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Hydrogels are promising as materials for soft actuators because of qualities such as softness, transparency, and responsiveness to stimuli. However, weak and slow actuations remain challenging as a result of low modulus and osmosis-driven slow water diffusion, respectively. We used turgor pressure and electroosmosis to realize a strong and fast hydrogel-based actuator. A turgor actuator fabricated with a gel confined by a selectively permeable membrane can retain a high osmotic pressure that drives gel swelling; thus, our actuator exerts large stress [0.73 megapascals (MPa) in 96 minutes (min)] with a 1.16 cubic centimeters of hydrogel. With the accelerated water transport caused by electroosmosis, the gel swells rapidly, enhancing the actuation speed (0.79 MPa in 9 min). Our strategies enable a soft hydrogel to break a brick and construct underwater structures within a few minutes.

The extracellular lipid matrix in the stratum corneum (SC) is crucial for generating a skin barrier (permeability) function. The lipid matrix contains three major components; ceramides, cholesterol, and free fatty acids. The broad diversity of ceramides depends on their molecular structures (e.g., hydroxylations and chain lengths) and plays a critical role in maintaining the structural integrity of the lipid matrix. Although recent studies identified a new subclass of ceramide, 1-O-acylceramide NP (CerENP), its precise role in the lipid matrix of SC is still elusive. Herein, we investigate the role of CerENP on the structure and permeability of the SC by molecular dynamics simulations. Our results suggest that the CerENP molecules induce a denser lipid matrix in the lateral dimension in the long periodicity phase model with a bilayer-slab- bilayer structure. Moreover, ethanol permeability analysis indicates that CerENP can suppress molecular permeability through the lipid matrix. This study provides insight into the role of a new subclass of ceramide in the SC, which can lead to our better understanding of skin organization and disease-related barrier dysfunction.

New ceramide (CER) NPs were prepared by linking fatty acids derived from oils of Korean traditional plants to phytosphingosine (PHS). The oils of Korean traditional plants were extracted from the seeds of Panax ginseng, Camellia sinensis, Glycine max napjakong, Glycine max seoritae, and Camellia japonica as sources of diverse fatty acids.The aim of this study was to investigate signaling bioactivities of HP-C. sinensis ceramide NP that was column purified to remove any residual PHS and to evaluate the skin barrier functions of the HP-C. sinensis ceramide NP in human skin.The expressions of genes related to epidermal differentiation were analyzed in vitro by qPCR. Human studies were also performed to determine the skin barrier functions with respect to TEWL and SC cohesion.The HP-C. sinensis CER NP significantly enhanced the expressions of FLG, CASP14, and INV indicates that the signaling biological activities of oil-derived ceramide NPs could be different depend on the natural oils. The control ceramide, C18-CER NP, had no effect on the expression of the three genes. HP-C. sinensis CER NP was selected for the in vivo human studies. Application of 0.5% HP-C. sinensis CER NP cream stimulated significantly faster recovery of a disrupted skin barrier than that of the control C18-CER NP. A significant enhancement of SC cohesion of the skin treated with 0.5% HP-C. sinensis CER NP was also observed.Taken all together, our results clearly demonstrate that HP-C. sinensis CER NP, P. ginseng CER NP, and other oil-derived CER NP could be a better choice for developing moisturizers to improve skin barrier function as they more closely mimic the endogenous CER composition of the actual human skin barrier.

We present a framework for automatically testing functional correctness of back-end servers. We created a pre-production environment where traffic between servers can be reconfigured dynamically. Production requests are sampled and replayed in our framework so that we can cover many corner cases of the system without having the developer manually write test cases. We also describe how to handle mutate requests and support checking the validity of back-end rewrites.

Ceramide NP is known to be the most abundant class of 12 ceramide (CER) families that form a permeability barrier in the human skin barrier. However, not many studies have been reported on the regulation of the biosynthesis of ceramide NP. Recently, it has been reported that phytosphingosine (PHS) treatment in the cultured keratinocytes (KC) notably increased the content of ceramide NP. However, the mechanism behind the PHS-induced enhancement of ceramide NP has not been elucidated. In this study, we investigated the effects of PHS on the expression of several essential genes for the biosynthesis of CER. Also, we determined the molecular mechanism behind the unique enhancement of ceramide NP upon treatment of PHS in the cultured KC. The expressions of all of the three genes (SPT, ceramide synthase 3 [CERS3], and ELOVL4) and their respective proteins were markedly increased in PHS-treated KC. In addition, the expression of the dihydroceramide C4-desaturase (DES2) responsible for conversion of dihydroceramide into ceramide NP was uniquely enhanced only by PHS treatment. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed that more than 20-fold increase of ceramide NP by PHS was observed while no significant enhancement of ceramide NS and NDS was observed. This study demonstrates that PHS plays a fundamental role in strengthening the epidermal permeability barrier by stimulating the overall processes of biosynthesis of all classes of CER in epidermis. The dramatic increase of ceramide NP upon PHS treatment seemed to be the outcome of transformation of dihydroceramide and/or ceramide NS by C4-hydroxylase activity.

The incidence of type 2 diabetes mellitus (DM) has been increasing rapidly, and the disease has become a serious sociomedical problem. Many skin problems, such as xerosis, pruritus, skin infections and delayed wound healing, that might be related to chronic impairment of skin barrier function decrease the quality of life in patients with DM. However, the status of the permeability and antimicrobial barrier of the skin in DM remains unknown. This study aimed to elucidate skin barrier impairment in patients with type 2 DM and its pathomechanisms using classic animal models of type 2 DM. Functional studies of the skin barrier and an analysis of stratum corneum (SC) lipids were compared between patients with type 2 DM and age- and sex-matched non-diabetes controls. Also, functional studies on the skin barrier, epidermal lipid analyses, and electron microscopy and biomolecular studies were performed using type 2 DM animal models, db/db and ob/ob mice. Patients with type 2 DM presented with epidermal barrier impairments, including SC hydration, which was influenced by blood glucose control (HbA1c level). In the lipid analysis of SC, ceramides, fatty acids and cholesterol were significantly decreased in patients with type 2 DM compared with controls. Type 2 DM murine models presented with severe hyperglycaemia, impairment of skin barrier homeostasis, decreases in epidermal proliferation and epidermal lipid synthesis, decreases in lamellar body (LB) and epidermal antimicrobial peptides (AMPs), an increase in receptors for advanced glycation end-product (AGE) in the epidermis and an increase in serum AGE. Impairment of the skin barrier was observed in type 2 DM, which results in part from a decrease in epidermal proliferation. Serum AGE and its epidermal receptors were increased in type 2 diabetic mice which display impaired skin barrier parameters such as epidermal lipid synthesis, LB production, epidermal AMP and SC lipids.

Interatomic potentials for the Mo-M (M = Al, Co, Cr, Fe, Ni, Ti) binary alloy systems have been newly developed based on the second nearest-neighbor modified embedded-atom method (2NN MEAM) formalism. The new interatomic potentials reproduce structural and thermodynamic properties of binary alloys reasonably well. They can be utilized to generate interatomic potentials for Pt-Mo-M multicomponent alloy systems. The present work extends the coverage of the atomistic simulations using 2NN MEAM interatomic potentials into Pt-based multicomponent systems, and the design of efficient noble metal catalysts using atomistic simulations is now enabled with a greater variety of alloying elements.

Matrix metalloproteinases (MMPs) are zinc-dependent proteases involved in the degradation of extracellular matrix proteins. As one of the isoforms, MMP-1 breaks down collagen, and its activity is known to be important in wound healing. Its timely and adequate level of expression is pivotal because MMP-1 is also involved in the damage or aging of skins as well as in certain types of cancers. Thus, both assaying the MMP-1 activity and developing its inhibitors are of great importance. We here developed an in-house assay system that gave us the high degree of freedom in screening peptide inhibitors of MMP-1. The assay system utilized a circularly permutated fusion of β-lactamase and its inhibitory protein through an MMP-1-sensitive linker so that the activity of MMP-1 could be translated into that of β-lactamase. As a proof of concept, we applied the developed assay system to initial screens of MMP-1 inhibitors and successfully identified one lead peptide that inhibited the collagenase activity of the enzyme.

Omega-hydroxyceramides (ω-OH-Cer) play a crucial role in maintaining the integrity of skin barrier. ω-OH-Cer are the primary lipid constituents of the corneocyte lipid envelope (CLE) covalently attached to the outer surface of the cornified envelope linked to involucrin to become bound form lipids in stratum corneum (SC). CLE becomes a hydrophobic impermeable layer of matured corneocyte preventing loss of natural moisturizing factor inside the corneocytes. More importantly, CLE may also play an important role in the formation of proper orientation of intercellular lipid lamellar structure by interdigitating with the intercellular lipids in a comb-like fashion. Abnormal barrier conditions associated with atopic dermatitis but also UVB-irradiated skins are known to have lowered level of bound lipids, especially ω-OH-Cer, which indicate that ω-OH-Cer play an important role in maintaining the integrity of skin barrier. In this study, protective effects of a novel synthetic C16 omega-hydroxyphytoceramides (ω-OH-phytoceramide) on skin barrier function were investigated. Epidermal barrier disruption was induced by UVB irradiation, tape-stripping in hairless mouse and human skin. Protective effect of damaged epidermis was evaluated using the measurement of transepidermal water loss and cohesion of SC. Increased keratinocyte differentiation was verified using cultured keratinocyte through western blot. Results clearly demonstrated that a synthetic C16 ω-OH-phytoceramide enhanced the integrity of SC and accelerated the recovery of damaged skin barrier function by stimulating differentiation process. In a conclusion, a synthetic C16 ω-OH-phytoceramide treatment improved epidermal homeostasis in several disrupted conditions.

The ability to control the degree of particle dispersion in polymer solutions has been a long-standing subject in colloidal science. While a generally accepted principle is that nonadsorbing polymers can induce depletion attraction, which is mostly temperature independent, the effects of adding adsorbing polymers are still poorly understood. In this study, we investigated the effects of adsorbing polymers on the temperature-dependent stability of nanoparticles. The model systems consisted of silica nanoparticles in low-molecular-weight poly(ethylene glycol) solutions. The detailed microstructures were determined with small-angle X-ray and neutron scattering measurements, while the dynamics of the temperature-dependent microstructures of the nanoparticles and polymers were probed with diffusing-wave spectroscopy. It was found that a poor solvent for polymer could drive adsorbed polymers to leave the particle substrate and return to the bulk solution due to a complicated interaction with surface, while the ...

This study is designed to optimise the extraction of a mangostin using supercritical carbon dioxide. The extraction parameters were optimised by Box Behnken Design (BBD) with 17-run experiments. The maximum yield of a mangostin is 58.7 wt% under optimum conditions as follows: extraction pressure of 20.01 MPa, thetemperature of 46.25 °C and percentage of co-solvent at 2.9 % of ethanol. To date, this is the first reportdepicting the optimisation of a mangostin from the pericarp of Garcinia Mangostana Linn using supercriticalcarbon dioxide.

Background Cell migration is an essential process for survival and differentiation of mammalian cells. Numerous diseases are induced or influenced by inappropriate regulation of cell migration, which plays a key role in cancer cell metastasis. In fact, very few anti-metastasis drugs are available on the market. SphKs are enzymes that convert sphingosine to sphingosine-1-phosphate (S1P) and are known to control various cellular functions, including migration of cells. In human, SphK2 is known to promote apoptosis, suppresses cell growth, and controls cell migration; in addition, the specific ablation of SphK2 activity was reported to inhibit cancer cell metastasis. Objective The previously identified SG12 and SG14 are synthetic analogs of sphingoid and can specifically inhibit the functions of SphK2. We investigated the effects of the SphK2 specific inhibitors on the migratory behavior of cells. Method We investigated how SG12 and SG14 affect cell migration by monitoring both cumulative and individual cell migration behavior using HeLa cells. Results SG12 and SG14 mutually showed stronger inhibitory effects with less cytotoxicity compared with a general SphK inhibitor, N,N-dimethylsphingosine (DMS). The mechanistic aspects of specific SphK2 inhibition were studied by examining actin filamentation and the expression levels of motility-related genes. Conclusion The data revealed that SG12 and SG14 resemble DMS in decreasing overall cell motility, but differ in that they differentially affect motility parameters and motility-related signal transduction pathways and therefore actin polymerization, which are not altered by DMS. Our findings show that SphK2 inhibitors are putative candidates for anti-metastatic drugs.

Ceramides in the human stratum corneum (SC) are a mixture of diverse N-acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N-acylated FAs and compare them with C18-ceramide N-stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer.

Myoung Jin Oh,1 Young Hoon Cho,1 So Yoon Cha,1 Eun Ok Lee,2 Jin Wook Kim,2 Sun Ki Kim,2 Chang Seo Park1 1Department of Chemical and Biochemical Engineering, Dongguk University, Chung-gu, Seoul, 2LCS Biotech, Gwonseon-gu, Suwon-si, Gyeonggi-do, Republic of Korea Abstract: Ceramides in the human stratum corneum (SC) are a mixture of diverse N-acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N-acylated FAs and compare them with C18-ceramide N-stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer. Keywords: fatty acid, chain length, phytoceramide, skin barrier, natural oil

The stratum corneum (SC) is the outermost layer of skin that functions as a barrier and protects against environmental influences and transepidermal water loss. Its unique morphology consists of keratin-enriched corneocytes embedded in a distinctive mixture of lipids containing mainly ceramides, free fatty acids, and cholesterol. Ceramides are sphingolipids consisting of sphingoid bases, which are linked to fatty acids by an amide bond. Typical sphingoid bases in the skin are composed of dihydrosphingosine (dS), sphingosine (S), phytosphingosine (P), and 6-hydroxysphingosine (H), and the fatty acid acyl chains are composed of non-hydroxy fatty acid (N), α-hydroxy fatty acid (A), ω-hydroxy fatty acid (O), and esterified ω-hydroxy fatty acid (E). The 16 ceramide classes include several combinations of sphingoid bases and fatty acid acyl chains. Among them, N-type ceramides are the most abundant in the SC. Mass spectrometry (MS)/MS analysis of N-type ceramides using chip-based direct infusion nanoelectrospray-ion trap mass spectrometry generated the characteristic fragmentation pattern of both acyl and sphingoid units, which could be applied to structural identification of ceramides. Based on the MS/MS fragmentation patterns of N-type ceramides, comprehensive fragmentation schemes were proposed. In addition, mass fragmentation patterns, which are specific to the sphingoid backbone of N-type ceramides, were found in higher m/z regions of tandem mass spectra. These characteristic and general fragmentation patterns were used to identify N-type ceramides in human SC. Based on established MS/MS fragmentation patterns of N-type ceramides, 52 ceramides (including different classes of NS, NdS, NP, and NH) were identified in human SC. The MS/MS fragmentation patterns of N-type ceramides were characterized by interpreting their product ion scan mass spectra. This information may be used to identify N-type ceramides in the SC of human, rat, and mouse skin.

A retromolar canal is an anatomical variation in the mandible. As it includes the neurovascular bundle, local anesthetic insufficiency can occur, and an injury of the retromolar canal during dental surgery in the mandible may result in excessive bleeding, paresthesia, and traumatic neuroma. Using imaging analysis software, we evaluated the cone-beam computed tomography (CT) images of two Korean patients who presented with retromolar canals. Retromolar canals were detectable on the sagittal and cross-sectional images of cone-beam CT, but not on the panoramic radiographs of the patients. Therefore, the clinician should pay particular attention to the identification of retromolar canals by preoperative radiographic examination, and additional cone beam CT scanning would be recommended.

Continuous exposure to ultraviolet (UV) irradiation leads to a variety of skin damage, such as sunburn, pigmentation, premature ageing, and photocarcinogenesis. Various phytochemical extracts have been identified to efficiently protect sun exposed skin from UV induced photodamage. A Ficus deltoidea (Mas cotek) water extract has been widely used for women’s health in Malaysia. In a previous study from this lab, the F. deltoidea extract exhibited strong anti-melanogenic effects towards cultured B16F1 melanoma cells. Additional studies were intended to evaluate the effects of the F. deltoidea extract on antiphotoageing activity using cultured human dermal fibroblasts and immortalised human keratinocytes (HaCaT). Both TNF-α and cyclooxygenase (COX-2) play primary roles in the inflammation process upon UV irradiation and are known to be stimulated by UVB irradiation. Treatment with the F. deltoidea extract dramatically inhibited the UVinduced TNF-α, IL-1α, IL-6, and COX-2 expression. The decreased collagen synthesis of fibroblasts as a result of UVB exposure was restored to a normal level after treatment with the F. deltoidea extract. In addition, the enhanced MMP-1 expression upon UVB irradiation was downregulated by the F. deltoidea extract in a dose-dependent manner. The overall findings indicate that the F. deltoidea extract may exert a protective effect against UVB-induced damage in the skin that is useful for anti-photoageing cosmetic products.

Sea buckthorn (Hippophae rhamnoides L.) seed, which has very high nutraceutical, cosmetoceutical and therapeutic properties, has been widely used to treat diseases in Tibetan and Mongolian traditional medicines. In this study, we measured the antioxidant activities of the solvent-dependent SBS (Sea buckthorn seed) extracts using the DPPH and Folin-Ciocalteu assays and we investigated the efficacy of SBS in protecting skin against UVB-induced damage using cultured human dermal fibroblasts. In addition, the inhibitory effects of SBS on UVB-induced skin photoaging were examined by determining the level of Metalloproteinase (MMP)-1 and procollagen after UVB-irradiation. The antioxidant capacity of the SBSE (alcoholic) extract was significantly higher than the SBSH (hexane) and SBSW (water) extracts, as measured based on the free-radical scavenging activity and total phenolic content. SBSE was chosen as the most suitable candidate antioxidant. In human dermal fibroblasts, the cell viability of SBSE extract at doses of 2.5, 5, and 10 μg/mL was higher than the UVB-treated control. By RT-PCR and Western blot, SBSE treatment inhibited UVB-induced IL-1β expression in cultured cells. In addition, SBSE restrained UVB-induced IL-6 and COX-2 gene expression in cultured fibroblasts in a dose-dependent manner. Treatment with the SBSE extract after UVB irradiation in human dermal fibroblasts significantly reduced MMP-1 expression and increased procollagen synthesis when compared with UVB-irradiation only. In this study, SBSE was shown to increase the synthesis of procollagen, decrease the expression of MMP-1, and inhibit the production of IL-1β, IL-6, and COX-2 in UVB-irradiated human fibroblasts. These findings suggest that the SBSE extract may be a potential therapeutic agent for preventing and treating skin photoaging.

For the purpose of production of GABA-rich tomato paste, this study was carried out to investigate GABA producing lactic acid bacteria from Korean traditional fermented food, Kimchi and optimize the culture conditions. As a result of fermentation, Lactobacillus brevis B3-20 among lactic acid bacteria isolated at the pre-experiments was the best producer of GABA at the tomato paste medium with 50%(wet-base) levels of dionized water. At the result of fermentation on the tomato paste medium with 0.5%(w/w) yeast extract, as a source of nitrogen, 3%(w/w) MSG(monosodium glutamate) and dionized water(the ratio of tomato paste and water was 2:8), Lb. brevis B3-20 produced the maximum GABA concentration, 143.38 mM. GABA-rich tomato paste showed the activity of free radical scavenging. Because GABA-rich tomato paste have functional ingredients such as ascorbic acid, lycopene, carotenoid, as well as GABA by lactic acid bacteria fermentation, GABA-rich tomato paste can be considered high functional materials. Key words: GABA, tomato paste, Lactobacillus sp., free radical scavenging

In this study, diagnostic reference levels (DRLs) were suggested and patient doses were analysed through the dose-area product value in dental radiography. In intraoral radiography, at three sites, i.e. molar, premolar and incisor on the maxilla and acquired third quartile values: 55.5, 46 and 36.5 mGy cm(2), respectively, were measured. In panoramic, cephalometric and cone beam computed tomography, the values were 120.3, 146 and 3203 mGy cm(2) (16 × 18 cm), respectively. It has been shown that, in intraoral radiography, the patient dose changes proportionally to the value of mA s, but the change in extraoral radiography in response to mA s could not be confirmed. The authors could confirm, however, the difference in dose according to the manufacturer in all dental radiography examinations, except for panoramic radiography. Depending on the size of hospital, there were some differences in patient dose in intraoral radiography, but no difference in patient dose in extraoral radiography.

Uncontrolled chronic hyperglycaemia including type 2 diabetes mellitus (DM) induces many skin problems related to chronic impaired skin barrier state. However, little is known about the skin barrier state of chronic hyperglycaemia patients, the dysfunction of which may be a major cause of their skin problems. In this study, we investigated whether a long-standing hyperglycaemic condition including type 2 DM impairs skin barrier homoeostasis in proportion to the duration and its pathomechanism. We utilized the Otsuka Long-Evans Tokushima Fatty (OLETF) rats as an animal model of long-standing hyperglycaemia and Long-Evans Tokushima Otsuka rats as a control strain. We confirmed that a long-standing hyperglycaemia delayed skin barrier homoeostasis, which correlated with haemoglobin A1c levels. OLETF rats as a long-standing hyperglycaemia model exhibited decreased epidermal lipid synthesis and antimicrobial peptide expression with increasing age. Decreased epidermal lipid synthesis accounted for decreased lamellar body production. In addition, OLETF rats had significantly higher serum levels of advanced glycation end products (AGEs) and elevated levels of the receptor for AGE in the epidermis. A long-standing hyperglycaemic condition impairs skin barrier function including permeability and antimicrobial barriers by accelerating skin ageing process in proportion to the duration of hyperglycaemia, which could be a major pathophysiology underlying cutaneous complications of DM.

Device performance and reliability characteristics of various types of Ru–Al-based metal gates on HfSiO gate dielectrics were investigated for p-type metal-oxide-semiconductor field effect transistor (pMOSFET) applications. Using the high work function of Ru and a dipole formed by Al atoms in a gate dielectric, the threshold voltage of the pMOSFET could be controlled successfully. However, the excessive diffusion of Al atoms generated more interface states and bulk trapping in the high-k dielectric layer and degraded the device performances and reliability characteristics. It was also found that the carefully tailored sequence of deposition and composition of Ru and Al metals can be used to prevent the excessive diffusion of Al atoms.

Ficus deltoidea (Mas cotek) water extract has been widely used for woman health in Malaysia. Our investigation focused to identify anti-melanogenic efficacy of F. deltoidea since it has been known to have strong anti-oxidant activities. Anti-melanogenic effect of F. deltoidea extract was analyzed using cultured B16F1 melanoma cells. Cytotoxicity of the extract was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and determined the highest concentration of the extract that did not affect cell viability as 0.1% (w/v). α-MSH-induced melanin synthesis was significantly inhibited with dose-dependent manner by treatment of F. deltoidea leave extract, which was comparable to that of kojic acid. The extract directly inhibited mushroom tyrosinase activity and intracellular tyrosinase activity of B16F1 as well. The inhibition of intracellular tyrosinase activity was found to be exerted at the protein expression level when analyzed by immunoblot and tyrosinase zymography. The expression of microphthalmia-associated transcription factor (MITF) was also reduced by the F. deltoidea extract. In conclusion, F. deltoidea extract has strong anti-melanogenic activity that is exerted by direct inhibition of tyrosinase enzyme activity and by down-regulation of the expression of genes involved in the melanogenesis pathways. Collectively, data shown in this study strongly suggest that F. deltoidea extract has potential to be used as a novel depigmenting agent for cosmetics.

According to the International Technology Roadmap for Semiconductors (ITRS), scaling to the 22 nm technology generation and beyond is facing significant challenges related to the timely implementation of high-k/metal gate stacks, including appropriate tuning of the metal gate work function, adequate channel mobility, and reliability. Scaling equivalent oxide thickness (EOT) becomes more challenging as it will reflect interfacial oxide layer (IL) scaling causing some issues such as mobility degradation and difficulty in achieving PMOSFET Vt target. This paper discusses issues on IL in the scaling the EOT of high-k/metal gates tacks.

In this study, we investigated the effects of a natural mineral extract on damaged skin keratinocytes. We have focused on the possible effects of the natural mineral extract on UV-irradiated normal human skin keratinocytes. Human keratinocytes were UV-irradiated and were treated with 0.1, 1.0, or 10% of natural mineral extract. Study controls included non-UV-irradiated cells, UV-irradiated cells (no extract), and UV-irradiated cells treated with 25 nM ascorbic acid. Cell viability following UV irradiation was significantly higher in the groups treated with the natural mineral extract at doses of 0.1, 1.0, and 10% than in the control group with UV irradiation only. The UV-irradiated cells demonstrated increased secretion of laminin relative to non-irradiated controls. We found that treating these UV-irradiated keratinocytes with natural mineral extract reduced vacuole size and number, and it dose-dependently increased laminin secretion and reduced IL-2 synthesis. Also, MMP-1 and MMP-2 activity were significantly less in cells treated with natural mineral extract than in UV-irradiated controls. The UV irradiation reduced MMP-1 levels to 45±5 ng/mL from 130±5 ng/mL. In addition, MMP-2 production in keratinocytes was significantly reduced by 11±1 ng/mL compared to the UV-irradiation control. In conclusion, the results of this work suggest that natural mineral extract has effects on keratinocytes damaged by UV exposure.

Rice bran contains various polyphenolic compounds with anti-oxidative activities, and it has long been known to inhibit melanogenesis, but the inhibition mechanism has not been fully elucidated. Cofermentation of rice bran with Lactobacillus rhamnosus and Saccharomyces cerevisiae significantly reduced the cytotoxicity of the resulting extract to B16F1 melanoma cells. Marked reduction of alpha-melanocyte stimulating hormone (MSH) induced melanin synthesis was also observed upon treatment with fermented rice bran extract but it had no direct inhibitory effect on tyrosinase activity, while the intracellular tyrosinase activity was reduced by the extract. This result was further confirmed by an immunoblot assay measuring the level of tyrosinase protein. In addition, the expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanogenesis, was significantly decreased by the extract. All together, the fermented rice bran extracts showed an inhibitory effect on melanogenesis through downregulation of MITF, along with reduced cytotoxicity.

In this work, a novel type of composite scaffold was designed, which has the suitability of both high biocompatibility and strong mechanical properties, for use in bioartificial dermis applications. The reinforced scaffold consisted of a lyophilized collagen sponge formed around a cross-linked collagen meshwork with an average thread diameter of approximately 55 μm. Fibroblasts were cultured in the reinforced collagen sponge for 7 days, during which time the pores in the sponge became filled with cells that secreted extracellular matrix (ECM) to form a bioartificial dermis. Results of ultimate tensile strength (UTS) measurements and compression tests indicated that the bioartificial dermis formed around the reinforced collagen sponge showed about ten times the strength of the bioartificial dermis formed around a typical collagen sponge (1.5 ± 0.05 vs. 0.15 ± 0.05 and 2.5 ± 0.1 vs. 0.2 ± 0.08 MPa, respectively). As a result, reinforced collagen mesh improved mechanical properties and this technique will be possible to make stronger scaffolds, not only for artificial skin applications but also various artificial tissues, such as synthetic cartilage, bone, and blood vessels.

In an effort to find topical agents that prevent or retard cutaneous aging, seven functional lipids were screened for their procollagen-upregulating and matrix metalloproteinase (MMP)-1-downregulating activities in human dermal fibroblasts by Western blotting. The preventive effect on ultraviolet (UV)-induced decrease of procollagen was demonstrated in phosphatidylserine (PS), lysophosphatidylserine (LPS), lysophosphatidic acid (LPA), N-acetyl phytosphingosine (NAPS), and tetraacetyl phytosphingosine (TAPS). Furthermore, PS, LPS, and LPA upregulated procollagen expression in unirradiated basal conditions. The inhibitory effect on UV-induced MMP-1 expression was seen in NAPS, TAPS, LPA, PS, lysophosphatidylglycerol, and LPS. PS was chosen as the most suitable candidate anti-aging chemical for the subsequent in vivo studies. We investigated the effects of PS on acute UV response and chronologic skin aging by topically applying it to young skin before UV irradiation and to aged human skin, respectively. Real-time PCR and Western blot revealed that in the young skin, PS treatment prevented UV-induced reduction in procollagen expression and inhibited UV-induced MMP-1 expression. PS also blocked UV-induced IL-6 and COX-2 gene expression in cultured fibroblasts dose-dependently. In the aged skin, PS caused increased procollagen transcription and procollagen immunostaining in the upper dermis, and a significant decrease in MMP-1 expression at both mRNA and protein levels. These results indicate that topical PS has anti-skin-aging properties and point to the potential use of PS as a therapeutic agent in the prevention and treatment of cutaneous aging.

In a search for the wound healing accelerators, we found that tetraacetyl-phytosphingosine (TAPS), a sphingolipid metabolite produced by phytosphingosine acetylation, has significant inhibitory potential on healing of rabbit ear wound. As angiogenesis is fundamental to proper wound healing, we examined the effect of TAPS on angiogenesis using human umbilical vein endothelial cells cultured in vitro. TAPS markedly decreased vascular endothelial growth factor (VEGF)-induced chemotactic migration and capillary-like tube formation. Recognizing its inhibitory potential on angiogenesis, we further investigated the action mechanism of TAPS. TAPS significantly inhibited VEGF-induced proteolytic enzyme production, including matrix metalloproteinase-2, urokinase-type plasminogen activator and plasminogen activator inhibitor-1. TAPS also suppressed VEGF-induced phosphorylation of p42/44 extracellular signal-regulated kinase and c-Jun N-terminal kinase. In addition, TAPS abolished VEGF-induced intracellular calcium increase, measured using laser scanning confocal microscopy. Together, these results suggest that TAPS exerts its inhibitory action on angiogenesis through the inhibition of mitogen-activated protein kinase activation and intracellular calcium increase, thereby affecting the process of wound healing negatively.

Electron trapping in high- gate dielectrics under constant voltage stress is investigated. It is suggested that the electron trapping occurs through a two-step process: resonant tunneling of the injected electron into the preexisting defects (fast trapping) and thermally activated migration of trapped electrons to unoccupied traps (slow trapping). Characteristics of the electron traps extracted based on the proposed model are in good agreement with the calculated properties of the negatively charged oxygen vacancies. The model successfully describes low-temperature threshold voltage instability in NMOS transistors with /TiN gate stacks.

Sphingosine 1-phosphate (S1P), a product of sphingosine kinases (SphK), mediates diverse biological processes such as cell differentiation, proliferation, motility, and apoptosis. In an effort to search and identify specific inhibitors of human SphK, the inhibitory effects of synthetic sphingoid analogs on kinase activity were examined. Among the analogs tested, we found two, SG12 and SG14, that have specific inhibitory effects on hSphK2. N,N-Dimethylsphingosine (DMS), a well-known SphK inhibitor, displayed inhibitory effects for both SphK1 and SphK2, as well as protein kinase C. In contrast, SG12 and SG14 exhibited selective inhibitory effects on hSphK2. Furthermore, SG14 did not affect PKC. In isolated platelets, SG14 blocked the conversion of sphingosine into sphingosine 1-phosphate significantly. This is the first report on the identification of a hSphK2-specific inhibitor, which may provide a useful tool for studying the biological functions of hSphK2.

Mortierella alpina was grown in a fed-batch culture using a 12-l jar fermenter with an initial 8-l working volume containing 20 g glucose l−1 and 10 g corn-steep powder l−1. Glucose was intermittently fed to give 32 g l−1 at each time. The pH of culture was maintained using 14% (v/v) NH4OH, which also acted as a nitrogen source. A final cell density of 72.5 g l−1 was reached after 12.5 days with a content of arachidonic acid (ARA) at 18.8 g l−1. These values were 4 and 1.8 times higher than the respective values in batch culture. Our results suggest that the combined feeding of glucose and NH 4 + to the growth of M. alpina could be applied for the industrial scale production of ARA.

Antigen-induced degranulation of mast cells plays a pivotal role in allergic and inflammatory responses. Recently, ceramide kinase (CERK) and its phosphorylated product ceramide 1-phosphate (C1P) have emerged as important players in mast cell degranulation. Here, we describe the synthesis of a novel F-12509A olefin isomer, K1, as an effective CERK inhibitor. In vitro kinase assays demonstrated that K1 effectively inhibits CERK without inhibiting sphingosine kinase and diacylglycerol kinase. Treating RBL-2H3 cells with K1 reduced cellular C1P levels to 40% yet had no effect on cell growth. Furthermore, treatment with K1 significantly suppressed both calcium ionophore- and IgE/antigen-induced degranulation, indicating that K1 interferes with signals that happen downstream of Ca(2+) mobilization. Finally, we show that K1 affects neither IgE/antigen-induced global tyrosine phosphorylation nor subsequent Ca(2+) elevation, suggesting a specificity for CERK-mediated signals. Our novel CERK inhibitor provides a useful tool for studying the biological functions of CERK and C1P. Moreover, to our knowledge, this is the first report demonstrating that inhibition of CERK suppresses IgE/antigen-induced mast cell degranulation. This finding suggests that CERK inhibitors might be a potential therapeutic tool in the treatment of allergic diseases.

We evaluated the feasibility of using an ultra thin aluminum nitride (AlN) buffer layer for dual metal gates CMOS process. Since the buffer layer should not affect the thickness of gate dielectric, it should be removed or consumed during subsequent process. In this work, it was shown that a thin AlN dielectric layer would be reacted with initial gate metals and would be consumed during subsequent annealing, resulting in no increase of equivalent oxide thickness (EOT). The reaction of AlN layer with tantalum (Ta) and hafnium (Hf) during subsequent annealing, which was confirmed with X-ray photoelectron spectroscopy (XPS) analysis, shifted the flat-band voltage of AlN buffered MOS capacitors. No contribution to equivalent oxide thickness (EOT) was also an indication showing the full consumption of AIN, which was confirmed with TEM analysis. The work functions of gate metals were modulated through the reaction, suggesting that the consumption of AlN resulted in new thin metal alloys. Finally, it was found that the barrier heights of the new alloys were consistent with their work functions.

Saccharomyces cerevisiae sphinganine C4-hydroxylase encoded by the SUR2 gene catalyses the conversion of sphinganine to phytosphingosine. We isolated the SUR2 gene from Pichia ciferrii using nucleotide sequence homology to S. cerevisiae SUR2 to study hydroxylation of sphinganine in the sphingoid base overproducing yeast P. ciferrii. A positive clone was confirmed by nucleotide sequencing. A syringomycin-E resistance phenotype of a S. cerevisiae sur2-null mutant was complemented by expression of the cloned P. ciferrii SUR2 gene. Restoration of phytosphingosine production in the complemented strain was also confirmed, indicating that the cloned gene is a functional homologue of S. cerevisiae SUR2. .

Obtaining a sufficient amount of healthy keratinocytes from a small tissue is difficult. However, ORS cells can be a good source of epithelium since they are easily obtainable and patients do not have to suffer from scar formation at donor sites. Accordingly, the current study modified the conventional primary culture technique to overcome the low propagation and easy aging of epithelial cells during culturing. In a conventional primary culture, the average yield of human ORS cells is 2.1×103 cells/follicle based on direct incubation in a trypsin (0.1%)/EDTA (0.02%) solution for 15 min at 37°C, however, our modified method was able to obtain about 6.9×103 cells/follicle using a two-step enzyme digestion method involving dispase (1.2 U/mL) and a trypsin (0.1%)/EDTA (0.02%) solution. Thus, the yield of primary cultured ORS cells could be increasd three times higher. Furthermore, a total of 2.0×107 cells was obtained in a serum-free medium, while a modified E-medium with mitomycin C-treated feeder cells produced a total of 6.3×107 cells over 17 days when starting with 7.5×104 cells. Finally, we confirmed the effectiveness of our ORS cell isolation method by presenting their ability for reconstructing the bioartificial skin epitheliumin vitro

Ficus deltoidea from the Moraceae family is a popular medicinal herb in Malaysia. It possesses strong antioxidant and antiinflammatory properties. In the present study, the anti-inflammatory effects of F. deltoidea extract on UVB-irradiated HaCaT Keratinocytes were investigated. HaCaT Keratinocytes were UVBirradiated (12.5 mJ/cm3) and were treated with 0.05, 0.08 or 0.1% of F. deltoidea extract. Cell viability following UVB irradiation was significantly higher in the groups treated with the F. deltoidea extract at doses of 0.05, 0.08 or 0.1% than in control group with UVB irradiation only. Tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), interleukin-6 (IL-6) and cyclooxygenase (COX-2) play primary roles in the inflammation process upon UV irradiation and are known to be stimulated by UVB irradiation. Treatment with the F. deltoidea extract dramatically inhibited the UV-induced TNF-α, IL-1α, IL-6, and COX-2 expression. These results suggest that the F. deltoidea extract inhibits the production of pro-inflammatory cytokines and may be an effective protective agent for the treatment of skin diseases., {"references":["K. B. Beckman, and B. N. Ames, \"The free radical theory of aging\nmatures,\". Physiol. Rev., vol. 78, pp. 547–581, 1998.","S. Pillai, C. Oresajo, and J. Hayward, \"Ultraviolet radiation and skin\naging: roles of reactive oxygen species, inflammation and protease\nactivation, and strategies for prevention of inflammation-induced matrix\ndegradation — a review,\". Int. J. Cosmet. Sci., vol. 27, pp. 17–34, 2005.","A. Pupe, R. Moison, P. De Haes, G. B. Van Henegouwen, L. Rhodes, H.\nDegreef, and M. Garmyn, \"Eicosapentaenoic acid, a n-3 polyunsaturated\nfatty acid differentially modulates TNF-alpha, IL-1alpha, IL-6 and PGE2\nexpression in UVB irradiated human keratinocytes,\". J. Invest.\nDermatol., vol. 118, pp. 692–698, 2002.","C. E. M. Griffiths, G. Russman, G. Majmudar, R. S. Singer, T. A.\nHamilton, and J. J. Voorhees, \"Restoration of collagen formation in\nphotodamaged human skin by tretinoin (retinoic acid),\". N. Engl. J.\nMed., vol. 329, pp. 530-534, 1993.","L. J. McCawley, and L. M. Matrisian, \"Matrix metalloproteinases:\nthey're not just for matrix anymore,\". Curr. Opin. Cell. Biol., vol. 13, pp.\n534–540, 2001.","E. J. Jung, J. Lee, J. Baek, K. Jung, S. Huh, S. Kim, J. Koh, and D. Park,\n\"Effect of Camellia japonica oil on human type I procollagen production and skin barrier function,\". J. Ethnopharmacol., vol. 112, pp. 127–131,\n2007.","S. R. Pinnell, \"Cutaneous photodamage, oxidative stress, and topical\nantioxidant protection\". J. Am. Acad. Dermatol., vol. 48, pp. 1–19, 2003.","I. A. Jahan, N. Nahar, M. Mosihuzzaman, B. Rokeya, L. Ali, A. K. Azad\nKhan, T. Makhmur, and M. Iqbal Choudhary, \"Hypoglycaemic and\nantioxidant activities of Ficus racemosa Linn. Fruits,\". Nat. Prod. Res.,\nvol. 23, pp. 399-408, 2009.","R. K. Singh, S. Mehta, D. Jaiswal, P. K. Rai, and G. Watal,\n\"Antidiabetic effect of Ficus bengalensis aerial roots in experimental\nanimals,\". J. Ethnopharmacol., vol. 123, pp. 110-114, 2009.\n[10] A. Grone, \"Keratinocytes and cytokines,\". Vet. Immunol.\nImmunopathol., vol. 88, pp. 1–12, 2002.\n[11] L. Rittie, and G. J. Fisher, \"UV-light-induced signal cascades and skin\naging,\". Ageing Res. Rev., vol. 1, pp. 705–720, 2002.\n[12] Z. Adam, M. Hamid, A. Ismail, and S. Khamis, \"Effect of Ficus\ndeltoidea extract on hepatic basal and insulin-stimulated glucose\nuptake,\". J. Biol. Sci., vol. 9, pp. 796-803, 2009.\n[13] M. R. Sulaiman, M. K. Hussain, Z. A. Zakaria, M. N. Somchit, S. Moin,\nA. S. Mohamad, and D. A. Israf, \"Evaluation of the antinociceptive\nactivity of Ficus deltoidea aqueous extract,\". Fitoterapia, vol. 79, pp.\n557-561, 2008.\n[14] M. J. Oh, M. Abdul Hamid, S. Ngadiran, Y. K. Seo, M. R. Sarmidi, and\nC. S. Park, \"Ficus deltoidea (Mas cotek) extract exerted antimelanogenic\nactivity by preventing tyrosinase activity in vitro and by\nsuppressing tyrosinase gene expression in B16F1 melanoma cells,\".\nArch. Dermatol. Res., vol. 303, pp. 161-170, 2010.\n[15] Z. Abdullah, H. Khalid, I. Zhari, and M. A. Rasadah, \"Antiinflammatory\nactivity of standardized extracts of leaves of three varieties\nof Ficus deltoidea,\". Int. J. Pharm. Clin. Res., vol. 1, pp. 100-105, 2009."]}

Superimposition has been used as a method to evaluate the changes of orthodontic or orthopedic treatment in the dental field. With the introduction of cone beam CT (CBCT), evaluating 3 dimensional changes after treatment became possible by superimposition. 4 point plane orientation is one of the simplest ways to achieve superimposition of 3 dimensional images. To find factors influencing superimposition error of cephalometric landmarks by 4 point plane orientation method and to evaluate the reproducibility of cephalometric landmarks for analyzing superimposition error, 20 patients were analyzed who had normal skeletal and occlusal relationship and took CBCT for diagnosis of temporomandibular disorder. The nasion, sella turcica, basion and midpoint between the left and the right most posterior point of the lesser wing of sphenoidal bone were used to define a three-dimensional (3D) anatomical reference co-ordinate system. Another 15 reference cephalometric points were also determined three times in the same image. Reorientation error of each landmark could be explained substantially (23%) by linear regression model, which consists of 3 factors describing position of each landmark towards reference axes and locating error. 4 point plane orientation system may produce an amount of reorientation error that may vary according to the perpendicular distance between the landmark and the x-axis; the reorientation error also increases as the locating error and shift of reference axes viewed from each landmark increases. Therefore, in order to reduce the reorientation error, accuracy of all landmarks including the reference points is important. Construction of the regression model using reference points of greater precision is required for the clinical application of this model.

Background Ultraviolet (UV) irradiation on the skin induces photoaging which is characterized by keratinocyte hyperproliferation, generation of coarse wrinkles, worse of laxity and roughness. Upon UV irradiation, nuclear factor kappa B (NF-κB) is activated which plays a key role in signaling pathway leading to inflammation cascade and this activation stimulates expression of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1alpha (IL-1α) and a stress response gene cyclooxygenase-2 (COX-2). In addition, activation of NF-κB up-regulates the expression of matrix metalloprotease-1 (MMP-1) and consequently collagen in dermis is degraded. Objective In this study, the effects of a NF-κB-derived inhibitor tripeptide on the UVB-induced photoaging and inflammation were investigated in vitro and in vivo. Methods A NF-κB-derived inhibitor tripeptide (NF-κB-DVH) was synthesized based on the sequence of dimerization region of the subunit p65 of NF-κB. Its inhibitory activity was confirmed using chromatin immunoprecipitation assay and in situ proximate ligation assay. The effects of anti-photoaging and anti-inflammation were analyzed by Enzyme-linked immunosorbent assay (ELISA), immunoblotting and immunochemistry. Results NF-κB-DVH significantly decreased UV-induced expression of TNF-α, IL-1α, MMP-1 and COX-2 while increased production of type I procollagen. Conclusion Results showed NF-κB-DVH had strong anti-inflammatory activity probably by inhibiting NF-κB activation pathway and suggested to be used as a novel agent for anti-photoaging.

Objective: To evaluate what type of surgery would be more reasonable among 3 types of laparoscopic hysterectomy and to evaluate the safety of cardio-pulmonary changes on these patients during these operations. Method: A retrospective study was carried out in 215 women who underwent laparoscopic hysterectomy including laparoscopic-assisted vaginal hysterectomy (LAVH), laparoscopic hysterectomy (LH), total laparoscopic hysterectomy (TLH). Blood gas analysis, end-tidal CO2 levels and vital signs were checked and compared with control and preceding values. Results: The average duration of operation was 102.5 min, 83.8 min and 118.3 min for LAVH (n = 97), LH (n = 75) and TLH (n = 43), respectively (p < 0.05). The average amount of bleeding was 297.5 ml, 152.3 ml and 149.2 ml for each type of hysterectomy, respectively. Hemoglobin decreased by an average of 1.6 g/100 ml, 0.9 g/100 ml and 0.8 g/100 ml, respectively. There was a lesser amount of bleeding for LH and TLH than for LAVH (p < 0.05). Profiles of blood gas analysis and expiratory CO2 varied significantly according to the operative stages under controlled anesthesia (p < 0.05), but were within the normal range. Conclusion: These results demonstrate that laparoscopic procedures advancing below the uterine vasculature can be considered effective for hysterctomies and that proper anesthesia can safely control the cardio-pulmonary changes during laparoscopic hysterectomy.

High work function (4.9 eV) on high-/spl kappa/ gate dielectric, which is suitable for bulk p-MOSFET, has been achieved using fully silicided (FUSI) Pt/sub x/Si gate without boron predoping of polysilicon. High concentration of Pt in FUSI Pt/sub x/Si using Ti capping layer on Pt in the FUSI process is a key to achieving high work function and reduced Fermi-level pinning on high-/spl kappa/ dielectric. By combining with substituted Al (SA) gate for nMOSFET, a wide range of work function difference (0.65 eV) between n and pMOSFETs is demonstrated, without any adverse effects of polysilicon predoping.

Contemporary and future programming languages for HPC promote hybrid parallelism and shared memory abstractions using a global address space. In this programming style, data races occur easily and are notoriously hard to find. Existing state-of-the-art data race detectors exhibit 10X-100X performance degradation and do not handle hybrid parallelism. In this paper we present the first complete implementation of data race detection at scale for UPC programs. Our implementation tracks local and global memory references in the program and it uses two techniques to reduce the overhead: 1) hierarchical function and instruction level sampling; and 2) exploiting the runtime persistence of aliasing and locality specific to Partitioned Global Address Space applications. The results indicate that both techniques are required in practice: well optimized instruction sampling introduces overheads as high as 6500% (65X slowdown), while each technique in separation is able to reduce it only to 1000% (10X slowdown). When applying the optimizations in conjunction our tool finds all previously known data races in our benchmark programs with at most 50% overhead when running on 2048 cores. Furthermore, while previous results illustrate the benefits of function level sampling, our experiences show that this technique does not work for scientific programs: instruction sampling or a hybrid approach is required.

Contemporary and future programming languages for HPC promote hybrid parallelism and shared memory abstractions using a global address space. In this programming style, data races occur easily and are notoriously hard to find. Previous work on data race detection for shared memory programs reports 10X-100X slowdowns for non-scientific programs. Previous work on distributed memory programs instruments only communication operations. In this paper we present the first complete implementation of data race detection at scale for UPC programs. Our implementation tracks local and global memory references in the program and it uses two techniques to reduce the overhead: 1) hierarchical function and instruction level sampling; and 2) exploiting the runtime persistence of aliasing and locality specific to Partitioned Global Address Space applications. The results indicate that both techniques are required in practice: well optimized instruction sampling introduces overheads as high as 6500% (65X slowdown), while each technique in separation is able to reduce it to 1000% (10X slowdown). When applying the optimizations in conjunction our tool finds all previously known data races in our benchmark programs with at most 50% overhead. Furthermore, while previous results illustrate the benefits of function level sampling, our experiences show that this technique does not work for scientific programs: instruction sampling or a hybrid approach is required.

Substituted aluminum (SA) metal gate on high-/spl kappa/ gate dielectric is successfully demonstrated. Full substitution of polysilicon with Al is achieved for a Ti-Al-polysilicon-HfAlON gate structure by a low-temperature annealing at 450/spl deg/C. The SA gate on HfAlON dielectric shows a very low work function of 4.25eV, which is well suitable for bulk nMOSFETs. The SA process is fully free from the Fermi-level pinning problem. In addition, the SA process also shows improved uniformity in leakage current distribution compared to fully silicided metal gate.

We demonstrate a top-surface aluminized and nitrided HfO/sub 2/ gate dielectric using a synthesis of ultrathin aluminum nitride (AlN) and HfO/sub 2/. The reaction of AlN with HfO/sub 2/ through a subsequent high-temperature annealing incorporates Al and N into an HfO/sub 2/ layer, which results in a synthesis of HfAlON near the top surface of HfO/sub 2/, forming an HfAlON-HfO/sub 2/ stack structure. This approach suppresses interfacial layer growth and improves thermal stability of the dielectric, resulting in significant improvement in leakage current. It also shows no adverse effects caused by N and Al incorporation at the bottom interface.

We demonstrate, for the first time, thermally stable fully silicided (FUSI) Hf-silicide gate electrode whose work function (4.2 eV) is very close to that of n/sup +/ polysilicon. No polysilicon depletion effect and excellent thermal stability with negligible change in equivalent oxide thickness and flatband voltage even after high-temperature annealing at 950 /spl deg/C are demonstrated. These results indicate that FUSI Hf-silicide is a promising candidate for n-MOSFET metal-gate electrode for dual-metal CMOS process.

The GCR1 gene product is required for maximal transcription of yeast glycolytic genes and for growth of yeast strains in media containing glucose as a carbon source. Dominant mutations in two genes, SGC1 and SGC2, as well as recessive mutations in the SGC5 gene were identified as suppressors of the growth and transcriptional defects caused by a gcr1 null mutation. The wild-type and mutant alleles of SGC1 were cloned and sequenced. The predicted amino acid sequence of the SGC1 gene product includes a region with substantial similarity to the basic-helix-loop-helix domain of the Myc family of DNA-binding proteins. The SGC1-1 dominant mutant allele contained a substitution of glutamine for a highly conserved glutamic acid residue within the putative basic DNA binding domain. A second dominant mutant, SGC1-2, contained a valine-for-isoleucine substitution within the putative loop region. The SGC1-1 dominant mutant suppressed the GCR1 requirement for enolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, and pyruvate kinase gene expression. Expression of the yeast enolase genes was reduced three- to fivefold in strains carrying an sgc1 null mutation, demonstrating that SGC1 is required for maximal enolase gene expression. Expression of the enolase genes in strains carrying gcr1 and sgc1 double null mutations was substantially less than observed for strains carrying either null mutation alone, suggesting that GCR1 and SGC1 function on parallel pathways to activate yeast glycolytic gene expression.

We propose and demonstrate a novel approach for dual metal gate CMOS process integration through the use of a very thin aluminum nitride (AlN/sub x/) buffer layer between metal and gate oxide. This buffer layer prevents the gate oxide from being exposed to a metal etching process which potentially causes oxide thinning and damage. Subsequent annealing consumes the very thin AlN/sub x/ layer and converts it into a new metal alloy film by reacting with gate metals, resulting in no increase in EOT due to this buffer layer. The work function of the original gate metal is also modified as a result of its reaction with AlN/sub x/, making this approach extremely attractive for engineering the work function for dual metal gate CMOS applications.