Vacuum ultraviolet photochemical selectivearea atomic layer deposition of Al2O3 dielectrics

We report the photochemical atomic layer deposition of Al2O3 thin films and the use of this process to achieve area-selective film deposition. A shuttered vacuum ultraviolet (VUV) light source is used to excite molecular oxygen and trimethyl aluminum to deposit films at 60 degrees C. In-situ QCM and post-deposition ellipsometric measurements both show that the deposition rate is saturative as a function of irradiation time. Selective area deposition was achieved by projecting the VUV light through a metalized magnesium fluoride photolithographic mask and the selectivity of deposition on the illuminated and masked regions of the substrate is a logarithmic function of the UV exposure time. The Al2O3 films exhibit dielectric constants of 8 - 10 at 1 MHz after forming gas annealing, similar to films deposited by conventional thermal ALD. (C) 2015 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License

Enhanced switching stability in Ta 2 O 5 resistive RAM by fluorine doping

The effect of fluorine doping on the switching stability of Ta2O5 resistive random access memory devices is investigated. It shows that the dopant serves to increase the memory window and improve the stability of the resistive states due to the neutralization of oxygen vacancies. The ability to alter the current in the low resistance state with set current compliance coupled with large memory window makes multilevel cell switching more favorable. The devices have set and reset voltages of <1V with improved stability due to the fluorine doping. Density functional modelling shows that the incorporation of fluorine dopant atoms at the two-fold O vacancy site in the oxide network removes the defect state in the mid bandgap, lowering the overall density of defects capable of forming conductive filaments. This reduces the probability of forming alternative conducting paths and hence improves the current stability in the low resistance states. The doped devices exhibit more stable resistive states in both dc and pulsed set and reset cycles. The retention failure time is estimated to be a minimum of 2 years for F-doped devices measured by temperature accelerated and stress voltage accelerated retention failure methods

The role of nitrogen doping in ALD Ta2O5 and its influence on multilevel cell switching in RRAM

The role of nitrogen doping on the stability and memory window of resistive state switching in N-doped Ta2O5 deposited by atomic layer deposition is elucidated. Nitrogen incorporation increases the stability of resistive memory states which is attributed to neutralization of electronic defect levels associated with oxygen vacancies. The density functional simulation with screened exchange hybrid functional approximation finds that the incorporation of nitrogen dopant atoms in the oxide network removes the O vacancy midgap defect states, thus nullifying excess defects and eliminating alternative conductive paths. By effectively reducing the density of vacancy-induced defect states through N doping, 3-bit multilevel cell switching is demonstrated, consisting of eight distinctive resistive memory states achieved by either controlling the set current compliance or the maximum voltage during reset. Nitrogen doping has a threefold effect; widening the switching memory window to accommodate more intermediate states, improving the stability of states, and providing gradual reset for multi-level cell switching during reset. The N-doped Ta2O5 devices have relatively small set and reset voltages (< 1 V) with reduced variability due to doping

The role of nitrogen doping in ALD Ta₂O₅ and its influence on multilevel cell switching in RRAM

The role of nitrogen doping on the stability and memory window of resistive state switching in N-doped Ta2O5 deposited by atomic layer deposition is elucidated. Nitrogen incorporation increases the stability of resistive memory states which is attributed to neutralization of electronic defect levels associated with oxygen vacancies. The density functional simulations with the screened exchange hybrid functional approximation show that the incorporation of nitrogen dopant atoms in the oxide network removes the O vacancy midgap defect states, thus nullifying excess defects and eliminating alternative conductive paths. By effectively reducing the density of vacancy-induced defect states through N doping, 3-bit multilevel cell switching is demonstrated, consisting of eight distinctive resistive memory states achieved by either controlling the set current compliance or the maximum voltage during reset. Nitrogen doping has a threefold effect: widening the switching memory window to accommodate the more intermediate states, improving the stability of states, and providing a gradual reset for multi-level cell switching during reset. The N-doped Ta2O5 devices have relatively small set and reset voltages (< 1 V) with reduced variability due to doping.The work has been funded by the Engineering and Physical Sciences Research Council (EPSRC) UK, project numbers EP/M00662X/1, EP/M009297/1, and EP/M006727/1

A lactate shuttle system between tumour and stromal cells is associated with poor prognosis in prostate cancer

Background In a malignant tumour, cancer cells are embedded in stromal cells, namely cancer-associated fibroblasts (CAFs). These CAFs are now accepted as important players in cancer dynamics, being involved in tumour growth and progression. Although there are various reports on the interaction between tumour and stromal cells, the clinico-pathological significance of this cross-talk is still largely unknown. In this study, we aimed to characterise the expression of key metabolic proteins involved in glucose transport, pyruvate/lactate shuttle system, glycolytic metabolism and fatty acid oxidation in CAFs and tumour cells in different stages of malignant transformation. We further aimed to contextualise the clinico-pathological significance of these protein expression profiles with reference to known prognostic indicators, including biochemical recurrence in pT stage. Methods Prostate tissues were obtained from 480 patients with a median age of 64 years following radical prostatectomy with no previous hormonal therapy. Tissues were analysed for the expression of several key metabolism-related proteins in glands and surrounding fibroblasts by immunohistochemistry. Reliable markers of prognosis such as pT stage and biochemical recurrence were assessed for each case. Results We observed that prostate cancer cells did not rely mainly on glycolytic metabolism, while there was a high expression of MCT4 and CAIX - in CAFs. This corroborates the hypothesis of the "Reverse Warburg effect" in prostate cancer, in which fibroblasts are under oxidative stress and express CAIX, an established hypoxia marker. We found that alterations in the expression of metabolism-related proteins were already evident in the early stages of malignant transformation, suggesting the continuing alteration of CAFs from an early stage. Additionally, and for the first time, we show that cases showing high MCT4 expression in CAFs with concomitant strong MCT1 expression in prostate cancer (PCa) cells are associated with poor clinical outcome, namely pT3 stage of the tumour. Conclusions In summary, this work demonstrates for the first time the clinico-pathological significance of the lactate shuttle in prostate cancer. It also suggests that other alterations in CAFs may be useful prognostic factors, and further supports the use of MCT1/MCT4 as targets for PCa therapy.NPG received a fellowship from the Portuguese Foundation for Science and Technology (FCT), refs. SFRH/BD/61027/2009. This work was supported by the FCT grant ref. PTDC/SAUMET/113415/2009, under the scope of "Programa Operacional Tematico Factores de Competitividade" (COMPETE) of "Quadro Comunitario de Apoio III" and co-financed by Fundo Comunitario Europeu FEDER. JA was supported by a Boehringer Ingelheim Fonds fellowship

Cell-to-cell variability in troponin I phosphorylation in a porcine model of pacing-induced heart failure

We tested the hypothesis that myocardial contractile protein phosphorylation and the Ca2+ sensitivity of force production are dysregulated in a porcine model of pacing-induced heart failure (HF). The level of protein kinase A (PKA)-dependent cardiac troponin I (TnI) phosphorylation was lower in the myocardium surrounding the pacing electrode (pacing site) of the failing left ventricle (LV) than in the controls. Immunohistochemical assays of the LV pacing site pointed to isolated clusters of cardiomyocytes exhibiting a reduced level of phosphorylated TnI. Flow cytometry on isolated and permeabilized cardiomyocytes revealed a significantly larger cell-to-cell variation in the level of TnI phosphorylation of the LV pacing site than in the opposite region in HF or in either region in the controls: the interquartile range (IQR) on the distribution histogram of relative TnI phosphorylation was wider at the pacing site (IQR = 0.53) than that at the remote site of HF (IQR = 0.42; P = 0.0047) or that of the free wall of the control animals (IQR = 0.36; P = 0.0093). Additionally, the Ca2+ sensitivities of isometric force production were higher and appeared to be more variable in single permeabilized cardiomyocytes from the HF pacing site than in the healthy myocardium. In conclusion, the level of PKA-dependent TnI phosphorylation and the Ca2+ sensitivity of force production exhibited a high cell-to-cell variability at the LV pacing site, possibly explaining the abnormalities of the regional myocardial contractile function in a porcine model of pacing-induced HF

Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.

Although paediatric high grade gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular and phenotypic characterisation of a series of paediatric high grade glioma cell lines in comparison to routinely used adult lines