agencies: The Swedish Research Council (VR) under Grant No. 2016-00889, The Swedish Governmental Agency for Innovation Systems (VINNOVA) under the Competence Center Program, Grant No. 2016-05190, The Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linköping University, Faculty Grant SFO Mat LiU No.2009-00971, The Swedish Foundation for Strategic Research (SSF), under Grant No. EM16-0024</p

    Epitaxy of group III-nitride materials using different nucleation schemes

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    Group III-nitride materials, gallium nitride (GaN), aluminum nitride (AlN) and indium nitride (InN) have direct band gaps with band gap energies ranging from the infrared (InN) to the ultraviolet (GaN) and to the deep ultraviolet (AlN) wave-lengths, covering the entire spectral range from 0.7 eV to 6.2 eV upon alloying. The invention of the GaN-based blue LEDs, for which the Nobel prize in Physics was awarded in 2014, has opened up avenues for exploration of III-Nitride mate-rial and device technologies, and has inspired generations of researchers in the semiconductor ïŹeld. Group III-nitrides have also been demonstrated to be among the most promising semiconductors for next generation of efïŹcient high-power, high-temperature and high-frequency electronic devices.  The need to build a sustainable and efïŹcient energy system motivates the development of vertical GaN transistors and diodes for applications with power ratings of 50-150 kW, e.g., in electric vehicles and industrial inverters. The key is to grow GaN layers with low concentration of defects (impurities and dislocations), which enables an expansion in both voltage and current ratings and reduction of cost. Despite intense investigations and impressive advances in the ïŹeld, defects are still a major problem which hinders exploiting the full potential of GaN in power electronics.  The aim of this thesis is to perform an in-depth investigation of the growth of GaN and AlGaN under several nucleation mechanisms provided by different underlying substrates. In that regard, four different epitaxial approaches based on different nucleation schemes have been studied: (i) growth of planar GaN layers trough NWs reformation. We investigated GaN layers with different thicknesses on reformed GaN NW templates and highlight this approach as an alternative to the expensive HVPE GaN substrates. The sapphire used as a substrate limits to some extent the reduction of threading dislocations, however, the resulting GaN material presents smooth surfaces and thermal conductivity close to the value for bulk GaN. (ii) Homoepitaxial GaN growth. We developed a hot-wall MOCVD epitaxial approach that enables low surface roughness and appropriate impurity levels for advanced vertical power device architectures. A comprehensive picture of GaN homoepitaxy on different GaN surfaces, GaN templates on SiC and HVPE GaN substrates, is established on the basis of experimental results and thermodynamic considerations. (iii) GaN growth on GaN NWs templates by hot-wall MOCVD resulted in an atomically ïŹ‚at smooth surface with reduction of threading dislocations when the optimum annealing conditions have been employed. (iv) Heteroepitaxial growth of low Al composition n-AlxGa1-xN on SiC substrates revealed 700 nm crack-free epi-layers for an Al composition up to 12%. The highest mobility corresponds to an Al content of 6.5% where we also get a reduction in screw and edge dislocations. The results show the potential application of AlxGa1-xN(x= 0 - 0.12) as the active material for drift layers.  Some of the epitaxial approaches developed in this thesis have been already implemented in the growth of power devices such as quasi-vertical GaN FinFETs on SiC substrates and fully-vertical GaN FinFETs on HVPE GaN substrates. Grupp III-nitrider Ă€r halvledare med direkta bandgap dĂ€r bandgapsenergierna spĂ€nner frĂ„n det infraröda till djupt ultravioletta banden. TillrĂ€knade i den gruppen Ă€r galliumnitrid (GaN), aluminiumnitrid (AlN) samt indiumnitrid (InN) som tillsammans kan realisera alla bandgapsenergier frĂ„n 0.7 eV (InN) till 6.2 eV (AlN) genom legering. Utvecklingen av GaN-baserade blĂ„ LED:er, som tilldelades 2014 Ă„rs Nobelpris i fysik, har öppnat mĂ„nga nya dörrar inom III-nitridforskning och skapat mĂ„nga nya tillĂ€mpningar av halvledarmaterial. Till exempel har grupp III-nitrider pĂ„visats mycket lovande som nĂ€sta generations högeffekts- och högfrekvenskomponenter inom elektroniken. EfterfrĂ„gan pĂ„ hĂ„llbara och effektiva energisystem har drivit utvecklingen av vertikala GaN-transistorer och dioder för tillĂ€mpning inom 50-150 kW omfĂ„nget, sĂ„ som elektriska fordon och industriella vĂ€xelriktare. Nyckeln ligger i att vĂ€xa lager av GaN med lĂ„g konsentration av defekter (orenheter och dislokations), som bĂ„de kan öka spĂ€nningsfönstret och strömstyrkan och samtidigt reducera kostnaden. Defekter har dĂ€remot varit svĂ„ra att kontrollera och trots mĂ€nger av framsteg Ă€r det fortfarande den stora utmaningen för att fullt kunna utnyttja potentialen av GaN inom elektronik. MĂ„let i denna avhandling Ă€r att utföra fördjupade undersökningar av GaN- och AlGaN-tillvĂ€xt vid olika betingade tillvĂ€xtmekanismer som funktion av tillvĂ€xtsubstrat. Fyra olika epitaxiella tillvĂ€gagĂ„ngsĂ€tt har studerats med tillhörande nukleationsmekanismer. (i) TillvĂ€xt av plana GaN-lager genom nanotrĂ„d-reformation. Vi har undersökt GaN med olika tjocklekar pĂ„ omformade GaN nanotrĂ„d-mallar och pĂ„visar att metoden Ă€r ett alternativ till dyra HVPE GaN-substrat. SaïŹren som anvĂ€nds som substrat begrĂ€nsar till viss del en reducering av slingrande dislokationer men den resulterande GaN-ytan Ă€r jĂ€mn och har en termisk ledningsförmĂ„ga nĂ€ra GaN i bulk. (ii) Homoepitaxiell GaN-tillvĂ€xt. Vi utvecklade en hetvĂ€ggs MOCVD-epitaxi som möjliggör en lĂ„g ytojĂ€mnhet och en lĂ„g nivĂ„ av orenheter för avancerade vertikala högeffektsarkitekturer. En omfattande ter-modynamisk och experimentell bild har etablerats av GaN homoepitaxi pĂ„ olika GaN-ytor, GaN-mallar pĂ„ SiC samt pĂ„ HVPE GaN-substrat. (iii) GaN tillvĂ€xt pĂ„ GaN nanotrĂ„dmallar via hetvĂ€ggs MOCVD resulterar i en atomĂ€rt jĂ€mn yta med en reducering av slingande dislokationer nĂ€r optimerad glödgning har utförts. (iv) Heteroepitaxiell tillvĂ€xt av lĂ„g-nivĂ„ Al inblandning i n-AlxGa1-xN pĂ„ SiC-substrat leder till 700 nm sprickfria epi-lager, för Al-inblandning upp till 12%. Den högsta uppmĂ€tta mobiliteten ïŹcks vid 6.5% Al dĂ€r ocksĂ„ en reducering av skruv- och kant- dislokationer noterades. Resultaten visar pĂ„ potentialen för n-AlxGa1-xN (x = 0 - 0.12) som aktiva material i driftlager. En del av de epitaxiella tillvĂ€gagĂ„ngssĂ€tten som utvecklats i denna avhandling har redan implementerats i tillvĂ€xt av högeffektskomponenter sĂ„ som quasi-vertikala GaN FinFETs pĂ„ SiC och vertikala GaN FinFETs pĂ„ HVPE GaN-substrat.  Funding agencies: Swedish Research Council (VR) under Grant No. 2016 − 00889, (ii) the Swedish Governmental Agency for Innovation Systems (VINNOVA) under the Competence Center Program, Grant No. 2016 − 05190, (iii) the Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linköping University, Faculty Grant SFO Mat LiU No. 2009 − 00971, and (iv) the Swedish Foundationfor Strategic Research (SSF), under Grant No. EM16 − 0024.</p

    Tuning of Quasi-Vertical GaN FinFETs Fabricated on SiC Substrates

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    In this work, we present the fabrication and investigation of the properties of quasi-vertical gallium nitride (GaN) fin field effect transistors (FinFETs) on silicon carbide (SiC) substrates and the influence of a postgate metallization annealing (PMA). The devices reveal low subthreshold swings (SSs) down to around 70 mV/dec. For a 1- ÎŒm\mu \text{m} -thick drift layer, a low ON-resistance below 0.05 mΩ⋅\text{m}\Omega \cdot cm2 (normalized on the fin area) and a breakdown voltage of 60 V were obtained. Devices with included PMA show a decreased threshold voltage and ON-resistance and by several orders of magnitude reduced gate leakage current compared to non-annealed devices. The devices show ohmic contact behavior and slightly negative threshold voltages, which indicates normally- ON behavior. The effective and field-effect mobility of the fin channel was obtained with a modeled carrier concentration and reveal to around 70 and 13 cm2/(Vs) at high gate voltages, which is in a good comparison to so far reported similar devices
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