Search

Acacetin, an important ingredient of acacia honey and a component of several medicinal plants, exhibits therapeutic effects such as antioxidative, anticancer, anti-inflammatory, and anti-plasmodial activities. However, to date, studies reporting a systematic investigation of the in vivo fate of orally administered acacetin are limited. Moreover, the in vitro physicochemical and biopharmaceutical properties of acacetin in the gastrointestinal (GI) tract and their pharmacokinetic impacts remain unclear. Therefore, in this study, we aimed to systematically investigate the oral absorption and disposition of acacetin using relevant rat models. Acacetin exhibited poor solubility (&le, 119 ng/mL) and relatively low stability (27.5&ndash, 62.0% remaining after 24 h) in pH 7 phosphate buffer and simulated GI fluids. A major portion (97.1%) of the initially injected acacetin dose remained unabsorbed in the jejunal segments, and the oral bioavailability of acacetin was very low at 2.34%. The systemic metabolism of acacetin occurred ubiquitously in various tissues (particularly in the liver, where it occurred most extensively), resulting in very high total plasma clearance of 199 &plusmn, 36 mL/min/kg. Collectively, the poor oral bioavailability of acacetin could be attributed mainly to its poor solubility and low GI luminal stability.

PF-543, the most potent sphingosine kinase (SK) inhibitor, does not demonstrate effective anticancer activity in some cancer cells, unlike other known SK1 inhibitors. PF-543 has a non-lipid structure with a unique toluene backbone, however, the importance of this structure remains unclear. Therefore, the purpose of this study was to investigate changes in SK inhibitory and anticancer activities and to explore the role of the tolyl group structure of PF-543 through various modifications. We transformed the methyl group of PF-543 into hydrogen, fluorine, and hydroxy. PF-543 derivatives in which the methyl group was substituted by hydrogen and fluorine (compound 5) demonstrated SK1 inhibitory and anticancer activities similar to PF-543. Moreover, we performed molecular modeling studies of PF-543 and compound 5. To assess the metabolic stability of PF-543 and compound 5, we determined their degree of degradation using the liver microsomes of four different animal species (human, dog, rat, and mouse). However, both PF-543 and compound 5 showed poor microsomal stability. Therefore, for the medical applications of PF-543, the structural modifications of its other parts may be necessary. Our results provide important information for the design of additional PF-543 analogs.

Background/Aim: Lung cancer shows the highest estimated deaths in both males and females in the Unites States. Importin 7 is overexpressed in lung adenocarcinoma tissues. In this study, we aimed to demonstrate the anticancer effect of importin 7 down-regulation, especially in lung cancer. Materials and Methods: Glycerol propoxylate triacrylate spermine (GPT-SPE) is a biocompatible carrier used for aerosol gene delivery. Repeated aerosol delivery of GPT-SPE/shImportin 7 complexes was performed to 10-week-old male K-rasLA1mice (a murine lung cancer model) twice a week for 4 weeks (8 times) in a nose-only exposure chamber. Results: Aerosol delivery of GPT-SPE/shImportin 7 inhibits lung cancer in K-rasLA1mice compared to control and scramble control groups. Moreover, importin 7-down-regulated stable cell-line demonstrates suppression of proliferation through Akt inhibition and apoptosis. Conclusion: Down-regulation of importin 7 significantly suppresses lung cancer in vitro and in vivo.

Lysyl-tRNA synthetase (KRS) can be released from cancer cells to cause inflammation, but the mechanism of KRS secretion is unknown. Kim et al. demonstrate that KRS is cleaved by caspase-8, which exposes a binding motif for syntenin and facilitates the secretion of KRS in exosomes., Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but the mechanism of their secretion is not understood. This study describes the secretion route of the ARS lysyl-tRNA synthetase (KRS) and how this process is regulated by caspase activity, which has been implicated in the unconventional secretion of other proteins. We show that KRS is secreted from colorectal carcinoma cells within the lumen of exosomes that can trigger an inflammatory response. Caspase-8 cleaved the N-terminal of KRS, thus exposing a PDZ-binding motif located in the C terminus of KRS. Syntenin bound to the exposed PDZ-binding motif of KRS and facilitated the exosomic secretion of KRS dissociated from the multi-tRNA synthetase complex. KRS-containing exosomes released by cancer cells induced macrophage migration, and their secretion of TNF-α and cleaved KRS made a significant contribution to these activities, which suggests a novel mechanism by which caspase-8 may promote inflammation.

Nonalcoholic fatty liver disease (NAFLD) refers to hepatic pathologies, including simple fatty liver (SFL), nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis, that may progress to hepatocellular carcinoma. These liver disease states may affect the activity and expression levels of drug-metabolizing enzymes, potentially resulting in an alteration in the pharmacokinetics, therapeutic efficacy, and safety of drugs. This study investigated the hepatic cytochrome P450 (CYP) 2B1-modulating effect of a specific NAFLD state in dietary rat models. Sprague-Dawley rats were given a methionine/choline-deficient (MCD) or high-fat (HF) diet to induce NASH and SFL, respectively. The induction of these disease states was confirmed by plasma chemistry and liver histological analysis. Both the protein and mRNA levels of hepatic CYP2B1 were considerably reduced in MCD diet-fed rats; however, they were similar between the HF diet-fed and control rats. Consistently, the enzyme-kinetic and pharmacokinetic parameters for CYP2B1-mediated bupropion metabolism were considerably reduced in MCD diet-fed rats; however, they were also similar between the HF diet-fed and control rats. These results may promote a better understanding of the influence of NAFLD on CYP2B1-mediated metabolism, which could have important implications for the safety and pharmacokinetics of drug substrates for the CYP2B subfamily in patients with NAFLD.

Alantolactone (ALA) is a major bioactive sesquiterpene lactone present in the roots of Inula helenium L. (Asteraceae) which has been used widely in traditional medicine against various diseases such as asthma, cancer and tuberculosis. The pharmacologic activities of alantolactone have been well characterized, yet information on the physicochemical and pharmacokinetic properties of alantolactone and their mechanistic elucidation are still limited. Thus, this study aims to investigate the oral absorption and disposition of alantolactone and their relevant mechanisms. Log P values of alantolactone ranged from 1.52 to 1.84, and alantolactone was unstable in biological samples such as plasma, urine, bile, rat liver microsomes (RLM) and simulated gastrointestinal fluids. The metabolic rate of alantolactone was markedly higher in rat liver homogenates than in the other tissue homogenates. A saturable and concentration-dependent metabolic rate profile of alantolactone was observed in RLM, and rat cytochrome P450 (CYP) 1 A, 2C, 2D and 3 A subfamilies were significantly involved in its hepatic metabolism. Based on the well-stirred model, the hepatic extraction ratio (HER) was estimated to be 0.890-0.933, classifying alantolactone as a drug with high HER. Moreover, high total body clearance (111 ± 41 ml/min/kg) and low oral bioavailability (0.323%) of alantolactone were observed in rats. Taken together, the present study demonstrates that the extensive hepatic metabolism, at least partially mediated by CYP, is primarily responsible for the high total body clearance of alantolactone, and that the low oral bioavailability of alantolactone could be attributed to its low stability in gastrointestinal fluids and a hepatic first-pass effect in rats. Copyright © 2016 John Wiley & Sons, Ltd.

An empirical, versatile finite-element model is developed to predict void formation in as-deposited or melt-quenched amorphous Ge2Sb2Te5 during annealing. This model incorporates void formation with nucleation and growth of the crystals along with thermal models that capture laser heating of the nano-structures during device fabrication. Modeling of void formation during Joule heating or furnace annealing can be implemented in a similar way. The modeling results are compared to example experimental results obtained from pore-cell phase change memory structures.

Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC50 values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 &mu, M and 44.7 &mu, M, while those of magnolol were 19.0 &mu, M and 47.3 &mu, M, respectively. Notably, the systemic exposure (AUC and Cmax) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration of intravenous honokiol or magnolol. The differential effects of the two phytochemicals on phenacetin and diclofenac in vivo pharmacokinetics could at least be partly attributed to their lower IC50 values for the inhibition of phenacetin metabolism than for diclofenac metabolism. In addition, the systemic exposure, CL, and Vss of honokiol and magnolol tended to be similar between the rat groups receiving phenacetin and diclofenac. These findings improve our understanding of CYP-mediated drug interactions with M. officinalis and its active constituents.

We report the synthesis of quaternary tungsten bronze nanocrystals (QTBN) doped with sodium and cesium, Na x Cs y WO z , which were prepared via a simple thermal decomposition process involving the combination of ammonium metatungstates with oleylamine as both the surfactant and the solvent. The QTBN capped with oleylamine had an average diameter of about 30 nm and exhibited a shielding property of approximately 97% of near-infrared radiation across a wavelength range of 780–2100 nm, while transmitting 64% of visible light at 432 nm upon dispersion in a non-polar solvent of toluene. Our characterizations showed that both sodium and cesium ions could successfully be intercalated into the framework of the cubic pyrochlore structure of tungsten oxide at a relatively low reaction temperature and within a short time, generating the quaternary compound of tungsten bronze nanoparticles. As a result, our procedure conferred near infrared absorption properties upon the QTBN that are superior to those of ternary tungsten bronze nanoparticles in terms of absorption range and intensity, suggesting a significantly advanced solution process capable of producing useful near infrared absorbents.

Magnolol (MAG; 5,5'-diallyl-2,2'-biphenyldiol) is a major bioactive component of Magnolia officinalis. We investigated the metabolic interactions of MAG with hepatic cytochrome P450 monooxygenase (CYP) through in vitro microsomal metabolism study using human (HLM) and rat liver microsomes (RLM). CYP2C and 3A subfamilies were significantly involved in the metabolism of MAG, while CYP1A subfamily was not in HLM and RLM. The relative contribution of phase I enzymes including CYP to the metabolism of MAG was comparable to that of uridine diphosphate glucuronosyltransferase (UGT) in RLM. Moreover, MAG potently inhibited the metabolic activity of CYP1A (IC50 of 1.62 μM) and 2C (IC50 of 5.56 μM), while weakly CYP3A (IC50 of 35.0 μM) in HLM and RLM. By the construction of Dixon plot, the inhibition type of MAG on CYP activity in RLM was determined as follows: uncompetitive inhibitor for CYP1A (Ki of 1.09-12.0 μM); competitive inhibitor for CYP2C (Ki of 10.0-15.2 μM) and 3A (Ki of 93.7-183 μM). Based on the comparison of the current IC50 and Ki values with a previously reported liver concentration (about 13 μM) of MAG after its seven times oral administration at a dose of 50 mg/kg in rats, it is suggested that MAG could show significant inhibition of CYP1A and 2C, but not CYP3A, in the in vivo rat system. These results could lead to further studies in clinically significant metabolism-mediated MAG-drug interactions.

The aim of this study was to elucidate the inhibition mechanism of 18β-glycyrrhetic acid (GLY) on cytochrome P450 (CYP) activity and in vivo pharmacokinetic consequences of single GLY dose in rats. An in vitro CYP inhibition study in rat liver microsomes (RLM) was conducted using probe substrates for CYPs. Then, an in vivo pharmacokinetics of intravenous and oral buspirone (BUS), a probe substrate for CYP3A, was studied with the concurrent administration of oral GLY in rats. In the in vitro CYP inhibition study, CYP3A was involved in the metabolism of GLY. Moreover, GLY inhibited CYP3A activity with an IC50 of 20.1 ± 10.7 μM via a mixed inhibition mechanism. In the in vivo rat pharmacokinetic study, single oral GLY dose enhanced the area under plasma concentration-time curve (AUC) of intravenous and oral BUS, but the extent of increase in AUC was only minimal (1.12-1.45 fold). These results indicate that GLY can inhibit the in vitro CYP3A-mediated drug metabolism in RLM via a mixed inhibition mechanism. However, the impact of single oral GLY dose on the pharmacokinetics of BUS in rats was limited, showing that GLY could function as merely a weak inhibitor for CYP3A-mediated drug metabolism in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

Polyurethane foams were synthesized by substituting a portion of petroleum base polyether pol-yol with castor oil-derived polyol(COP). Contact angle tester and surface tensionmeter were used to examine the compatibility of petroleum base polyether polyol and COP. To investigate the optimum content of COP and surfactant, the content of COP has been changed from 0 wt% to 80 wt%. From the results of polyurethane foams synthesized by surfactant L-580K, DC-5950 and BF-2470, the best mechanical properties was observed when the content of COP was 30wt% and surfactant BF-2470.Key words : polyurethane foam, castor oil polyol, property, compatibility 1) I. 서 론 1894년 독일의 Wurtz와 Hoffman이 최초로 하이드록실기(hydroxyl group) 화합물과 이소시아네이트(isocyanate)와의 반응을 발표하면서 세상에 알려진 폴리우레탄은 1937년 Otto Bayer에 의하여 상업적인 용도로 개발되었다. 오늘날 폴리우레탄은 조선(ship-building), 건축, 자동차, 신발에 이르기까지 많은 산업 † 교신저자:ksb@kgu.ac.kr에서 중요한 역할을 한다. 경질 폴리우레탄 폼은 가정용 냉장고에서 LNG선박 및 저장탱크용 단열재에 이르기까지 다양하게 이용되고 있는 효과적인 단열재이다. 편안하고 튼튼한 매트리스와 자동차, 가정용 의자는 연질 폴리우레탄 폼으로부터 제조 된다. 또한 신발 밑창, 스포츠 장비, 자동차 범퍼들은 폴리우레탄 엘라스토머의 형태로 만들어진다[1]. 폴리우레탄은 하이드록실기를 가지는 폴리올 (po-lyol)과 폴리이소시아네이트(polyisocyanate)와의 발열 반응으로 만들어 지게 되는데 현재 이 두 물질들은 KIGAS Vol. 16, No. 5, pp 66~75, 2012 http://dx.doi.org/10.7842/kigas.2012.16.5.66(Journal of the Korean Institute of Gas)

We study the drift behavior of RESET resistance RRESET and threshold switching voltage Vth in phase-change memory (PCM) and their temperature dependence. To extend the temperature-dependent measurement to microsecond time scales, we integrate an innovative micro-thermal stage (MTS) on the PCM cell. The MTS changes the temperature of the programmed region of the PCM cell within a few microseconds by placing the Pt heater in close proximity of the programmed region. First, we experimentally verify the existing phenomenological RRESET and Vth drift model for constant annealing temperature at various temperatures between 25°C and 185°C down to 100 μs and show that the measured temperature dependence of the drift coefficient agrees well with what is expected from the existing drift models. Based on the existing drift model for a constant annealing temperature, we derive the analytical expression for the RRESET drift for time-varying annealing temperature and experimentally verify the analytical expression. The derived analytical expression is important to understand the impact of thermal disturbance on PCM reliability such as variations in RRESET and Vth.

We discuss options for metal-oxide-semiconductor field-effect transistor (MOSFET) gate stack scaling with thin titanium nitride metal gate electrodes and high-permittivity ('high-k') gate dielectrics, aimed at gate-first integration schemes. Both options are based on further increasing permittivity of the dielectric stack. First, we show that hafnium-based stacks such as TiN/HfO"2 can be scaled to capacitance equivalent thickness in inversion (T"i"n"v) of 10A and equivalent oxide thickness (EOT) of 6A by using silicon nitride instead of silicon oxide as a high-k/channel interfacial layer. This is based on the higher dielectric constant of Si"3N"4 and on its resistance to oxidation. Although the nitrogen introduces positive fixed charges, carrier mobility is not degraded. Secondly, we investigate whether Ti-based 'higher-k' dielectrics have the potential to ultimately replace Hf. We discuss oxygen loss from TiO"2 as a main challenge, and identify two migration pathways for such oxygen atoms: In addition to well-known down-diffusion and channel Si oxidation, we have newly observed oxygen up-diffusion through the TiN metal gate, forming SiO"2 at the poly-Si contact. We further address the performance of Si"3N"4 and HfO"2 as oxygen barrier layers.

A highly sensitive bioanalytical method for the quantification of acacetin in human plasma was developed and comprehensively validated using liquid chromatography-tandem mass spectrometry (LC–MS/MS). A minimal volume of human plasma sample (20 μL) was prepared by simple deproteinization with 80 μL of acetonitrile. Chromatographic separation was performed using Kinetex C18 column with an isocratic mobile phase consisting of water and acetonitrile (20:80, v/v) containing 0.1 % formic acid at a flow rate of 0.3 mL/min over a total run time of 2.0 min. Mass spectrometric detection was performed using multiple reaction-monitoring modes at the mass/charge transitions m/z 285.22 → 242.17 for acacetin and m/z 277.59 → 175.04 for chlorpropamide (internal standard). The calibration curve was linear over the range of 0.1–500 ng/mL with a lower limit of quantitation of 0.1 ng/mL. The coefficients of variation for both intra- and inter-day validation were less than 11.9 %, and the intra- and inter-day accuracy ranged from 96.8 to 108 %. Mean recovery of acacetin in human plasma was within the range of 91.5–95.6 %. This validated LC–MS/MS method was successfully applied to a human plasma protein binding study that indicated extensive and concentration-independent protein binding of acacetin in human plasma.

Lipase from Candida rugosa was entrapped by drop-wise addition of an aqueous mixture of sodium alginate and the biocatalyst to a hardening solution of a Ca 2+ salt. Effects of immobilization conditions such as alginate concentration, CaCl 2 concentration, ratio by weight of enzyme to alginate (E/A) and bead size on loading efficiency (percent of total enzyme entrapped) and immobilization yield (specific activity ratio of entrapped lipase to free lipase) were investigated. An increase in alginate concentration raised loading efficiency, but decreased immobilization yield. CaCl 2 concentration was expected to have a similar effect on loading efficiency and immobilization yield, but the effect was small in the tested range of 50–300 mM. With increasing bead size, immobilization yield decreased due to mass transfer resistance, but loading efficiency was unchanged. In order to prevent enzyme from leaking out of the gel beads, beads were coated with chitosan and silicate. Compared to non-coated beads, coated alginate beads showed the higher re-usability, illustrating the effectiveness of the coating method. When coated with silicate, lipase-entrapped beads retained the highest catalytic activity.

We demonstrate techniques for measuring thermoelectric voltages and generating on-chip power using a silicon-on-insulator substrate. Our design uses lateral heat conduction in the silicon overlayer to establish temperature gradients, which dramatically reduces microfabrication complexity compared to competing designs based on a free-standing membrane. This letter characterizes the thermoelectric power of a metal-semiconductor structure involving a doped SbTe alloy that is relevant for phase-change memory. The thermoelectric power of the SbTe-TiW thermocouple is 24 μV/K, and the power generation output achieves up to 0.56 μW/cm2 with a temperature gradient of 18°K.

Puerarin (8-β-D-glucopyranosyl-7-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a major pharmacological component of Puerariae Radix, the root of Pueraria lobata. We investigated the effect of puerarin on hepatic cytochrome P450-mediated drug metabolism in rats and humans. The in vitro cytochrome P450 inhibitory effect of puerarin in human and rat liver microsomes was evaluated using the following model cytochrome P450 substrates: phenacetin for CYP1A, diclofenac for CYP2C, dextromethorphan for CYP2D, and testosterone for CYP3A. The in vivo pharmacokinetics of intravenous and oral buspirone, a probe substrate for CYP3A, was studied with single simultaneous intravenous coadministration of puerarin in rats. In the in vitro cytochrome P450 inhibition study, the rate of disappearance of testosterone was significantly reduced in the presence of 10 µM PU, while that of other cytochrome P450 substrates was not significantly affected in both human and rat liver microsomes, suggesting that puerarin inhibits the in vitro hepatic CYP3A-mediated metabolism in the human and rat systems (IC50 = 15.5 ± 3.9 µM). After intravenous administration of buspirone with single simultaneous coadministration of intravenous puerarin at a dose of 10 mg/kg in rats, the total area under the plasma concentration–time curve from time zero to time infinity was increased while time-averaged total body clearance decreased. When buspirone was orally administered in rats with the 10 mg/kg intravenous puerarin coadministration, both total area under the plasma concentration–time curve from time zero to time infinity and the extent of absolute oral bioavailability were significantly increased. Therefore, results of the in vitro microsomal and in vivo pharmacokinetic studies suggest the possible inhibition of hepatic CYP3A-mediated drug metabolism by puerarin administration, potentially leading to metabolism-mediated herb–drug interactions with clinical significance.

Hybrid nanocomplex formulations, based on amphiphilic hyaluronic acid-ceramide (HACE) and lipids, were fabricated for the delivery of 20(S)-ginsenoside Rg 3 [(S)-Rg3]. Nanocomplexes with less than 200 nm mean diameter, narrow size distribution, spherical shape, and negative zeta potential were prepared. The maintenance of the structural stability of the hybrid nanocomplexes in the blood stream was demonstrated by measuring their particle size in serum. Nanocomplexes based on HACE, phosphatidylcholine (PC), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) showed a sustained drug release profile compared with other formulations. Blank nanocomplexes exhibited negligible cytotoxicity within the tested concentration range in A549 human lung adenocarcinoma cells. The cellular uptake efficiency of hybrid nanocomplexes was improved compared with the HACE-based nanoparticles probably because of interactions between lipids and the cellular membrane. The results of a pharmacokinetic study in rats revealed decreased in vivo clearance of (S)-Rg3, especially in the HACE/PC/DSPE-PEG-based hybrid nanocomplex (F3) group. The hybrid nanostructure and the outer PEG chain likely contributed to improve in vivo performance of the F3 group. Thus, these developed hybrid nanocomplexes could serve as good candidates for tumor-targeted delivery of anticancer agents.

Thermal interfaces play a key role in determining the programming energy of phase-change memory (PCM) devices. This letter reports the picosecond thermoreflectance measurements of thermal boundary resistance (TBR) at TiN/GST and Al/TiN interfaces, as well as the intrinsic thermal conductivity measurements of fcc GST between 30°C and 325°C. The TiN/GST TBR decreases with temperature from ~26 to ~18 m2·K/GW, and the Al/TiN ranges from ~7 to 2.4 m2·K/GW. A TBR of 10 m2·K/GW is equivalent in thermal resistance to ~192 nm of TiN. The fcc GST conductivity increases with temperature between ~0.44 and 0.59 W/m/K. A detailed understanding of TBR is essential for optimizing the PCM technology.

Anacetrapib is a potent and selective CETP inhibitor and is undergoing phase III clinical trials for the treatment of dyslipidemia. A simple and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the quantification of anacetrapib in rat plasma was developed and validated using an easily purchasable compound, chlorpropamide, as an internal standard (IS). A minimal volume of rat plasma sample (20 μL) was prepared by a single-step deproteinization procedure with 80 μL of acetonitrile. Chromatographic separation was performed using Kinetex C18 column with a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid at a flow rate of 0.3 mL/min. Mass spectrometric detection was performed using selected reaction monitoring modes at the mass/charge transitions m/z 638 → 283 for anacetrapib and m/z 277 → 175 for IS. The assay was validated to demonstrate the selectivity, linearity, precision, accuracy, recovery, matrix effect and stability. The lower limit of quantification was 5 ng/mL. This LC-MS/MS assay was successfully applied in the rat plasma protein binding and pharmacokinetic studies of anacetrapib. The fraction of unbound anacetrapib was determined to be low (ranging from 5.66 to 12.3%), and the absolute oral bioavailability of anacetrapib was 32.7%.

Phase change memory (PCRAM) is an ideal embedded memory due to its simple BEOL process and low voltage operation. Industrial and automotive applications of PCRAM, however, have not been realized because of poor high temperature properties of the conventional Ge 2 Sb 2 Te 5 phase-change material [1–3]. We have previously reported a special Ge x Sb y Te z material along the Ge and Sb 2 Te 3 tie line that showed superior high temperature performance. In this work we have further enhanced our previous “golden” material by incorporating nitrogen and engineering the Ge/N concentration. In order to rapidly explore a range of new materials a fast method to test retention behavior by laser melt-quenching is adopted which yields retention data on blanket films consistent with device results. A new material with special Ge/N concentration with excellent high temperature retention is discovered. The new material demonstrated nearly 100% yield in a 256 Mb test chip after 160 oC, 84 hrs baking, with projected 10-year retention at 120 oC. (> 9,000 years at 85 oC.)

Application of phase change memory (PCM) has been limited by the high power required to reset the device (changing from crystalline to amorphous state by melting the phase change material). Utilizing the poor thermal and electrical conductivity of TaN we have designed a simple structure that thermally insulates the bottom electrode and thus drastically reduces the heat loss. A 39nm bottom electrode with a TaN thermal barrier and 1.5nm of TiN conductor has demonstrated 30µA reset current, representing a 90% reduction. The benefit of thermal insulation is understood through electrothermal simulation, and the benefit is demonstrated in a 256Mb test chip. The low reset current also improves the reliability and excellent cycling endurance >1E9 is observed. This low power device is promising for expanding the application for PCM.

Background: Curcumin (CUR) is a polyphenolic component derived from an herbal remedy and dietary spice turmeric (Curcuma longa). Objective: The aim of this study was to investigate inhibitory effects of CUR on in vitro cytochrome P450 (CYP) activity and in vivo pharmacokinetic consequences of single CUR dose in rats. Materials and Methods: An in vitro CYP inhibition study in rat liver microsomes (RLM) was conducted using probe substrates for CYPs. Then, an in vivo pharmacokinetics of intravenous buspirone (BUS), a probe substrate for CYP3A, was studied with the concurrent administration of oral CUR in rats. Results: In the in vitro CYP inhibition study, CUR inhibited the CYP3A-mediated metabolism of testosterone (TES) with a half maximal inhibitory concentration of 11.0 ± 3.3 μM. However, the impact of a single oral CUR dose on the pharmacokinetics of BUS in rats is limited, showing that CUR cannot function as an inhibitor for CYP3A-mediated drug metabolism in vivo. Conclusion: To the best of our knowledge, our results are the first reported data regarding the inhibition of in vitro CYP3A-mediated metabolism of TES and the in vivo impact of a single CUR dose on the pharmacokinetics of BUS in rats. Further study is required to draw a confirmative conclusion on whether CUR can be a clinically relevant CYP3A4 inhibitor. SUMMARY CUR can inhibit the in vitro CYP3A-mediated metabolism of TES in RLM. However, the impact of a single oral CUR dose on the pharmacokinetics of BUS in rats is limited, showing that CUR cannot function as an inhibitor for CYP3A-mediated drug metabolism in vivo.

We report on the stability of high-permittivity (high-k) TiO2 films incorporated in metal-oxide-silicon capacitor structures with a TiN metal gate electrode, focusing on oxygen migration. Titanium oxide films are deposited by either Ti sputtering [physical vapor deposition (PVD)] followed by radical shower oxidation or by plasma-enhanced atomic layer deposition (PEALD) from titanium isopropoxide (Ti{OCH(CH3)2}4) and O2 plasma. Both PVD and PEALD films result in near-stoichiometric TiO2 prior to high-temperature annealing. We find that dopant activation anneals of TiO2-containing gate stacks at 1000 °C cause 5 A or more of additional SiO2 to be formed at the gate-dielectric/Si-channel interface. Furthermore, we demonstrate for the first time that oxygen released from TiO2 diffuses through the TiN gate electrode and oxidizes the poly-Si contact. The thickness of this upper SiO2 layer continues to increase with increasing TiO2 thickness, while the thickness of the regrown SiO2 at the gate-dielectric/Si inter...

Thermal conduction in GeSbTe films strongly influences the writing energy and time for phase change memory (PCM) technology. This study measures the thermal conductivity of Ge2Sb2Te5 between 25 and 340°C for layers with thicknesses near 60, 120, and 350nm. A strong thickness dependence of the thermal conductivity is attributed to a combination of thermal boundary resistance (TBR) and microstructural imperfections. Stoichiometric variations significantly alter the phase transition temperatures but do not strongly impact the thermal conductivity at a given temperature. This work makes progress on extracting the TBR for Ge2Sb2Te5 films, which is a critical unknown parameter for PCM simulations.