Oxide-ion diffusion in brownmillerite-type Ca2AlMnO5+δ from first-principles calculations.

Oxide-ion diffusion pathways in brownmillerite oxides Ca2AlMnO5 and Ca2AlMnO5.5 are systematically investigated using first-principles calculations. These structures reversibly transform into each other by oxidation and reduction. We examine oxide-ion migration in Ca2AlMnO5 and Ca2AlMnO5.5 using the nudged elastic band method. In the reduced structure (Ca2AlMnO5), oxide-ion migration through a vacancy channel is found to have the lowest migration energy barrier, at 0.58 eV. The migration energy barrier of the second-lowest energy path, perpendicular to the vacancy channel, is found to be 0.98 eV. In the oxidized structure (Ca2AlMnO5.5), oxide-ion migration within AlO6 layers has migration energy barriers of 0.55 eV and 0.56 eV in the [100] and [001] directions, respectively. Oxide-ion migration perpendicular to the AlO6 layer has a migration energy barrier of 1.33 eV, suggesting that oxide-ion diffusion in the [010] direction is difficult even at elevated temperature. These results indicate that diffusion in the reduced phase is predominantly one-dimensional whereas it is two-dimensional in the oxidized phase.

Characterisation of the temperature-dependent M1 to R phase transition in W-doped VO2 nanorod aggregates by Rietveld refinement and theoretical modelling.

Understanding the mechanism of the insulator-metal transition (IMT) in VO2 is a necessary step in optimising this material's properties for a range of functional applications. Here, Rietveld refinement of synchrotron X-ray powder diffraction patterns is performed on thermochromic V1-xWxO2 (0.0 ≤ x ≤ 0.02) nanorod aggregates over the temperature range 100 ≤ T ≤ 400 K to examine the effect of doping on the structure and properties of the insulating monoclinic (M1) phase and metallic rutile (R) phase. Precise measurement of the lattice constants of the M1 and R phases enabled the onset (Ton) and endset (Tend) temperatures of the IMT to be determined accurately for different dopant levels. First-principles calculations reveal that the observed decrease in both Ton and Tend with increasing W content is a result of Peierls type V-O-V dimers being replaced by linear W-O-V dimers with a narrowing of the band gap. The results are interpreted in terms of the bandwidth-controlled Mott-Hubbard IMT model, providing a more detailed understanding of the underlying physical mechanisms driving the IMT as well as a guide to optimising properties of VO2-based materials for specific applications.

Induced Pluripotent Stem Cell-Derived Podocyte-Like Cells as Models for Assessing Mechanisms Underlying Heritable Disease Phenotype: Initial Studies Using Two Alport Syndrome Patient Lines Indicate Impaired Potassium Channel Activity.

Renal podocyte survival depends upon the dynamic regulation of a complex cell architecture that links the glomerular basement membrane to integrins, ion channels, and receptors. Alport syndrome is a heritable chronic kidney disease where mutations in α3, α4, or α5 collagen genes promote podocyte death. In rodent models of renal failure, activation of the calcium-sensing receptor (CaSR) can protect podocytes from stress-related death. In this study, we assessed CaSR function in podocyte-like cells derived from induced-pluripotent stem cells from two patients with Alport Syndrome (AS1 & AS2) and a renal disease free individual [normal human mesangial cell (NHMC)], as well as a human immortalized podocyte-like (HIP) cell line. Extracellular calcium elicited concentration-dependent elevations of intracellular calcium in all podocyte-like cells. NHMC and HIP, but not AS1 or AS2 podocyte-like cells, also showed acute reductions in intracellular calcium prior to elevation. In NHMC podocyte-like cells this acute reduction was blocked by the large-conductance potassium channel (KCNMA1) inhibitors iberiotoxin (10 nM) and tetraethylammonium (5 mM), as well as the focal adhesion kinase inhibitor PF562271 (N-methyl-N-(3-((2-(2-oxo-2,3-dihydro-1H-indol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino)-methyl)-pyridin-2-yl)-methanesulfonamide, 10 nM). Quantitative polymerase chain reaction (qPCR) and immunolabeling showed the presence of KCNMA1 transcript and protein in all podocyte-like cells tested. Cultivation of AS1 podocytes on decellularized plates of NHMC podocyte-like cells partially restored acute reductions in intracellular calcium in response to extracellular calcium. We conclude that the AS patient-derived podocyte-like cells used in this study showed dysfunctional integrin signaling and potassium channel function, which may contribute to podocyte death seen in Alport syndrome.

Systematic analysis of electron energy-loss near-edge structures in Li-ion battery materials.

Electrical conductivity, state of charge and chemical stability of Li-ion battery materials all depend on the electronic states of their component atoms, and tools for measuring these reliably are needed for advanced materials analysis and design. Here we report a systematic investigation of electron energy-loss near-edge structures (ELNES) of Li-K and O-K edges for ten representative Li-ion battery electrodes and solid-state electrolytes obtained by performing transmission electron microscopy with a Wien-filter monochromator-equipped microscope. While the peaks of Li-K edges are positioned at about 62 eV for most of the materials examined, the peak positions of O-K edges vary within a range of about 530 to 540 eV, and the peaks can be categorised into three groups based on their characteristic edge shapes: (i) double peaks, (ii) single sharp peaks, and (iii) single broad peaks. The double peaks of group (i) are attributable to the d0 electronic configuration of their transition metal ions bonded to O atoms. The origin of the different peak shapes of groups (ii) and (iii) is more subtle but insights are gained using density functional theory methods to simulate O-K ELNES edges of group (ii) material LiCoO2 and group (iii) material LiFePO4. Comparison of their densities of states reveals that in LiCoO2 the Co-O hybrid orbitals are separated from Li-O hybrid orbitals, resulting in a sharp peak in the O-K edge, while Fe-O, Li-O and P-O hybrid orbitals in LiFePO4 partially overlap each other and produce a broad peak.

Density functional study of the phase stability and Raman spectra of Yb2O3, Yb2SiO5 and Yb2Si2O7 under pressure.

The phase stability and Raman spectra of Yb2O3, Yb2SiO5 and Yb2Si2O7 under hydrostatic pressure are investigated using density functional theory calculations. The calculated energies of polymorphs of each compound show that the stable phases at zero pressure, viz., C-type Yb2O3, X2-Yb2SiO5 and ß-Yb2Si2O7, exhibit a pressure-induced phase transition as compressive pressure increases, which is consistent with available experimental data. The theoretical Raman spectra at zero pressure are in good agreement with experimental results for the stable phases and can be used to identify each polymorph. Although the calculated pressure dependence of Raman peak positions of C-type Yb2O3 is overestimated compared to available experimental data, piezospectroscopic coefficients extracted from Raman peaks of X2-Yb2SiO5 and ß-Yb2Si2O7 suggest that Raman spectroscopy can be used to measure stresses and strains in Yb silicates. Normal mode analyses reveal that characteristic Raman peaks of Yb silicates at frequencies above 600 cm-1 are strongly associated with vibrations of Si-O bonds in SixOy tetrahedral units.

Identification of microRNA biomarker candidates in urine and plasma from rats with kidney or liver damage.

MicroRNAs (miRNA) are short single-stranded RNA sequences that have a role in the post-transcriptional regulation of genes. The identification of tissue specific or enriched miRNAs has great potential as novel safety biomarkers. One longstanding goal is to associate the increase of miRNA in biofluids (e.g., plasma and urine) with tissue-specific damage. Next-generation sequencing (miR-seq) was used to analyze changes in miRNA profiles of tissue, plasma and urine samples of rats treated with either a nephrotoxicant (cisplatin) or one of two hepatotoxicants (acetaminophen [APAP] or carbon tetrachloride [CCL4 ]). Analyses with traditional serum chemistry and histopathology confirmed that toxicant-induced organ damage was specific. In animals treated with cisplatin, levels of five miRNAs were significantly altered in the kidney, 14 in plasma and six in urine. In APAP-treated animals, five miRNAs were altered in the liver, 74 in plasma and six in urine; for CCL4 the changes were five, 20 and 6, respectively. Cisplatin treatment caused an elevation of miR-378a in the urine, confirming the findings of other similar studies. There were 17 in common miRNAs elevated in the plasma after treatment with either APAP or CCL4 . Four of these (miR-122, -802, -31a and -365) are known to be enriched in the livers of rats. Interestingly, the increase of serum miR-802 in both hepatotoxicant treatments was comparable to that of the well-known liver damage marker miR-122. Taken together, comparative analysis of urine and plasma miRNAs demonstrated their utility as biomarkers of organ injury. Copyright © 2016 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.

Atomic-Scale Observations of (010) LiFePO4 Surfaces Before and After Chemical Delithiation.

The ability to view directly the surface structures of battery materials with atomic resolution promises to dramatically improve our understanding of lithium (de)intercalation and related processes. Here we report the use of state-of-the-art scanning transmission electron microscopy techniques to probe the (010) surface of commercially important material LiFePO4 and compare the results with theoretical models. The surface structure is noticeably different depending on whether Li ions are present in the topmost surface layer or not. Li ions are also found to migrate back to surface regions from within the crystal relatively quickly after partial delithiation, demonstrating the facile nature of Li transport in the [010] direction. The results are consistent with phase transformation models involving metastable phase formation and relaxation, providing atomic-level insights into these fundamental processes.

The beagle dog MicroRNA tissue atlas: identifying translatable biomarkers of organ toxicity.

BACKGROUND: MicroRNAs (miRNA) are varied in length, under 25 nucleotides, single-stranded noncoding RNA that regulate post-transcriptional gene expression via translational repression or mRNA degradation. Elevated levels of miRNAs can be detected in systemic circulation after tissue injury, suggesting that miRNAs are released following cellular damage. Because of their remarkable stability, ease of detection in biofluids, and tissue specific expression patterns, miRNAs have the potential to be specific biomarkers of organ injury. The identification of miRNA biomarkers requires a systematic approach: 1) determine the miRNA tissue expression profiles within a mammalian species via next generation sequencing; 2) identify enriched and/or specific miRNA expression within organs of toxicologic interest, and 3) in vivo validation with tissue-specific toxicants. While miRNA tissue expression has been reported in rodents and humans, little data exists on miRNA tissue expression in the dog, a relevant toxicology species. The generation and evaluation of the first dog miRNA tissue atlas is described here. RESULTS: Analysis of 16 tissues from five male beagle dogs identified 106 tissue enriched miRNAs, 60 of which were highly enriched in a single organ, and thus may serve as biomarkers of organ injury. A proof of concept study in dogs dosed with hepatotoxicants evaluated a qPCR panel of 15 tissue enriched miRNAs specific to liver, heart, skeletal muscle, pancreas, testes, and brain. Dogs with elevated serum levels of miR-122 and miR-885 had a correlative increase of alanine aminotransferase, and microscopic analysis confirmed liver damage. Other non-liver enriched miRNAs included in the screening panel were unaffected. Eli Lilly authors created a complimentary Sprague Dawely rat miRNA tissue atlas and demonstrated increased pancreas enriched miRNA levels in circulation, following caerulein administration in rat and dog. CONCLUSION: The dog miRNA tissue atlas provides a resource for biomarker discovery and can be further mined with refinement of dog genome annotation. The 60 highly enriched tissue miRNAs identified within the dog miRNA tissue atlas could serve as diagnostic biomarkers and will require further validation by in vivo correlation to histopathology. Once validated, these tissue enriched miRNAs could be combined into a powerful qPCR screening panel to identify organ toxicity during early drug development.

The Rat microRNA body atlas; Evaluation of the microRNA content of rat organs through deep sequencing and characterization of pancreas enriched miRNAs as biomarkers of pancreatic toxicity in the rat and dog.

BACKGROUND: MicroRNAs (miRNA) are ~19-25 nucleotide long RNA molecules that fine tune gene expression through the inhibition of translation or degradation of the mRNA through incorporation into the RNA induced silencing complex (RISC). MicroRNAs are stable in the serum and plasma, are detectable in a wide variety of body fluids, are conserved across veterinary species and humans and are expressed in a tissue specific manner. They can be detected at low concentrations in circulation in animals and humans, generating interest in the utilization of miRNAs as serum and/or plasma based biomarkers of tissue injury. MicroRNA tissue profiling in rodents has been published, but sample an insufficient number of organs of toxicologic interest using microarray or qPCR technologies for miRNA detection. Here we impart an improved rat microRNA body atlas consisting of 21 and 23 tissues of toxicologic interest from male and female Sprague Dawley rats respectively, using Illumina miRNA sequencing. Several of the authors created a dog miRNA body atlas and we collaborated to test miRNAs conserved in rat and dog pancreas in caerulein toxicity studies utilizing both species. RESULTS: A rich data set is presented that more robustly defines the tissue specificity and enrichment profiles of previously published and undiscovered rat miRNAs. We generated 1,927 sequences that mapped to mature miRNAs in rat, mouse and human from miRBase and discovered an additional 1,162 rat miRNAs as compared to the current number of rat miRNAs in miRBase version 21. Tissue specific and enriched miRNAs were identified and a subset of these miRNAs were validated by qPCR for tissue specificity or enrichment. As an example of the power of this approach, we have conducted rat and dog pancreas toxicity studies and examined the levels of some tissue specific and enriched miRNAs conserved between rat and dog in the serum of each species. The studies demonstrate that conserved tissue specific/enriched miRs-216a-5p, 375-3p, 148a-3p, 216b-5p and 141-3p are candidate biomarkers of pancreatic injury in the rat and dog. CONCLUSIONS: A microRNA body atlas for rat and dog was useful in identifying new candidate miRNA biomarkers of organ toxicity in 2 toxicologically relevant species.

Optimization of tetrahydronaphthalene inhibitors of Raf with selectivity over hERG.

Investigations of a biaryl ether scaffold identified tetrahydronaphthalene Raf inhibitors with good in vivo activity; however these compounds had affinity toward the hERG potassium channel. Herein we describe our work to eliminate this hERG activity via alteration of the substituents on the benzoic amide functionality. The resulting compounds have improved selectivity against the hERG channel, good pharmacokinetic properties and potently inhibit the Raf pathway in vivo.

Lithium and sodium battery cathode materials: computational insights into voltage, diffusion and nanostructural properties.

Energy storage technologies are critical in addressing the global challenge of clean sustainable energy. Major advances in rechargeable batteries for portable electronics, electric vehicles and large-scale grid storage will depend on the discovery and exploitation of new high performance materials, which requires a greater fundamental understanding of their properties on the atomic and nanoscopic scales. This review describes some of the exciting progress being made in this area through use of computer simulation techniques, focusing primarily on positive electrode (cathode) materials for lithium-ion batteries, but also including a timely overview of the growing area of new cathode materials for sodium-ion batteries. In general, two main types of technique have been employed, namely electronic structure methods based on density functional theory, and atomistic potentials-based methods. A major theme of much computational work has been the significant synergy with experimental studies. The scope of contemporary work is highlighted by studies of a broad range of topical materials encompassing layered, spinel and polyanionic framework compounds such as LiCoO2, LiMn2O4 and LiFePO4 respectively. Fundamental features important to cathode performance are examined, including voltage trends, ion diffusion paths and dimensionalities, intrinsic defect chemistry, and surface properties of nanostructures.

Particle shapes and surface structures of olivine NaFePO4 in comparison to LiFePO4.

The expansion of batteries into electric vehicle and grid storage applications has driven the development of new battery materials and chemistries, such as olivine phosphate cathodes and sodium-ion batteries. Here we present atomistic simulations of the surfaces of olivine-structured NaFePO4 as a sodium-ion battery cathode, and discuss differences in its morphology compared to the lithium analogue LiFePO4. The calculated equilibrium morphology is mostly isometric in appearance, with (010), (201) and (011) faces dominant. Exposure of the (010) surface is vital because it is normal to the one-dimensional ion-conduction pathway. Platelet and cube-like shapes observed by previous microscopy studies are reproduced by adjusting surface energies. The results indicate that a variety of (nano)particle morphologies can be achieved by tuning surface stabilities, which depend on synthesis methods and solvent conditions, and will be important in optimising electrochemical performance.

Fluorotetrahydroquinolines from diethyl 2-fluoromalonate ester.

A short series of fluorotetrahydroquinolines was synthesised in two steps from diethyl fluoromalonate and appropriate ortho-nitrobenzyl bromide precursors.

Molecular mechanism of altered ezetimibe disposition in nonalcoholic steatohepatitis.

Ezetimibe (EZE) lowers serum lipid levels by blocking cholesterol uptake in the intestine. Disposition of EZE and its pharmacologically active glucuronide metabolite (EZE-GLUC) to the intestine is dependent on hepatobiliary efflux. Previous studies suggested that hepatic transporter expression and function may be altered during nonalcoholic steatohepatitis (NASH). The purpose of the current study was to determine whether NASH-induced changes in the expression and function of hepatic transporters result in altered disposition of EZE and EZE-GLUC. Rats fed a methionine- and choline-deficient (MCD) diet for 8 weeks were administered 10 mg/kg EZE either by intravenous bolus or oral gavage. Plasma and bile samples were collected over 2 h followed by terminal urine and tissue collection. EZE and EZE-GLUC concentrations were determined by liquid chromatography-tandem mass spectrometry. The sinusoidal transporter Abcc3 was induced in MCD rats, which correlated with increased plasma concentrations of EZE-GLUC, regardless of dosing method. Hepatic expression of the biliary transporters Abcc2 and Abcb1 was also increased in MCD animals, but the biliary efflux of EZE-GLUC was slightly diminished, whereas biliary bile acid concentrations were unaltered. The cellular localization of Abcc2 and Abcb1 appeared to be internalized away from the canalicular membrane in MCD livers, providing a mechanism for the shift to plasma drug efflux. The combination of induced expression and altered localization of efflux transporters in NASH shifts the disposition profile of EZE-GLUC toward plasma retention away from the site of action. This increased plasma retention of drugs in NASH may have implications for the pharmacological effect and safety of numerous drugs.

Atomic-Level Changes during Electrochemical Cycling of Oriented LiMn2O4 Cathodic Thin Films.

Spinel LiMn2O4 is an attractive lithium-ion battery cathode material that undergoes a complex series of structural changes during electrochemical cycling that lead to rapid capacity fading, compromising its long-term performance. To gain insights into this behavior, in this report we analyze changes in epitaxial LiMn2O4 thin films during the first few charge-discharge cycles with atomic resolution and correlate them with changes in the electrochemical properties. Impedance spectroscopy and scanning transmission electron microscopy are used to show that defect-rich LiMn2O4 surfaces contribute greatly to the increased resistivity of the battery after only a single charge. Sequences of {111} stacking faults within the films were also observed upon charging, increasing in number with further cycling. The atomic structures of these stacking faults are reported for the first time, showing that Li deintercalation is accompanied by local oxygen loss and relaxation of Mn atoms onto previously unoccupied sites. The stacking faults have a more compressed structure than the spinel matrix and impede Li-ion migration, which explains the observed increase in thin-film resistivity as the number of cycles increases. These results are used to identify key factors contributing to conductivity degradation and capacity fading in LiMn2O4 cathodes, highlighting the need to develop techniques that minimize defect formation in spinel cathodes to improve cycle performance.

Dealumination of small-pore zeolites through pore-opening migration process with the aid of pore-filler stabilization.

Small-pore zeolites are gaining increasing attention owing to their superior catalytic performance. Despite being critical for the catalytic activity and lifetime, postsynthetic tuning of bulk Si/Al ratios of small-pore zeolites has not been achieved with well-preserved crystallinity because of the limited mass transfer of aluminum species through narrow micropores. Here, we demonstrate a postsynthetic approach to tune the composition of small-pore zeolites using a previously unexplored strategy named pore-opening migration process (POMP). Acid treatment assisted by stabilization of the zeolite framework by organic cations in pores is proven to be successful for the removal of Al species from zeolite via POMP. Furthermore, the dealuminated AFX zeolite is treated via defect healing, which yields superior hydrothermal stability against severe steam conditions. Our findings could facilitate industrial applications of small-pore zeolites via aluminum content control and defect healing and could elucidate the structural reconstruction and arrangement processes for inorganic microporous materials.

Variations in ATP-binding cassette transporter regulation during the progression of human nonalcoholic fatty liver disease.

Transporters located on the sinusoidal and canalicular membranes of hepatocytes regulate the efflux of drugs and metabolites into blood and bile, respectively. Changes in the expression or function of these transporters during liver disease may lead to a greater risk of adverse drug reactions. Nonalcoholic fatty liver disease (NAFLD) is a progressive condition encompassing the relatively benign steatosis and the more severe, inflammatory state of nonalcoholic steatohepatitis (NASH). Here, we present an analysis of the effect of NAFLD progression on the major ATP-binding cassette (ABC) efflux transport proteins ABCC1-6, ABCB1, and ABCG2. Human liver samples diagnosed as normal, steatotic, NASH (fatty), and NASH (not fatty) were analyzed. Increasing trends in mRNA expression of ABCC1, ABCC4-5, ABCB1, and ABCG2 were found with NAFLD progression, whereas protein levels of all transporters exhibited increasing trends with disease progression. Immunohistochemical staining of ABCC3, ABCB1, and ABCG2 revealed no alterations in cellular localization during NAFLD progression. ABCC2 staining revealed an alternative mechanism of regulation in NASH in which the transporter appears to be internalized away from the canalicular membrane. This correlated with a preferential shift in the molecular mass of ABCC2 from 200 to 180 kDa in NASH, which has been shown to be associated with a loss of glycosylation and internalization of the protein. These data demonstrate increased expression of multiple efflux transporters as well as altered cellular localization of ABCC2 in NASH, which may have profound effects on the ability of patients with NASH to eliminate drugs in an appropriate manner.

Analysis of global and absorption, distribution, metabolism, and elimination gene expression in the progressive stages of human nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is characterized by a series of pathological changes that range from simple fatty liver to nonalcoholic steatohepatitis (NASH). The objective of this study is to describe changes in global gene expression associated with the progression of human NAFLD. This study is focused on the expression levels of genes responsible for the absorption, distribution, metabolism, and elimination (ADME) of drugs. Differential gene expression between three clinically defined pathological groups-normal, steatosis, and NASH-was analyzed. Genome-wide mRNA levels in samples of human liver tissue were assayed with Affymetrix GeneChip Human 1.0ST arrays. A total of 11,633 genes exhibited altered expression out of 33,252 genes at a 5% false discovery rate. Most gene expression changes occurred in the progression from steatosis to NASH. Principal component analysis revealed that hepatic disease status was the major determinant of differential ADME gene expression rather than age or sex of sample donors. Among the 515 drug transporters and 258 drug-metabolizing enzymes (DMEs) examined, uptake transporters but not efflux transporters or DMEs were significantly over-represented in the number of genes down-regulated. These results suggest that uptake transporter genes are coordinately targeted for down-regulation at the global level during the pathological development of NASH and that these patients may have decreased drug uptake capacity. This coordinated regulation of uptake transporter genes is indicative of a hepatoprotective mechanism acting to prevent accumulation of toxic intermediates in disease-compromised hepatocytes.

Oxide-ion and proton conducting electrolyte materials for clean energy applications: structural and mechanistic features.

This critical review presents an overview of the various classes of oxide materials exhibiting fast oxide-ion or proton conductivity for use as solid electrolytes in clean energy applications such as solid oxide fuel cells. Emphasis is placed on the relationship between structural and mechanistic features of the crystalline materials and their ion conduction properties. After describing well-established classes such as fluorite- and perovskite-based oxides, new materials and structure-types are presented. These include a variety of molybdate, gallate, apatite silicate/germanate and niobate systems, many of which contain flexible structural networks, and exhibit different defect properties and transport mechanisms to the conventional materials. It is concluded that the rich chemistry of these important systems provides diverse possibilities for developing superior ionic conductors for use as solid electrolytes in fuel cells and related applications. In most cases, a greater atomic-level understanding of the structures, defects and conduction mechanisms is achieved through a combination of experimental and computational techniques (217 references).

Status and Prospects of Cubic Silicon Carbide Power Electronics Device Technology.

Wide bandgap (WBG) semiconductors are becoming more widely accepted for use in power electronics due to their superior electrical energy efficiencies and improved power densities. Although WBG cubic silicon carbide (3C-SiC) displays a modest bandgap compared to its commercial counterparts (4H-silicon carbide and gallium nitride), this material has excellent attributes as the WBG semiconductor of choice for low-resistance, reliable diode and MOS devices. At present the material remains firmly in the research domain due to numerous technological impediments that hamper its widespread adoption. The most obvious obstacle is defect-free 3C-SiC; presently, 3C-SiC bulk and heteroepitaxial (on-silicon) display high defect densities such as stacking faults and antiphase boundaries. Moreover, heteroepitaxy 3C-SiC-on-silicon means low temperature processing budgets are imposed upon the system (max. temperature limited to ~1400 °C) limiting selective doping realisation. This paper will give a brief overview of some of the scientific aspects associated with 3C-SiC processing technology in addition to focussing on the latest state of the art results. A particular focus will be placed upon key process steps such as Schottky and ohmic contacts, ion implantation and MOS processing including reliability. Finally, the paper will discuss some device prototypes (diodes and MOSFET) and draw conclusions around the prospects for 3C-SiC devices based upon the processing technology presented.